MERCK SHARP & DOHME CORP. v. ACTAVIS LABORATORIES FL, INC. et al

Filing 223

MEMORANDUM and ORDER that claim 11 of the 5,661,151 patent is not invalid under pre-AIA 35 U.S.C. § 102(a); that claim 12 of the 151 patent is not invalid under pre-AIA 35 U.S.C. § 103(a). Signed by Judge Peter G. Sheridan on 9/28/2017. (km)

UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF NEW JERSEY

MERCK SHARP & DOHME CORP.,
Plaintiff,
v.
ACTAVIS LABORATORIES FL, INC.,
ANDRX CORPORATION, ACTAVIS
PHARMA, INC. AND ACTAVIS, INC.,
Defendants.

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Civil Action No:
15-cv-6075 (PGS)(DEA)

MEMORANDUM
AND
ORDER

SHERIDAN, U.S.D.J.
This is a patent infringement action brought by Merck Sharp & Dohme Corp. (“Merck” or
“Plaintiffs”) against Actavis Laboratories FL, Inc., Andrx Corporation, Actavis Pharma, Inc. and
Actavis, Inc. (collectively, “Actavis” or “Defendants”) for filing an Abbreviated New Drug
Application (“ANDA”) with the Food & Drug Administration (“FDA”), pursuant to 21 U.S.C. §
355(b)(2), for approval to engage in the commercial manufacture, use or sale of a generic version
of Merck’s Noxafil® (posaconazole). See 35 U.S.C. § 271(e)(2).
Merck listed the U.S. Patent No. 5,661,151 (“the ’151 patent”) with the FDA’s Approved
Drug Products with Therapeutic Equivalence Applications, commonly known as the Orange Book,
in order to market and sell a generic version of Noxafil®. See 21 U.S.C. § 355(b)(1). The ’151
patent is directed to the synthesis and clinical use of the antifungal compound posaconazole, which
is used for treating or preventing fungal infections.
Merck alleges that by filing the ANDA application with the FDA, and in particular making
a Paragraph IV certification with their filing, Actavis had indicated that Merck’s ’151 patent is

“invalid or will not be infringed by the manufacture, use, or sale of [Actavis’] new drug for which
the application is submitted.” See 21 U.S.C. § 355(j)(2)(A)(vii)(IV).
Accordingly, pursuant to 21 U.S.C. § 355(j)(5)(B)(iii), Merck initiated this suit against
Actavis because Actavis’ request to market the generic version of Noxafil® is prior to the
expiration of the ’151 patent.
In this action, a seven-day bench trial was held in July 2017. During trial, Actavis set forth
the defense that filing of the ANDA application does not infringe the ’151 patent because the
asserted claims 11 and 12 of the ’151 patent are invalid. In particular, Actavis asserted that—(i)
claim 11 of the ’151 patent is invalid because it is inherently anticipated by the European Patent
Application EP 0 539 938 A1 (“EP ’938”); and (ii) claim 12 is invalid because it is obvious to a
person of ordinary skill in the art (“POSA”) in view of the EP ’938 reference.
In contrast, Merck argued that claims 11 and 12 of the ’151 patent are valid because Actavis
has not shown by a clear and convincing evidence that the asserted claims are rendered inherently
anticipated or inherently obvious in view of the EP ’938 reference. Further, Merck argued that the
EP ’938 reference is not a prior art reference under 35 U.S.C. §§ 102(a) and 103(a) because the
inventive concepts recited in claims 11 and 12 of the ’151 patent were invented on April 14, 1993,
and diligently reduced to practice prior to or soon thereafter. As such, antedating the EP ’938
reference, published on May 5, 1993.
Actavis arguably asserted that claim 12 is invalid because it is inherently anticipated by the
EP ’938 reference; however, the parties later stipulated that claim 12 is not inherently anticipated
by the EP ’938 reference. (See D.I. 199).
After careful review and consideration of the evidence presented at the bench trial, the
Court finds that Merck has provided that the subject matter recited in claims 11 and 12 of the ’151

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patent was conceived on April 14, 1993, which was diligently reduced to practice thereafter.
Thereby, rendering the EP ’938 reference not a prior art reference to the ’151 patent. As such, the
Court finds that claim 11 of the ’151 patent is not invalid under 35 U.S.C. § 102(a); and claim 12
of the ’151 patent is not invalid under 35 U.S.C. § 103(a).
A. GOVERNING LAW
As we know the Leahy-Smith America Invents Act (“AIA”) substantially changed the
patent law on September 16, 2011. One such change amended the prior law from a ‘first to invent’
to ‘first to file’ system except in certain cases. The AIA further provided that the amendments set
forth in the AIA would not take effect until eighteen (18) months after enactment (March 16,
2013). This matter arises prior to the effective date. As such, the pre-existing law applies. (See
Manual of Patent Examining Procedure (“MPEP”), Section 2159.01); also see AIA 125 Stat. at
*293 (Sec. 3(n)(1)).
B. PROCEDURAL BACKGROUND
The patent application of the ’151 patent was filed on June 2, 1995, which later issued on
August 26, 1997, to Schering Corporation (“Schering”). On August 30, 2012, Schering assigned
its rights in the ’151 patent to Merck.1 The ’151 patent was listed in the FDA’s Orange Book in
three different New Drug Applications (“NDA”), which are directed to an intravenous infusion
solution (300MG/16.7ML (18MG/ML)); oral suspension (40MG/ML); and oral tablet with
delayed release (100MG). The NDA, N205053, for the oral tablet with delayed release (100MG),
is the one that Actavis seeks approval from the FDA to market and sell a generic version in the
United States. (See Complaint (“Compl.”) at ¶ 19; D.I. 1).On November 25, 2013, the FDA

1

See Image File Wrapper (“IFW”) of the ’151 patent. Reel/Frame: 028884/0151; Recorded: 8/30/2012; available at
https://portal.uspto.gov/pair/PublicPair (last visited, July 25, 2017).

