JANSSEN PHARMACEUTICALS, INC. et al v. TEVA PHARMACEUTICALS USA, INC. et al

Filing 271

OPINION. Signed by Judge Claire C. Cecchi on 10/8/2021. (ams, )

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UNITED STATES DISTRICT COURT
DISTRICT OF NEW JERSEY
JANSSEN PHARMACEUTICALS, INC. and
JANSSEN PHARMACEUTICA NV,

Civil Action No.: 18-734
OPINION

Plaintiffs,
v.
TEVA PHARMACEUTICALS USA, INC.,
Defendant.
CECCHI, District Judge.
This patent case was brought by Plaintiffs Janssen Pharmaceuticals, Inc. and Janssen
Pharmaceutica NV (collectively, “Plaintiffs” or “Janssen”) against Defendant Teva
Pharmaceuticals USA, Inc. (“Defendant” or “Teva”). This action specifically concerns the validity
of Claims 1–21 of U.S. Patent No. 9,439,906 (the “’906 Patent” or the “Patent-in-Suit”). ECF No.
133 (“Final Pretrial Order”) at 2. The ’906 Patent covers “a dosing regimen for administering
paliperidone palmitate to a psychiatric patient in need of treatment for schizophrenia,
schizoaffective disorder, schizophreniform disorder, or other psychotic disorders.” Id.
The Court held a two-week bench trial in this matter that began on October 13, 2020, and
concluded on October 30, 2020. ECF Nos. 135–37, 140–41, 145–49, 151. The parties submitted
post-trial briefing and proposed findings of fact and conclusions of law in December 2020. ECF
Nos. 164 (“Pls. Br.”), 165 (“PFOF”), 167 (“Def. Br.”), 167-1 (corrected at 168-1 (“DFOF”)). On
January 8, 2021, the parties submitted responsive briefs. ECF Nos. 188 (“Pls. Reply Br.”), 189
(“Def. Reply Br.”). Closing arguments were held on March 5, 2021. ECF No. 199.
In a letter dated December 5, 2017, Teva notified Janssen that it had submitted Abbreviated

1

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New Drug Application (“ANDA”) No. 211149 to the United States Food and Drug Administration
(“FDA”) “seeking FDA approval to engage in the commercial manufacture, use, sale, offer for
sale in, and/or importation into the United States of generic paliperidone palmitate extendedrelease injectable suspension products . . . prior to the expiration of the 906 Patent.” Final Pretrial
Order at 2. Defendant does not contest infringement of the ’906 Patent. Id. Therefore, the only
the issue for this Court to decide is whether the Patent-in-Suit is invalid based on the following
legal principles: (1) obviousness; (2) lack of written description; and (3) indefiniteness. 1 Id. at 2–
3.
This Opinion constitutes the Court’s findings of fact and conclusions of law pursuant to
Federal Rule of Civil Procedure 52(a). The findings of fact are based on the Court’s observations
and credibility determinations of the witnesses who testified at trial, and a thorough review of all
the evidence admitted at trial. While the Court has reviewed all of the evidence presented, given
the length of the trial record, the Court includes references only to the evidence most pertinent to
its analysis. 2 For the reasons set forth below, the Court finds that the Patent-in-Suit is not invalid.
I.

BACKGROUND
A. Parties
Plaintiff Janssen Pharmaceuticals, Inc. is a corporation organized and existing under the

laws of the Commonwealth of Pennsylvania, and has its principal place of business at 1125
Trenton-Harbourton Road, Titusville, New Jersey 08560. Id. at 4. Plaintiff Janssen Pharmaceutica
1

Post-trial, in July 2021, Teva filed a motion to amend pursuant to Federal Rule of Civil Procedure
15(b)(2), asking the Court to deem its pleadings amended with a count for patent invalidity due to
incorrect inventorship under 35 U.S.C. § 102(f). ECF No. 244. The Court will discuss this motion
and the potential additional invalidity challenge later in this Opinion.
2
At the request of the Court, the parties submitted motions shortly after trial presenting their
arguments on certain evidentiary issues. ECF Nos. 152–153. All relevant evidentiary issues raised
in that briefing, any in limine motions, and elsewhere (e.g., ECF No. 98), are resolved in this
Opinion.
2

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NV is a corporation organized and existing under the laws of Belgium, and has its principal place
of business at Turnhoutseweg, 30, B-2340 Beerse, Belgium. Id. Janssen Pharmaceutica NV “is
the owner of the entire right, title, and interest in and to the ’906 Patent.” Id. at 5. Defendant Teva
is a corporation organized and existing under the laws of Delaware, and has its principal place of
business at 1090 Horsham Road, North Wales, Pennsylvania 19454. Id. at 4.
B. Background of the Invention
The dosing regimens at issue in this case provide detailed information concerning the use
of paliperidone palmitate to treat schizophrenia and other psychotic disorders. To this end, the
’906 Patent discloses unique combinations of dose amounts, dosing schedules, injection sites, and
formulation properties. PFOF ¶ 7. 3 The main dosing regimen contained in Claim 2 consists of a
150 mg-eq. 4 first loading dose of paliperidone palmitate in the deltoid muscle on the first day of
treatment, a second loading dose of 100 mg-eq. in the deltoid muscle during the sixth to tenth day
of treatment, and successive monthly (± 7 days) maintenance doses of 25 mg-eq. to about 150 mgeq. in either the deltoid or gluteal muscle. ’906 Patent (DTX-1/PTX-1) col. 32:11–36. The main
dosing regimen for patients with renal impairment contained in Claim 10 consists of a loading
dose from about 75 mg-eq. in the deltoid muscle on the first day of treatment, a second loading
dose from about 75 mg-eq. in the deltoid muscle on the sixth to tenth day of treatment, and
successive monthly (± 7 days) maintenance doses of 25 mg-eq. to about 75 mg-eq. in either the
deltoid or gluteal muscle. Id. col. 33:3–27.
3

The parties have agreed to a representative set of claims for purposes of this matter. Final Pretrial
Order at 9. Claim 2 of the ’906 Patent represents Claims 1, 3–7, and 15; Claim 10 represents
Claims 8–9; Claim 13 represents Claims 11–12, 14, and 16; Claim 20 (as it depends from Claims
1 or 8) represents no other claims; and Claim 21 (as it depends from Claims 1 or 8) represents
Claims 17–19. Id. These Claims will be collectively referred to as the “Representative Claims.”
4
Doses of paliperidone palmitate are typically expressed in terms of their equivalent amount of
paliperidone (expressed as “milligram-equivalent” or “mg-eq.”) rather than their actual weight.
PFOF ¶ 6.
3

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This section will first provide the scientific background of the claimed invention. Next,
the Court will provide the relevant research and patent history for the Patent-in-Suit.
1.

Scientific Background

Schizophrenia is a chronic psychotic disorder that affects approximately one percent of the
world’s population. DFOF ¶ 52; PFOF ¶ 11. The disorder is most commonly characterized by
“disorganized behavior and speech, delusions, and hallucinations.” PFOF ¶ 11. Schizophrenia
often manifests “in young people between the ages of 15 and 30,” and is typically diagnosed after
an individual suffers an acute psychotic episode. Id. ¶ 12; Trial Tr. (Kohler) at 1883:4–12.
Antipsychotic medication is the main form of treatment for schizophrenia, and its aim is to achieve
remission such that a person with schizophrenia can manage their symptoms and function
independently. DFOF ¶¶ 53, 55; PFOF ¶ 12. There is currently no cure for schizophrenia, and
each psychotic episode inflicts permanent damage upon the brain and reduces the chances of
achieving remission. PFOF ¶¶ 12–13.
Schizophrenia is generally treated with antipsychotic drugs which have been available
since the 1950s. DFOF ¶ 54; PFOF ¶ 15. These drugs are typically administered orally or as longacting injectable formulations (“LAI”), sometimes referred to as a “depot.” DFOF ¶¶ 56–57; PFOF
¶¶ 14–15. Schizophrenia is challenging to treat because the symptoms of the disease make it
difficult for patients to comply with their prescribed treatment, particularly when it comes to daily
oral antipsychotics. DFOF ¶ 57; PFOF ¶ 14. When patients stop taking their medicine or miss a
dose, they often have a relapse in the form of an acute psychotic episode, which can set off a cycle
of worsening symptoms, additional missed treatment, and possibly institutionalization. Id.
“First-Generation” LAIs developed in the 1950s include “Prolixin (fluphenazine)
decanoate, Prolixin (fluphenazine) enanthate, and Haldol (haloperidol) decanoate.” PFOF ¶ 15.
These LAIs were accompanied by serious mental side effects such as dullness and cognitive
4

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impairment. Id. ¶ 16; see also DFOF ¶ 497. They were also associated with extrapyramidal
symptoms (“EPS”) consisting of serious motor impairments, painful muscle contractions, tremors,
and stiffness. PFOF ¶ 16; see also DFOF ¶¶ 497–498. Due to the severe mental and physical side
effects associated with First-Generation LAIs, they were generally restricted to institutionalized
patients who could not function in society. PFOF ¶ 17.
“Second-Generation” antipsychotics, developed in the 1980s and 1990s, were viewed as a
major improvement from First-Generation antipsychotics because they had less frequent and less
severe side effects (including EPS). Id. ¶ 19. Most of the Second-Generation antipsychotic drugs
were administered orally, with Janssen’s Risperdal Consta serving as the only Second-Generation
LAI on the market for some period of time. Id. Risperdal Consta, however, requires oral
supplementation for the first three weeks of treatment and provides only two weeks of therapeutic
benefits, making biweekly injections necessary. Id. ¶ 20.
Janssen sought to improve upon these limitations, and eventually received FDA approval
for Invega Sustenna in 2009. Id. ¶ 60. Invega Sustenna is seen as a vastly superior product to
Risperdal Consta due to its unique dosing regimen consisting of high loading dose injections to
initiate treatment and monthly maintenance injections thereafter. Id. ¶ 175–76. The dosing
regimen does not require oral supplementation, is initiated in a uniform manner, and has led to
important benefits such as improved treatment adherence and reduced risk of relapse. Id. ¶¶ 176,
190. Invega Sustenna is a “blockbuster” drug, and since 2013, it has accounted for the largest
revenue share in the LAI antipsychotic market, with net sales of $1.7 billion in 2019 alone. Id. ¶¶
187–88. When dosed according to its label, Invega Sustenna practices the claims of the ’906
Patent. Id. ¶ 171.
2.

Research and Patent History

Invega Sustenna was developed over the course of more than a decade, in a process
5

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involving multiple stages of research, numerous clinical trials, and various unexpected setbacks.
Id. ¶¶ 26, 36. The initial preclinical stage of the process consisted of formulation development
and animal research. Id. Following the preclinical stage, Janssen began Phase I clinical trials.
During Phase I, Janssen studied the formulation of paliperidone palmitate to be used in the drug,
eventually choosing formulation F13. Id. ¶ 27. Janssen also studied single versus multiple-dose
regimens, and deltoid versus gluteal injection sites in Phase I. Id. ¶¶ 27–29. In the BEL-7 Phase I
clinical trial, 5 Janssen observed better results with a loading dose regimen of double doses on day
1 followed by monthly maintenance doses, and chose this regimen for further development. Id. ¶
28. In the USA-3 Phase I clinical trial, Janssen observed that injections in the deltoid led to “higher
peak plasma concentrations compared to gluteal injections.” Id. ¶ 29. Based on these findings,
Janssen used the gluteal muscle for all injections in Phase II clinical trials because higher plasma
concentrations present a greater risk of severe side effects. Id.
After seven years of Phase I clinical trials, Janssen began Phase II clinical trials in October
2003. Id. ¶ 30. These clinical trials were designed to measure efficacy, and Janssen was excited
by the results of its SCH-201 Phase II clinical trial that indicated rapid efficacy compared to
placebo by day 8 of treatment. Id. ¶¶ 30–31. As Dr. An Vermeulen, a named inventor of the ’906
Patent, testified at trial, this was the “first study to demonstrate efficacy of” paliperidone, it
“confirmed safety and tolerability,” and “efficacy was achieved quickly within the first week.”
Trial Tr. (Vermeulen) at 776:8–12; ’906 Patent (DTX-1/PTX-1).

The Court credits Dr.

Vermeulen’s trial testimony, and notes that she is currently an internal consultant in the
Quantitative Sciences Consulting Group at Janssen. Trial Tr. (Vermeulen) at 744:3–6.

5

The Court notes that this Research and Patent History section only discusses a subset of the most
relevant studies that were conducted during the development of Invega Sustenna.
6

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In Phase III, Janssen developed three different trials to build on the SCH-201 trial. PFOF
¶ 32. The PSY-3004 and PSY-3003 trials compared equal doses of paliperidone palmitate in the
F11 and F13 formulations, with all injections given in the gluteal muscle on days 1/8/36/64, and
efficacy measured by assessing changes in PANSS scores. Id. ¶ 32. PANSS refers to the Positive
and Negative Syndrome Scale, a questionnaire administered to a patient asking about the
symptoms of schizophrenia. Id. ¶ 30. PSY-3002 was a non-inferiority study which tested the F11
and F13 formulations of paliperidone palmitate against Risperdal Consta in 749 patients. Id. ¶ 33.
Subjects in this study received 50 mg-eq. of paliperidone palmitate in the gluteal muscle on days
1 and 8, followed by either 25, 50, 75, or 100 mg-eq. doses monthly. Id.
All three trials were unexpected failures. Id. ¶¶ 36, 52. The results of PSY-3004 came in
May 2006 and were a major disappointment to Janssen as they showed no effectiveness in subjects
in the United States. Id. ¶ 34. Next, the PSY-3003 results arrived in August 2006 and brought
additional bad news as that study failed to demonstrate superiority of any dose of paliperidone
palmitate in the United States when compared to placebo. Id. ¶ 35. The results of PSY-3002,
which were also disappointing to Janssen, did not arrive until later and are discussed below.
In response to the disappointing results of PSY-3004 and PSY-3003, Janssen assembled a
task force of clinical, pharmaceutical, preclinical, bioanalytical, clinical pharmacology, and
pharmacometric 6 specialists to understand the results from these studies and formulate a path
forward. Id. ¶ 38. The task force, relying in large part on population pharmacokinetic modeling

6

Pharmacometrics is a discipline that applies advanced modeling techniques to make sense of data
across entire populations concerning pharmacokinetics (how the body handles a drug), taking into
account the patient-specific characteristics that lead to variability in individual exposure profiles.
PFOF ¶ 25. This work requires patient data and patient-specific characteristics to build a
mathematical model with both explanatory and predictive power. Id. The goal of this modeling is
to identify dosing regimens that are effective for the majority of subjects. Id.
7

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done by Dr. Vermeulen, found that body mass index had an impact on the levels of paliperidone
palmitate in the blood and found that choice of injection site had a significant effect as well. Id. ¶
42. In order to overcome these issues, the task force recommended a dosing regimen of 150 mgeq. in the deltoid muscle on day 1, followed by a dose of 25, 50, 100, or 150 mg-eq. in the deltoid
or gluteal muscle on day 8, and monthly maintenance doses. Id. ¶ 43.
This new dosing regimen was tested in the PSY-3007 and PSY-3006 Phase III clinical
trials. Id. ¶ 44. Dr. Srihari Gopal, a senior director in the Psychiatry Department at Janssen
Research and Development, LLC, led the design of these new trials. Id. ¶ 44; Final Pretrial Order
at 29. PSY-3007, which began in March 2007, compared a dosing regimen of 150 mg-eq. in the
deltoid muscle on day 1 followed by equal doses of either 25, 100, or 150 mg-eq. in the gluteal or
deltoid muscle against a placebo. PFOF ¶ 44. PSY-3006, which began the same month, was a
non-inferiority study comparing the F13 formulation of paliperidone palmitate to Risperdal
Consta. Id. ¶ 45. Patients in this study received 150 mg-eq. in the deltoid muscle on day 1 and 50
mg-eq. on day 8 in the gluteal or deltoid muscle, followed by monthly maintenance doses. Id.
After the results of PSY-3002 finally came back in May 2007 and failed to demonstrate noninferiority to Risperdal Consta, Janssen decided to modify the PSY-3006 study to change the day
8 dose from 50 mg-eq. in the gluteal or deltoid muscle to 100 mg-eq. in the deltoid muscle. Id. ¶¶
52–53. Around the same time, Dr. Mahesh Samtani, currently a senior scientific director at
Janssen, 7 took over for Dr. Vermeulen (Dr. Vermeulen had been promoted) and further developed
the population pharmacokinetic model. Id. ¶ 48; Trial Tr. (Samtani) at 1342:6–7. Dr. Samtani’s
new model ran simulations of different dosing regimens by varying sequencing, dose amount, and

7

As discussed later in this Opinion, Janssen asserts that Dr. Samtani and Dr. Gopal should be
added as named inventors of the ’906 Patent.
8

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administration site, to determine if Janssen’s preferred dosing regimen could achieve rapid efficacy
without oral supplementation in as many individuals as possible without risking severe side effects.
PFOF ¶ 50.
While awaiting the results of PSY-3007 and PSY-3006, Janssen began the FDA approval
process based in large part on Dr. Samtani’s modeling. Id. ¶¶ 56–57. In October 2007, Janssen
submitted a New Drug Application seeking approval for a 100/100 mg-eq., day 1/day 8 deltoid
muscle dosing regimen because it had Phase III safety data available for this regimen. Id. ¶ 57.
The FDA responded in August 2008 and suggested that Janssen consider a lower dosing regimen
of 75 or 100 mg-eq. on day 1, followed by 75 or 100 mg-eq. on day 8. Id. ¶ 58. Janssen countered
the FDA’s recommendation, using Dr. Samtani’s models, as well as the PSY-3007 results received
in the spring of 2008 and the PSY-3006 results received around July 2009, to show that the 150
mg-eq. day 1 and 100 mg-eq. day 8 dosing regimen (eventually claimed in the ’906 Patent) resulted
in more patients obtaining therapeutic levels of paliperidone by day 8. Id. ¶ 59–60. With this
showing, the FDA approved Janssen’s higher dosing regimen that Invega Sustenna practices in
2009. Id. ¶ 60. Janssen contends that this was a novel approach that went against the traditional
dosing philosophy generally used for LAI antipsychotics at the time. Id. ¶ 58. 8
C. Patent-in-Suit and Relevant Prosecution History
The ’906 Patent, entitled “Dosing Regimen Associated With Long Acting Injectable
Paliperidone Esters,” issued on September 13, 2016, and expires on January 26, 2031. ’906 Patent
(DTX-1/PTX-1). The asserted claims generally relate to:

8

The Court notes that the parties have different views regarding the development process of Invega
Sustenna, as Janssen claims that “the extraordinary skill of Janssen’s scientists” led to the project’s
success in spite of unexpected setbacks (Pls. Br. at 12), while Teva argues that “the alleged
difficulties Janssen faced during development were avoidable” (Def. Br. at 55). Given these
positions, further details on the drug development process will be discussed below.
9

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a dosing regimen for administering paliperidone esters to a psychiatric patient in
need of treatment comprising administering intramuscularly in the deltoid a first
loading dose from about 100 mg-eq. to about 150 mg-eq. of paliperidone as a
paliperidone palmitate formulated in a sustained release formulation on the first
day of treatment; administering intramuscularly a second loading dose from
about 100 mg to about 150 mg-eq. of paliperidone as a paliperidone palmitate
formulated in a sustained release formulation between about the 6th to 10th day
of treatment; and administering intramuscularly in the gluteal a maintenance
dose of about 25 to about 150 mg-eq. of paliperidone as a paliperidone ester in a
sustained release formulation on between about the 34th and about the 38th day
of treatment.
Id. col. 2:12–25. More specifically, the various claims of the ’906 Patent provide details about the
injection site, injection timing, and dosage amounts of paliperidone palmitate that should be used
(Claim 2), alternative dosing regimens for renally impaired patients whose kidneys do not clear
paliperidone as effectively as non-renally impaired patients (Claims 10 and 13), and precise
characteristics of the paliperidone palmitate formulation that must be used (Claims 20 and 21).
PFOF ¶¶ 7–9; see also ’906 Patent (DTX-1/PTX-1).
On December 19, 2007, Janssen filed U.S. Provisional Application No. 61/014,918 (the
“’918 Provisional”). PFOF ¶ 66. The ’906 Patent claims the benefit of both the ’918 Provisional
and U.S. Provisional Application 61/120,276 filed on December 5, 2008. ’906 Patent (DTX1/PTX-1) col. 1:8–10. Janssen subsequently filed application number 12/337,144 on December
17, 2009, which eventually matured into the ’906 Patent. Final Pretrial Order at 5. The ’906 Patent
then issued on September 13, 2016. ’906 Patent (DTX-1/PTX-1).
II.

ISSUES TO BE DECIDED
By Stipulation and Order dated June 8, 2020, Teva has agreed that for purposes of this

lawsuit, it “will not contest that the making, using, offering to sell, or sale of Teva’s Proposed
Generic Products within the United States . . . would infringe and/or induce infringement of any
valid Asserted Claim.” ECF No. 88 at 2. Accordingly, the question before this Court is whether

10

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the ’906 Patent is invalid based upon Teva’s asserted challenges.
III.