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approved Merck’s NDA N205053, directed to oral tablet with delayed release (100MG), for use
in “prophylaxis of invasive aspergillus and candida infections.”2
In its ANDA filing with the FDA, Actavis included a written certification (¶ IV
Certification) alleging that the claims of the ’151 patent are invalid or otherwise will not be
infringed by Actavis’ ANDA product. (See id. at ¶ 20; see also 21 U.S.C. § 355(j)(2)(A)(vii)(IV)).
Consequently, on August 6, 2015, Merck initiated this suit against Actavis; alleging that
Actavis’ request to market the generic version of Noxafil® is prior to the expiration of the ’151
patent. As such, infringing Merck’s intellectual property rights granted under the ’151 patent. (See
id. at ¶¶ 26-30; see also 35 U.S.C. § 271(e)(2)).
Merck asserted claims 11 and 12 of the ’151 patent against Actavis in this suit. (See First
Amended Invalidity Contentions at 5; D.I. 67). Independent claim 11 being directed to the
compound posaconazole, and dependent claim 12 being directed to a pharmaceutical composition
comprising the posaconazole of claim 11 and a pharmaceutically acceptable carrier. Claim 12
depends from claim 11. (Id. at 6). In its invalidity contentions, Actavis asserted, inter alia, that
claims 11 and 12 of the ’151 patent are invalid because—(i) claim 11 is inherently anticipated by
the EP ’938 reference (see id. at 21); (ii) claim 12 is inherently anticipated by the EP ’938 reference
(see id. at 23); (iii) claim 11 is obvious in view of multiple grounds (see id. at 23-34); and (iv)
claim 12 is obvious in view of the EP ’938 reference (see id. 35-36).
At trial, Actavis bearing the burden to invalidate the asserted claims of the ’151 patent,
presented mainly expert evidence to show that the asserted claims 11 and 12 of the ’151 patent as

2
See U.S. Food & Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence
Evaluations. Patent and Exclusivity for: N205053. Product 001, Posaconazole (Noxafil) Tablet, Delayed Release
100MG, (Patent Use Code: U-1454), available at
https://www.accessdata.fda.gov/scripts/cder/ob/patent_info.cfm?Product_No=001&Appl_No=205053&Appl_type=
N (last visited, July 25, 2017).

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being invalid as noted above. The experts were—Dr. Paul Ortiz De Montellano; Dr. Stanley
Roberts; Dr. Wei Lu; Dr. Gary Glick; Dr. Edwin P. Alyea; and portions of videotaped depositions
of Dr. Viyoor M. Girijavallabhan (“Dr. Giri”), Dr. Frank Bennett, and Mr. Frank Lovey.
On the other hand, Merck defended the ’151 patent by arguing that the asserted claims 11
and 12 are not inherently anticipated or rendered obvious in view of the EP ’938 reference. Further,
Merck argued that the EP ’938 reference does not qualify as a prior art reference because the
posaconazole compound recited in claim 11 and the pharmaceutical composition recited in claim
12 were conceived before the publication date of the EP ’938 reference (May 5, 1993), and
diligently reduced to practice soon thereafter. In order to advance these positions, Merck relied on
the following witnesses and experts—Dr. Birendra N. Pramanik; Dr. Anil Saksena; Dr. Roland
Dolle; Dr. Fredrick P. Guengerich; Dr. Mahmoud Ghannoum; Dr. Kieren Marr; Dr. Giri; Dr.
Raymond Lovey; and Dr. Frank Bennett.
At the end of the trial, the parties submitted proposed findings of fact and conclusions of
law, followed by reply papers. (See Pl.’s Findings of Fact (“FoF”), D.I. 200; Def.’s FoF, D.I. 201;
Def.’s Conclusions of Law (“CoL”), D.I. 204; Pl.’s CoL, D.I. 205; Def.’s Reply, D.I. 208; Pl.’s
Reply, D.I. 209).
The issues litigated before the Court were whether—(1) Merck can antedate the EP ’938
reference by showing that the claimed subject matter of claims 11 and 12 were conceived before
the publication date of the EP ’938 reference, and diligently reduced to practice soon thereafter;
and (2) if the EP ’938 reference is a prior art reference to the ’151 patent, is claim 11 inherently
anticipated by the EP ’938 reference under the pre-law; and (3) if the EP ’938 reference is prior
art, is claim 12 rendered obvious under the pre-law. (See Def.’s FoF at ¶ 3; see also Pl.’s FoF at ¶
16).

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C. CONVENTIONAL TECHNOLOGY & DRUG DEVELOPMENT
In or around 1993 (the time of the inventive concepts disclosed in the ’151 patent) there
was a need for broad-spectrum antifungal agents with increased solubility and favorable activity
profile for treating systemic fungal infections. In particular, systemic fungal infections such as,
Aspergillus, Candida, Cryptococcus and opportunistic infections, needed to be treated. (See the
’151 patent, col. 2, ll. 27-32).
During the early 1990s, when the HIV/AIDS disease was very high, and there were many
immune-suppressed patients, medical professionals in this field were aware of the need to cure or
treat fungal infections more effectively. (See Plaintiff’s Expert, Dr. Kieren Marr’s testimony
Transcript (“Trans.”) at 1185:19-24, 1195:21—1196:10 (Marr), dated July 19, 2017). Dr. Marr
testified that there are two types of fungal infections—local and systemic functions. Distinguishing
between them, she stated that a local fungal infection, such as athlete’s foot is limited to an external
part of the body; but systematic fungal infections involve fungal invasion of more than one organ
system, such as the blood, lungs, or brain, which are caused by yeasts and molds such as
Aspergillus, Candida, Zygomycetes, Cryptococus, and Coccidioides. Systemic fungal infections
being prevalent in persons who have compromised immune systems. (See Trans. at 1191:22—
1194:10 (Marr); see also Pl.’s FoF at ¶¶ 70-73).
Dr. Marr, “an expert in infection diseases, particularly the pathogenesis, diagnosis and
prevention and treatment of fungal infections” (see Trans. at 1188:3-6), testified that one of the
drugs available to physicians in the year 1993 to treat people with fungal infections was
Amphotericin B, which was administered intravenously. The side effect of this drug was that it
caused severe kidney destruction; resulting in fevers and chills. (See Trans. at 1194:16-25 (Marr);
see also Pl’s FoF at ¶¶ 79, 81).

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Next, Dr. Marr noted that the other conventional drugs included—Flucytosine,
Ketoconazole, Fluconazole, and Itraconazole. (See PX 1057). Dr. Marr testified that in 1993, the
only antifungal drugs available for physicians to prescribe for systemic fungal infections were the
aforementioned drugs. (See Trans. at 1202:3-7). All of these conventional drugs have a broader
spectrum than their predecessor, but they have significant side effects. For example, Flucytosine
had limited usage because fungal infections became rapidly resistant to this drug (see Trans. at
1196:20-23); Ketoconazole, approved by the FDA in 1981, created toxicities in the liver when it
interacted with the P450 enzyme (see Trans. at 1197:1-6; see also Pl.’s FoF at ¶¶ 83, 84);
Fluconazole, which was considered very safe, had activity against Candida species, but had no
activity against molds (i.e., Zygomycetes) (see Trans. at 1198:19—1199:3, 1200:9-10); and lastly,
Itraconazole, approved by the FDA in 1992, was effective against molds (Aspergillus); but
Itraconazole was not very effective in treating people with suppressed immune systems, and was
not safe for patients with heart defects. (See Trans. at 1200:11-25; see also Pl.’s FoF at ¶ 86).
Moreover, Dr. Marr testified that in the late 1980s and the early ‘90s there were no FDA
approved drugs available to prevent or treat patients that were susceptible to fungal infections,
there was only conventional amphotericin B. (See Trans. 1203:24—1204:1). As such, there was a
pressing need for a broad spectrum drug that could be administered for preventive use for diabetic
patients, AIDS patients and transplant patients. (See Pl.’s FoF at ¶ 88).
Similarly, Dr. Dolle, Merck’s expert in drug discovery and medicinal chemistry (see Trans.
at 538:18-21), concurred with Dr. Marr about the ongoing need for antifungal drugs. In 1940s,
Benzimidazole, a forerunner of azole class, was introduced in the market, which had weak activity
against fungi. (See PX 1017). Then in the 1960s, Miconazole, a topical agent to treat things like
fungus and ringworm, was approved by the FDA around 1960s. Thereafter, in 1977, Ketoconazole

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was approved, which was the first oral active agent. (See Trans. at 727:12-25 (Dolle)).
Ketoconazole, the first orally active compound, lead further interest by the scientific community
into following up on azoles in treating antifungal infections. (Id. at 728:3-8 (Dolle)).
Dr. Dolle further noted that developing a new antifungal drug is a long drawn out process.
(See PX 1002). He explained that the pre-clinical phase a lead compound is identified, optimized,
and then tested in animals. Whereas, under the clinical phase, the lead compound is tested in
humans; and the assessment of the lead compound’s efficacy and safety in humans is determined,
before being approved by the FDA. (See Trans. at 541:25—542:1-7 (Dolle)).
In summary, Dr. Dolle noted that it is an industry average that around 10,000 compounds
that are synthesized or evaluated for their biological activity under the pre-clinical phase. Only
0.1% percent of those compounds enter the clinical phase, out of which only 10% have a chance
of getting FDA approval. (See Trans. at 542:8-23 (Dolle)). Consequently, the entire process may
exceed ten (10) years from possessing a lead compound through the clinical phase and obtaining
FDA approval. (See Trans. 542:21—543:3 (Dolle)).
D. DEVELOPMENT OF POSACONAZOLE
In early 1993, Schering performed studies on Compound IIc (i.e., SCH-51048). The
research and studies indicated that when Compound IIc was administered to mice, there was a
compound within mice’s blood that had better antifungal activity than its parent compound
(Compound IIc). This suggested to the scientists at Schering, in particular Dr. Saksena, that some
metabolite of Compound IIc was more active than the parent compound itself. (See Pl.’s FoF at ¶
108; citing Trans. at 472:4-19; 1353:16-19; JX 44.0027; JX 44.0036). This active metabolite was
called “Metabolite A.”

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Although Dr. Saksena learned about the existence of this active metabolite, Metabolite A,
he did not have any idea or mental conception of the structure of this active metabolite. (See Pl.’s
FoF at ¶ 114). As such, Dr. Saksena and his colleagues attempted to learn more about the structure
of this metabolite by undertaking further research. (Id. at ¶ 117). On April 13 and 14, 1993, Dr.
Larry Heimark, a mass spectrometrist, performed serum samples of the antifungally active CF-1
mouse metabolite of Compound IIc. (Id. at ¶ 118; citing JX 7.0003-05). Dr. Birendra Pramanik, a
senior mass spectrometrist and Dr. Heimark’s supervisor, analyzed the mass spectra provided by
Dr. Heimark and wrote down the results of his analysis in his lab notebook. (Id. at ¶¶ 119-120).
These results are shown below—