DISCUSSION
Issued patents are presumed valid. See 35 U.S.C. § 282(a). To rebut this presumption,

Defendant bears the burden of proving invalidity by clear and convincing evidence. Titan Tire
Corp. v. Case New Holland, Inc., 566 F.3d 1372, 1376 (Fed. Cir. 2009) (“Because of this
presumption, an alleged infringer who raises invalidity as an affirmative defense has the ultimate
burden of persuasion to prove invalidity by clear and convincing evidence, as well as the initial
burden of going forward with evidence to support its invalidity allegation.”).
A. Obviousness (35 U.S.C. § 103)
To prove that an asserted claim of a patent is invalid as obvious under 35 U.S.C. § 103, a
patent challenger bears the burden of establishing by clear and convincing evidence that the
“differences between the subject matter sought to be patented and the prior art are such that the
subject matter as a whole would have been obvious at the time the invention was made to a person
having ordinary skill in the art.” 35 U.S.C. § 103; 9 see also Pfizer, Inc. v. Apotex, Inc., 480 F.3d
1348, 1360–61 (Fed. Cir. 2007). A person of ordinary skill in the art will hereinafter be referred
to as a “POSA.” Obviousness is a question of law that is predicated on several factual inquiries.
See Graham v. John Deere Co. of Kansas City, 383 U.S. 1, 17 (1966). Specifically, there are four
basic factual inquiries that concern: (1) the scope and content of the prior art; (2) the level of
ordinary skill in the art; 10 (3) the differences between the claimed subject matter and the prior art;
9

The parties assert that the pre-America Invents Act version of 35 U.S.C. applies to the Patent-inSuit. Final Pretrial Order at 2.
10
Although the parties presented slightly different definitions of a POSA, they agree that any
differences are immaterial. See Trial Tr. (Closing Argument) at 122:9–123:10. Plaintiffs offer that
a POSA would have “an M.D., Ph.D., PharmD, or equivalent work experience in drug formulation,
pharmacy, pharmacokinetics, or medicine.” PFOF ¶ 77 n.7. Defendant proposes that “[a] POSA
is a person who would have an advanced degree such as an M.D., Ph.D., PharmD, master’s degree,
or other advanced degree in an area related to chemistry, pharmaceutics, medicine or biology, with
11

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and (4) objective indicia (secondary considerations) of nonobviousness, including commercial
success, long-felt but unsolved need, failure of others, and other indicia. See id.
Defendant asserts that the Patent-in-Suit is invalid because it is obvious in view of prior art
that would have motivated a POSA to arrive at the claimed dosing regimens with a reasonable
expectation of success. Def. Br. at 18. Defendant further argues that secondary considerations do
not overcome the prima facie case of obviousness. Id. at 44. Defendant also argues that a
presumption of obviousness applies to the Patent-in-Suit, stating that the Representative Claims
merely recite dosing and particle size ranges that overlap with ranges disclosed in the prior art. Id.
at 9–12. The Court will address these arguments in turn.
To establish obviousness, Defendant primarily relied on three prior art references at trial:
(1) a summary protocol for Janssen’s PSY-3003 clinical study titled “A Randomized, DoubleBlind, Placebo-Controlled, Parallel-Group, Dose-Response Study to Evaluate the Efficacy and
Safety of 3 Fixed Doses (50 Mg eq., 100 Mg eq., and 150 Mg eq.) of Paliperidone Palmitate in
Subjects With Schizophrenia” (the “’548 Protocol”); (2) U.S. Patent No. 6,555,544 (the “’544
Patent”), a patent assigned to Plaintiff Janssen Pharmaceutica, N.V. titled “Aqueous Suspensions
of Submicron 9-Hydroxyrisperidone Fatty Acid Esters”; and (3) International Patent Publication
Number WO 2006/114384 (the “WO’384 Publication”), an international patent publication filed
on behalf of Plaintiff Janssen Pharmaceutica, N.V. See PFOF ¶¶ 89, 93, 101; DFOF ¶¶ 138–39,
141, 178–80, 214; see also PTX-54, -55, -66; DTX-54, -55, -72. 11 Defendant also relies upon

several years of experience in the pertinent field and be capable of working in a team comprising
others in the field or related fields.” DFOF ¶ 136 (internal quotation marks omitted).
11
The Court notes that the United States Patent and Trademark Office (“USPTO”) considered a
number of the prior art references at issue in this case and concluded that the Patent-in-Suit was
not obvious in light of these references.
12

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various other prior art references, which the Court will address throughout this Opinion where
applicable.
In support of its obviousness arguments, Defendant proffered the following experts at trial:
(1) Dr. Daniel Paul H. Wermeling, Pharm.D., FCCP, FASHP, Emeritus Professor at the University
of Kentucky, College of Pharmacy, 12 and (2) Ivan T. Hofmann, Vice President and Managing
Director of Gleason IP. 13 DFOF ¶¶ 14–16, 26–28; Final Pretrial Order at 41, 43–45. 14
Plaintiffs contend that Defendant’s obviousness arguments fail because a POSA would not
have been motivated to create the claimed dosing regimens based on the prior art with a reasonable
expectation of success. See Pls. Br. at 25–41. Plaintiffs further assert that secondary considerations
support a finding of nonobviousness. Id. at 41–53. Plaintiffs also argue that no presumption of
obviousness applies here, and that even if a presumption is applied, it has been rebutted. Pls. Br.
at 54. In support of their arguments, Plaintiffs rely on the following experts: (1) Dr. Patrick J.
Sinko, Ph.D., R.Ph, Distinguished Professor of Pharmaceutics in the Ernest Mario School of

12

Dr. Wermeling is a named author on over 35 peer-reviewed publications related to
pharmacokinetics, pharmacodynamics, and bioavailability. Final Pretrial Order at 42. He has also
worked as a clinical investigator on studies related to pharmacokinetics and pharmacodynamics,
and has received over 60 grants for such studies and is a named inventor on six U.S. patents,
including two related to pharmaceutical compositions and methods of treatment using the
pharmaceutical composition. Id.
13
Mr. Hofmann’s work experience includes litigation support and consulting engagements with a
variety of pharmaceutical and biologics companies. Final Pretrial Order at 44. In his work in the
pharmaceutical and life sciences industry, Mr. Hofmann has performed financial and economic
analysis for hundreds of prescription pharmaceutical and biologic products, including virtually
every major therapeutic class of drugs. Id.
14
The Court will also consider the testimony of Dr. René S. Kahn, M.D., Ph.D., an expert who
“testified . . . in the fields of psychiatry, psychotic disorders, and schizophrenia,” to the extent he
also opined on obviousness at trial. DFOF ¶ 9 (internal quotation marks omitted). Dr. Kahn is the
Esther and Joseph Klingenstein Professor and System Chair of Psychiatry at the Icahn School of
Medicine at Mount Sinai. Final Pretrial Order at 40. Dr. Kahn has conducted extensive research
on schizophrenia and its treatment, has published over 900 research papers, and has been awarded
multiple honors for his work in the field of psychiatry, including a Fulbright Scholarship. Id. at 40.
13

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Pharmacy at Rutgers, The State University of New Jersey 15 (Trial Tr. at 1469:1–8; DFOF ¶ 42;
Final Pretrial Order at 36–37); (2) Dr. Christian G. Kohler, M.D., Clinical Director of
Neuropsychiatry in the Neuropsychiatry Division of the Department of Psychiatry at the Perelman
School of Medicine of the University of Pennsylvania 16 (Trial Tr. at 1874:23–1875:6; DFOF ¶ 46;
Final Pretrial Order at 37–38); and (3) Carla S. Mulhern, Managing Principal at Analysis Group 17
(Trial Tr. at 2576:24–2577:5; DFOF ¶ 49; Final Pretrial Order at 38–39). Plaintiffs also rely on
the following fact witnesses: Dr. An Vermeulen, Dr. Srihari Gopal, and Dr. Mahesh Samtani.
Final Pretrial Order at 29–31.
The Court has examined all asserted prior art references, both alone and in combination, as
well as all expert testimony and secondary considerations to determine whether it would have been
obvious to a POSA to arrive at the claimed dosing regimens. For the reasons discussed below, the
Court finds that Defendant has failed to prove by clear and convincing evidence that the Patentin-Suit is invalid based on obviousness pursuant to 35 U.S.C. § 103.
1.

Scope of the Prior Art and Differences Between the Prior Art and the
Claimed Invention

The Patent-in-Suit generally provides for a dosing regimen comprised of administering a
150 mg-eq. first loading dose of a sustained-release paliperidone palmitate formulation in the
15

Dr. Sinko has over thirty years of research experience in drug formulation, drug delivery
technology, and drug targeting. Final Pretrial Order at 36. Dr. Sinko has given approximately 169
lectures and published 175 articles, and serves as a grant reviewer for the National Institute of
Health. Id. at 37.
16
Dr. Kohler is the author of more than 80 peer reviewed research publications concerning
neuropsychiatric disorders and their treatment, has over twenty years of teaching experience, and
serves as a reviewer for a number of neuropsychiatry journals. Final Pretrial Order at 38.
17
Ms. Mulhern has offered analyses of economic matters across a variety of industries, including
pharmaceuticals, medical devices, automotive, computer hardware and software, consumer
products, entertainment, semiconductors, and telecommunications over the course of her 25 years
at Analysis Group. Final Pretrial Order at 39. Ms. Mulhern has been designated as a testifying
expert in several forums, including federal and state courts, the International Trade Commission,
the Patent Trial and Appeal Board, and various private arbitration tribunals. Id.
14

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deltoid muscle on the first day of treatment, followed by a second loading dose of 100 mg-eq. in
the deltoid muscle sometime during the sixth to tenth day of treatment, and then successive
monthly (± 7 days) maintenance doses of 25 mg-eq. to about 150 mg-eq. in either the deltoid or
gluteal muscle. See generally ’906 Patent (DTX-1/PTX-1). The ’906 Patent further provides for
reduced loading and maintenance doses for renally impaired patients. See id. Therefore, to prove
obviousness, Defendant must show by clear and convincing evidence that the claimed invention –
which consists of a precise combination of dose amounts, dose timing, sites of administration, and
particle size, designed for a patient in need of treatment for schizophrenia and other psychiatric
disorders – would have been obvious to a POSA.
Defendant points to various scientific and patent publications that it contends render the
claimed invention obvious. 18 The main prior art references focused on by the parties relate to the
initiation of treatment with loading doses (the ’548 Protocol), a specific formulation of
paliperidone palmitate (the WO’384 Publication), 19 and monthly administration of aqueous

18

In Teva’s Proposed Findings of Fact and Conclusions of Law, it offers the following
combinations of prior art references: (1) “Claim 2 is obvious in view of the ’544 Patent and/or WO
’384 in combination with the ’548 Regimen, in view of Gibaldi, Goodman, Ereshefsky 1990,
Ereshefsky 1993, Karagianis, Revill, and/or Janicak”; (2) “Claims 20 and 21 are obvious in view
of the ’544 Patent, WO’384, and ’548 Regimen, in view of Gibaldi, Goodman, Ereshefsky 1990,
Ereshefsky 1993, Karagianis, Revill, and/or Janicak”; (3) “Claims 10 and 13 are obvious in view
of the ’544 Patent, WO’384, and ’548 Regimen, in view of Gibaldi, Goodman, Ereshefsky 1990,
Ereshefsky 1993, Karagianis, Revill, Janicak, the ’591 Application, Cleton 2007, and/or the 2006
Invega ER Label.” DFOF ¶¶ 64–66. The Court has considered all of these prior art references,
individually and in combination, insofar as they were presented at trial and in the parties’ written
submissions.
19
The WO’384 Publication is an international patent publication filed by Janssen with the World
Intellectual Property Organization describing a new process for creating raw paliperidone
palmitate crystals, as opposed to a final paliperidone palmitate formulation such as the one utilized
in the ’906 Patent. DFOF ¶¶ 178, 203; PTX-66. The new method uses a “sterilization process
replacing radiation with aseptic filters.” Def. Br. at 22; see also DFOF ¶ 198. With respect to
particle size, the WO’384 Publication states that the particles should have a “specific surface
area>4m2/g,” meaning “that at least 90% of the particles have a diameter of less than 2,000 nm.”
15

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nanoparticle suspensions of paliperidone palmitate formulations to treat schizophrenia (the ’544
Patent). 20 See Def. Br. at 18–26. Defendant asserts that, when considering these references and
the other prior art in the record individually and in combination, a POSA would have been
motivated to arrive at the claimed dosing regimens with a reasonable expectation of success. See
id. at 18–43. Plaintiffs counter that the references on which Teva relies would not have motivated
a POSA to create the claimed dosing regimens, that Teva’s obviousness defense is based on
impermissible hindsight, and that at least some of the references actually taught away from the
claimed invention. See Pls. Br. at 25–41. Furthermore, Plaintiffs contend that any motivation to
modify the prior art can only be found now with the benefit of non-public information, including
Janssen’s proprietary scientific data and the unpublished failures of Janssen’s clinical trials. See
id. at 29.
The Court will first address the ’548 Protocol individually given that Teva’s prior art
combinations all involve modifying this prior art which discusses a dosing regimen for initiating
treatment of paliperidone palmitate. See Pls. Br. at 29; Def. Br. at 23. The Court will then discuss
all of the prior art in connection with a POSA’s motivation to arrive at the specific claims. As
explained below, Teva has failed to show that a POSA would have been motivated to arrive at the

DFOF ¶ 200; PTX-66 cols. 5:23–25, 7:25–26. The publication also instructs that particle size can
be altered through a milling process. DFOF ¶¶ 201–202.
20
The ’544 Patent teaches how to make a sustained-release paliperidone palmitate formulation
that is therapeutically effective for at least three weeks, but does not teach the use of loading doses
or other key features of the ’906 Patent such as uniform dosing or particularized injection sites.
DFOF ¶ 145; PFOF ¶¶ 94–97; PTX-55. The ’544 Patent describes four different formulations of
paliperidone palmitate with varying particle sizes and pertinent characteristics, and teaches
intramuscular injection of the formulation every three weeks at a dosage range from about 2 to 4
mg/kg of body weight. DFOF ¶¶ 156, 167, 174; PTX-55.
16

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claimed dosing regimens with a reasonable expectation of success based on any of the prior art,
considered alone or in combination, discussed at trial. 21
2.

The Prior Art Would Not Have Motivated a POSA to Arrive at the
Dosing Regimens Claimed in the ’906 Patent
a) The ’548 Protocol

The ’548 Protocol is a published two-page summary protocol of Janssen’s unsuccessful
PSY-3003 clinical trial aimed at measuring the safety and efficacy of administering “fixed doses”
of either 50, 100, or 150 mg-eq. of paliperidone palmitate “in the gluteal muscle” for “treating
subjects with schizophrenia.” DTX-55 at 1; see also DFOF ¶ 557. 22 In the study, equal doses were
to be administered on “Days 1, 8, 36, and 64.” DTX-55 at 1; see also DFOF ¶ 557. The
“hypothesis” of the study was “that the 3 fixed doses of paliperidone are each more efficacious
than placebo in treating subjects with schizophrenia.” DTX-55 at 1; see also PFOF ¶ 91. 23 Janssen
received the PSY-3003 results in August 2006. PFOF ¶ 35. The results indicated that PSY-3003
“failed to demonstrate superiority of any dose of [paliperidone palmitate] as compared to placebo
21

The Court notes that the parties presented very little testimony and evidence on the Janicak and
Revill prior art references at trial and only refer to these references in passing in their briefing.
Nonetheless, the Court has considered these references in its obviousness analysis and finds that
they do not render the claimed invention obvious based on their discussion of oral paliperidone
and other meaningful differences. See PFOF ¶¶ 118–19; DFOF ¶¶ 232–33, 264–67.
22
Plaintiffs argue that Defendant failed to establish that the ’548 Protocol qualifies as prior art
because it was printed on March 8, 2018, from a frequently-updated Internet database and does
not indicate which portions were publicly available in 2007. See PFOF ¶ 90. This argument is
unpersuasive. A cursory review of the versions of the ’548 Protocol in the record indicate that the
document was “[u]pdated” on September 20, 2005, and show the “[v]iew . . . on” September 20,
2005. PTX-54 at 1; DTX-55 at 1. The Court will therefore consider the ’548 Protocol in its
entirety.
23
Over the course of the PSY-3003 study, a “medical kit allocation error” caused some subjects
assigned to the placebo treatment group to receive 150 mg-eq. doses and some subjects assigned
to the 150 mg-eq. treatment group to receive the placebo. DFOF ¶ 559. As a result, only thirty
subjects consistently received the four intended 150 mg-eq. doses during the study. Id.; see also
Trial Tr. (Gopal) at 1063:23–1064:8. At trial, however, Dr. Vermeulen acknowledged that the
error “had nothing to do with the 150-milligram dose regimen itself” and “was just an error in the
way the study was conducted[.]” DFOF ¶ 560 (internal citations and quotation marks omitted).
17

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in the United States,” “failed to show superiority of the 50 and 150 mg-eq. doses world-wide,” and
showed that the 100 mg-eq. dose—the only dose to establish statistical efficacy—was not
fast-acting, first demonstrating superiority on Day 36. Id. ¶ 35; see also DFOF ¶ 558.
The parties agree that the ’548 Protocol does not contain clinical results or safety data, and
that a POSA would have to look beyond this reference in order to understand how the ’548 Protocol
worked in subjects. Pls. Br. at 30–31; Def. Br. at 25. At trial, Dr. Wermeling, Defendant’s
obviousness expert, explicitly acknowledged that the ’548 Protocol “is a protocol without any
results” and “does not provide any safety or efficacy data.” Trial Tr. (Wermeling) at 423:20–21,
471:10–14.
The ’548 Protocol and the ’906 Patent differ in several material respects. The ’548 Protocol
discloses equal doses of paliperidone palmitate administered in the gluteal muscle on fixed
treatment days, while the ’906 Patent contains regimens comprised of unequal doses (Claim 2),
two of which must be administered in the deltoid muscle (Claims 2 and 10), and a broader dosing
window for the second and monthly maintenance doses (Claims 2 and 10). Defendant asserts that
the ’548 Protocol provides a proper starting point for arriving at the claimed dosing regimens
because it “provided guidance on using loading doses followed by monthly administration of
paliperidone palmitate.” Def. Br. at 23, 26. But Defendant fails to adequately explain why a POSA
would modify the ’548 Protocol’s teachings in the precise ways required to achieve the dosing
regimens claimed in the ’906 Patent, and the mere fact that the ’548 Protocol and the ’906 Patent
contain some similar features is not enough to show obviousness. See Belden Inc. v. Berk-Tek LLC,
805 F.3d 1064, 1073 (Fed. Cir. 2015) (noting that “obviousness concerns whether a skilled artisan
not only could have made but would have been motivated to make the combinations or
modifications of prior art to arrive at the claimed invention”); Heidelberger Druckmaschinen AG

18

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v. Hantscho Commercial Prods., Inc., 21 F.3d 1068, 1072 (Fed. Cir. 1994) (“When the patented
invention is made by combining known components to achieve a new system, the prior art must
provide a suggestion or motivation to make such a combination.”).
One issue with starting from the ’548 Protocol is that it contains no information about the
safety of the dosing regimen or its efficacy (the study was actually ineffective as discussed above),
and Defendant has failed to persuasively argue, among other things, how a POSA would know to
alter the equal doses in the gluteal muscle described in the ’548 Protocol to arrive at the unequal
loading doses in the deltoid claimed by the ’906 Patent without knowing the results of the trial.
As Dr. Sinko credibly testified, without such safety and efficacy information, a POSA would have
had no reason to alter the regimen disclosed in the reference. See Trial Tr. (Sinko) at 1580:2–16
(“[T]here’s no safety data available or efficacy data available that would give the motivation to
make any changes. . . . And so there would be no motivation for a person of skill to consider
[adopting unequal loading doses to initiate treatment] because once again, there’s no data to
support that change.”). 24 In fact, the only way to know how to modify the ’548 Protocol to match
the ’906 Patent would be to look back at the protocol later with its results in hand, but that type of
hindsight analysis is impermissible here. 25

24

Janssen also asserts that Teva presents an internally inconsistent argument by claiming “that a
person skilled in the art would have selected the dosing regimens of the 548 Protocol in order to
avoid oral supplementation, reach therapeutic plasma levels faster, and reduce the risk of relapse,”
and simultaneously contending “that these same motivations would have led one to modify the
548 Protocol dosing regimens to arrive at the claimed inventions.” Pls. Reply Br. at 17 (internal
citations and quotation marks omitted). While the Court acknowledges that there may be some
inconsistency in Teva’s argument, it nevertheless examines the substance of Teva’s arguments on
this matter.
25
Dr. Wermeling also appeared to rely on impermissible hindsight in forming his obviousness
opinion. As the Federal Circuit has made clear, “[o]bviousness ‘cannot be based on the hindsight
combination of components selectively culled from the prior art to fit the parameters of the
patented invention.’” Cheese Sys., Inc. v. Tetra Pak Cheese & Powder Sys., Inc., 725 F.3d 1341,
1352 (Fed. Cir. 2013) (quoting ATD Corp. v. Lydall, Inc., 159 F.3d 534, 546 (Fed. Cir. 1998)).
19

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At trial, Dr. Wermeling asserted that motivation to modify the ’548 Protocol to align with
the dosing regimen of the ’906 Patent can be derived from Ereshefsky’s teachings about high
loading doses and a desire to use LAIs to treat “acute life-threatening circumstances.” Trial Tr.
(Wermeling) at 321:13–14, 372:15–24, 475:10–17. As discussed in more depth below, Ereshefsky
did not discuss paliperidone palmitate, uniform dosing, or unequal loading doses, all of which are
present in and integral to the ’906 Patent. Moreover, Dr. Wermeling’s assertion about the use of
LAIs in acute life-threating circumstances was contradicted by the testimony of Dr. Kahn,
Defendant’s other technical expert. According to Dr. Kahn, “long-acting injectables are not
designed to be used in emergency situations” because “[t]hey don’t work fast enough.” Trial Tr.
(Kahn) at 90:12–19. This inconsistency between the experts’ testimony belies Defendant’s theory
of motivation, and Defendant has not carried its burden to establish motivation to modify the ’548
Protocol by clear and convincing evidence. See Heidelberger Druckmaschinen, 21 F.3d at 1072. 26

During his deposition, Dr. Wermeling conceded that he “formed [his] opinions on obviousness”
by “look[ing] at the ’906 Patent claims first” and then “went back to see if [he] could find the
elements that are in the ’906 Patent claims in these other references next.” Trial Tr. (Wermeling)
at 359:21–360:15. Although he attempted to disavow this testimony at trial on the basis that it was
“not particularly accurate” and did not “fully accurately describe” his “process,” he elsewhere
admitted that his “memory from a year ago is going to be better than a year later.” Id. at 357:12–
25, 358:14–359:5, 359:21–360:15. Dr. Wermeling’s testimony also contained inconsistencies
regarding his views on “routine optimization.” See, e.g., Trial Tr. (Wermeling) at 361:25–364:24.
Thus, considering Dr. Wermeling’s testimony in its entirety, the Court finds that Dr. Wermeling’s
deposition admissions undermine his obviousness opinion and that Dr. Wermeling’s testimony has
credibility issues.
26
Plaintiffs further contend that the claimed invention is not obvious because it solved a problem
that was not known in the prior art. Pls. Br. at 34–35. Specifically, they argue that because the
’548 Protocol study was designed to achieve rapid and sustained efficacy, and because the prior
art did not disclose the unexpected failures of the study, a POSA would have had no reason to
solve the problems with the ’548 Protocol’s equal dose regimen. Id. “[W]here a problem was not
known in the art, the solution to that problem may not be obvious, because ordinary artisans would
not have thought to try at all because they would not have recognized the problem.” Forest Lab’ys,
LLC v. Sigmapharm Lab’ys, LLC, 918 F.3d 928, 935 (Fed. Cir. 2019) (internal citation and
quotation marks omitted). As Dr. Wermeling conceded, the ’548 Protocol does not contain any
results or data on safety or efficacy. Trial Tr. (Wermeling) at 423:20–21, 471:10–14. Indeed, as
20

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The ’548 Protocol is a failed study conducted by Janssen that examined using paliperidone
palmitate to treat schizophrenia. Yet, for the reasons stated above, even starting from this protocol,
Teva has failed to show that a POSA would be motivated to modify the ’548 Protocol to comport
with the ’906 Patent without utilizing safety/efficacy information that was unavailable or
impermissible hindsight. The Court will next further analyze Teva’s motivation to modify the
prior art, including the ’548 Protocol, with respect to each claim.
b) Claim 2 – Primary Dosing Regimen
Claim 2 provides for a dosing regimen of high, unequal loading doses in the deltoid muscle
followed by monthly maintenance doses in the deltoid or gluteal muscle. PFOF ¶ 7. Specifically,
the claim instructs administering 150 mg-eq. of a sustained-release paliperidone palmitate
formulation in the deltoid muscle on the first day of treatment, followed by administering 100 mgeq. in the deltoid muscle six to ten days later, and then successive monthly (±7 days) maintenance
doses of 25 to 150 mg-eq. in either the gluteal or deltoid muscle. ’906 Patent (DTX-1/PTX-1).
Defendant argues that a POSA would have been motivated to arrive at Claim 2 in view of the prior
art. See Def. Br. at 26–28. After careful consideration of the entire record, the Court is not
persuaded.
i.

Claim 2 – Deltoid Administration

A key component of Claim 2 is the requirement that the first and second loading doses are
given in the deltoid muscle. ’906 Patent (DTX-1/PTX-1) col. 32:15–24. Contrary to Defendant’s
assertions, the prior art would not have motivated a POSA to initiate treatment with deltoid
injections as is instructed in the ’906 Patent. Indeed, as Dr. Wermeling conceded at trial, none of
discussed above, Janssen only discovered a solution to the study’s problems after conducting
additional internal studies and reviewing internal data. Therefore, a POSA would not have
recognized the problems associated with the ’548 Protocol regimen, and this fact further supports
a finding of nonobviousness.
21

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the three primary prior art references—the ’548 Protocol, the ’544 Patent, or the WO’384
Publication (discussed above)—teach deltoid administration of loading doses. See Trial Tr.
(Wermeling) at 477:16–25 (Dr. Wermeling testified that he “would have [his] own reasoning as a
POSA to understand that’s an option.”), 504:25–505:8, 512:20–24. As explained above, the ’548
Protocol involved gluteal injections, not deltoid injections. DTX-55 at 1. Additionally, as Dr.
Wermeling admitted, the WO’384 Publication would not “point you in the direction of giving a
Day 1 dose and a second dose on Day 6 to 10 in the deltoid specifically.” Trial Tr. (Wermeling) at
512:20–24. As to the ’544 Patent, the testing described therein involved an “injection . . . given in
the biceps femoris of the left hind paw” of “a beagle dog,” not deltoid administration in humans.
Trial Tr. (Wermeling) at 504:25–505:8; see also Trial Tr. (Sinko) at 1533:19–22 (noting that the
’544 Patent does not “provide any guidance on a preferred injection site for a human”). While Dr.
Wermeling opined that a POSA knew “you could use various [injection] sites” for dosing, such as
the deltoid, gluteus, and vastus lateralis, he conceded that selecting the deltoid was only “an
option” and that “[o]ther options would have been reasonable too.” Trial Tr. (Wermeling) at
323:4–11, 476:19–23. As explained above, however, the obviousness inquiry “concerns whether
a skilled artisan not only could have made but would have been motivated to make the
combinations or modifications of prior art to arrive at the claimed invention.” See Belden Inc., 805
F.3d at 1073; see also InTouch Techs., Inc. v. VGO Commc’ns, Inc., 751 F.3d 1327, 1352 (Fed.
Cir. 2014).
Defendant also argues that two textbooks—(1) “Goodman & Gilman’s The
Pharmacological Basis of Therapeutics” (“Goodman”); and (2) “Gibaldi’s Drug Delivery Systems
in Pharmaceutical Care” (“Gibaldi”)—would motivate a POSA to arrive at the claimed regimens
because they teach that deltoid injections lead to faster absorption than gluteal injections. Def. Br.