(See JX 7.0001). Dr. Pramanik’s handwritten remarks (above) are difficult to read but in substance
the notes state that this structure, as labeled as “SCH 51048 Metabolite,” is—(i) data of the

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metabolite sample indicated that the compound is a secondary alcohol; (ii) oxidation occurred at
the side chain (X) (annotated in the figure); and (iii) additional work is in progress.
On the same day, April 14, 1993, Dr. Pramanik discussed his findings and mass spectra
with Drs. Saksena and Giri. Based on the evidence before them, Drs. Pramanik, Saksena and Giri
perceived that Metabolite A could have any of seven possible structures. These seven possibilities
included—two primary alcohols, four secondary alcohols, and one tertiary alcohol. (See Pl.’s FoF
at ¶¶ 121-124). “Primary” and “secondary” refer to the specific carbon to which the OH group is
attached. (See Def.’s Br. at 4). The tertiary alcohol was quickly ruled out during this meeting, and
on April 14, 1993, they decided to synthesize and test each of the six alcohols to determine which
one of the six alcohols had antifungal activity. (See Pl.’s FoF at ¶ 127; citing Trans. at 476:13-20
(Saksena); 1145:21—1146:2 (Giri); and 1337:25—1338:2 (Glick)).
The six alcohols were synthesized as three pairs of racemates (i.e., as three mixtures, each
containing a pair of two distinct stereoisomers) for purposes of synthetic convenience, as the three
racemates could be more quickly prepared; resulting in an early evaluation of the biological
activity of the compounds. (See Pl.’s FoF at ¶¶ 128-129).
Both posaconazole and SCH-51048 are each single “stereoisomers.” In a general sense,
this means that each compound has a corresponding pair compound that has the same atoms,
attached in the same way, but with a non-superimposable mirror-image configuration in threedimensional space, similar to left and right hands. (See Trans. at 60:11-61:17; 62:23-63:23) (Ortiz
De Montellano). These mirror-image compounds are denoted as “(R)” and “(S)” forms of the
compound. (See Trans. at 62:20-22; 63:24-64:3) (Ortiz De Montellano). The different
stereoisomers of a molecule often have different biological activity and/or toxicity. One wellknown example of this phenomenon is the drug thalidomide. The (R) form of thalidomide is

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effective against morning sickness, while the (S) form causes birth defects. (See Trans. at 64:2365:11) (Ortiz De Montellano). See Def.’s FoF at ¶¶ 11-12.
The purpose of synthesizing the six alcohols was to test their activity against fungal agents,
both in vivo and in vitro, and ultimately determine if any of these compounds could be developed
into marketable drugs. (Id. at ¶ 132). To test each of the six alcohols in vivo, each of them would
have to be formulated as a pharmaceutical composition containing a potentially antifungally
effective amount of posaconazole suitable for administration to laboratory animals suffering from
fungal infections. (Id. at ¶ 133).
The synthesis of the six alcohols, which were determined during the April 14, 1993,
meeting between Dr. Giri, Dr. Saksena and Dr. Pramanik, was assigned to Mr. Raymond Lovey.
(Def.’s FoF at ¶ 25). Mr. Lovey was tasked to synthesize three racemic mixture, or racemate,
(mixtures of two stereoisomers), SCH-55801, SCH-55803, and SCH55805. (Id. at ¶ 26; Pl.’s FoF
at ¶ 148). The three pairs of the racemic mixtures are shown below—

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(See Pl.’s FoF at ¶ 180). SCH-55801 and SCH-55803 corresponded to the four secondary alcohols
of SCH-51048, and SCH-55805 corresponded to the two primary alcohols of SCH-51048. (Id. at
¶ 181).
During the April 14, 1993 meeting, Drs. Giri and Saksena provided Mr. Lovey with an
outline of the synthetic steps to make the racemates. (See Pl.’s FoF at ¶ 150). Mr. Lovey’s fivestep synthesis of SCH-55801 started on April 26, 1993 and was completed by May 26, 1993. (Id.
at ¶ 154). The five-steps included—(i) dihydroxylation of 2-pentene (step 1); (ii) protection of 2,3pentanediol (step 2); (iii) sulfonation of SEM protected 2,3 pentanediol (step 3); (iv) coupling of
triazole core (step 4); and (v) deprotection to remove SEM protecting group, yielding posaconazole
and its enantiomer (step 5). (See PX 1010; Pl.’s FoF at ¶ 182-183).

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On May 26, 1993, Mr. Lovey made SCH 55801, posaconazole, as a one-to-one mixture
with the R,R isomer. (See Pl.’s FoF at ¶¶ 184-185). A mass spectra analysis done on June 14, 1993
indicated SCH-55801 had the distinctive fragmentation pattern of the secondary alcohol analogs
of SCH-51048. (Id. at ¶ 187). The three racemic mixtures Mr. Lovey synthesized were tested in in
vitro experiments, which showed that all had activity and that they were more active than SCH51048. (Id. at ¶ 190).
After the three racemic mixtures—SCH-55801, SCH-55803 and SCH-55805—were tested
for in vitro antifungal activity, Drs. Giri and Saksena directed their team to make the six alcohols
in pure form. (Id. at ¶ 197). Dr. Bennett, one of the Schering scientists tasked with making the pure
form, began his work on June 30, 1993, and concluded the synthesis of pure posaconazole on
August 20, 1993. (Id. at ¶ 200). Dr. Bennett began with synthetic routes to the azole core and the
piperazine linker ‘in hand,’ and attached the side chain necessary to make posaconazole as a pure
compound. (Id. at ¶¶ 159-160). As such, Dr. Bennett was the first person to make SCH-56592,
which was later known as posaconazole, not in a mixture with its RR enantimoer. (Id. at ¶ 199).
The in vivo testing showed that SCH 56592 (posaconazole) had the best oral activity, the best
pharmacokinetics, and the best efficacy of the six individual stereoisomers. (Id. at ¶ 203).
By October 18, 1993, a protocol for testing all six secondary and primary alcohol analogs
of SCH-51048, including posaconazole, in mice infected with Candida albicans was in place; and
testing of the six alcohols as pharmaceuticals began. (Id. at ¶ 209). Between October 18, 1993 and
December 21, 1993, posaconazole was tested in vivo, the results were analyzed, and 171,083 patent
application (“’083 patent application”) was filed. (Id. at ¶ 211).

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E. THE ’151 PATENT
A. EARLIEST PRIORITY DATE
The parties agree that the earliest priority date of the ’151 patent is December 21, 1993.
(See First Amended Invalidity Contentions at 6). The ’151 patent is a continuation-in-part (“CIP”)3
application of a PCT application, and the PCT application is a CIP application of the ’083 patent
application (“’083 patent application”).
B. DISCLOSURE OF THE ’151 PATENT
The ’151 patent is generally directed to the synthesis and clinical use of antifungal
compound posaconazole, which is used for treating and/or preventing fungal infections. (See
Abstract of the ’151 patent). Posaconazole is an azole antifungal, which means it is a particular
class of chemical compounds that are known to have antifungal activity. (See Trans. at 7:8-14).
The ’151 patent discloses antifungal compounds of formula I and pharmaceutical compositions,
which are expected to exhibit anti-allergic, anti-inflammatory and immunomodulating activities.
The pharmaceutical composition contains a fungicidally effective amount of other antifungal
compounds. (Id. at col. 56, ll. 40-67).
The chemical structure of posaconazole, which shows the arrangement of the atoms within
the molecules and which atoms are bonded together, and whether single, double or triple bonds
are formed between, is illustrated in claim 11—

3
See MPEP 201.08 (“A continuation-in-part application is an application filed during the lifetime of an
earlier nonprovisional application, repeating some substantial portion or all of the earlier nonprovisional
application and adding matter not disclosed in the earlier nonprovisional application.”).   

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(see the ’151 patent, col. 78, ll. 1-20; see also Def.’s Br. at 2; D.I. 162; see also Def.’s FoF at ¶ 9
(“there are three parts to the posaconazole structure, the azole core, the piperazine linker and the
side chain.”); see also Pl.’s FoF at ¶ 134). Dr. Dolle, Merck’s expert, testified that the chemical
structure of the posaconazole compound is a three-dimensional structure, wherein the dashed lines
and the bold solid lines, as illustrated above, represent groups behind the plane and coming out of
the plane, respectively. (See Trans. 563:24—564:3 (Dolle)).
The ’151 patent further discloses that pharmaceutical compositions are formulated by
combining the compound of formula I or an equivalent amount of a pharmaceutically acceptable
salt of compound I with a suitable, inert, pharmaceutically acceptable carrier or diluent. Examples
of suitable pharmaceutical compositions include solid or liquid compositions for oral
administration such as tablets, capsules, pills, powders, granules, solutions, suppositories, troches,
lozenges, suspensions or emulsions. (Id. at col. 57, ll. 40-50).
Further, the ’151 patent discloses that a solid carrier can be one or more substances which
may act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders or tablet
disintegrating agents, or as an encapsulating material. The carrier can also be a finely divided solid
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which is in admixture with the finely divided active compound. In a tablet form, for example, the
active compound is mixed with the carrier that has the necessary binding properties. The carrier
is added in suitable proportions such that the tablet is compacted in the desired shape and size. (Id.
at col. 57, ll. 45-55).
During prosecution of the patent application of the ’151 patent, the examiner rejected the
claimed subject matter. The Applicant amended the then pending claims to include claim term “in
vivo” to differentiate over the cited art. (See Image File Wrapper of the ’151 patent, Applicant’s
Arguments/Remarks Made in an Amendment, filed May 24, 1996). This amendment was made in
response to patent examiner’s rejection mailed on November 22, 1995. Additionally, arguments
against the obviousness rejection under 35 U.S.C. § 103 were also made. (Id.)
After mailing a final rejection on August 21, 1996, the examiner conducted a personal
interview with the Applicant’s representative. During the personal interview, the enablement
rejection under pre-AIA 35 U.S.C. § 112, first paragraph, was discussed, and the Applicants agreed
to provide an affidavit demonstrating that enablement exists for use of “in vivo” esters. (See
Examiner Interview Summary Record mailed on December 19, 1996).
Thereafter, the Applicant filed a response to the outstanding Office action with a
declaration from Dr. Ashit K. Ganguly, a co-inventor of the ’151 patent. In the response, the
Applicant essentially argued that based on the specification a POSA would be able to readily
determine which of the ester compounds would be soluble or suspendible in a pharmaceutically
acceptable aqueous media. (See Applicant’s Arguments/Remarks filed on January 29, 1997; citing
Declaration of Dr. Ganguly at ¶ 17).
Further, Applicants noted that they are “amending claim 17 of this application to cover a
preferred embodiment, and to recite that such esters of the compounds of the claimed invention