22

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at 20; DFOF ¶¶ 223, 225, 227; PTX-64, -65; DTX-91, -93. 27 A holistic review of these references
indicates, however, that neither discloses deltoid administration of LAI loading doses. Indeed,
while Dr. Wermeling relied on a passage from Goodman stating that “[g]enerally, the rate of
absorption following injection of an aqueous preparation into the deltoid or vastus lateralis is faster
than when the injection is made into the gluteus maximus,” Goodman goes on to note that “[s]low,
constant absorption from the intramuscular site results if the drug is . . . suspended in various other
repository (depot) vehicles.” Trial Tr. (Wermeling) at 323:2–324:23, DDX3-84, DTX-93 at 32;
see also PTX-65 at 8 (characterizing absorption rate of drug suspended in repository vehicle as
“[v]ery slow”). As Dr. Sinko persuasively conveyed through his testimony, Goodman suggests
that in the context of drug suspensions, such as the “aqueous particle nanosuspensions” or “depot
formulation” claimed in the ’906 Patent, “the formulation,” rather than the injection site, “would
be controlling the rate of absorption.” Trial Tr. (Sinko) at 1533:23–1536:21. Thus, the Court finds
that Goodman would not motivate a POSA to use deltoid injections for the claimed formulation.
Similarly, the Court finds that the Gibaldi reference would not have motivated a POSA to
initiate treatment with deltoid injections as claimed in the ’906 Patent. In support of its position,
Defendant cites to Gibaldi’s teachings that “[t]he [intramuscular] injection site is usually the
deltoid muscle . . . or the vastus lateralis muscle,” that the absorption rate “of drugs depend[s] on
biopharmaceutical factors such as formulation characteristics and the physiology of the injection
site,” that deltoid injections “are absorbed faster than gluteal injections . . . likely due to the
increased blood flow in the deltoid muscle . . .,” and that “[intramuscular] injections are available
in immediate-release formulations as well as depot formulations for sustained release.” DTX-91

27

As Defendant notes, although the parties presented two different editions of Goodman (see PTX65, DTX-93), “the teachings relied on are the same in both.” DFOF ¶ 226.
23

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at 4–5; DFOF ¶¶ 221, 223–25. Defendant’s argument fails to adequately address, however, that
Gibaldi also teaches that depot injections are not indicated for treatment initiation, as claimed in
the ’906 Patent. Indeed, as Gibaldi expressly states, “[d]epot injections release the drug slowly”
and “are long-acting dosage formulations indicated for maintenance treatment rather than initiation
of therapy.” DTX-91 at 5; see also PTX-64 at 38 (explaining that “[i]n the acute phase of
schizophrenia, short-acting injections may be required because of their quick action,” while “[i]n
the maintenance phase of therapy for schizophrenia, administration of an atypical agent in a longacting or depot dosage formulation may be desirable”). When Dr. Wermeling was questioned
about this teaching on cross-examination, he admitted that Gibaldi “says that [about depot
injections], but that’s not my usage of Gibaldi.” Trial Tr. (Wermeling) at 472:2–9. In other words,
Dr. Wermeling’s testimony suggests that he selectively relied on only some of Gibaldi’s teachings
in forming his opinion rather than the reference as a whole. The Federal Circuit has made clear,
however, that the prior art “must be considered in its entirety, i.e., as a whole, including portions
that would lead away from the invention in suit.” Panduit Corp. v. Dennison Mfg. Co., 810 F.2d
1561, 1568 (Fed. Cir. 1987). Thus, when viewed as a whole, the Court cannot say that Gibaldi
would motivate a POSA to initiate treatment using deltoid injections as directed in Claim 2.
Finally, Defendant contends that patient preference would have motivated a POSA to use
deltoid administration. See Def. Br. at 20–21. This argument is not fully supported by the record.
For example, as Dr. Gopal explained, the participants in the PSY-3007 study were divided “about
half and half” between choosing deltoid and gluteal injections. Trial Tr. (Gopal) at 1180:20–1181:2
(explaining that “in the United States, the patients tend to prefer getting the injections in the arm
because you don’t have to pull down your pants and stigmatize yourself; whereas in other
countries, like in Asia, they tend to be lighter, so they prefer getting the injection in the gluteal”).

24

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In addition, Gibaldi generally suggests administering depots in the gluteal muscle over the deltoid
muscle “because [a deltoid injection] causes discomfort and pain at the injection site.” DTX-91 at
15. Moreover, as Plaintiffs correctly note, even if some patients prefer deltoid injections, such
preferences would suggest at most using deltoid administration on an individualized basis. Pls.
Reply at 20. The ’906 Patent, however, claims a generalized dosing regimen. In essence,
Defendant’s argument is that “a POSA would not have been dissuaded from deltoid injections,”
(Def. Br. at 26), but this assertion does not satisfy Defendant’s burden. See Endo Pharm. Sols.,
Inc. v. Custopharm Inc., 894 F.3d 1374, 1380 (Fed. Cir. 2018) (“To meet its burden, Custopharm
needed to do more than merely show that the prior art does not preclude lowering the dose of
TU.”). Accordingly, the Court finds that Defendant has not established motivation to use deltoid
injections by clear and convincing evidence.
ii.

Claim 2 – Unequal Loading Doses

A second key feature of Claim 2 is the use of unequal loading doses. ’906 Patent (DTX1/PTX-1) col. 32:15–24. The Court also finds that Defendant has not met its burden of showing
that a POSA would have been motivated to use unequal loading doses as claimed in the ’906
Patent. According to Defendant, two articles by Dr. Larry Ereshefsky et al.—a 1990 article titled
“Kinetics and Clinical Evaluation of Haloperidol Decanoate Loading Dose Regimen”
(“Ereshefsky 1990”) and a 1993 article titled “A Loading-Dose Strategy for Converting From Oral
to Depot Haloperidol” (“Ereshefsky 1993”)—and a 2001 article by Dr. James L. Karagianis et al.
titled “Rapid Tranquilization With Olanzapine in Acute Psychosis: A Case Series” (“Karagianis”)
render the claimed regimens obvious. See Def. Br. at 24–25, 27, 29; DTX-88, -89, -96.

25

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Defendant’s argument fails for three reasons. 28 First, as their titles suggest, neither the Ereshefsky
nor Karagianis references concern paliperidone palmitate; the Ereshefsky references involve
haloperidol decanoate dosing, and Karagianis relates to oral olanzapine. Trial Tr. (Wermeling) at
312:17–313:20; DTX-88, -89, -96. As Dr. Sinko explained, because these references concern
“different drugs and different formulations” than paliperidone palmitate, their “pharmacokinetics
and how they act are . . . different.” Trial Tr. (Sinko) at 1566:18–1567:5. Defendant’s expert Dr.
Wermeling agreed with this opinion. See Trial Tr. (Wermeling) at 513:17–24 (agreeing that
“haloperidol decanoate and paliperidone palmitate have different PK or pharmacokinetic
profiles”). Thus, a POSA would know that “you really can’t correlate” their teachings to “an
injectable version of paliperidone palmitate.” Trial Tr. (Sinko) at 1566:18–1567:11.
Second, unlike the ’906 Patent, the Ereshefsky and Karagianis references teach
individualized, rather than generalized, dosing. Indeed, as Dr. Wermeling acknowledged at trial,
Ereshefsky 1990 involved dosing patients “on an individual basis” (Trial Tr. (Wermeling) at
517:10–518:6), and Dr. Sinko similarly testified that Ereshefsky taught “patient-specific
approaches” (Trial Tr. (Sinko) at 1569:18–1570:1, 1573:19–1574:13). Furthermore, Karagianis
states that the patients in the case series were “not dosed according to a protocol-dosing regimen.”
DTX-96 at 4; see also Trial Tr. (Sinko) at 1577:4–12 (noting that patients in Karagianis received
“a personalized dose”). This distinction between dosing approaches undercuts Defendant’s
argument that Ereshefsky and Karagianis would lead a POSA to the claimed dosing regimens.

28

Defendant also cites Karagianis’s teaching on “rapid neuroleptization,” which Defendant
characterizes as an “older loading dose strategy” involving very high doses of oral or short-acting
injectables, to argue that Karagianis suggests using a high-loading dose strategy. DFOF ¶¶ 258–
62; Trial Tr. (Kahn) at 2383:18–2384:11. This argument is unavailing. As Defendant’s own expert
Dr. Kahn explained, rapid neuroleptization “has nothing to do with the use of long-acting
injectables” and treatment providers “don’t do this anymore.” Trial Tr. (Kahn) at 2382:8–2384:11.
26

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Lastly, these references do not disclose unequal loading doses as claimed in the ’906
Patent. Specifically, Defendant contends that Ereshefsky 1993 taught initiating therapy with
unequal dose amounts. See Def. Br. at 27. While Ereshefsky 1993 does note that the loading dose
was “administer[ed] . . . in two or more sequential injections” of “consecutive divided doses” for
safety reasons, the reference does not teach the use of unequal loading dose amounts. DTX-89 at
4. To the contrary, it provides that patients received initial “consecutive divided doses of 100 to
200 mg every three to seven days until the full amount is given,” and the haloperidol decanoate
doses were not reduced until “the second and third months.” Id.; Trial Tr. (Wermeling) at 322:17–
323:1. Ereshefsky 1990 contains similar teachings. See DTX-88 at 3, 5–7 (citing case studies and
disclosing initial “consecutive divided doses . . . until the full amount was administered”). 29 Claim
2 of the ’906 Patent, by contrast, directs two loading doses of unequal amounts of paliperidone
palmitate. ’906 Patent (DTX-1/PTX-1). Accordingly, the Court finds that a POSA would not have
been motivated to create the Claim 2 dosing regimen in view of the prior art.
c) Claims 10 and 13 – Renal Impairment Claims
Claims 10 and 13 set forth dosing regimens for patients with renal impairment. Under
these claims, renally impaired patients receive reduced loading doses of from about 75 mg-eq. of
paliperidone palmitate in the deltoid muscle on both the first day of treatment and sixth to about
tenth day of treatment, followed by successive monthly maintenance doses (± 7 days) of about 25
mg-eq. to about 75 mg-eq. in either the deltoid or gluteal muscle. See ’906 Patent (DTX-1/PTX1). According to Defendant, Claims 10 and 13 are obvious because several prior art references
taught reduced doses for renal impairment. See Def. Br. at 36–38. The Court disagrees.

29

Ereshefsky 1990 also notes that certain patients did not actually “receive a true loading dose”
because those doses were “not given as a single injection.” DTX-88 at 7.
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First, the references on which Dr. Wermeling relied would not have motivated a POSA to
achieve the claimed regimens. At trial, Dr. Wermeling testified that, in addition to the three
primary prior art references (the ’548 Protocol, the ’544 Patent, and the WO’384 Publication), a
combination of three other references teach “a 50 percent dose reduction from the maximum dose
for patients with mild renal impairment.” Trial Tr. (Wermeling) at 332:25–333:12; see also DFOF
¶ 375. The three additional references are a clinical trial abstract titled “PII-46[:] Effects of Renal
Impairment on the Pharmacokinetic Profile of Paliperidone Extended-Release Tablets” (referred
to by the parties as “Cleton 2007”), the Invega (paliperidone) Extended Release Tablets label (the
“Invega ER Label”), and U.S. Patent Application No. 2007/0197591 (the “’591 Application”). Dr.
Wermeling opined that based upon these three prior art references, “it would have been reasonable
to do the 50 percent reduction for the loading dose strategy.” Trial Tr. (Wermeling) at 333:9–12.
Dr. Wermeling’s conclusions, however, are unsupported by the record.
Cleton 2007 concerned orally administered paliperidone, rather than the LAI paliperidone
palmitate at issue here. PTX-56; DTX-84; Trial Tr. (Sinko) at 1586:11–15; Trial Tr. (Wermeling)
at 530:15–531:18 (admitting that Cleton 2007 is not “talking about an injectable paliperidone
palmitate”). In addition, while Dr. Wermeling testified that Cleton 2007 teaches that “the two
measures of exposure . . . the maximum concentration, . . . and the total exposure by AUC, as area
under the curve, is basically doubling for patients who have renal impairment” and “would be a
strong consideration for reducing the dose” in a renally impaired patient (Trial Tr. (Wermeling) at
330:19–331:9), his conclusion ignored that Cleton 2007 only suggests dose reductions for patients
with moderate and severe renal impairment. Indeed, contrary to Dr. Wermeling’s assertions,
Cleton 2007 did not suggest a reduction in dosing for patients with mild renal impairment. PTX56; DTX-84; Trial Tr. (Sinko) at 1586:12–1587:8 (explaining that Cleton 2007 suggests “no dose

28

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reduction for mild renal impairment”). In contrast, the ’906 Patent “focuses on mild renal
impairment.” Pls. Br. at 70.
Defendant’s reliance on the Invega ER Label is similarly unavailing. Like Cleton 2007,
the Invega ER Label concerns oral paliperidone, not injectable paliperidone palmitate. PTX-57;
DTX-102; Trial Tr. (Wermeling) at 531:15–18. Additionally, while Defendant argues that the
Invega ER Label can be read to suggest a 50 percent reduction from the maximum recommended
dose for patients with normal renal function to the maximum recommended dose for patients with
mild renal impairment (with Janssen challenging that suggestion), a POSA developing a dosing
regimen would not start from the maximum recommended dose, but instead would start with the
general recommended dose for patients with normal renal function. See Trial Tr. (Sinko) at
1587:20–22 (“[I]t’s actually more appropriate to start with the recommended dose in healthy
patients.”); PTX-57 at 26; DTX-102 at 26. Furthermore, as Dr. Sinko convincingly testified, the
label does not teach “just a straight 50 percent” reduction for dosing patients with renal impairment
as it provides a range of maximum recommended doses that are dependent on a patient’s level of
renal impairment. Trial Tr. (Sinko) at 1587:20–1588:6.
Defendant further argues that the ’591 Application teaches that doses must be reduced for
patients with renal impairment. See Def. Br. at 37. As Defendant concedes, however, the ’591
Application “is directed to . . . patients with hepatic (or liver) impairment,” not renal impairment.
Id. at 36; PTX-69; DTX-108. Moreover, while Defendant contends that the ’591 Application
teaches that paliperidone is excreted through the kidneys, this purported teaching does not, alone
or in combination with Cleton 2007 as Defendant suggests, render the claimed regimens obvious.
See Def. Br. at 36–37; DFOF ¶ 272. As explained above, the dosing regimens address patients
with mild renal impairment, and neither the ’591 Application nor Cleton 2007 expressly teach LAI

29

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paliperidone palmitate dose reductions for mild renal impairment. See PTX-69; DTX-108; Trial
Tr. (Sinko) at 1586:12–1587:8. Therefore, the Court finds that Cleton 2007, the Invega ER Label,
and the ’591 Application, whether considered individually or in combination, would not motivate
a POSA to arrive at the claimed dosing regimens for patients with mild renal impairment.
Finally, even if the Court were to find that the prior art teaches a 50 percent dose reduction
for patients with mild renal impairment, this teaching would not actually lead to the claimed
invention. Indeed, if the 150/100 mg-eq. loading doses of Claim 2 were reduced by half, the
regimen would consist of 75/50 mg-eq. loading doses, not 75/75 mg-eq. as claimed in the Patentin-Suit. Thus, applying a 50 percent reduction would not yield the regimens disclosed in Claims
10 and 13.
d) Claims 20 and 21 – Paliperidone Palmitate Properties
Claims 20 and 21 recite the properties of the paliperidone palmitate formulation used in
the claimed dosing regimens. See ’906 Patent (DTX-1/PTX-1) col. 34:32–51. Specifically, these
claims direct, among other things, that the sustained release depot formulation “is an aqueous
nanoparticle suspension consist[ing] essentially of . . . paliperidone palmitate having an average
particle size (d50) of from about 1600 nm to about 900 nm.” Id. d50 refers to a distribution of
particle size which indicates that 50 percent of the particles are below the reported size. DFOF ¶
625. Defendant contends that a POSA would have been motivated to select the claimed particle
sizes in view of the prior art. The Court is not persuaded.
Both parties’ obviousness experts testified that particle size affects dosing strategy. See,
e.g., Trial Tr. (Wermeling) at 291:12–19 (noting that “the pharmacokinetic properties of such a
formulation are derived from the formulation itself” and “if you wanted to impart changes in the
pharmacokinetics, you could change the particle size”); Trial Tr. (Sinko) at 1544:1–6 (explaining

30

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that particle size “controls the rate of dissolution, release and, ultimately, absorption for a formula
like this”). Of the three primary prior art references—the ’548 Protocol, the ’544 Patent, and the
WO’384 Publication—only the ’548 Protocol discloses a treatment initiation regimen for
paliperidone palmitate. See DTX-55. This reference, however, neither specifies the characteristics
of the formulation used in the study, nor any information about the formulation’s particle size. See
id. Furthermore, while the two other primary art references discuss particle size for paliperidone
palmitate formulations, they do not suggest that that these formulations are appropriate for a
treatment initiation regimen. See DTX-54; DTX-72; Trial Tr. (Sinko) at 1538:2–1539:6, 1543:9–
13, 1550:18–24, 2256:12–14; Trial Tr. (Wermeling) at 506:24–507:1, 511:15–512:8.
With respect to the ’544 Patent, it describes four different paliperidone palmitate
formulations, referred to as Formulations A, B, C, and D. DTX-54 cols. 8–9; Trial Tr. (Wermeling)
at 483:3–11.

The d50 particle sizes for the formulations reported in the ’544 Patent are:

(1) “Formulation A,” d50 of 6030 nm; (2) “Formulation B,” d50 of 1380 nm; (3) “Formulation
C,” d50 of 740 nm; and (4) “Formulation D,” d50 of 520 nm. DTX-54 col. 9:25–31; Trial Tr.
(Wermeling) at 486:23–487:11. Thus, only Formulation B has a d50 particle size that falls within
the particle size limitations recited in the ’906 Patent, which requires “an average particle size
(d50) of from about 1600 nm to about 900 nm.” ’906 Patent (DTX-1/PTX-1) col. 34:32–51; Trial
Tr. (Sinko) at 1530:15–1531:1.
A problem with Formulation B—the only formulation with a proper d50 particle size as
claimed in the ’906 Patent—is that the ’544 Patent expressly teaches away from using this
formulation based on its effective particle size limitations, which require that the formulation has
a d90 particle size of “less than 2000 nanometers.” DTX-54 cols. 3:42–44, 5:16–21, 9:25–31,
10:27–29. d90 is another form of measurement and refers to a distribution of particle size which

31

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indicates that 90 percent of the particles are below the reported size. DFOF ¶ 625. Formulation B
has a d90 particle size of 6830 nm, which is significantly above 2000 nm. DTX-54 col. 9:25–31.
Consequently, as Dr. Sinko credibly opined, a POSA considering the ’544 Patent would have been
dissuaded from selecting Formulation B. See Trial Tr. (Sinko) at 1783:4–1785:1 (testifying that a
POSA would “eliminate . . . [Formulation] B” from further consideration based on “the two critical
parameters, the particle size and the specific surface area” taught in the ’544 Patent). 30 Thus,
because the prior art “must be considered in its entirety, i.e., as a whole, including portions that
would lead away from the invention in suit,” the Court finds that the ’544 Patent would not
motivate a POSA to arrive at the claimed particle size. Panduit Corp., 810 F.2d at 1568.
Defendant argues that Formulation C, having a d50 of 740 nm, would also motivate a
POSA to select the claimed particle size ranges. See Def. Br. at 34. This argument is unpersuasive.
As Plaintiffs correctly note, Dr. Wermeling’s opinion that Formulation C’s d50 particle size of 740
nm is covered by the ’906 Patent is contradicted by Defendant’s own assertion in its proposed
findings of fact that a “d50 of 600–800 nm” is “outside the claimed range.” Pls. Reply Br. at 22;
compare Trial Tr. (Wermeling) at 494:16–22 (testifying that he “would consider 740 [to be] in the
range” of the claimed “about 900 nanometers” d50 particle size), with DFOF ¶ 527 (arguing that
the
).
Finally, Defendant’s argument that the WO’384 Publication, in combination with the ’544
Patent, would motivate a POSA to arrive at Claims 20 and 21 is unavailing. See Def. Br. at 34–36.

30

Formulations C and D were also “the only formulations that were tested for stability.” Trial Tr.
(Wermeling) at 491:14–22; DTX-54 col. 9:33–35. As Dr. Sinko explained, a POSA would have
understood that the selection of Formulations C and D for stability testing suggests that they “had
the most promising attributes that you want to study further.” Trial Tr. (Sinko) at 1529:24–1530:8.
32

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By Defendant’s own concession, the WO’384 Publication “made no new disclosure on particle
size,” and a POSA would refer back to the ’544 Patent’s teachings on particle size. Id. at 23, 34–
36; see also DTX-72. Indeed, Dr. Wermeling agreed at trial that the WO’384 Publication
discussed measurements of raw materials before milling, and “none of [the 32 measurements for
particle size described in the WO’384 Publication] have a d50 of between about 1600 and 900
nanometers.” Trial Tr. (Wermeling) at 511:10–14. Dr. Wermeling further agreed that the WO’384
Publication teaches that “what you want is an average particle size d90 of less than 2000
nanometers corresponding to a specific surface area greater than 4 meters squared per gram”—the
same teaching as the ’544 Patent. Id. at 560:24–561:5; DTX-72 at 6. Thus, the WO’384
Publication does not alter the Court’s analysis, and Defendant has failed to show that a POSA
would have been motivated to select the claimed particle size.
3.

A POSA Would Not Have a Reasonable Expectation of Success in
Arriving at the Claimed Dosing Regimens

In addition to motivation, “[a]n obviousness determination requires that a skilled artisan
would have perceived a reasonable expectation of success in making the invention in light of the
prior art.” Amgen Inc. v. F. Hoffman-La Roche Ltd, 580 F.3d 1340, 1362 (Fed. Cir. 2009); see also
Procter & Gamble Co. v. Teva Pharm. USA, Inc., 566 F.3d 989, 994 (Fed. Cir. 2009) (“A party
seeking to invalidate a patent based on obviousness must demonstrate ‘by clear and convincing
evidence that a skilled artisan would have been motivated to combine the teachings of the prior art
references to achieve the claimed invention, and that the skilled artisan would have had a
reasonable expectation of success in doing so.’”) (quoting Pfizer, Inc. v. Apotex, Inc., 480 F.3d
1348, 1361 (Fed. Cir. 2007). The Federal Circuit has noted that “[t]he presence or absence of a
reasonable expectation of success is . . . a question of fact.” Novartis Pharm. Corp. v. W.-Ward

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Pharm. Int’l Ltd., 923 F.3d 1051, 1059 (Fed. Cir. 2019) (internal citation and quotation marks
omitted). The Court finds that Defendant has not met its burden for several reasons.
First, the unpredictability of developing treatment initiation regimens using LAIs supports
a finding of nonobviousness.