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have a solubility in a pharmaceutically acceptable media of at least about 1 to about 50 mg/ml.”
(Id. at 6). Thereafter, on February 7, 1997, a notice of allowance was mailed by the patent
examiner, which was later followed by a corrected notice of allowance on February 27, 1997. No
reasons for allowance in-particular were provided by the patent examiner when issuing the notice
of allowance.
F. THE EP ’938 REFERENCE & THE NOMEIR 2008 REFERENCE
The EP ’938 reference, assigned to Schering, is the prior art primarily relied upon by
Actavis to invalidate asserted claims 11 and 12 of the ’151 patent as being inherently anticipated
and obvious. Since the EP ’938 reference became publicly available on May 5, 1993, and the patent
application date of the ’151 patent being December 21, 1993, Actavis argues that the EP ’938
reference is a prior art reference. (See Trans. at 6:8—7:5; 43:21-23).4 Notably, the inventors of the
EP ’938 reference are Dr. Saksena, Dr. Ganguly and Mr. Lovey.
The EP ’938 reference identifies that there is a need for broad spectrum antifungal agents
to treat systematic fungal infections, especially Aspergillus and Candida infections. (See the EP
’938 reference at page 3, ll. 28-29). The EP ’938 reference describes three compounds, designated
as Compounds IIa, IIb, and IIc, wherein Compound IIc being the “more preferred” compound. (Id.
at page 3, ll. 54). Compound IIa referred to SCH-50001; Compound IIb referred to SCH-50002;
and Compound IIc referred to SCH-51048, respectively. (See Pl.’s FoF at ¶ 104). The EP ’938
reference discloses that itraconazole, fluconazole, and saperconazole were tested for in vivo oral

4

Actavis’ Counsel: (“[C]laim 11 is anticipated by […] [EP-938 because] EP-938 describes administering a compound
called compound IIc [SCH-51048] to mice. […] Compound IIc, when it’s administered to [a] mice, it necessarily
metabolizes to the claimed compound posaconazole. And under the Federal Circuit’s precedent, particularly the
Schering decision, that makes claim 11 anticipated or inherently anticipated by EP-938. […] With respect to claim 12,
Actavis is going to prove by clear and convincing evidence that a person of ordinary skill in the art […] would have
combined [compound IIc] with a pharmaceutically acceptable carrier, and would have a reasonable expectation of
success.”).

17

antifungal activity in a Candida systemic model using CF-1 male mice, average weight being 20
grams. (See the EP ’938 reference at page 33, ll. 6-14).
Dr. Ortiz de Montellano, Actavis’ expert in the field of drug metabolism and the
identification of drug metabolites (see Trans. at 58:6-11), relied upon page 15, column 37-50, of
the EP ’938 reference, to testify that this reference discloses the administration of Compound IIc
or SCH-51048 into CF-1 male mice who are infected with Candida allergens (a fungal strain).
(See Trans. at 90:2-8). Compound IIc, which includes— the azole core, the piperazine linker, and
the side chain—similar to posaconazole, has the following chemical structure—

(see the EP ’938 reference at page 15, ll. 35-50; see also Def.’s FoF at ¶ 10 (“[Compound IIc] has
the same structure as posaconazole except for the omission of an OH, or hydroxyl, group on the
side chain.” (citing Trans. at 59:3—60:3)); see also Pl.’s FoF at ¶ 135). Dr. Ortiz de Montellano
testified that in his opinion when Compound IIc is administered to a 20 gram CF-1 male mice, it
is metabolized by the mice’s liver into posaconazole. Dr. Ortiz de Montellano based this opinion
both on literature disclosures regarding the in vivo metabolism of Compound IIc and on in vitro

18

experiments conducted in his laboratory. (See Trans. at 98:7-15, 98:25—99:1-2; see also Opening
Expert Report of Dr. Ortiz De Montellano at ¶ 4; Cross Exhibit (“CX”) 0742.0001).
Additionally, relying on a publication from 2008, commonly referred to as the Nomeir
2008 publication (JX 0033)5, Dr. Ortiz de Montellano testified that the Nomeir 2008 publication
describes how pre-clinical metabolism studies with SCH-51048 or Compound IIc led to the
development of currently marketed drug posaconazole (SCH-56592). In particular, Dr. Ortiz de
Montellano notes that the Nomeir 2008 publication discloses that when SCH-51048 was dosed to
various mammal species, the presence of an active metabolite6 (“Metabolite A”) was discovered.
(See Expert Report of Dr. Ortiz De Montellano at ¶ 15 (citing Nomeir 2008 at 512-517); CX 07420010-0011; see also Trans. at 91:18-24 (Dr. Ortiz De Montellano):
“Note that they did not actually go looking for an active metabolite, they actually
just administered looking at the kinetics to see how long the drug would be active
in the mice, and what they basically found is that in fact activity lasted much longer
than the compound SCH-51048 which implicated an active metabolite. And this
eventually led to the discovery of posaconazole.”
The Nomeir 2008 publication discusses that when Compound IIc was administered to
different species—mice, rabbits, dogs and cynomolgus monkeys—the majority of radioactivity
determined in serum was due to metabolites rather than the parent compound (i.e., Compound IIc).
Presence of two metabolite peaks (A and B) were identified. (See JX 33.0006-0007). The
electrospray mass spectral data established that the molecular weight of metabolite A was 701
Daltons, which was 16 mass units greater than the parent Compound IIc (m/z 685). (Id.). Based

5
See Nomeir, Amin A., et al., “Posaconazole (Noxafil, SCH 56592), a new azole antifungal drug, was a
discovery based on the isolation and mass spectral characterization of a circulating metabolite of an earlier
lead (SCH 51048).” JOURNAL OF MASS SPECTROMETRY, 43:509-517 (2008).
6

See Trans. at 237:17-21 (“[Actavis’ Counsel] Q: Dr. [Wei] Lu, what is a metabolite? A: Metabolite is as
Dr. Ortiz mentioned last Thursday, some apparent compounds or drugs can be structured can change in
vivo or in vitro situation, to others structures, that is identified as metabolite.”).