The Federal Circuit has noted that “evidence showing

unpredictability in the art” suggests “that one of ordinary skill would not have been motivated to
combine the references with a reasonable expectation of success.” Honeywell Int’l Inc. v.
Mexichem Amanco Holding S.A. DE C.V., 865 F.3d 1348, 1354 (Fed. Cir. 2017). Moreover, “even
if it was obvious to experiment with [certain] options,” an invention is not obvious where “there
is nothing to indicate that a skilled artisan would have had a reasonable expectation that such an
experiment would succeed.” Leo Pharm. Prods., Ltd. v. Rea, 726 F.3d 1346, 1357 (Fed. Cir. 2013)
(internal citation and quotation marks omitted). Here, the record establishes that developing a
generalized multi-dose regimen using an LAI to initiate therapy was an unpredictable process. As
Dr. Wermeling acknowledged, there were “a large number of possibilities for combining” the dose
amounts disclosed in the ’548 Protocol with “different injection sites.” Trial Tr. (Wermeling) at
473:19–474:19. He further testified that different injection sites, dosing intervals, and dose
amounts can affect therapeutic blood levels. Id. at 279:3–8; 312:7–16. While Dr. Wermeling
opined that the WO’384 Publication disclosed a safe and effective dosing range of 25 to 150 mgeq., he did not credibly explain how a POSA could expect to develop effective multi-dose
treatment regimens, such as those claimed in the ’906 Patent, from this range. Id. at 321:23–322:13.
Indeed, as noted above, Dr. Wermeling clearly stated that the WO’384 Publication itself “does not
disclose anything about a dosing regimen,” does not discuss deltoid or gluteal administration, and

34

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does not “point you in the direction of giving a Day 1 dose of 150 mg equivalents in the deltoid
and a second dose in the deltoid of 100 mg equivalents on Day 6 to 10.” Id. at 511:15–512:8.
The record further indicates that, in contrast to single doses, multi-dose regimens must
account for effects like “accumulation” and “fluctuations [in a patient’s blood levels] between
administrations.” Trial Tr. (Sinko) at 1597:17–1600:10. Therefore, to successfully arrive at a
multi-dose regimen based on the prior art, a POSA would need safety, efficacy, and
pharmacokinetic data in order to evaluate how a generalized dosing regimen would perform in
patients. See Id. at 1583:24–1584:16 (noting that without “this triumvirate of pharmacokinetics,
efficacy and safety [data], you have no way to understand if some random combination of elements
would lead to an effective dosing regimen”). The prior art, however, contained no such data. Id.
at 1582:19–1583:18. While Dr. Wermeling testified that the ’548 Protocol involved a Phase III
trial, which is a clinical trial that “use[s] doses that are thought to be safe and effective,” he
admitted that this reference is “a protocol without any results.” Trial Tr. (Wermeling) at 316:4–23,
423:20–21. Moreover, as Dr. Wermeling conceded, “most drugs fail” the drug development
process. Id. at 543:7–10. On these facts, and given the difficulty the Janssen inventors encountered
during the invention process described in detail above, the Court finds that the unpredictability of
the art weighs against a reasonable expectation of success. See Sanofi v. Watson Lab’ys Inc., 875
F.3d 636, 641, 646–50 (Fed. Cir. 2017) (affirming finding of no reasonable expectation of success
where prior art disclosed large-scale clinical trial’s hypothesis but not results); Endo Pharm. Inc.
v. Actavis LLC, 922 F.3d 1365, 1377 (Fed. Cir. 2019) (noting that finding of no reasonable
expectation of success was “further supported by the fact that the inventors of the ’779 patent

35

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engaged in extensive experimentation, involving much failure, to ultimately produce the
oxymorphone of the Asserted Claims”).
In addition, a POSA would not have had a reasonable expectation of successfully initiating
treatment with LAI loading doses in view of the prior art. For instance, as discussed above, the
Gibaldi reference on which Dr. Wermeling relies expressly teaches that “[d]epot injections are . .
. indicated for maintenance treatment rather than initiation of therapy.” DTX-91 at 5. Moreover,
as set forth in detail below, both parties’ experts agreed that the traditional dosing paradigm for
treating schizophrenia used lower initial doses followed by slow upward adjustments. See, e.g.,
Trial Tr. (Kahn) at 168:19–169:5 (for dosing risperidone, it is “recommended” to begin with an
“initial dose” and then “work your way up in small increments until you get to your target dose or
your effective dose range”); Trial Tr. (Kohler) at 1905:12–17 (explaining that the initial dose of
Risperdal Consta “was limited to 25 milligrams or less, which was in many people not the eventual
dose required to manage the psychosis,” followed by subsequent higher doses weeks later). The
Goodman reference also instructed initiating low doses of risperidone and watching for side effects
as dose amounts are increased. See DTX-93 at 339 (“Low doses of risperidone have been reported
to attenuate negative symptoms of schizophrenia with a low incidence of extrapyramidal side
effects. Extrapyramidal effects are commonly seen, however, with doses of risperidone in
excess of 6 mg/day.”). Even the FDA and an external panel of experts suggested that Janssen use
lower initial doses. PTX-92 at 1, PFOF ¶¶ 57–58; PTX-94 at 59, 61. Contrary to the prior art
teachings and traditional dosing strategy, the ’906 Patent claims high-loading dose regimens using

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depot injections. Thus, the Court is not persuaded that a POSA would have had a reasonable
expectation of successfully achieving the claimed regimens. 31
4.

The Cleton 2008 References Support a Finding of Nonobviousness

Defendant contends that four additional references—two abstracts published in Clinical
Pharmacology & Therapeutics in March 2008 titled “PI-74” and “PI-75” and two corresponding
posters allegedly presented at an April 2008 conference (collectively, “Cleton 2008”)—render
Claim 2 obvious. Def. Br. at 33–34; DTX-18, -19, -20. 32 Plaintiffs counter that the Cleton 2008
references are not prior art because the claimed invention antedated them and the inventors had
possession of the information disclosed in the references prior to their publication. Pls. Br. at 58–
64. The Court finds that even if it considers the Cleton 2008 references, they weigh in favor of
nonobviousness. 33

31

No additional showing has been required of Teva despite its presentation of testimony and
argument concerning motivation to alter the prior art in order to achieve rapid and long-term
efficacy with paliperidone palmitate. See, e.g., Trial Tr. (Wermeling) at 469:2–470:13 (Dr.
Wermeling agreed that the ’906 Patent claims dosing regimens that provide both “rapid efficacy”
and “long-term efficacy.”); 311:18–23 (testifying that a POSA would be motivated to modify the
’544 Patent and WO’384 Publication to “accelerate the onset of effect”); 321:1–22 (noting that a
POSA “would be motivated to use the maximum effective and safe dose” when initiating treatment
of an “acutely agitated” patient). Nonetheless, a party raising an argument at trial places that
argument at issue. See Immunex Corp. v. Sandoz Inc., 964 F.3d 1049, 1066 (Fed. Cir. 2020), cert.
denied, 209 L. Ed. 2d 751 (May 17, 2021) (rejecting post-trial argument due to party’s focus on
challenged issue during trial).
32
The Cleton 2008 references all reflect work done by or associated with Janssen. See DFOF ¶¶
287, 298; Pls. Br. at 58–59.
33
Janssen offers strong arguments in support of its view that Cleton 2008 is not prior art. Pls. Br.
at 58–64. Janssen asserts that the claimed invention was conceived and reduced to practice in the
Summer of 2007 prior to the publication of Cleton 2008, citing to testimony and evidence from
Drs. Gopal and Samtani. Id. at 61. As discussed later in this Opinion, Janssen is seeking to add
Drs. Gopal and Samtani as inventors of the ’906 Patent. Janssen further contends, citing to the
’918 Provisional as evidence, that the inventors had possession of the information disclosed in
Cleton 2008 before these references were published. Id. at 63–64. Regardless, even considering
the Cleton 2008 references as prior art does not alter this Court’s analysis regarding obviousness.
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PI-74 and its corresponding poster do not support Defendant’s obviousness arguments
because they relate to a single-dose, rather than multi-dose, regimen. See DTX-18, -19. As
Dr. Wermeling noted, PI-74 “is a single dose [proportionality] study” in which “[e]ach subject
received a single injection of paliperidone palmitate” in “either the deltoid or the gluteal muscle.”
Trial Tr. (Wermeling) at 378:3–12; see also DTX-18, -19. Unlike the dosing regimens claimed in
the ’906 Patent, PI-74 did not involve any loading or maintenance doses. Trial Tr. (Wermeling) at
378:13–21. Moreover, Dr. Wermeling allowed that PI-74 neither contains efficacy data nor
“disclose[s] giving a Day 1 loading dose of 150 mg. equivalents in the deltoid and a second loading
dose in the deltoid of 100 mg. equivalents on Days 6 to 10.” Trial Tr. (Wermeling) at 392:9–18. 34
As discussed above, multi-dose regimens like the claimed invention differ from single doses
because they need to account for “accumulation,” and “fluctuations [in a patient’s blood levels]
between administrations.” Trial Tr. (Sinko) at 1597:17–1600:10. To develop an effective multidose regimen, a POSA would need efficacy data, which these references lack. See Id. at 1583:24–
1584:16, 1605:17–1606:25. Thus, when viewed as a whole, the Court cannot say that this
reference renders the claimed invention obvious.
Similarly, the Court finds that PI-75 and its corresponding poster would not change the
obviousness analysis. PI-75 concerns a “fixed-dose” study of four equal doses of 100 mg-eq. of

34

The Court also notes that Cleton 2008 would not create a reasonable expectation of success.
DTX-18, -19, -20. Contrary to Defendant’s assertion that “Cleton 2008 provides the confirmatory
data that Dr. Sinko desired” (Def. Br. at 33), none of these references contain efficacy data. See
Trial Tr. (Wermeling) at 392:9–13, 408:23–25; Trial Tr. (Sinko) at 1603:11–20; DTX-18, -19, -20.
At most, Cleton 2008 discloses average pharmacokinetic data, not patient-level data. Without
efficacy data, a POSA would “have to do . . . controlled clinical studies to prove that those [target
blood] levels were actually effective.” Trial Tr. (Sinko) at 1540:5–1541:9; see also id. at 2134:1–
2134:11 (noting that “the correlation between the target range and what a clinical investigator
determines is efficacy is not straightforward” and the two “may not be linked”). Thus, the Court
finds that Cleton 2008 does not change the above analysis.
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paliperidone palmitate administered in either the deltoid or gluteal muscle on days 1, 8, 36, and
64. DTX-18; Trial Tr. (Wermeling) at 394:6–395:4. Similar to PI-74, PI-75 does not contain any
efficacy data that would motivate a POSA to modify the reference’s equal dose regimen to arrive
at the dose regimens claimed in the ’906 Patent. Trial Tr. (Sinko) at 1603:11–20, 1604:7–10; see
also Trial Tr. (Wermeling) at 396:10–16 (conceding that “PI-75 [does not] give any indication as
to whether the first dose of 100 mg equivalence was effective or ineffective”). Moreover, PI-75
and its corresponding poster would dissuade a POSA from using deltoid injections. Indeed, as Dr.
Wermeling allowed, PI-75 disclosed “more fluctuation in drug content in the blood” and “more
variation in drug absorption between different individuals when they were injected in the deltoid
as opposed to the gluteal muscle.” Trial Tr. (Wermeling) at 397:12–21. The corresponding poster
makes similar disclosures. See DTX-20 at 6–7 (noting higher incidence of adverse events,
“clinically relevant difference” in injection site pain, and greater fluctuation index for deltoid
treatment group compared to gluteal treatment group). As Dr. Sinko credibly explained, a POSA
would “want to keep . . . fluctuations at a minimum because that means changes in blood levels,”
which can “correspond[ to] . . . toxicity.” Trial Tr. (Sinko) at 1601:13–21, 1605:7–14.
Accordingly, given the “higher fluctuation index and larger subject variability,” a POSA
considering PI-75 “would not look at injecting into the deltoid.” Id. at 1605:7–14. Thus, the Court
finds that the Cleton 2008 references support a finding of nonobviousness. 35
5.

Objective Indicia of Nonobviousness

As part of its obviousness analysis, the Court must also consider evidence regarding
objective considerations of nonobviousness when present. In re Cyclobenzaprine Hydrochloride
35

Defendant also contends that the claimed regimens are obvious in view of another poster
reporting on the results of the SCH-201 Phase II trial (“Kramer”). See Def. Br. at 17–18, 30.
Plaintiffs assert that the Court should not consider Kramer because: (1) it was not disclosed in
Defendant’s obviousness contentions, expert reports, or the trial testimony of its experts; and (2) it
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Extended-Release Capsule Patent Litig., 676 F.3d 1063, 1075–77 (Fed. Cir. 2012). Such evidence
is used to “guard against slipping into use of hindsight, . . . and to resist the temptation to read into
the prior art the teachings of the invention in issue.” Graham, 383 U.S. at 36 (internal citation and
quotation marks omitted). Secondary considerations such as unexpected results, commercial
success, long felt but unsolved needs, and the failure of others may be relevant indicia of
nonobviousness. See id. at 17–18; Eli Lilly & Co. v. Zenith Goldline Pharm., Inc., 471 F.3d 1369,
1380 (Fed. Cir. 2006). Moreover, evidence of copying, industry praise, and skepticism may also
be considered. See Diamond Rubber Co. v. Consol. Rubber Tire Co., 220 U.S. 428, 441 (1911);
WBIP, LLC v. Kohler Co., 829 F.3d 1317, 1335 (Fed. Cir. 2016); Geo. M. Martin Co. v. Alliance
Mach. Sys. Int’l LLC, 618 F.3d 1294, 1304–05 (Fed. Cir. 2010).
Plaintiffs presented evidence of certain objective indicia that they argue support a finding
of nonobviousness. A number of witnesses opined on the existence of these objective indicia
including, for the Plaintiffs, (1) Dr. Srihari Gopal; (2) Dr. An Vermeulen; (3) Dr. Mahesh Samtani;
(4) Dr. Christian Kohler; and (5) Ms. Carla Mulhern (Final Pretrial Order at 29–31, 38); and for
the Defendant, (1) Dr. René Kahn; and (2) Mr. Ivan Hofmann (Final Pretrial Order at 39, 43). 36
While both parties offered evidence on the issue of secondary considerations, the burden always
remains on Defendant to prove by clear and convincing evidence that the claimed invention is
obvious. In re Cyclobenzaprine Hydrochloride, 676 F.3d at 1075–79 (concluding that, when
considering secondary considerations of nonobviousness, the burden never shifts to the patentee

was found not to be prior art in a parallel foreign litigation in Canada. Pls. Reply at 14–15, 23–24.
While the Court acknowledges Janssen’s assertions and fairness concerns, even considering the
Kramer reference, the Court’s obviousness analysis would be unaltered because, unlike the ’906
Patent, Kramer discloses equal doses injected into the gluteal muscle only.
36
These witnesses’ relevant backgrounds and qualifications have been described in earlier sections
of this Opinion.
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to prove nonobviousness and instead always remains on the party challenging the validity of the
patent to prove by clear and convincing evidence that the patent at issue is obvious).
As to the objective indicia, Defendant challenges whether there is a sufficient nexus
between the merits of the claimed invention and the objective evidence. Plaintiffs counter that the
appropriate nexus between the objective evidence and the claims of the ’906 Patent is present.
Here, the Court finds that the secondary considerations have a sufficient nexus to the claimed
invention because the proffered evidence is linked to the high loading dose deltoid injections and
subsequent maintenance injections described in the ’906 Patent. 37 See WBIP, LLC, 829 F.3d at
1330 (internal citations and quotation marks omitted) (“Where the allegedly obvious patent claim
is a combination of prior art elements, we have explained that the patent owner can show that it is
the claimed combination as a whole that serves as a nexus for the objective evidence; proof of
nexus is not limited to only when objective evidence is tied to the supposedly ‘new’ feature(s).”);
Tokai Corp. v. Easton Enters., Inc., 632 F.3d 1358, 1369–70 (Fed. Cir. 2011) (concluding that, to
establish a nexus to the merits of a claimed invention, the offered secondary consideration must
actually result from what is both claimed and novel in the patent). To the extent more specific
arguments concerning nexus were made by the parties, such assertions are addressed in the relevant
sections.
a) Unexpected Results
Unexpected or surprising results can support nonobviousness. To demonstrate unexpected
results, a party must “show that the claimed invention exhibits some superior property or advantage
that a person of ordinary skill in the relevant art would have found surprising or unexpected.” In

37

Because the Court finds that there is a nexus between the claimed invention and the objective
indicia, the Court need not address Janssen’s argument that a presumption of nexus should apply
here (Pls. Br. at 42).
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re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995). “The principle applies most often to the less predictable
fields, . . . where minor changes in a product or process may yield substantially different results.”
Id. Furthermore, “when unexpected results are used as evidence of nonobviousness, the results
must be shown to be unexpected compared with the closest prior art.” Kao Corp. v. Unilever U.S.,
Inc., 441 F.3d 963, 970 (Fed. Cir. 2006) (internal citation and quotation marks omitted). Plaintiffs
assert that the claimed dosing regimens produced the unexpected outcome of a second-generation
LAI that successfully treated schizophrenia and other psychotic disorders without the need for oral
supplementation, due to the dosing regimens’ use of high initial loading doses to achieve rapid
efficacy and monthly maintenance doses to achieve sustained efficacy. Pls. Br. at 45–46.
Defendant disagrees that these properties were unexpected. Def. Br. at 54–58.
The Court finds that the Representative Claims led to unexpected results. Prior to the
invention of Invega Sustenna, the conventional wisdom for both first-generation and secondgeneration antipsychotics was to “start low and go slow.” PFOF ¶ 163 (internal citation and
quotation marks omitted). Indeed, experts for both Plaintiffs and Defendant agreed that the
traditional dosing paradigm for treating schizophrenia involved beginning with lower doses and
slowly making upward adjustments. See Trial Tr. (Kahn) at 168:19–169:5 (for dosing risperidone,
it is “recommended” to begin with an “initial dose” and then “work your way up in small
increments until you get to your target dose or your effective dose range”), 2392:23–2393:1
(according to label, “the preferred approach” for dosing haloperidol decanoate “is to begin with
lower initial doses and to adjust the dose upward as needed”); Trial Tr. (Kohler) at 1905:12–17
(explaining that initial dose of Risperdal Consta “was limited to 25 milligrams or less, which in
many people was not the eventual dose required to manage the psychosis,” followed by subsequent
higher doses weeks later). Moreover, as the Gibaldi prior art reference indicated, “[d]epot

42

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injections are long-acting dosage formulations indicated for maintenance treatment rather than
initiation of therapy.” PTX-64 at 5. The claimed dosing regimens run contrary to these prior art
teachings because they use depot injections of high, rather than low, loading doses to initiate
treatment.
In addition, as explained above, the claimed invention also led to unexpected results in
view of the ’548 Protocol prior art reference. In multi-dose regimens, such as those covered by
the Representative Claims, there are many possible combinations of dose amounts, schedule, and
sites of administration. PFOF ¶ 248. The ’548 Protocol, which Defendant identifies as one of the
closest prior art references, tested three different combinations of equal doses of paliperidone
palmitate administered in the gluteal muscle and failed to properly initiate treatment in a rapid
manner to aid with treatment adherence. Id. ¶ 249. By contrast, the ’906 Patent regimens, which
are comprised of high loading doses that must be administered in the deltoid muscles for the first
two doses, succeeded. Id. ¶ 60. Therefore, the Court finds that in view of the prior art, the claimed
invention led to unexpected results.
Defendant’s primary argument against a finding of unexpected results is that “the alleged
difficulties Janssen faced during development were avoidable.” Def. Br. at 55. This argument is
unpersuasive. As set forth above, Plaintiffs’ inventors expected the Phase III clinical trials to be a
success, especially because they built on the promising results of the SCH-201 study, which
showed rapid efficacy. PFOF ¶ 36. Contrary to their expectations, however, the inventors
encountered several clinical failures during Phase III, including a “high dropout rate” of patients
discontinuing treatment because of “lack of efficacy.” Trial Tr. (Vermeulen) at 784:3–10, 793:12–
794:5; see also PTX-284 at 66–67. The evidence at trial showed that Invega Sustenna improved
patient treatment adherence through its use of high initial loading doses that rapidly achieved

43

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therapeutic concentrations of paliperidone palmitate and monthly loading doses which maintained
these concentrations. Trial Tr. (Kohler) at 1910:9–1912:13 (Dr. Kohler providing a detailed and
persuasive analysis of the benefits of Invega Sustenna); see also PTX-627 at 51.

Such a

“difference between an effective and safe drug and one with significant side effects that caused
many patients to discontinue treatment” has been found to “constitute an unexpected difference in
kind.” Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1307 (Fed. Cir. 2015). Thus, the unexpected
results indicator weighs in favor of nonobviousness.
b) Skepticism
“Evidence of industry skepticism” is relevant to the obviousness inquiry. WBIP, LLC, 829
F.3d at 1335. “If industry participants or skilled artisans are skeptical about whether or how a
problem could be solved or the workability of the claimed solution, it favors non-obviousness.”
Id. The Federal Circuit has “recognize[d] a range of third-party opinion that can constitute
skepticism,” including “testimony that third parties were ‘worried’ or ‘surprised’” as “sufficient to
establish skepticism.” Neptune Generics, LLC v. Eli Lilly & Co., 921 F.3d 1372, 1378 (Fed. Cir.
2019) (citing Circuit Check Inc. v. QXQ Inc., 795 F.3d 1331, 1337 (Fed. Cir. 2015)).
Here, Plaintiffs have proffered evidence of skepticism that supports a finding of
nonobviousness. The trial record indicates that on February 28, 2007, in response to Janssen
scientists’ proposal of the dosing regimen of 150 mg-eq. on the first day of treatment and 100 or
50 mg-eq. on the eighth day, a panel of external advisors “expressed their opinion” that a lower
dosing regimen with “lesser risk” should be considered. PTX-92 at 1.
These external advisors were not the only industry participants to express doubt regarding
aspects of the claimed invention. Indeed, after Janssen initially applied for regulatory approval of
a dosing regimen of “100/100 mg-eq., day 1/8, deltoid dosing regimen” in October 2007, the FDA
suggested that Janssen use even lower initiation doses starting at 75 mg-eq. up to 100 mg-eq. on
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the first and eighth days of treatment. PFOF ¶¶ 57–58; PTX-94 at 59, 61. Although the FDA’s
recommendation comported with the “start low, go slow” conventional wisdom of the time (see
PTX-808 at 3 (internal quotation marks omitted)), it also evidenced skepticism toward the highloading dose strategy later claimed in the ’906 Patent.
Moreover, even after Invega Sustenna received FDA approval, treating psychiatrists had
reservations about the claimed dosing regimens. See Trial Tr. (Kohler) at 1907:2–1908:4 (credibly
explaining that when Invega Sustenna first became available, psychiatrists found the treatment
initiation guidelines “unusual,” “very different from what we had been familiar and, to some
extent, comfortable with,” and thought it might “lead to side effects that would prevent the person
from continuing with treatment”). Such concerns weigh in favor of nonobviousness. See Neptune
Generics, LLC, 921 F.3d at 1378 (affirming finding of skepticism based on FDA concerns); Cir.
Check Inc., 795 F.3d at 1337 (testimony that customers were “worried” about using claimed
invention supported finding of skepticism).
Defendant’s arguments against a finding of skepticism are unpersuasive. Defendant
contends that Plaintiffs have failed to establish skepticism because: (1) they rely on inadmissible
hearsay from fact witness testimony; and (2) the FDA’s statements were merely advice in keeping
with its regulatory duties, rather than skepticism. See Def. Br. at 52–54.

With respect to

Defendant’s first argument, the Court finds that even if it were to exclude the testimony cited by
Plaintiffs regarding the outside experts’ concerns as inadmissible hearsay, 38 Plaintiffs nevertheless
proffered sufficient evidence of the panel’s skepticism in the form of meeting minutes. See PTX-

38

Dr. Gopal testified, for example, that in regard to the 150 mg-eq. day 1 and 100 mg-eq. day 8
dosing regimen, outside experts “didn’t think it was necessary. They thought it actually was risky.
They thought that the dose was too high and that we should go for a lower dose.” Trial Tr. (Gopal)
at 1075:14–16.
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92. These minutes, which relate to the February 28, 2007, “Clinical Pharmacokinetic and Dosing
Advisory Board Meeting,” documented the outside experts’ skepticism of a high-dosing regimen,
rather than, as Defendant argues, merely the probability of receiving regulatory approval. They
are an admissible business record under Federal Rule of Evidence 803(6). See Fed. R. Evid. 803(6)
(recognizing exception to rule against hearsay for records of regularly conducted activities); 39
PTX-92 at 1 (noting that compared with the “[p]roposed dosing regimen,” “[a] more acceptable
regimen from a regulatory viewpoint would be 100 mg eq. (Day 1) followed by either 100 or 50
mg eq. on Day 8” because it “provides therapeutic concentrations early and in a safe range”).
Defendant’s contention regarding the FDA’s statements is similarly unavailing. According
to Defendant, the FDA’s suggestion of a 75 mg-eq. dose is not probative of skepticism, but instead
“‘reflect[ed] attention to the FDA’s normal duties ensuring the safety and efficacy of new drugs.’”
Def. Br. at 53 (quoting Bayer Healthcare Pharm., Inc. v. Watson Pharm., Inc., 713 F.3d 1369,
1377 (Fed. Cir. 2013)). Defendant’s reliance on Bayer, however, is misplaced. In Bayer, the
Federal Circuit found an FDA request for efficacy and safety data regarding an element of the
proposed dosing regimen insufficient to establish skepticism. Bayer Healthcare Pharm., Inc., 713
F.3d at 1377. The Bayer court concluded that the FDA’s request was in keeping with the agency’s

39

“The business records exception allows admission of records of regularly conducted activity
through the testimony of a custodian or other qualified witness,” if the records meet the other
requirements of Federal Rule of Evidence 803(6). Crash Dummy Movie, LLC v. Mattel, Inc., 601
F.3d 1387, 1392 (Fed. Cir. 2010) (citing Fed. R. Evid. 803(6)). At trial, Dr. Samtani confirmed
that PTX-92 contains the minutes of Janssen’s February 28, 2007, meeting with the external
advisors, which he attended, and the Court finds that Plaintiffs have laid a sufficient foundation
for the admission of the minutes as a business record. See Trial Tr. (Samtani) at 1346:16–1347:2.
Furthermore, the Court finds that Defendant has not met its burden of showing that the meeting
minutes “indicate a lack of trustworthiness,” as required for exclusion under Rule 803(6). Fed. R.
Evid. 803(6). Finally, and in any event, both parties agree that PTX-92 may be admitted to show
its effect on the listener, rather than for its truth. See Trial Tr. (Gopal) at 1074:16–1076:3; Fed. R.
Evid. 801(c)(2) (excluding only out-of-court statements offered “to prove the truth of the matter
asserted in the statement”). Therefore, the Court will consider the minutes in its analysis.
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regulatory duties “requiring actual data to corroborate statements in a new drug application” and
“in no way indicates that FDA experts would have been surprised to receive such data.” Id. Here,
by contrast, the FDA’s statement is not a simple request for data, but rather a recommendation to
move away from the high-loading dose strategy proposed by Janssen. See PTX-94 at 59, 61. As
the FDA’s suggestion concerned aspects of the invention at issue, the Court finds that it is evidence
of industry skepticism and weighs in favor of nonobviousness. See Neptune Generics, LLC, 921
F.3d at 1378 (affirming skepticism finding based on FDA’s disagreement with patentee’s proposed
course of action during clinical trial).
c) Praise
“Evidence that the industry praised a claimed invention or a product which embodies the
patent claims weighs against an assertion that the same claim would have been obvious. Industry
participants, especially competitors, are not likely to praise an obvious advance over the known
art.” WBIP, LLC, 829 F.3d at 1334; see also Institut Pasteur & Universite Pierre Et Marie Curie,
738 at 1347 (noting that “industry praise . . . provides probative and cogent evidence that one of
ordinary skill in the art would not have reasonably expected [the invention at issue]”). Plaintiffs
identify several sources of industry praise in support of their position, including Dr. Kohler’s
testimony that Invega Sustenna is his “first choice” LAI, trade publication articles, an FDA
employee’s remarks at a 2013 industry conference, and Invega Sustenna’s nomination for the Prix
Galien award. Pls. Br. at 49–50; PFOF ¶ 208. The Court finds that certain of the cited trade
publications are the most probative evidence of praise, while affording lesser weight to others.
At trial, Plaintiffs introduced articles touting the benefits of Invega Sustenna. One such
article is titled “New Label for LAI Paliperidone Breaks FDA Ground by Including Real-World
Data” from the trade publication Psychiatric News. This article noted that the results of the
Paliperidone Palmitate Research In Demonstrating Effectiveness study indicated that “the average
47

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time before any treatment failure was about six months longer in the LAI group compared with
the oral antipsychotic group.” PTX-131 at 1, 3. According to the article, “[t]he improvements seen
were due in part to better adherence rates of the medication, which is an advantage of LAIs as the
medication is administered at clinics.” Id.; see also PFOF ¶ 206. Another article, published by
Thomas R. Einarson et al. in the Journal of Medical Economics, stated that “[s]ince [paliperidone
palmitate]-LAI is the drug with the lowest cost per patient treated and the highest number of
[quality adjusted life years], it dominates the other two atypical antipsychotic depots” and “should
be considered the drug of choice in many situations.” PTX-134 at 5. While Defendant asserts that
the results discussed in Einarson were limited to the Czech Republic (see Def. Br. at 50–51), the
Court finds that the article nevertheless amounts to praise of the claimed invention.
Plaintiffs point to two other articles as evidence of industry praise. Pls. Reply Br. at 41.
The first article, “Efficacy and Safety Profile of Paliperidone Palmitate Injections in the
Management of Patients with Schizophrenia: An Evidence-Based Review” (PTX-133), reported
on clinical trials confirming the importance of Invega Sustenna’s high initial loading doses. See
Trial Tr. (Kahn) at 2412:9–20. The second article, “Paliperidone palmitate: a new long-acting
injection for schizophrenia” (PTX-506), noted advantages to using Invega Sustenna over Risperdal
Consta. See Trial Tr. (Kahn) at 2422:1–4. Defendant notes that both articles were funded or
reviewed by Janssen. See Def. Br. at 51. Nevertheless, the Court acknowledges Plaintiffs’
contention that these articles were peer-reviewed and data driven (see Pls. Reply Br. at 41) and
finds that Defendant has not provided persuasive evidence of bias or improper influence by Janssen
sufficient to reject these articles entirely.
Similarly, Janssen argues that the selection of Invega Sustenna as a finalist for the Prix
Galien award is evidence of industry praise. Pls. Br. at 49. The Court acknowledges the Prix

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Galien is an important award that has been compared to the Nobel Prize in the pharmaceutical
world. PFOF ¶¶ 188, 208. While Teva raised issues regarding who nominated Invega Sustenna
for this award, the Court gives some weight to this item given Janssen was a finalist. 40 See, e.g.,
Genzyme Corp. v. Dr. Reddy’s Lab’ys, Ltd., No. 13-1506, 2016 WL 2757689, at *15 (D. Del. May
11, 2016), aff’d, 716 F. App’x 1006 (Fed. Cir. 2017).
d) Copying
It is well settled that the copying of an invention can be indicative of nonobviousness.
Diamond Rubber, 220 U.S. at 440–41 (finding “imitation” of a certain tire as a “concession to its
advance beyond the prior art and of its novelty and utility”). Generally, copying is not considered
evidence of nonobviousness in the ANDA context “because a showing of bioequivalence is
required for FDA approval.” Bayer Healthcare Pharm., Inc., 713 F.3d at 1377 (citing Purdue
Pharma Prods. L.P. v. Par Pharm., Inc., 377 F. App’x 978, 983 (Fed. Cir. 2010)). Copying may,
however, be probative of nonobviousness where the generic manufacturer “rel[ies] on the accused
process.” Merck Sharp & Dohme Corp. v. Hospira, Inc., 874 F.3d 724, 728, 731 (Fed. Cir. 2017)
(finding evidence of copying where defendant “tried five alternative formulations in an attempt to
avoid copying” before relying on patent owner’s process because the “[Hatch-Waxman] Act does
not . . . require the generic manufacturer to copy the NDA holder’s process of manufacturing the
drug”); see also Dey, L.P. v. Teva Parenteral Meds., Inc., 6 F. Supp. 3d 651, 681 (N.D.W. Va.
2014), aff’d sub nom. DEY LP v. Teva Parenteral Meds., Inc., 600 F. App’x 773 (Fed. Cir. 2015)
(Copying was established where “Teva could have developed its own solution using different
excipients, but instead chose to reverse engineer Dey’s formulation based on Dey’s patents. This

40

To the extent that Invega Sustenna’s market share is also presented as evidence corroborating
industry praise of the drug as a “first choice” LAI (Pls. Br. at 49), the Court discusses this factor
in its commercial success analysis.
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provides a strong indication that the prior art provided Teva with no obvious alternative to Dey’s
invention.”).
Here, Plaintiffs have proffered evidence of copying and the Court affords some limited
weight to this factor to support the nonobviousness conclusion the Court independently reaches.
In its ANDA submission, Defendant stated that the

PTX-26 at 176; PFOF ¶ 209. While Defendant contends that it

(DFOF ¶ 528),
See Trial Tr. (Sinko) at 1625:1–6
; see also
PFOF ¶ 209. Absent such a requirement,
the claimed invention. See Merck Sharp & Dohme Corp., 874
F.3d at 728, 731; Dey, L.P., 6 F. Supp. 3d at 681.
In addition, Defendant argues that there is no evidence of copying because before it filed
its ANDA, “Janssen submitted a Citizen’s Petition to the FDA seeking a heightened
bioequivalence standard that, if granted, would serve to implicitly regulate the particle size of
Teva’s ANDA product.” Def. Br. at 46. This argument is similarly unavailing. The record
contains no evidence that the FDA responded to the petition, and, as of the date of this decision,
the petition appears to remain pending. Thus, because the petition has not imposed particle size
regulations on generic manufacturers, it does not weaken the evidence of copying. 41

41

Defendant cites Liqwd, Inc. v. L’Oreal USA, Inc., 941 F.3d 1133, 1138 (Fed. Cir. 2019) to argue
that the similarities between the particle sizes of its generic product and Invega Sustenna and the
’906 Patent are not probative of copying. Def. Br. at 47. While the court in Liqwd, Inc. did note
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e) Long-Felt Need and Failure ofOthers
"The existence of a long-felt but unsolved need that is met by the claimed invention is . . .
objective evidence of non-obviousness." Millennium Pharm., Inc. v. Sandoz Inc., 862 F.3d 1356,
1369 (Fed. Cir. 2017); see also WBIP, LLC, 829 F.3d at 1332 ("Evidence of a long felt but
unresolved need tends to show non-obviousness because it is reasonable to infer that the need
would have not persisted had the solution been obvious."). In order to show satisfaction of long­
felt need, one must establish that (1) a POSA recognized a problem that existed for a long period
of time without a solution; (2) the long-felt need had not been satisfied by another before the
claimed invention; and (3) the invention in fact satisfied the long-felt need. See Newell Cos., Inc.

v. Kenney Mfg. Co., 864 F.2d 757, 768 (Fed. Cir. 1988); In re Cavanagh, 436 F.2d 491, 495-96
(C.C.P.A. 1971); In re Gershon, 372 F.2d 535, 538-39 (C.C.P.A. 1967).
The ti·ial evidence showed that the claimed invention satisfied the long-felt need for an LAI
that could successfully initiate and maintain ti·eatment without oral supplementation. Prior to the
invention of Invega Sustenna, all antipsychotics on the market had significant limitations. For
example, first-generation antipsychotics had unfavorable side effect profiles and required oral
preu-eatment and individualized dosing. PFOF ,i,i 15-18. Similarly, Risperdal Consta, the only
second-generation LAI to predate Invega Sustenna, provided only two weeks of therapeutic
benefits and required oral supplementation for the first three weeks of u-eatment. Id. ,nf 19-20.
These limitations conti·ibuted to patient non-adherence, a significant baITier to ti·eatment. Id. ,i,i 14,

that "more is needed than merely showing that similarity exists between the patent and the
competitor's accused product," it nevertheless went on to explain that "access to an issued patent
coupled with circumstantial evidence regarding changes to a competitor's desi is sufficient to
su ort co in ." Li wd,Inc. 941 F.3d at 1137-38 internal citation omitted.

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17–20. Thus, as Drs. Kahn and Kohler testified, prior to Invega Sustenna, none of the secondgeneration treatments on the market were able to provide monthly dosing without the need for oral
supplementation. See Trial Tr. (Kahn) at 2410:8–17 (agreeing that “there [were] no secondgeneration antipsychotics that were dosed monthly without the need for oral supplementation”);
Trial Tr. (Kohler) at 1910:6–1912:19 (describing clinical benefits of Invega Sustenna and noting
that “none of the previous long-acting injectables were able to provide all these benefits”).
Contemporaneous documentary evidence confirmed the need for an LAI that could achieve
the benefits that Invega Sustenna provides. Indeed, in an email dated September 22, 2006, a
Janssen clinician noted that the then-used dosing regimens were “not getting sufficient numbers
of subjects into a therapeutic range early enough” and that “[i]t is not sufficient to say that they get
there by day 22 or 36 - that is too late for subjects with schizophrenia and will not lead to the
efficacy that this product needs to have in the market place.” PTX-812 at 1; PFOF ¶ 174. During
the paliperidone palmitate project development process, Janssen made it its goal to overcome these
treatment limitations. See PFOF ¶ 21; Trial Tr. (Vermeulen) at 751:13–23 (explaining that the
“target protocol” for the project was “to have a better product that started releasing quickly after
injection and then not need supplementation”); PTX-166 at 19.
The ’906 Patent fulfilled this long-felt need. As Drs. Sinko and Kohler agreed, Invega
Sustenna is an LAI that initiates and maintains therapeutic levels of paliperidone palmitate without
oral supplementation. See Trial Tr. (Sinko) at 1473:3–5; Trial Tr. (Kohler) at 1911:9–22. Unlike
earlier treatment options, Invega Sustenna is a well-tolerated medication that uses a uniform
initiation regimen. See Trial Tr. (Kohler) at 1910:6–1912:19.

Moreover, it has “improved

adherence” among patients. Id. at 1912:8–9; see also PTX-627 at 51. While Defendant relies on
Dr. Kahn’s testimony to argue that the claimed invention did not resolve any long-felt need (see

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Def. Br. at 61), Dr. Kahn’s testimony is unsupported by the record. According to Dr. Kahn, “the
major change” in schizophrenia treatment “occurred in the mid-1950s,” when chlorpromazine, the
first antipsychotic, was introduced. Trial Tr. (Kahn) at 2296:15–17. Since that time, Dr. Kahn
asserted, “even though many antipsychotics ha[ve] been introduced, it hasn’t materially changed
the outcome in schizophrenia.” Trial Tr. (Kahn) at 2296:22–24. These contentions, however, are
contradicted by a reference relied on by Defendant’s other expert Dr. Wermeling and the
prescription frequency data for various medications. See DTX-104 at 5 (explaining that
“Chlorpromazine and other first-generation antipsychotics . . . do not improve and may even
exacerbate the negative symptoms of schizophrenia and are associated with dose-limiting
extrapyramidal symptoms (EPS)”); PTX806B at 66–73 (chart showing total days of treatment for
various schizophrenia medication from 2015 through 2018); see also PFOF ¶¶ 178–79. Thus, in
view of the trial record as a whole, and the fact that Defendant did not credibly rebut Dr. Sinko’s
assertion that Invega Sustenna practices Representative Claims 2, 19, 20, and 21 when dosed in
accordance with its label, the Court finds that the objective indicator of long-felt need weighs in
favor of nonobviousness. See Trial Tr. (Sinko) at 1610:8–1614:19; Trial Tr. (Kahn) at 2337:1–
2338:16, 2344:2–18; Eli Lilly & Co., 471 F.3d at 1380 (finding of “need for a safer, less toxic, and
more effective” alternative to existing treatment options provided a basis for unmet need); WBIP,
LLC, 829 F.3d at 1331 (holding that a nexus can be presumed when the asserted objective indicia
is tied to a specific product and the product is the invention claimed in the patent).
f) Commercial Success
“The commercial response to an invention is significant to determinations of obviousness.
. . .” Demaco Corp. v. F. Von Langsdorff Licensing Ltd., 851 F.2d 1387, 1391 (Fed. Cir. 1988).
For evidence of commercial success to be accorded significant weight, there must be “a nexus
between the claimed invention and the commercial success.” Ormco Corp. v. Align Tech., Inc.,
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463 F.3d 1299, 1312 (Fed. Cir. 2006). The claimed invention need not, however, be “solely
responsible for the commercial success, in order for this factor to be given weight appropriate to
the evidence.” Cont’l Can Co. USA, Inc. v. Monsanto Co., 948 F.2d 1264, 1273 (Fed. Cir. 1991).
Here, Plaintiffs demonstrated that the claimed dosing regimens contributed to Invega
Sustenna’s commercial success.

The record indicates that, when adjusted for rebates and

discounts, Invega Sustenna’s net sales in the United States have grown annually since its launch
in 2009 and have exceeded $1 billion from 2015 through 2019. PTX-8, -9, -806B at 3; Trial Tr.
(Mulhern) at 2579:11–2580:1; Trial Tr. (Hofmann) at 2741:24–2742:7, 2833:18–2834:21.
Furthermore, Invega Sustenna has accounted for over 50 percent of all revenue generated by sales
of LAI antipsychotics in the United States annually from 2013 through 2019. PTX-806B at 91–
92. 42 In the fourth quarter of 2019 alone, Invega Sustenna had 30.9 percent of the market share
based on days of treatment among second-generation long-acting treatments—more than twice the
share of its closest competitor. Id. at 37 (noting next closest competitor Abilify Maintena had 12.6
percent fourth quarter 2019 market share based on days of treatment). Defendant’s economic
expert did not dispute the underlying market data relied on by Plaintiffs (see Trial Tr. (Hofmann)
at 2741:22–2742:7, 2833:18–2835:8, 2836:18–22), and Plaintiffs’ economic expert opined that
“[b]ased on [her] review of the economic evidence, it’s quite clear that Invega Sustenna has
achieved substantial success in the marketplace no matter how you look at it, sales or market
penetration” (Trial Tr. (Mulhern) at 2586:2–5). See also Trial Tr. (Hofmann) at 2838:10–21
(agreeing that none of the competing LAIs introduced after Invega Sustenna’s launch “has

42

The LAI antipsychotic market consists of two first-generation and eight second-generation
products. PTX-806B at 91–92; PFOF ¶ 188.
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managed to displace Invega Sustenna from its position as the best-selling second-generation
antipsychotic[] in the United States”).
The record further establishes that the benefits of the patented dosing regimens contributed
to Invega Sustenna’s success on the market. At trial, Defendant’s economic expert did not refute
Janssen’s assertion that Invega Sustenna’s dosing regimen consisting of a monthly injectable
without oral supplementation “is a factor contributing to [its] marketplace performance.” Trial Tr.
(Hofmann) at 2852:17–2853:7. Janssen highlighted these features in its marketing materials,
which, as Plaintiffs’ expert, Carla Mulhern, credibly opined, suggests that they were viewed as
“the key differentiators that distinguish their product from the competition.” Trial Tr. (Mulhern)
at 2594:12–21. Indeed, Janssen’s “[c]ore [m]essage” for Invega Sustenna emphasized that
“patients can receive two starting doses . . . in 7 days with rapid & sustained plasma-levels for up
to one month and no need for oral supplementation.” PTX-416 at 33; see also, e.g., PTX-395 at 6,
-417 at 76, -456 at 111. Furthermore, market research indicated that the claimed benefits “are
differentiators

for

healthcare

providers.”

Trial

Tr.

(Mulhern)

at

2597:8–2598:6;

PTX-410, -412, -415, -417, -421.
In addition, LAI market data demonstrates that the patented benefits helped contribute to
Invega Sustenna’s commercial success. The record establishes that paliperidone palmitate is the
only second-generation antipsychotic whose market share is greater for its long-acting form than
for its short-acting oral form. Trial Tr. (Mulhern) at 2599:8–18 (“Invega Sustenna has substantially
outperformed the performance of the paliperidone molecule in the short-acting segment, and this
stands apart from the other molecules in the long-acting space. We can see – for most of them, we
see the opposite relationship.”). Indeed, it holds approximately 31 percent of the long-acting
market share compared to about 1 percent of the short-acting market share. Trial Tr. (Mulhern) at

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2600:5–7; PTX-454, -806B at 74–81. The difference in paliperidone palmitate’s short- and longacting market shares indicates “that there is something besides the molecule that is explaining or
contributing to the success of Invega Sustenna.” Trial Tr. (Mulhern) at 2599:19–21.
Defendant asserts that Invega Sustenna’s commercial success can be attributed to factors
other than the claimed dosing regimens, such as Janssen’s marketing efforts, its industry
reputation, its rebates and sampling program, and off-label usage of the product. 43 Def. Br. at 66–
67; Def. Reply Br. at 29–30. This argument is unpersuasive. With respect to marketing, the trial
evidence established that Janssen’s promotional expenditures for Invega Sustenna were lower than
that of its competitors (see PTX-806B at 124, Trial Tr. (Mulhern) at 2665:21–2666:4), and the
marketing intensity for the product was lower than the industry average. See Trial Tr. (Mulhern)
at 2615:16–24, PTX-806B at 9, 122–24. Moreover, Defendant’s economic expert testified that he
did not have any alternative data comparing the marketing activities of Janssen and its competitors.
Trial Tr. (Hofmann) at 2846:5–8, 2848:13–22. While Defendant contends that Janssen’s discount
and rebate offers drove prescriptions of Invega Sustenna (see Def. Br. at 67), its economic expert
conceded that he did not have data on rebates and discounts offered by Janssen’s competitors (Trial
Tr. (Hofmann) at 2848:17–22), and Plaintiffs’ economic expert found that, based on publiclyavailable information, the “discounts and rebates for Invega Sustenna are in line with the
pharmaceutical industry as a whole.” Trial Tr. (Mulhern) at 2615:25–2616:20. Furthermore,
Janssen’s sampling program does not weaken the commercial success evidence because Janssen’s
competitors also maintain sampling programs and Defendant’s economic expert did not have any
data to show that Janssen’s sampling efforts were stronger than its competitors’ efforts. Trial Tr.

43

Defendant’s argument that blocking patents undermine the evidence of Invega Sustenna’s
commercial success is discussed below. Def. Br. at 60–65.
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(Mulhern) at 2616:7–13; Trial Tr. (Hofmann) at 2848:9–16. Thus, the Court finds that Plaintiffs’
marketing efforts did not meaningfully distinguish Invega Sustenna from its competitors. Trial Tr.
(Mulhern) at 2615:25–2616:20.
Defendant’s argument regarding the impact of Janssen’s reputation on sales is similarly
unavailing. As Plaintiffs correctly point out, Invega Sustenna has substantially outperformed other
Janssen products on the market, belying Defendant’s assertion that the Janssen brand is responsible
for Invega Sustenna’s success. Trial Tr. (Mulhern) at 2616:24–2618:1; see also PTX-806B at 10.
Furthermore, Defendant’s contentions regarding off-label usage do not overcome Plaintiffs’
evidentiary showing.

, which was repeatedly objected
to by Janssen, the trial record as a whole indicates that Janssen’s core marketing message
emphasized the claimed dosing regimens (see PTX-416 at 33), and Plaintiffs’ economic expert
explained that her analysis was not based on any “explicit assumptions about whether every sale
used the dosing regimen.” Trial Tr. (Mulhern) at 2642:4–6. Thus, the Court finds that the off-label
usage evidence does not change the above analysis or refute evidence of nexus, and the commercial
success indicator as a whole supports a finding of nonobviousness.
i.