19

on the testing conducted, and by a process of deduction, the active metabolite A was “pinpointed,
isolated, purified, and by the use of the powerful LCMS/MS [liquid chromatography-tandem mass
spectrometry] technology was very quickly characterized as a secondary alcohol. [As such] […]
posaconazole emerged as the compound with the best overall profile.” (Id. at 0033.0009; see also
Trans. at 92:20-25).
Dr. Wei Lu, Actavis’ expert witness, testified that based on his study of the Compound IIc
disclosed in the EP ’938 reference, and reliance on the disclosure of the Nomeir 2008 publication,
he was able to conclude that posaconazole is necessarily formed in a mouse’s liver starting from
the Compound IIc. That is, the Nomeir 2008 publication describes the discovery of posaconazole
based on the metabolism of the Compound IIc. (See Trans. at 240:12-16; 241:3-97; 247:15-22).
In his laboratory, Dr. Lu employed liver microsomes prepared from 20 gram CF-1 male
mice, in order to metabolize the Compound IIc. Through experimentation, he collected data that
recorded retention time, mass, and fragmentation pattern of an incubation mixture. Dr. Lu analyzed
the incubation mixture to confirm that posaconazole is present. (See Trans. at 245:14-19; see also
Def.’s FoF at ¶ 4).
Dr. Gary Glick, also Actavis’ witness, testified that the EP ’938 reference discloses when
Compound IIc, which when administered to CF-1 male mice it is necessarily metabolized into
posaconazole. Dr. Glick based this opinion on a series of documents made available by Schering
and testing performed by Dr. Lu and synthesis of Compound IIc performed by Dr. Stanley Roberts.
(See Trans. at 316:14-24). Dr. Glick noted that goal of Dr. Lu’s experiments was to indicate that
metabolite A or posaconazole was formed upon treating animals with Compound IIc, and the only

7
(“Q: Why did you obtain only these four standards? A: Because they cited in the Nomeir paper, year 2008,
that these four structures of interest is the secondary alcohol generated in their experiment.”).

20

thing left to do was to determine the stereochemistry8 of the metabolite. (See Trans. at 330:10-13
(“Q: Do you agree with Dr. Lu’s conclusion that posaconazole is formed from the incubation of
SCH-51048 [Compound IIc] in CF-1 mouse liver microsomes? A: Based on the data that I have
reviewed, yes.”).
Further, in relying upon the Nomeir 2008 publication, Dr. Glick testified that this reference
discloses that Schering was in the process of testing Compound IIc in animals as it was a very
promising compound, and during the process of routine testing, an active metabolite was
discovered. The structure of this active metabolite was deduced using standard experiments in
organic chemistry such as mass spectrometry and LCMS/MS. (See Trans. at 317:23—318:9).
In referring to the Nomeir 2008 publication, in particular the mouse model shown in figure
2 of this reference, Dr. Glick testified that Compound IIc was injected into the mice, and after a
period of time blood was obtained from the injected mice, and the blood samples were analyzed,
wherein metabolite A was found. The structure of which was deduced using the LCMS/MS
technology. (See Trans. at 320:12-23). Further, in reference to figure 8 of the Nomeir 2008
publication, Dr. Glick testified that as to the structure of metabolite A, the scientists at Schering
noted that there were three possible places that the hydroxyl (OH) group could be placed on the
side chain. And, based on the potential chemical stability of the resulting product that the tertiary

8
See Trans. at 326:15-24 (“[Actavis’ Counsel] Q: And when you say stereochemistry what do you mean?
A: So where it was pointing in space dictates the chemical nature of the molecule, and molecular atoms that
point in different orientations in space are defined as different -- they're call stereoisomers. […]. Q: How
many stereoisomers are there for metabolite A? A: There are four possible stereoisomers, one of which is
posaconazole.”).
Also see Trans. at 895:13—896:19, in understanding the concept of “stereoisomer,” Merck’s Counsel, Mr.
Chesler, put forth a shoe analogy on re-direct examination of Dr. Dolle. (“Q: What if any relevance does
[shoe] analogy have to the stereochemistry that relates to what Mr. Lovey made in May of 1993? A: […]
Mr. Lovey made the one-to-one mixture of posaconazole in the mixture, it’s basically the right hand – it’s
a right hand and a left hand, he made a mixture of both of those. So […] if you go back to the shoe analogy
[…] this is a case where he synthesized the pair and clearly posaconazole is there.”).

21

carbon was not going to be a site of metabolism. Instead, primary or secondary carbons were the
site of metabolism. (See Trans. at 323:2-11).

With respect to figure 4 of the Nomeir 2008 publication, Dr. Glick testified that the bottom
graph illustrated in figure 4 shows mass spectral data of metabolite A. Figure 4 showing molecular
weight (m/z) along a x-axis and intensity measure along a y-axis. The lines generated in the spectra
from the data collected enable chemists to determine or propose the actual chemical structure. Dr.
Glick noted that the bottom graph of figure 4 illustrates a proposed structure of metabolite A.
Unlike the chemical structure illustrated in the top portion of figure 4, which depicts the
chemical structure of Compound IIc, the bottom portion of figure 4 illustrates the chemical
structure of metabolite A with the hydroxyl group as part of the side chain. The hydroxyl group in
22