The Alleged “Blocking Patents” Do Not Undermine Evidence of
Long-Felt Need or Commercial Success

Defendant argues that evidence of Invega Sustenna’s commercial success, or any long-felt
need resolved by the product, is not probative of nonobviousness because three alleged blocking
patents owned by Plaintiffs precluded competitors from arriving at or practicing the claimed dosing

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regimens. 44 See Def. Br. at 60–65; DFOF ¶ 416. On the facts of this case, the Court finds
Defendant’s contentions unpersuasive.
A patent is considered “a ‘blocking patent’ where practice of a later invention would
infringe the earlier patent.” Acorda Therapeutics, Inc. v. Roxane Lab’ys, Inc., 903 F.3d 1310, 1337
(Fed. Cir. 2018). “Where ‘market entry by others was precluded [due to blocking patents], the
inference of non-obviousness of [the asserted claims], from evidence of commercial success, is
weak.’” Galderma Lab’ys, L.P. v. Tolmar, Inc., 737 F.3d 731, 740 (Fed. Cir. 2013) (quoting Merck
& Co. v. Teva Pharm. USA, Inc., 395 F.3d 1364, 1377 (Fed. Cir. 2005)) (alterations in original).
The Federal Circuit has explained, however, that “the mere existence or sheer number of blocking
patents does not, without more, ‘necessarily detract from evidence of commercial success of a
product or process.’” Acorda Therapeutics, Inc., 903 F.3d at 1338 (quoting Merck Sharp & Dohme
Corp., 874 F.3d at 731). Rather, whether commercial success evidence should be discounted
because of a blocking patent is “a fact-specific inquiry.” Merck Sharp & Dohme Corp., 874 F.3d
at 731.
As an initial matter, Plaintiffs correctly note that Defendant did not proffer any technical
expert opinion on the scope of the alleged blocking patents. See Pls. Br. at 50–51. Indeed, at trial,
Defendant originally indicated that it intended to recall Dr. Wermeling, its obviousness expert, for
rebuttal on the issue of secondary considerations. See Trial Tr. at 412:17–19. After Dr. Wermeling
completed his initial testimony, however, Defendant advised the Court that it would not recall him

44

The three alleged blocking patents are the ’544 Patent, U.S. Patent No. 5,254,556 (the “’556
Patent”), and U.S. Patent No. 6,077,843 (the “’843 Patent”). All three patents are directed towards
paliperidone palmitate. See DTX-157, -159, -160. Although Defendant identified U.S. Patent No.
5,352,459 (the “’459 Patent”) as a fourth alleged blocking patent in a pretrial submission (see Final
Pretrial Order at 28), it did not discuss the ’459 Patent in its post-trial briefing. The Court therefore
will not specifically address the ’459 Patent, but notes that it would be subject to the analysis of
blocking patents below.
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(id. at 2456:23–2457:2), and instead solely relied on the opinion of Mr. Hofmann, its economic
expert, on the subject of blocking patents. Mr. Hofmann admitted, however, that he was not
qualified to assess the scope of the prior patents himself, that prior to trial he had considered Dr.
Wermeling’s reply expert report in forming his opinion, that he knew that Dr. Wermeling had not
read the ’556 Patent, and that he did not know whether Dr. Wermeling had analyzed the scope of
the ’843 Patent. Trial Tr. (Hofmann) at 2786:24–2787:2, 2788:11–14, 2798:2–6, 2812:18–22;
2813:11–16. The Court finds that these admissions considerably weaken the probative value of
Mr. Hofmann’s testimony.
Defendant does not dispute that Mr. Hofmann made these admissions, but instead urges
the Court to find a technical foundation for his testimony from other evidence in the record, such
as the ’544, ’556, and ’843 Patents themselves, Dr. Sinko’s opinions, and Janssen’s representations
to the FDA and USPTO. Def Br. at 63 n.14. Defendant’s contentions are unavailing. Even if the
Court were to assume that Mr. Hofmann had an adequate foundation for his opinions, Defendant’s
blocking patent arguments are nevertheless unpersuasive in light of the countervailing evidence
proffered by Plaintiffs. As Plaintiffs properly note, Mr. Hofmann testified that he understood it
was possible to practice Claim 2 of the ’906 Patent—which, as explained above, includes the
dosing regimen of Claim 1 on which Claims 20 and 21 depend—without infringing the claims of
the ’544 and ’843 Patents. Trial Tr. (Hofmann) at 2820:23–2821:10; 2823:16–21. In other words,
neither the ’544 nor ’843 Patent would have blocked a competitor from commercializing the
claimed dosing regimens at any time.
Moreover, and in any event, even if the Court assumes that the ’544, ’556, and ’843 Patents
are blocking patents, the record demonstrates that they did not in fact deter competition in this
case. Indeed, as Mr. Hofmann conceded, the governing patent infringement statute contains “a

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safe harbor [provision] that allows companies to develop a drug in research and development using
patented technology without infringing the patent.” Id. at 2824:3–8; see also 35 U.S.C. § 271(e)(1)
(“It shall not be an act of infringement to make, use, offer to sell, or sell within the United States
or import into the United States a patented invention . . . solely for uses reasonably related to the
development and submission of information under a Federal law which regulates the manufacture,
use, or sale of drugs or veterinary biological products.”). Both parties’ economic experts further
agreed that the drug development process can take many years, even up to a decade or longer. Trial
Tr. (Hofmann) at 2823:22–2824:2; Trial Tr. (Mulhern) at 2628:21–2629:10. Given this drug
development timeline and the fact that the last alleged blocking patent expired in November
2018, 45 the Court finds that these patents created little, if any, disincentives to innovate as of the
claimed December 19, 2007, priority date or the December 5, 2008, application date.
Finally, the evidence presented at trial establishes that competitors in fact had incentives
to develop competing products during the allegedly blocked periods, and did so. Indeed, contrary
to Mr. Hofmann’s testimony that “[n]o one would have an economic motivation to try and research
and discover [] the alleged novelties of the ’906 patent” because of Janssen’s “patent fortress
around paliperidone palmitate for the treatment of schizophrenia,” Defendant itself filed a
provisional patent application involving the purification and preparation of paliperidone palmitate
on January 10, 2008. Trial Tr. (Hofmann) at 2752:15–24; PTX-813 at 1. The application noted
that paliperidone is “[m]arketed under the trade name Invega” and “is an anti-psychotropic agent
approved in the United States for the treatment of schizophrenia.” PTX-813 at 9. Furthermore,
Mr. Hofmann conceded that there was an incentive to research and develop paliperidone palmitate

45

The ’556 Patent expired on October 27, 2012, the ’843 Patent expired on May 12, 2017, and the
’544 Patent expired on November 10, 2018. DTX-157, -159, -160.
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as of December 2007, that entities other than Janssen in fact conducted such clinical trials, and that
a competitor began seeking FDA approval for an alternative risperidone LAI in 2009—ten years
prior to the expiration of the patents covering Janssen’s Risperdal Consta product, belying
Defendant’s argument that Janssen maintained a monopoly over the market. Trial Tr. (Hofmann)
at 2826:19–2828:6, 2829:4–10. On these facts, the Court finds that the alleged blocking patents
did not discourage innovation in this case. Therefore, Plaintiffs’ evidence of commercial success
and long-felt unmet need should not be discounted.
6.

Presumption of Obviousness

Defendant argues that the Representative Claims should be presumed obvious because they
merely recite limitations from ranges disclosed in the prior art. Def. Br. at 5–12. Janssen argues
that no presumption of obviousness applies here because “the unique combinations of dose
amounts, dosing schedule, injection sites and particle size range claimed in the 906 Patent go far
beyond simply picking a dose amount within a range.” Pls. Br. at 54. Janssen cites to Iron Grip
Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1320 (Fed. Cir. 2004) to argue that where “an
invention is contended to be obvious based upon a combination of elements across different
references, there is no presumption, and the patent challenger must prove that there was motivation
to combine.” Pls. Br. at 54 (internal citations and quotation marks omitted). Plaintiffs make
convincing arguments that cause the Court to question the applicability of the “range” cases here,
where the claimed invention at issue is composed of a unique combination of elements that are not
all easily defined with numerical values that can be found in the prior art (such as injection site,
unequal loading doses, and characteristics of the paliperidone formulation). See Pls. Reply Br. at
Moreover, the differences between the prior art and the claimed invention go beyond numerical
ranges, and the invention took place in an unpredictable field of art. See Pls. Reply Br. at 3–8.

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Regardless, even if the Court were to apply a presumption of obviousness here, Plaintiffs have
proffered sufficient evidence to rebut any such presumption.
The Federal Circuit has recognized that “where there is a range disclosed in the prior art,
and the claimed invention falls within that range, there is a presumption of obviousness.” Iron Grip
Barbell Co., 392 F.3d at 1322. This presumption may be rebutted, however, “with evidence that
(1) the prior art taught away from the claimed invention; (2) there were new and unexpected results
relative to the prior art; or (3) there are other pertinent secondary considerations.” Allergan, Inc.,
796 F.3d at 1305 (quoting Galderma Lab’ys, L.P., 737 F.3d at 738).
Here, Plaintiffs have demonstrated that, at a minimum, the prior art taught away from the
invention, the claimed dosing regimens led to unexpected results, certain elements of the dosing
regimen were not known to be result-effective, there were a large number of possible combinations
of the relevant claim parameters, and there are other pertinent secondary considerations that
support a finding of nonobviousness. See Pls. Reply Br. at 9–16. As both parties’ experts agreed,
the traditional dosing paradigm for schizophrenia treatment involved low initiation doses followed
by gradual dose increases. See Trial Tr. (Kahn) at 168:19–169:5, 2392:23–2393:1; Trial Tr.
(Kohler) at 1905:12–17. Furthermore, the Gibaldi reference taught the use of depot injections for
treatment maintenance rather than initiation. DTX-91 at 5. When Janssen inventors deviated from
these teachings during Phase III, including by initiating therapy with two high-loading doses
administered in the deltoid muscle, they were able to overcome the failures of the earlier clinical
trials, including the ’548 Protocol/PSY-3003 study, and develop successful dosing regimens. See
PFOF ¶ 60.
Similarly, as explained above, compared to the prior art, the claimed regimens
unexpectedly achieved successful initiation and maintenance treatment goals. Where the ’548

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Protocol taught the use of equal doses administered in the gluteal muscle and failed (see PFOF ¶
249), the ’906 Patent dosing regimens, comprised of high initial loading doses administered in the
deltoid muscle followed by maintenance doses in either the deltoid or gluteal muscle, succeeded.
Additionally, it was not known in the prior art that using a LAI in the deltoid to initiate treatment
would have such a major impact on blood levels of paliperidone palmitate (Trial Tr. (Vermeulen)
at 770:23–771:14) and there were so many potential combinations of the claimed dosing regimen
that Janssen relied on complex modeling and simulations to make their discovery (id. at 756:6–
23). These considerations further rebut a presumption of obviousness from applying here. See E.I.
du Pont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018); Allergan, Inc.,
796 F.3d at 1305.
Other secondary considerations, discussed at length above, further rebut any alleged
presumption of obviousness. Plaintiffs have proffered evidence of commercial success, industry
praise and skepticism, copying, and long-felt need related to the claimed dosing regimens
sufficient to support a conclusion of nonobviousness. Thus, even if the Court were to assume
arguendo a presumption of obviousness applied here, it would not alter the Court’s obviousness
analysis because Plaintiffs have clearly rebutted the presumption. Having found that Teva has
failed to meet its burden of showing that the ’906 Patent is invalid as obvious, the Court next
considers Teva’s written description challenge.
B. Written Description (35 U.S.C. § 112)
A patent specification “shall contain a written description of the invention.” 35 U.S.C.
§ 112. The specification must “reasonably convey[] to those skilled in the art that the inventor had
possession of the claimed subject matter as of the filing date.” Ariad Pharms., Inc. v. Eli Lilly &
Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). The test for written description “requires an objective
inquiry into the four corners of the specification from the perspective of a [POSA].” Id. “[W]hether
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a patent complies with the written description requirement will necessarily vary depending on the
context. Specifically, the level of detail required to satisfy the written description requirement
varies depending on the nature and scope of the claims and on the complexity and predictability
of the relevant technology.” Id. (internal citation omitted). When reviewing a patent according to
these principles, “[w]ritten description is a question of fact, judged from the perspective of [a
POSA] as of the relevant filing date.” Falko-Gunter Falkner v. Inglis, 448 F.3d 1357, 1363 (Fed.
Cir. 2006) (citing Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563–64 (Fed. Cir. 1991)).
Defendant argues that the Patent-in-Suit is invalid because the specification does not
provide sufficient written description of the invention described in Claims 10, 13, 20, and 21. Def.
Br. at. 67–70. In response, Plaintiffs contend that the specification is sufficiently detailed and that
Defendant failed to prove these Claims lack adequate written description by clear and convincing
evidence. Pls. Br. at 68–71.
In support of their arguments, the parties rely on the testimony of Defendant’s expert Dr.
Kahn and Plaintiffs’ expert Dr. Kohler, whose qualifications were discussed previously in this
Opinion. For the reasons set forth below, the Court finds that Defendant has failed to prove
invalidity based on the written description requirement by clear and convincing evidence, and
therefore the Patent-in-Suit is not invalid under 35 U.S.C. § 112.
1.

Overview of the Parties’ Positions

Defendant argues that Claims 10, 13, 20, and 21 (together, the “Renal Impairment
Claims”), which claim a dosing regimen for administering paliperidone palmitate to a renally
impaired psychiatric patient, lack written description because these Claims do not specify the
severity of renal impairment addressed by the dosing regimens, with only renal impairment and
mild renal impairment discussed in the ’906 Patent. Def. Br. at 67–68. Defendant notes that there
are only two passages in the ’906 Patent specification that discuss patients with renal impairment.
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One passage instructs administering loading doses of about 100/75 or 75/75 mg-eq. to patients
with renal impairment. Id. at 68. A second passage instructs adjusting loading doses for renally
impaired patients to account for increased exposure levels to paliperidone, clarifying that for
patients “with mild renal impairment the loading doses should be reduced to 75 mg-eq. for the first
two loading doses.” Id. (internal citations and quotation marks omitted). In Teva’s view, the ’906
Patent fails the written description requirement because it does not advise how patients with
moderate or severe renal impairment would be dosed. Id. Teva also contends that the claims are
invalid because they do not provide an upper limit “in terms of degree of renal impairment or
maximum dose.” Id. at 69.
Plaintiffs’ first response is procedural as they argue that Teva presented a “brand-new
written description challenge at trial” that was not identified in the Final Pretrial Order and is
therefore waived. Pls. Br. at 69. Janssen argues that Defendant’s expert, Dr. Kahn, initially
asserted that the dosing regimen in the Renal Impairment Claims contained no upper limit, but
later abandoned that theory to now argue that the Claims failed to properly specify the type of
renally impaired patient that can be treated with the claimed dosing regimen. Id. at 69; PFOF ¶¶
225–26. While the Court acknowledges Plaintiffs’ argument regarding Teva’s evolving positions
on this issue, this Opinion addresses the issue regardless.
Turning to the merits of Teva’s written description challenge, Plaintiffs assert that the ’906
Patent contemplates loading doses for patients with renal impairment that allow a physician to use
medical judgment when dosing. Pls. Br. at 70. Plaintiffs further argue that a POSA would
recognize the ’906 Patent’s focus on mild renal impairment (specifically highlighted in the
specification), and would not treat a patient with moderate or severe renal impairment using Invega

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Sustenna. 46 Pls. Reply Br. at 48. In addition, Plaintiffs contend that the experts agreed at trial that
the renal impairment doses range from about 75 mg-eq. to an upper limit of 150 mg-eq., and that
the ’906 Patent contains several representative embodiments of dosing regimens for renally
impaired patients. Pls. Br. at 70.
2.

The Claims Relevant to the Written Description Challenge

Claim 10 of the ’906 Patent covers the “dosing regimen of claim 8 wherein the sustained
release formulation is an aqueous nanoparticle suspension.” ’906 Patent (DTX-1/PTX-1) col.
33:26–27. The dosing regimen of Claim 8 is “for administering paliperidone palmitate to a renally
impaired psychiatric patient in need of treatment for schizophrenia, schizoaffective disorder, or
schizophreniform disorder” and consists of (1) a loading dose in the deltoid muscle “of from about
75 mg-eq. of paliperidone” on day 1; (2) a second loading dose in the deltoid muscle “of from
about 75 mg-eq. of paliperidone . . . on the 6th to about 10th day of treatment”; and (3) a maintenance
dose in the deltoid or gluteal muscle “of about 25 mg-eq. to about 75 mg-eq. of paliperidone” a
month (± 7 days) after the second loading dose. Id. cols. 32:66–33:20.
Claim 13 of the ’906 Patent covers the “dosing regimen of claim 11 wherein the psychiatric
patient is in need of treatment for of a psychotic disorder wherein the psychotic disorder is
schizophrenia.” Id. col. 33:50–52.

The dosing regimen of Claim 11 is “for administering

paliperidone palmitate to a renally impaired psychiatric patient in need of treatment for psychotic
disorder” and consists of (1) a loading dose in the deltoid muscle “of from about 75 mg-eq. of
paliperidone” on day 1; (2) a second loading dose in the deltoid muscle “of from about 75 mg-eq.
of paliperidone . . . on the eighth day of treatment”; and (3) a maintenance dose in the deltoid or
gluteal muscle “of about 25 mg-eq. to about 50 mg-eq. of paliperidone” one month (± 7 days) after
46

The Invega Sustenna label states that Invega Sustenna “is not recommended in patients with
moderate or severe renal impairment.” PTX-105 at 6.
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the second loading dose. Id. col. 33:28–47. 47
The ’906 Patent contains additional discussion of renal impairment beyond its claims. In
the “Detailed Description” section, for instance, the Patent-in-Suit directs that “patients with renal
impairment will have a higher total exposure to paliperidone after i.m. injections of paliperidone
palmitate. For patients with renal impairment it would [be] desirable to adjust the loading doses
to account for the increased exposure levels of patients with renal impairment.” Id. col. 5:54–58.
This section also instructs that “[f]or patients with mild renal impairment the loading doses should
be reduced to 75 mg-eq. for the first two loading doses” and that “[f]or the purpose of this patent
application renal function is estimated by glomerular filtration rate (GFR) usually measured by the
creatinine clearance (best calculated from a 24-hour urine collection) . . . . Patients with mild renal
impairment have a creatinine clearance of 50 to <80 mL/minute.” Id. cols. 5:59–6:15.
3.

Analysis

The Court finds that the ’906 Patent sufficiently describes the claimed loading doses for
renally impaired patients. A patent must include sufficient details such that a POSA could
understand the subject invention and recognize that the inventor possessed it. Ariad Pharm. Inc.,
598 F.3d at 1351. However, this requirement does not necessarily mean that the specification of
the patent must include every nuanced detail as “a patent need not teach, and preferably omits,
what is well known in the art.” Falko-Gunter Falkner, 448 F.3d at 1365 (quoting Spectra-Physics,
Inc. v. Coherent, Inc., 827 F.2d 1524, 1534 (Fed. Cir. 1987)). Here, Teva has failed to show by
clear and convincing evidence that the Renal Impairment Claims lack adequate written description.
See Ariad Pharms., Inc., 598 F.3d at 1351 (“[T]he test for sufficiency is whether the disclosure of
47

While Claims 20 and 21 (which generally describe the characteristics of the paliperidone
palmitate formulation) are included in Teva’s written description challenge as they refer back to
the dosing regimens for patients with renal impairment, they are not independently analyzed by
the parties.
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the application relied upon reasonably conveys to those skilled in the art that the inventor had
possession of the claimed subject matter as of the filing date.”).
a) Relevant Testimony
Based on the testimony and evidence presented at trial, the Court finds that a POSA would
have understood that the inventors of the ’906 Patent had possession of the invention embodied in
the Renal Impairment Claims as of the filing date of the ’906 Patent. Experts for both parties in
fact agreed that the ’906 Patent instructs that paliperidone palmitate doses must be lowered when
given to patients with renal impairment because paliperidone is cleared through the kidneys and
renally impaired patients have reduced kidney function. See Trial Tr. (Kahn) at 116:1–3 (“It
specifies to mild renal impairment, which wasn’t in the other two, and that the loading dose should
be reduced to 75 milligrams.”); Trial Tr. (Kohler) at 1997:8–13 (agreeing that the ’906 Patent
states that “for patients with mild renal impairment, the loading doses should be reduced to 75milligrams equivalent for the first two loading doses”).
Further, both experts agreed that Invega Sustenna is not designed to be given to patients
with moderate or severe renal impairment. See Trial Tr. (Kahn) at 105:12–15 (“Q. And then you
may have said this, but for moderate and severe renal impairment, would a psychiatrist give Invega
Sustenna to those patients? A. Well, it’s not recommended, so I doubt it.”); Trial Tr. (Kohler) at
1998:6–8 (“The way I read these specifications and the patent claims is that you do not administer
paliperidone palmitate to people with moderate or severe renal impairment.”).
Finally, the experts further agreed that the highest dose listed in the ’906 Patent, 150 mgeq., would be the upper limit for dosing any patient with renal impairment. See Trial Tr. (Kahn) 48
48

In Dr. Kahn’s opening expert report, he wrote that “nothing in the ’906 Patent indicates to a
skilled artisan that the inventors were in possession of dosing regimens for administering
paliperidone palmitate in schizophrenia patients with renal impairment in doses ranging from 75
mg eq. to infinity.” Kahn Opening Expert Report at 14–15. The Court notes that Dr. Kahn’s
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at 145:12–14 (“I said, you know, the upper limit -- I am willing to accept that the upper limit is
150 milligrams.”); Trial Tr. (Kohler) at 1935:7 (agreeing with Dr. Kahn that “the upper limit for
the initiation doses for any patient is 150-milligram equivalents”). In addition, both experts
testified that, at the time of the filing of the ’906 Patent, it would have been well known to a POSA
how to measure a patient’s level of renal impairment. See Trial Tr. (Kahn) at 146:9–10 (“I mean,
in general it can be done with a GFR. By assessing the GFR, yes.”); Trial Tr. (Kohler) at 1936:17–
19 (“Renal function is estimated by the glomerular filtration rate, or GFR, and which we can use
the creatinine clearance as a proxy.”).
Based on this testimony and the text of the ’906 Patent, the Court finds that the Renal
Impairment Claims are adequately described. The ’906 Patent clearly conveys a dosing regimen
for patients with renal impairment, supported by the specification which specifically discusses
dosing for patients suffering from mild renal impairment. It would have been reasonably conveyed
to a POSA that the maximum dose listed in the ’906 Patent is 150 mg-eq. and that Invega Sustenna
is not recommended for patients with moderate to severe renal impairment. As the written
description requirement does not mandate that a patent expressly state all information currently
known in the art, the Court finds the ’906 Patent is not invalid.
b) Relevant Caselaw
The law is clear that written description must focus on whether a patent reasonably conveys
possession of the claimed subject matter to those skilled in the art. Ariad Pharms., Inc., 598 F.3d
at 1351. The written description requirement is highly contextual and fact-dependent, taking into
account the nature and scope of the claims, what is already known in the art, and the complexity
of the invention. See id. (“[T]he level of detail required to satisfy the written description
written description testimony evolved to acknowledge that the ’906 Patent contains an upper limit
for dosing, as indicated above.
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requirement varies depending on the nature and scope of the claims and on the complexity and
predictability of the relevant technology.”). The following cases are instructive.
The Court in In re Wertheim, 541 F.2d 257 (C.C.P.A. 1976), held that a patent’s
specification and what is well-known in the art must be read together when conducting a written
description analysis. Id. at 265. Applying this holding, the court rejected a written description
challenge over the claimed invention, finding that the patent sufficiently described the invention
in light of its specific embodiments and what was known in the prior art. Id. at 264–65. Here, the
Renal Impairment Claims set out a dosing regimen containing specific dosing instructions which
are sufficiently described when combined with the information contained in the ’906 Patent and
known in the art that: the maximum dosage listed in the ’906 Patent for any patient is 150 mg-eq.,
levels of renal impairment can be measured using standardized methods, and Invega Sustenna is
not suitable for patients with moderate to severe renal impairment. As such, the Renal Impairment
Claims are supported by adequate written description because “[i]t is not necessary that the
application describe the claim limitations exactly . . . but only so clearly that persons of ordinary
skill in the art will recognize from the disclosure that appellants invented processes including those
limitations.” Id. at 262.
Further, in Nalpropion Pharmaceuticals, Inc. v. Actavis Laboratories FL, Inc., 934 F.3d
1344 (Fed. Cir. 2019), the Federal Circuit held that “[i]t is not necessary that the exact terms of a
claim be used in haec verba in the specification.” Id. at 1350. On this basis, the court rejected a
written description challenge wherein the claim and the specification used different terms and
methods to describe a process, finding the different language did not create a written description
issue. Id. at 1351. As with the patent at issue in Nalpropion, the Court finds that the specification
and the Renal Impairment Claims of the ’906 Patent can be read and understood together despite

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not using the exact same language. Accordingly, a “flexible, sensible interpretation” of the Patentin-Suit shows that the inventors of the ’906 Patent had possession of the invention embodied in
the Renal Impairment Claims as of the filing date. Nalpropion Pharms., Inc., 934 F. 3d at 1351;
see also Martek Biosciences Corp. v. Nutrinova, Inc., 579 F.3d 1363, 1371 (Fed. Cir. 2009) (“[A]
patent claim is not necessarily invalid for lack of written description just because it is broader than
the specific examples disclosed.”).
The cases on which Defendant relies do not alter the Court’s analysis. Each of these cases
is factually distinguishable from this matter, or in fact supports the Court’s finding and reaffirms
that the proper written description inquiry is whether the ’906 Patent reasonably conveys
possession of the claimed subject matter to those skilled in the art.
Synthes USA, LLC v. Spinal Kinetics, Inc., 734 F.3d 1332 (Fed. Cir. 2013), essentially
hinged on the meaning of a single word and how it was understood within a given field based on
extensive evidence and testimony presented at trial. Id. at 1342. Here, as in Synthes, the Court
makes its written description decision based upon evidence and testimony presented at trial. The
evidence presented to the Court was clear that Invega Sustenna should not be used to treat patients
with moderate or severe renal impairment (see Trial Tr. (Kahn) at 105:12–15; Trial Tr. (Kohler)
at 1999:6–14) and confirmed that the Renal Impairment Claims convey possession of a dosing
regimen for patients with mild renal impairment.
In Pernix Ireland Pain DAC v. Alvogen Malta Operations Ltd., 323 F. Supp. 3d 566 (D.
Del. 2018), the district court found the patents at issue invalid because “the invention is a method
of treating pain that consists of administering a particular formulation to patients,” but the patents
failed to identify the class of formulations that will work and were drafted in functional terms. Id.
at 625–26. Accordingly, the Court found that the patents “merely describe[] the problem to be

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solved and claim[] all solutions to it.” Id. Unlike in Pernix, the Renal Impairment Claims are not
written in functional terms, but rather recite specific dose amounts to be used in a specific manner
at specific times when treating a renally impaired psychiatric patient in need of treatment for
schizophrenia or psychotic order. ’906 Patent (DTX-1/PTX-1) cols. 32:67–34:47. Additionally,
as noted above, Invega Sustenna is not recommended for patients with moderate or severe renal
impairment, and the ’906 Patent makes no reference to these types of renal impairment. In this
factual context the dosing regimens for patients with renal impairment contained within the Renal
Impairment Claims are a stark contrast to the claims at issue in Pernix.
Eli Lilly & Co. v. Perrigo Co., 202 F. Supp. 3d 918 (S.D. Ind. 2016) is also distinguishable
from the present matter as the patent at issue in Eli Lilly contained a claim calling for a “at least
one dermal penetration enhancer present in an amount of from 10 to 10,000[%] based on the weight
of the testosterone,” and there was inadequate guidance from the patent specification or examples
that could help narrow the entire expansive range of 10–10,000%. Id. at 929, 996–97. Here, the
specification of the ’906 Patent contains multiple embodiments and discussions of the renal
impairment claims, specifically discussing how to utilize the dosing regimen (which recites
specific dose amounts, sites of injection, and dose timing) for patients with mild renal impairment
and how to calculate mild renal impairment. Id. col. 3:27–56, col. 5:53–6:14.
Thus, the Court finds that the Renal Impairment Claims, when read in context of what is
described in the specification, and what is detailed in the embodiments, reasonably convey to those
skilled in the art possession of the claimed invention. Based on the testimony and evidence
presented at trial, as well as the arguments presented to the Court at closing arguments and in the
parties’ papers, the Court finds that Teva has failed to show by clear and convincing evidence that
the Renal Impairment Claims fail based on a lack of written description. Next, the Court addresses

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Teva’s indefiniteness challenge.
C. Indefiniteness (35 U.S.C. § 112)
“[A] patent is invalid for indefiniteness if its claims, read in light of the specification
delineating the patent, and the prosecution history, fail to inform, with reasonable certainty, those
skilled in the art about the scope of the invention.” Nautilus, Inc. v. Biosig Instruments, Inc., 572
U.S. 898, 901 (2014).

Indefiniteness is a question of law, which may rely on subsidiary

determinations of underlying facts. Akzo Nobel Coatings, Inc. v. Dow Chem. Co., 811 F.3d 1334,
1343 (Fed. Cir. 2016). A patent is presumed to be valid; the challenger bears the burden of
establishing invalidity by clear and convincing evidence. 35 U.S.C. § 282(a); Microsoft Corp. v.
i4i Ltd. P’ship, 564 U.S. 91, 95 (2011).
Defendant argues that the Patent-in-Suit is invalid as indefinite for two reasons. First,
Defendant argues that Claims 20 and 21 fail to properly characterize the claimed d50 range given
that d50 can be measured and expressed in a number of different ways. Def. Br. at 70. Second,
Defendant contends that Claims 10, 20, and 21 fail to properly characterize the term “aqueous
nanoparticle suspension” which lacks a typical meaning in the art. Id. at 74. Plaintiffs argue that
Claims 20 and 21 are not indefinite because Teva failed to show that different methods or
expressions of measurement lead to meaningfully different results. Pls. Br. at 65. Plaintiffs further
contend that Claims 10, 20, and 21 are not indefinite because the ’906 Patent defines the term
aqueous nanoparticle suspension and makes clear the d50 ranges that encompass a nanoparticle.
Id. at 68. In support of their arguments, the parties rely on the testimony of the following
witnesses:

Defendant’s expert Lawrence Block, Ph.D., 49 and Plaintiffs’ expert Dr. Sinko

49

Defendant’s expert Lawrence Block, Ph.D., is a Professor Emeritus of Pharmaceutics at the
School of Pharmacy and Graduate School of Pharmaceutical Sciences at Duquesne University.
Final Pretrial Order at 42. Dr. Block is recognized as a leader in the field of pharmaceutics and is
a Fellow of both the American Association of Pharmaceutical Scientists and the American
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(introduced above). For the reasons set forth below, the Court finds that Defendant has failed to
prove invalidity based on indefiniteness by clear and convincing evidence, and therefore the
Patent-in-Suit is not invalid under 35 U.S.C. § 112.
1.

Overview of the Parties’ Positions
a) d50 Indefiniteness

Defendant argues that Claims 20 and 21 are indefinite because although they require “an
average particle size (d50) of from about 1600 nm to about 900 nm,” this requirement fails to
properly limit the claims due to numerous variations that affect particle size measurements. Def.
Br. at 70. Defendant notes that the paliperidone palmitate particles described in the ’906 Patent
are asymmetrical and their size is reported as the diameter of a hypothetical equivalent sphere
which can be measured using different techniques and expressed in different ways. Id. at 70–71.
Defendant also notes that the type of instrument used to make measurements, and the conditions
under which particles are measured, can influence measurements. Id. at 71.
Plaintiffs respond that “a claim term is not indefinite for failure to specify which method
should be used to measure a quantity unless different methods lead to significantly different results,
and there is no evidence of that here.” Pls. Br. at 65. Plaintiffs further argue that different
measurements of particle size taken at different times are equally correct, that instrument error
accounts for the only meaningful discrepancy in particle size measurement discussed at trial, and
that no ordinary scientist would have difficulty measuring the particle size of paliperidone
palmitate suspensions, also noting that scientists at the FDA and USPTO did not have any
difficulty taking particle size measurements during the relevant agency proceedings. Id. at 66–68.
Pharmacists Association - Academy for Pharmaceutical Research and Science. Id. Dr. Block has
authored or co-authored over 120 publications and his research interests include excipient
technology, rheology, drug and cosmetic delivery systems, pharmaceutical engineering,
biopharmaceutics, and pharmacokinetics. Id. at 42–43.
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b) Aqueous Nanoparticle Suspension Indefiniteness
Defendant argues that Claims 10, 20, and 21 are “invalid for failing to define the bounds of
the term aqueous nanoparticle suspension.” Def. Br. at 74 (internal quotation marks omitted).
Defendant maintains that this term has no typical meaning in the art, that no definite bounds of
particle size are provided, and that the ’906 Patent incorporates “suitable aqueous depot
formulations” from the ’843 Patent that exceed the particle sizes listed in the ’906 Patent, making it
impossible for a POSA to determine with reasonable certainty whether a formulation is a
nanoparticle suspension or not. Id. at 74–75.50
Plaintiffs argue that the ’906 Patent adequately defines the term aqueous nanoparticle
suspension and “makes clear that suspensions having an average particle size d50 within the ranges
disclosed in the patent’s specification and claims qualify as nanoparticle suspensions.” Pls. Br. at 68
(internal quotation marks omitted). Plaintiffs also stress that “[e]ven if an ordinarily skilled person
might be interested in further information about particle size distribution for other purposes, they would
have no difficulty determining the ‘scope of the invention’ with reasonable certainty,” which is all that
is required to render a claim definite. Id. (citing Nautilus, Inc., 572 U.S. at 901).
2.

The Claims Relevant to Indefiniteness

Claim 10 of the ’906 Patent covers the “dosing regimen of claim 8 wherein the sustained
release formulation is an aqueous nanoparticle suspension.” ’906 Patent (DTX-1/PTX-1) col.
33:26–27. The dosing regimen of Claim 8 is “for administering paliperidone palmitate to a renally
impaired psychiatric patient in need of treatment for schizophrenia, schizoaffective disorder, or
50

To the extent Teva also argues that the term aqueous nanoparticle suspension is indefinite
because the ’906 Patent incorporates the ’843 Patent and ’544 Patent into its disclosure, Teva has
not supported this argument with persuasive testimony or evidence presented at trial. The Court
also notes that “nanoparticle” does not appear in the ’843 Patent and finds that the incorporation
by reference of these patents does not render the term aqueous nanoparticle suspension indefinite
for the reasons discussed below.
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schizophreniform disorder” and consists of (1) a loading dose in the deltoid muscle “of from about
75 mg-eq. of paliperidone” on day 1; (2) a second loading dose in the deltoid muscle “of from
about 75 mg-eq. of paliperidone . . . on the 6th to about 10th day of treatment”; and (3) a maintenance
dose in the deltoid or gluteal muscle “of about 25 mg-eq. to about 75 mg-eq. of paliperidone” a
month (± 7 days) after the second loading dose. Id. cols. 32:66–33:20.
Claim 20 of the ’906 Patent covers the “dosage regimen of claim 19 wherein the buffering
agents contained in the aqueous nanoparticle suspension are citric acid monohydrate, disodium
hydrogen phosphate anhydrous, sodium dihydrogen phosphate monohydrate, sodium hydroxide.”
Id. col. 34:44–48. Claim 19 of the ’906 Patent provides details on the aqueous nanoparticle
suspension to be used as a sustained release depot formulation in the dosing regimens of Claims
1, 4, 8, or 11. Id. col. 34:32–34. Specifically, it instructs that the aqueous nanoparticle suspension
should consist of: (1) 156 mg/ml of paliperidone palmitate “having an average particle size (d50)
of from about 1600 nm to about 900 nm”; (2) 12 mg/ml of polysorbate 20; (3) one or more
buffering agents sufficient to give the composition a pH of 8.5; (4) 30 mg/ml of the suspending
agent polyethylene glycol 4000; and (5) “water q.s. ad 100%.” Id. col. 34:34–43.
Claim 21 of the ’906 Patent covers the “dosage regimen of claim 19 wherein the pH of the
aqueous nanoparticle suspension is in the range of pH 7 to 7.5.” Id. col. 34:49–51.
3.

Analysis
a) d50 Indefiniteness

The Court finds that Claims 20 and 21 51 are not invalid for indefiniteness as “the mere
possibility of different results from different measurement techniques does not render a claim
indefinite.” Ball Metal Beverage Container Corp. v. Crown Packaging Tech., Inc., 838 F. App’x
51

Claim 10 will be discussed in connection with the aqueous nanoparticle suspension
indefiniteness analysis below.
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538, 542 (Fed. Cir. 2020) (internal citations and quotation marks omitted). Teva has failed to
provide clear and convincing evidence that possible variations in d50 measurement methodology
and procedure would lead to materially different results such that Claims 20 and 21 “fail to inform,
with reasonable certainty, those skilled in the art about the scope of the invention.” Nautilus, Inc.,
572 U.S. at 901.
i.

Relevant Testimony

The testimony of Defendant’s expert, Dr. Block, and Plaintiffs’ expert, Dr. Sinko, is
largely consistent on a number of key issues relevant to this Court’s analysis. Both experts agree
that a POSA would be able to use different methods to measure a particle size of d50. See Trial
Tr. (Block) at 589:6–13 (testifying that the specification “tells one to measure [d50] by artknown conventional techniques,” and “gives examples of art-known conventional techniques,”
such as “Sedimentation field flow fractionation, photon correlation spectroscopy and disk
centrifugation”); Trial Tr. (Sinko) at 1554:1–3 (“[T]here were several methods for measuring.
And this is just some of the machines that were listed in those relevant sections that I discussed.
These are a few examples.”).
Both experts further agree that that using different methods, tools, or expressions of
measuring d50 can lead to the same or materially similar results, and that different d50
measurements of the same particle size can all be “correct” measurements that vary because of
the conditions under which the particle was measured. See Trial Tr. (Block) at 613:13–16 (“Q.
So we’ve talked about a lot of different techniques this morning and this afternoon. Is there one
technique that’s more correct than others? A. No.”); Id. (Block) 630:18–25 (“Q. Sure. Whether
or not there are significant differences between number-weighted, volume-weighted and
intensity-weighted d50 measurements would depend on various factors, right? A. Yes. Q. And

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the differences may or may not be significant, depending upon those factors, right? A. That’s
true.”); Trial Tr. (Sinko) at 2194:16–20 (“Q. And if you use all those different methods, you’d
come up with a different diameter, potentially, right? A. Maybe. Q. Maybe you would, right?
A. And maybe you wouldn’t.”); Id. (Sinko) 2195:19–2196:2 (“Q. You agree, Doctor, that the
’906 patent does not limit the d50 value expressly to any particular type of diameter
measurement, right? A. It states a d50, that’s true. But as we saw from the data from, you know,
from Janssen, from Teva, you know, using multiple methods, you get the same answer. . . . And
they use different methods with different diameters, and they get the same answer.”).
Finally, both experts agree that throughout the development of Invega Sustenna, the
prosecution of the Patent, and the development of Teva’s ANDA, there was no apparent
confusion over how to measure or express d50 that cannot be explained by artificial error. See
Trial Tr. (Block) at 650:8–11 (“Q. And Teva was able to determine the d50 value for its
paliperidone palmitate suspension and report that value to the FDA, right? A. Apparently.”);
Trial Tr. (Sinko) at 1563:7–9 (“Q. Was there any suggestion that either the FDA or Teva had any
difficulty understanding a d50 particle size distribution? A. No, there was not.”).
The relevant disagreement here comes almost entirely from counsel, as they disagree
over the legal significance of the largely congruent testimony of Dr. Block and Dr. Sinko. A
review of the relevant caselaw cited by the parties, however, confirms that any asserted
differences in measuring and expressing d50 particle size present in this matter do not render
Claims 20 and 21 invalid because a POSA would understand, “with reasonable certainty,” the
scope of the d50 particle measurement within Claims 20 and 21.
ii.

Relevant Caselaw

A review of the relevant caselaw demonstrates that the differing methods of measuring and

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representing d50 particle size must lead to meaningfully different results in order to render Claims
20 and 21 indefinite. In PPG Industries, Inc. v. Guardian Industries Corp., 75 F.3d 1558 (Fed.
Cir. 1996), the party challenging patent validity argued that the claims at issue were indefinite
because “the inventors failed to state the method they used to measure the ultraviolet transmittance
of the invention.” PPG Indus., Inc., 75 F.3d at 1562. The Federal Circuit rejected this argument,
finding that the evidence presented “established that, setting aside the equipment error that plagued
PPG’s testing procedures, all of the conventional methods of testing ultraviolet transmittance
produce essentially identical results.” Id. at 1563. 52 Similarly, in Ethicon Endo-Surgery, Inc. v.
Covidien, Inc., 796 F.3d 1312 (Fed. Cir. 2015), the Federal Circuit found that slight variations in
measurements taken through different methods did not render the claims at issue indefinite because
they were “simply due to natural variances in real-world testing conditions.” Id. at 1319–20, 1322.
In Takeda Pharmaceutical Co., Ltd. v. Zydus Pharmaceuticals USA, Inc., 743 F.3d 1359 (Fed. Cir.
2014), the Federal Circuit stressed that “there is no evidence that the differences between these
techniques are in fact significant; there was evidence before the trial court that although the results
may be different, there is a high degree of correlation for the results between the two techniques, .
. . indeed, there was no evidence in this case that different measurement techniques in fact
produced significantly different results for the same sample.” Id. at 1367 (internal citations and

52

PPG Industries is also instructive because in the present case Teva seeks to place great weight
on an outlier measurement taken with a defective device. Def. Br. at 72 (noting differences in
measurements Janssen obtained using “Coulter counter” and “Mastersizer”). As PPG Industries
instructs, the Court does not find that this outlier measurement renders the claims at issue indefinite
because it has been adequately explained (with no persuasive rebuttal) as an equipment defect. See
Trial Tr. (Sinko) at 1558:4–9 (“So basically using three different methods they came up with, in
essence, the same particle size distribution, and therefore they could conclude that that Coulter and
the artifact that they thought existed was definitely an artifact or an artificial result. And so they
could rely on their laser diffraction original method, the Malvern Mastersizer.”); Trial Tr. (Block)
at 662:6–17 (testifying that Janssen found artificial differences between the Coulter and the
Malvern device measurements).
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quotation marks omitted). Based on this evidence, the Federal Circuit held that “[a]ny theoretical
minor differences between the two techniques are therefore insufficient to render the patent
invalid.” Id.
Cases that find patents invalid based upon different methods of measurement crucially
contain evidence that the different methods are likely to lead to significantly different results. In
Dow Chemical Co. v. Nova Chemicals Corp. (Canada), 803 F.3d 620 (Fed. Cir. 2015), the Federal
Circuit found the claims at issue invalid as “[t]here is no question that each of these four methods
may produce different results, i.e., a different slope” based on Dow’s expert testimony which
conceded that “the 10% secant tangent method, the final slope method, the most linear method,
and the method he invented could produce different results. In comparison to the three other
methods, [the Dow expert]’s method would produce a higher value.” Id. at 633–635.

In Teva

Pharmaceuticals USA, Inc. v. Sandoz, Inc., 789 F.3d 1335 (Fed. Cir. 2015), the indefiniteness
analysis hinged on the term “molecular weight” which can be measured and expressed in multiple
forms. Id. at 1338. The Federal Circuit found these different forms of molecular weight rendered
the patent at issue invalid as “[t]he parties agree that ‘molecular weight’ could refer to [peak
average molecular weight, number average molecular weight, or weight average molecular
weight]. And they agree that each of these measures is calculated in a different way and would
typically yield a different result for a given polymer sample.” Id. at 1341, 1345.

Otsuka

Pharmaceutical Company, Ltd. v. Torrent Pharmaceuticals, Ltd., Inc., 151 F. Supp. 3d 525 (D.N.J.
2015), involved the question of whether the term “mean particle size” was indefinite “because it’s
amenable to multiple meanings.” Id. at 544. In finding this term indefinite, the district court first
noted that “Otsuka readily acknowledges the susceptibility of ‘mean particle size’ to multiple
measurements, each of which could yield varied results,” and found that the record showed a lack

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of uniform understanding of the term in the relevant scientific community, and that the patent at
issue provided “no information from which to divine, with reasonable certainty, the appropriate
measure of the ‘mean.’” Id. at 546–48.
Here, the ’906 Patent does discuss methods of measuring d50 and does contain examples
wherein those methods are utilized. See Trial Tr. (Block) at 637:2–11 (“Q. The patent reports a
particle size distribution was measured by laser diffraction, correct? A. Yes. Q. So you would
agree that a person of skill in the art reading the patent would know that they could measure particle
size by laser diffraction, right? A. Yes. Q. And if you measure particle size by laser diffraction,
you typically get a volume-weighted measure of d50, right? A. That’s my understanding.”).
Additionally, the evidence and testimony admitted during the bench trial showed that the different
methods of measuring and expressing d50 were likely to produce substantially similar values. See
Trial Tr. (Block) at 651:25–652:7

; Trial Tr. (Sinko) at 2196:5–10 (“I don’t think it
needs to be. I mean, that’s – everyone uses the methods. And they know that the software that
every manufacturer uses for their different methods normalizes for all this because otherwise, no
one would be able to rely on it. And everyone does rely on it. Teva relies on it. Janssen relies on
it. My lab relies on it.”). As the ’906 Patent provides examples of how to measure d50 particle
size and different methods or expressions of measurement lead to essentially identical values, the
differing methods or expressions would have no effect on a POSA’s ability to understand the scope
of the claims with reasonable certainty. Additionally, the Court notes that both experts testified at
trial that throughout the relevant agency proceedings there were no issues with measuring d50,

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providing further evidence to support the finding that differing methods or expressions of d50 do
not render Claims 20 and 21 indefinite. See Trial Tr. (Block) at 650:8–11; Trial Tr. (Sinko) at
1563:7–9.
Based on all of the evidence and testimony presented at trial, the Court finds that Teva has
failed to show by clear and convincing evidence that the different methods or expressions of d50
particle size render Claims 20 and 21 invalid.
b) Aqueous Nanoparticle Suspension Indefiniteness
The Court also finds that Claims 10, 20, and 21 are not invalid for indefiniteness based on
their utilization of the term “aqueous nanoparticle suspension.” That term is defined with
reasonable certainty.
i.

Relevant Testimony

At trial, Dr. Block, Teva’s expert, agreed that the ’906 Patent describes “characteristics of
the nanoparticle suspension,” such as the range of 1600 nanometers to 400 nanometers for particle
size d50, but maintained that the term is indefinite because “there could be particles potentially
outside that range on the upper end and some particles below that range.” Trial Tr. (Block) at
670:10–14; 672:8–18. Dr. Sinko, Janssen’s expert, disagreed with Dr. Block and stated that the
’906 Patent adequately defines the term because “it says, an aqueous formulation would preferably
be a nanoparticle suspension of wherein the nanoparticles would fit in average sizes of less than
2000 nanometers to about 100 nanometers. And then it goes on and on. But basically, you know,
it defines what an aqueous nanoparticle suspension is.” Trial Tr. (Sinko) at 1560:24–1561:4.
The Court agrees with Dr. Sinko that the term “aqueous nanoparticle suspension” is defined
with reasonable certainty in the ’906 Patent and rejects the arguments proffered by Teva that this
definition is lacking.

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ii.

Relevant Caselaw

In Vapor Point LLC v. Moorhead, No. 11-4639, 2013 WL 11275459 (S.D. Tex. Dec. 18,
2013), the district court found the term “micro-sized particles” not indefinite, noting that “[a]n
issued claim is presumed valid.” Vapor Point LLC, 2013 WL 11275459, at *17 (internal citations
and quotation marks omitted). The Vapor Point plaintiffs argued that the term micro-sized
particles was indefinite because it was used in a manner contrary to its ordinary meaning, but the
court rejected that argument as it found that the “specification communicates a deliberate and clear
preference for an alternative definition.” Id. The court also noted that “close questions of
indefiniteness” are resolved in favor of the valid patent. Id. Finally, the court found “no clear
conflict” in the patent’s specification that “micro-sized particles may vary in range between 5–500
microns, although smaller and larger particles may also be used with embodiments described
herein.” Id.
These holdings make clear that the ’906 Patent is not indefinite based on the term aqueous
nanoparticle suspension. As in Vapor Point, the ’906 Patent provides a clear definition of the term
aqueous nanoparticle suspension such that there does not need to be an ordinary meaning of the
term.

Specifically, the ’906 Patent states that the aqueous nanoparticle suspension would

preferably have nanoparticles of an average size of less than 2000 nm to about 100 nm, and
provides further details on the preferred d50 and d90 measurements for nanoparticles. ’906 Patent
(DTX-1/PTX-1) col. 7:24–32. In addition, Vapor Point instructs that the ’906 Patent’s failure to
define what is not an aqueous nanoparticle suspension does not render it indefinite, as the court in
that case found the patent’s reference to “smaller and larger particles” did not render the claims at
issue indefinite.

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For all of the reasons discussed at length above, the Court finds Teva has failed to show
by clear and convincing evidence that Claims 10, 20, and 21 fail as indefinite based on the
testimony and evidence presented at trial.
D. Rule 52(c) Motions
During the bench trial, both parties made motions for judgment on partial findings pursuant
to Federal Rule of Civil Procedure 52(c). ECF Nos. 138, 150. Rule 52(c) reads:
If a party has been fully heard on an issue during a nonjury trial and the
court finds against the party on that issue, the court may enter judgment
against the party on a claim or defense that, under the controlling law,
can be maintained or defeated only with a favorable finding on that issue.
The court may, however, decline to render any judgment until the close
of the evidence. A judgment on partial findings must be supported by
findings of fact and conclusions of law as required by Rule 52(a).
Fed. R. Civ. P. 52(c). Thus, Rule 52(c) permits a judge to enter judgment as a matter of law on
partial findings once “a party has been fully heard on an issue.” Id. “To grant a [motion for
judgment as a matter of law] under Rule 52(c), a district judge must weigh the evidence and resolve
credibility.” Yamanouchi Pharm. Co. v. Danbury Pharmacal, Inc., 231 F.3d 1339, 1343 (Fed. Cir.
2000). “A judgment on partial findings is made after the court has heard all the evidence bearing
on the crucial issue of fact.” Fed. R. Civ. P. 52(c) advisory committee’s note to 1991 amendment.
Consistent with the terms of Rule 52(c), the Court exercised its discretion to reserve
judgment on the motions during trial. Fed. R. Civ. P. 52(c) (“The court may, however, decline to
render any judgment until the close of the evidence.”). The Court now concludes that the best
course of action is to render a judgment based on all of the evidence, testimony, and applicable
law. Accordingly, the Rule 52(c) motions (ECF Nos. 138, 150) are denied.
E. Motion to Correct Inventorship (35 U.S.C. § 256)
Along with its post-trial submissions, Plaintiffs also filed a renewed motion (in lieu of a

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previously withdrawn motion) 53 “for the entry of an Order pursuant to 35 U.S.C. § 256(b) directing
the United States Patent and Trademark Office [] to issue a certificate adding Drs. Srihari Gopal
and Mahesh Samtani as inventors of U.S. Patent No. 9,439,906.” ECF No. 166 at 1. 54 Plaintiffs
rely on the trial record as well their post-trial briefs, proposed findings of fact, and proposed
conclusions of law in support of this motion. Id. at 1–2. Plaintiffs argue that Drs. Gopal and
Samtani should be added as inventors of the ’906 Patent based on trial testimony describing their
substantial contributions to the claimed invention and corroborating contemporaneous evidence
introduced and admitted at trial. Pls. Br. at 72–73. Teva did not file a separate brief in opposition
to Plaintiffs’ renewed motion to correct inventorship, but instead argued against the motion in its
post-trial submissions. See Def. Br. at 42–43; Def. Reply Br. at 42–47. Teva contends that Janssen
has improperly changed its position on inventorship insofar as it asserted that there were four
additional inventors of the ’906 Patent in the Final Pretrial Order, but now only seeks to add Drs.
Gopal and Samtani. Def. Br. at 42–43. Teva also argues that the testimony presented at trial
establishes that there were numerous additional individuals who made contributions to the ’906
Patent and could be considered inventors, that the entire inventive entity must be correct, and that
Janssen failed to provide corroborating evidence confirming that Drs. Gopal and Samtani should
be added as inventors. Id.; Def. Reply Br. at 43–47.
District courts may order the correction of patent inventorship by the USPTO “on notice

53

Plaintiffs initially filed a motion to amend/correct inventorship pursuant to 35 U.S.C. § 256(b)
on June 17, 2020. ECF No. 91. After full briefing on that motion (ECF Nos. 91-2, 115, 118) and
oral argument (ECF No. 127), that motion was withdrawn by Plaintiffs who indicated they would
file a renewed motion after trial to conform with the evidence presented to the Court. See ECF No.
127. Janssen now renews the motion as to Drs. Gopal and Samtani. ECF No. 166; PFOF ¶ 296.
54
The Court also notes that in 2017, Janssen directly filed an application with the USPTO asking
it to correct inventorship of the ’906 Patent, but the USPTO has not taken action with respect to
that application. Final Pretrial Order at 12.
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and hearing of all parties concerned.” 35 U.S.C. § 256(b). The concerned parties are “named
inventors, omitted inventors, and assignees.” See Nichols Inst. Diagnostics, Inc. v. Scantibodies
Clinical Lab’y, Inc., 218 F. Supp. 2d 1243, 1250 (S.D. Cal. 2002). 35 U.S.C. § 116(a) provides
the standard for joint inventorship:
When an invention is made by two or more persons jointly, they shall
apply for patent jointly and each make the required oath, except as
otherwise provided in this title. Inventors may apply for a patent jointly
even though (1) they did not physically work together or at the same time,
(2) each did not make the same type or amount of contribution, or (3)
each did not make a contribution to the subject matter of every claim of
the patent.
“[A] joint invention is simply the product of a collaboration between two or more persons working
together to solve the problem addressed.” Fina Oil & Chem. Co. v. Ewen, 123 F.3d 1466, 1473
(Fed. Cir. 1997) (citing Burroughs Wellcome Co. v. Barr Lab’ys, Inc., 40 F.3d 1223, 1227 (Fed.
Cir. 1994)). To be a joint inventor, one must:
(1) contribute in some significant manner to the conception or reduction
to practice of the invention, (2) make a contribution to the claimed
invention that is not insignificant in quality, when that contribution is
measured against the dimension of the full invention, and (3) do more
than merely explain to the real inventors well-known concepts and/or the
current state of the art.
Pannu v. Iolab Corp., 155 F.3d 1344, 1351 (Fed. Cir. 1998). “Because the issuance of a patent
creates a presumption that the named inventors are the true and only inventors, the burden of
showing . . . nonjoinder of inventors is a heavy one and must be proved by clear and convincing
evidence.” Falana v. Kent State Univ., 669 F.3d 1349, 1356 (Fed. Cir. 2012) (internal citation
omitted). To meet the clear and convincing evidence standard, putative joint inventors must
provide some corroborating evidence instead of relying solely on their own testimony. Symantec
Corp. v. Comput. Assocs. Int’l, Inc., 522 F.3d 1279, 1295 (Fed. Cir. 2008). This requirement for
corroboration “addresses the concern that a party claiming inventorship might be tempted to
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describe his actions in an unjustifiably self-serving manner in order to obtain a patent.” Chen v.
Bouchard, 347 F.3d 1299, 1309 (Fed. Cir. 2003). As such, the corroboration requirement only
applies to a putative joint inventor’s testimony; documentary evidence does not need corroboration
before a court may consider it. Price v. Symsek, 988 F.2d 1187, 1195 (Fed. Cir. 1993).
As an initial matter, there are numerous cases holding that “alleged infringers have no
innate right to participate in correction-of-inventorship proceedings, whether before the USPTO
or a court on the complaint of a party to a patent.” Cobra Int’l, Inc. v. BCNY Int’l, Inc., No. 0561225, 2014 WL 11321379, at *3 (S.D. Fla. Dec. 10, 2014); see also Nichols Inst. Diagnostics,
Inc., 218 F. Supp. 2d at 1250 (“An alleged infringer is not a necessary party to a motion for
correction under § 256.”). Nonetheless, Teva functionally raises arguments on behalf of other
potential omitted inventors and maintains that the Court cannot correct the ’906 Patent by only
adding two omitted inventors when Janssen previously indicated there were four. Against the
backdrop of the caselaw discussed above defining and limiting the interested parties to correction
of inventorship proceedings pursuant to 35 U.S.C. § 256, the Court notes that Teva has now
separately sought leave to amend its affirmative defenses to assert that the ’906 Patent is invalid
due to incorrect inventorship.
The Court finds more than adequate support in the record to confirm that Drs. Gopal and
Samtani should be added as inventors of the ’906 Patent. 55 At trial, Dr. Gopal testified credibly
about his contributions to the ’906 Patent, describing how he revised the dosing regimens,

55

Janssen asserts the correction of inventorship is rather straightforward because the named
inventors, patent assignee, and proposed inventors to be added all agree that inventorship of the
’906 Patent should be corrected to add Drs. Gopal and Samtani. See Pls. Br. at 71 n.10 (“All
concerned parties have waived their right to a hearing and/or participated in a trial on the subject
matter of this motion, and they have consented to adding Drs. Gopal and Samtani as inventors of
the 906 Patent.”). Given the evidence and testimony presented at trial on this issue, however, the
Court reviews the substance of the motion to correct inventorship in this Opinion.
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examined results of the failed PSY-3002 study, and proposed the claimed dosing regimen. Trial
Tr. (Gopal) at 1071:5–16 (“Q. Now, did you play a role in selecting the dosing regimen for the
new trials? A. Yes, I did. Q. And what was your role? A. So my role was from the perspective
of a physician and a clinician treating patients. So we would work closely with the modelers to
tell them what was realistic, what potential scenarios to come up with, because they didn’t have
clinical training by background. So we would tell them what different doses to study, what
injection sites, what time periods, and other factors that helped adjust the model.”); id. at 1089:8–
12 (discussing his analysis of results of failed PSY-3002 study: “So I was looking to try to figure
out what went wrong in the study because a lot of people were asking me in senior management.
So based on my looking at the data, these are the four points that I thought were potentially
responsible for it.”).
This testimony was corroborated by contemporaneous documents which were admitted
into evidence. See, e.g., PTX-235 at 3–4 (PowerPoint presentation created by Dr. Gopal in March
2007 titled “R092670-PSY-3007 Protocol Overview” which instructed investigators running
clinical trials on study protocol); PTX-253 at 1 (email from Dr. Gopal regarding results of PSY3002 study and discussing potential explanations for unexpected failure); PTX-256 at 1 (May 29,
2007 letter to investigators regarding temporary halt of PSY-3006 and PSY-3007 studies as Dr.
Gopal and his team considered how to modify these studies in light of PSY-3002 results); PTX263 at 9–10 (internal Janssen presentation that Dr. Gopal helped prepare, dated June 7, 2007, titled
“Paliperidone Palmitate PSY-3002 Results & Implications for PSY-3006”).
Dr. Samtani also testified with credibility about his contributions to the ’906 Patent in the
form of developing dosing windows for claims 2, 10, 13, 20, and 21, and developing the renal
impairment dosing regimen. Trial Tr. (Samtani) at 1345:18–1346:8 (“Q. I understand you’re not

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a lawyer, but can you explain to the best of your ability what your significant contributions were
to the ’906 patent? A. So there are two distinct contributions that I can remember. The first one
is the development of a dosing recommendation for psychiatric patients who also have mild renal
impairment. So this particular dosing recommendation was designed only on the basis of modeling
and simulation. And the other piece that I can remember is the designing of dosing windows
around the regularly scheduled monthly maintenance injection and also a dosing window around
the Day 8 loading dose for paliperidone palmitate. And so it is these dosing recommendations that
are contributions that I can recollect are my contributions, among others, to this particular
patent.”); id. at 1349:5–11 (discussing PTX-251, a PowerPoint presentation given in April 2007,
and stating, “So I had been working on this project for about two months, and at this point I had
made a couple of major breakthroughs that were important findings that I was able to incorporate
into the population PK models. And it was this update that I wanted to give to An Vermeulen, and
this presentation was prepared as a project update for An Vermeulen in April of 2007.”).
This testimony was also corroborated by contemporaneous documents described at trial
and admitted into evidence. See, e.g., PTX-251 at 19–20, 27 (presentation authored by Dr. Samtani
dated April 27, 2007, titled: “AM&S Application: POP-PK Paliperidone Palmitate” discussing
major updates developed through use of deconvolution analysis and the Hirano concept); PTX278A at 35–36, 118–19 (draft population pharmacokinetic report from August 3, 2007, titled,
“Clinical

Pharmacology

Advanced

PK/PD

Modeling

and

Simulation

-

Population

Pharmacokinetic Analysis - R092760 (Paliperidone Palmitate),” which discussed comparisons of
initiation regimes and documented that 150/100 mg-eq. day 1/day 8 dosing regimen is optimal);
PTX-288 (final report submitted to FDA as part of Janssen’s New Drug Application submission
in Fall 2007 that included Dr. Samtani’s modeling and findings); PTX-294A (PowerPoint sent by

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Dr. Samtani to Janssen team in October 2007 summarizing population pharmacokinetic modeling
and simulation). Accordingly, the Court finds that based on the testimony and evidence presented
at trial, there is clear and convincing evidence that Drs. Gopal and Samtani should be added as
inventors of the ’906 Patent. 56
F. Teva’s Motion to Amend the Pleading
On July 7, 2021, Teva filed a motion to amend pursuant to Federal Rule of Civil Procedure
15(b)(2), asking the Court to deem its pleadings amended with a count for patent invalidity due to
incorrect inventorship under 35 U.S.C. § 102(f), and to enter judgment in its favor on that claim.
ECF No. 244. In its brief in support (ECF No. 245), Teva argues that Janssen both “expressly
consented to trying the issue of inventorship” and conceded that the inventive entity of the ’906
Patent is incorrect by seeking an order to correct inventorship under 35 U.S.C. § 256. Id. at 2–3.
Teva makes a number of arguments in support of its motion. Teva argues that Janssen did not
meet its burden under section 256 to add Drs. Gopal and Samtani as inventors of the ’906 Patent.
Id. at 4. In connection with this argument, Teva asserts that even adding Drs. Gopal and Samtani
as inventors does not properly correct inventorship because Janssen previously indicated (in its
now withdrawn pretrial motion) that there were four inventors to be added to the ’906 Patent. Id.
at 5–6. Teva also contends that Janssen did not offer any testimony or evidence as to Dr. LewynBriscoe or Dr. Kusumakar despite previously indicating that they are also inventors of the ’906
Patent. Id. Additionally, Teva argues that the record evidence presented at trial demonstrates that
tens of people inside and outside Janssen contributed to the ’906 Patent and that these people
56

Teva also argues that Dr. Gopal at one point pushed for a higher second loading dose and only
“acquiesced” to the dosing regimen in Claim 2. Def. Reply Br. at 45. This argument misses the
focus of joint inventorship analysis, and fails to acknowledge the difficult and fluid process that
Janssen went through in developing Invega Sustenna. Teva’s arguments regarding Dr. Samtani’s
modeling efforts (id. at 46) similarly miss the mark.
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should also be named as inventors. Id. at 4–5.
Janssen filed its brief in opposition on August 2, 2021. ECF No. 252. Janssen argues that
Teva cannot assert a section 102(f) defense because it did not raise such a defense in its invalidity
contentions as required by Local Patent Rule 3.3 and that Teva waived this argument by failing to
include it in the Final Pretrial Order, raise it at trial, or brief the issue post-trial. Id. at 13–15.
Janssen further argues that it did not consent to trying a section 102(f) defense, that no section
102(f) defense was implicitly tried, and that it would be greatly prejudiced if such a defense were
introduced into the case at this time. Id. at 16–18. Janssen also asserts that there is no trial evidence
to support a section 102(f) defense and that Teva has the burden of proof on this issue. Id. at 19–
20. Finally, Janssen argues that even if the Court were to reach the merits of the section 102(f)
invalidity challenge, the ’906 Patent would not be rendered invalid under any potential scenario.
Id. at 20–23.
Teva filed its reply in support on August 9, 2021. ECF No. 258. Echoing its original
arguments, Teva maintains that Janssen placed inventorship at issue during trial, Janssen failed to
provide evidence showing that Drs. Gopal and Samtani should be added as inventors of the ’906
Patent, and that Teva has carried its burden of establishing invalidity by showing that inventorship
of the ’906 Patent is incorrect. Id. at 2–4. 57
Rule 15(b)(2) allows for amendment of a complaint during or after trial when a claim not
included in the complaint is tried by express or implied consent. Swiatek v. Bemis Co., 542 F.
App’x 183, 188 (3d Cir. 2013). It is difficult to find that Janssen expressly consented to Teva

57

While Teva attempts to frame this amendment request solely in terms of inventorship, they in
fact ask the Court “to deem Teva’s pleadings amended with a count for patent invalidity under 35
U.S.C. § 102(f).” ECF No. 245 at 1. Thus, the correct inquiry here is whether Janssen gave express
or implied consent to trying the issue of invalidity based upon incorrect inventorship.
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raising a section 102(f) invalidity challenge. As Janssen noted in its opening post-trial brief, “Teva
has not asserted an inventorship defense pursuant to 35 U.S.C. § 102(f)” prior to its pending
motion. Pls. Br. at 74. Thus, Janssen did not raise any arguments against a section 102(f) challenge
in any of its post-trial submissions, as would be expected if the issue had been raised, or if evidence
relevant to such a challenge had been presented at trial. Id.
In determining whether there was implied consent to try an issue, the court must consider
“whether the parties recognized that the unpleaded issue entered the case at trial, whether the
evidence that supports the unpleaded issue was introduced at trial without objection, and whether
a finding of trial by consent prejudiced the opposing party’s opportunity to respond.” Liberty
Lincoln-Mercury, Inc. v. Ford Motor Co., 676 F.3d 318, 327 (3d Cir. 2012) (internal citations and
quotation marks omitted). Neither party appeared to recognize that a section 102(f) invalidity
challenge entered the trial as this topic was never meaningfully discussed, and the only evidence
and testimony relevant to inventorship heard at trial was presented in connection with adding Drs.
Gopal and Samtani to the ’906 Patent, as discussed above. Furthermore, “[t]he main consideration
in determining whether leave to amend under Rule 15(b) should be granted is prejudice to the
opposing party.” Swiatek, 542 F. App’x at 188. Janssen argues persuasively that it would be
greatly prejudiced by allowing Teva to amend its pleadings as it would “have prepared for and
proceeded at trial much differently,” including by calling witnesses and presenting evidence as to
Drs. Lewyn-Briscoe and Kusumakar. ECF No. 252 at 18–19 (citing Swiatek, 542 F. App’x at 188).
While there are certainly fairness and prejudice concerns implicated by allowing Teva to
assert a new invalidity defense approximately four months after closing arguments, six months
after the close of briefing, and nine months after the conclusion of live testimony, the Court finds
that even considering Teva’s invalidity defense based upon incorrect inventorship, Teva has

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clearly failed to carry its burden on this point. The trial record contains testimony and evidence
which support granting Janssen’s motion to correct inventorship by adding Drs. Samtani and Gopal
as inventors (as discussed and analyzed above), but the record is devoid of any testimony or
evidence showing that there are additional issues with inventorship of the ’906 Patent. Teva
attempts to avoid this dearth of support by citing to arguments outside of the trial record, largely
focused on Janssen’s withdrawn initial motion to correct inventorship. Such attempt to rely on
materials outside of the trial record is improper and is rejected. See Mass Engineered Design, Inc.
v. Planar Sys., Inc., No. 16-1510, 2018 WL 3323762, at *5 (D. Or. July 6, 2018) (“Moreover, at
the bench trial, the Court will only consider admissible evidence in making its findings of fact and
conclusions of law.”); Deere & Co. v. FIMCO Inc., 260 F. Supp. 3d 830, 835 (W.D. Ky. 2017)
(“Initially, the Court notes that both parties should be mindful that this case is set for a bench trial
rather than a jury trial. As such, the Court can and will only consider the evidence it has found to
be relevant and admissible at trial.”); Armco, Inc. v. Burns & McDonnell, Inc., 809 F. Supp. 43,
45 n.3 (S.D. Ohio 1992) (“At the bench trial of this case, this Court will be careful to only consider
evidence ultimately admitted into evidence in rendering its decision.”); see also Caldwell-Baker
Co. v. S. Illinois Railcar Co., 225 F. Supp. 2d 1243, 1259 (D. Kan. 2002) (“Withdrawal of a motion
has a practical effect as if the party had never brought the motion.”). Here, the Court must
determine whether Teva has shown by clear and convincing admissible evidence that the ’906
Patent is invalid for failing to name the correct inventors. See Pannu, 155 F.3d at 1350 (“When a
party asserts invalidity under § 102(f) due to nonjoinder, a district court should first determine
whether there exists clear and convincing proof that the alleged unnamed inventor was in fact a
co-inventor.”). The Court finds that Teva has not done so.
Teva’s section 102(f) invalidity challenge relies almost exclusively on testimony and

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evidence presented during its cross-examination of Janssen’s witnesses that briefly addressed
named and unnamed individuals’ work on developing Invega Sustenna. These cursory exchanges
regarding “teamwork,” and touching upon other individuals who worked in largely unspecified
capacities on Invega Sustenna, are wholly inadequate to support a section 102(f) challenge. See
Trial Tr. (Vermeulen) at 755:11–16, 1004:21–1005:5, 1005:18–21, 1013:14–17, and 1024:13–17;
see also Trial Tr. (Gopal) at 1172:3–16. This testimony does not show that a correct inventor of
the ’906 Patent has been omitted as clearly not every person who works on an invention that is
later patented is an inventor in the eyes of the law. Fina Oil & Chem. Co., 123 F.3d at 1473 (“[T]o
be a joint inventor, an individual must make a contribution to the conception of the claimed
invention that is not insignificant in quality, when that contribution is measured against the
dimension of the full invention.”). Teva presents no persuasive argument or evidence to show that
any of the other individuals involved with Invega Sustenna should be named as inventors, as mere
testimony confirming that individuals worked on a project in some capacity falls woefully short
of the required clear and convincing evidence required to show inventorship is incorrect. See, e.g.,
Gemstar-TV Guide Int’l, Inc. v. Int’l Trade Comm’n, 383 F.3d 1352, 1382 (Fed. Cir. 2004)
(“[A]lleged co-inventors must prove their contribution to the conception of the invention with
more than their own testimony concerning the relevant facts.”).
Additionally, while Teva states without any legal or factual support that inventorship of
the ’906 Patent is “uncorrectable,” (ECF No. 245 at 4), the Court rejects this meritless argument.
It is well-settled that even if the Court were to find incorrect inventorship, Janssen would be given
an opportunity remedy this issue. See Pannu, 155 F.3d at 1350 (“Upon such a finding of incorrect
inventorship, a patentee may invoke section 256 to save the patent from invalidity. Accordingly,
the patentee must then be given an opportunity to correct inventorship pursuant to that section.”);

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Roche Palo Alto LLC v. Ranbaxy Lab’ys Ltd., 551 F. Supp. 2d 349, 359 (D.N.J. 2008) (A patent
owner is “entitled to an opportunity to correct inventorship through the district court, even if it did
absolutely nothing to correct the improper inventorship beforehand”). While Teva has failed to
meet its burden on its section 102(f) challenge, it has also failed to show that Janssen would not
be able to cure inventorship.
Accordingly, the Court has considered Teva’s invalidity challenge under section 102(f)
despite the issues noted with its motion to amend the pleadings pursuant to Rule 15(b)(2) (ECF
No. 244), and finds that the trial record does not contain adequate evidence or testimony to show
that the ’906 Patent is invalid due to failure to include all proper inventors.
IV.

CONCLUSION
For the foregoing reasons, the Court finds that Defendant has failed to show by clear and

convincing evidence that the Patent-in-Suit is invalid. An appropriate Order accompanies this
Opinion.
DATE: October 8, 2021
s/ Claire C. Cecchi
CLAIRE C. CECCHI, U.S.D.J.

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