metabolite A is drawn in such a way with “sort of a line in the middle of what looks like a bond,
because at this point the authors had not determined which atom it’s attached to, so that’s meant
to mean indeterminate.” (See Trans. at 321:1—322:13).
In conclusion, based on his review of the EP ’938 reference and the Schering’s internal
documents, Dr. Glick concluded that it was clearly evident that posaconazole is necessarily and
inevitably formed when Compound IIc is metabolized by the liver microsomes extracted from the
CF-1 male mice. (See Trans. at 316:14-16).
STANDARD OF PROOF
By statute a patent is valid upon issuance. See 35 U.S.C. § 282(a). “Since we must presume
a patent valid, the patent challenger bears the burden of proving the factual elements of invalidity
by clear and convincing evidence ... The trial court has the responsibility to determine whether the
challenger has met its burden by clear and convincing evidence by considering the totality of the
evidence, including any rebuttal evidence presented by the patentee.” Pfizer, Inc. v. Apotex, Inc.,
480 F.3d 1348, 1359-60 (Fed. Cir. 2007); see also Microsoft Corp. v. i4i Ltd. P’ship, et al., 131
S.Ct. 2238, 2239 (2011).
Invalidity is an affirmative defense that “can preclude enforcement of a patent against
otherwise infringing conduct.” Commil USA, LLC v. Cisco Systems, Inc., 135 S.Ct. 1920, 1929
(2015) (citing 6A Chisum on Patents § 19.01, p. 19-5 (2015)); see also 35 U.S.C. § 282(b)(2). The
claims of a patent can be invalid for “fail[ing] to meet the conditions for patentability within the
meaning of the patent law, Title 35 § 101 et seq., including, but not limited to, §§ 101, 102, 103
and/or 112.” Senju Pharmaceutical Co., Ltd. v. Apotex, Inc., 921 F.Supp.2d 297, 303-304 (D.Del.
2013).

23

35 U.S.C. § 102
Under 35 U.S.C. § 102, the anticipation inquiry, “invalidity [] requires that the four corners
of a single[ ] prior art document describe every element of the claimed invention, either expressly
or inherently, such that a person of ordinary skill in the art could practice the invention without
undue experimentation.” Advanced Display Sys., Inc. v. Kent State Univ., 212 F.3d 1272, 1282
(Fed. Cir. 2000).
A single prior art reference may expressly anticipate a claim where the reference explicitly
discloses each and every claim limitation. However, the prior art need not be ipsissimis verbis (i.e.,
use identical words as those recited in the claims) to be expressly anticipating. Structural Rubber
Prods. Co. v. Park Rubber Co., 749 F.2d 707, 716 (Fed. Cir. 1984). A single prior art reference
also may anticipate a claim where one of ordinary skill in the art would have understood each and
every claim limitation to have been disclosed inherently in the reference. Cont'l Can Co. USA Inc.
v. Monsanto Co., 948 F.2d 1264, 1268 (Fed. Cir. 1991).
The Federal Circuit has explained that an inherent limitation is one that is necessarily
present and not one that may be established by probabilities or possibilities. Id. That is, “the mere
fact that a certain thing may result from a given set of circumstances is not sufficient.” Id. The
Federal Circuit also has observed that “inherency operates to anticipate entire inventions as well
as single limitations within an invention.” Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373,
1380 (Fed. Cir. 2003).
The burden of proof to show anticipation rests on the party asserting invalidity and can be
met only by clear and convincing evidence. Microsoft Corp., 131 S.Ct. 2238. The Federal Circuit
discussed the standards for inherent disclosure:
“[A] prior art reference may anticipate without disclosing a feature of the claimed
invention if that missing characteristic is necessarily present, or inherent, in the
24

single anticipating reference. However, a patent claim cannot be anticipated by a
prior art reference if the allegedly anticipatory disclosures cited as prior art are not
enabled. The standard for what constitutes proper enablement of a prior art
reference for purposes of anticipation under section 102, however, differs from the
enablement standard under section 112. It is well-settled that utility or efficacy need
not be demonstrated for a reference to serve as anticipatory prior art under section
102.”
Verizon Services Corp. v. Cox Fibernet Virginia, Inc., 602 F.3d 1325, 1337 (Fed. Cir. 2010)
(internal quotation marks and citations omitted).
35 U.S.C. § 103
Under 35 U.S.C. § 103(a), the obviousness inquiry, “a patent may not be obtained “if 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 to a person having ordinary skill in the art.”
Obviousness is a question of law that is predicated on several factual inquiries. Richardson—Vicks
v. Upjohn Co., 122 F.3d 1476, 1479 (Fed. Cir. 1997).
Specifically, the trier of fact is directed to assess four considerations: (1) the scope and
content of the prior art; (2) the level of ordinary skill in the art; (3) the differences between the
claimed subject matter and the prior art; and (4) secondary considerations of non-obviousness,
such as commercial success, long felt but unsolved need, failure of others, acquiescence of others
in the industry that the patent is valid, and unexpected results. See Graham v. John Deere Co., 383
U.S. 86 S.Ct. 684, 694 (1966).
A party seeking to challenge the validity of a patent based on obviousness must
demonstrate by “clear and convincing evidence” that the invention described in the patent would
have been obvious to a person of ordinary skill in the art at the time the invention was made. Cubist
Pharmaceuticals, Inc. v. Hospira, Inc., 75 F.Supp.3d 641, 663 (D.Del.2014).

25

Perfecting Priority
Priority and its issues of conception and reduction to practice are questions of law
predicated on subsidiary factual findings. Cooper v. Goldfarb, 154 F.3d 1321, 1327
(Fed.Cir.1998).
More recently, the Federal Circuit noted the applicant must show he was in possession of
the later claimed invention before the effective date of the reference in order to perfect priority.
The Federal Circuit stated:
“When the issue of priority concerns the antedating of a reference, the applicant is
required to demonstrate, with sufficient documentation, that the applicant was in
possession of the later-claimed invention before the effective date of the reference.
Demonstration of such priority requires documentary support, from which factual
findings and inferences are drawn, in application of the rules and law of conception,
reduction to practice, and diligence.”

In re Steed, 802 F.3d 1311, 1316 (Fed.Cir.2015). The purpose is to determine “whether the
applicant was in possession of the claimed invention sufficiently to overcome the teachings and
effect of an earlier publication of otherwise invalidating weight.” Id., 802 F.3d at 1316. Priority of
a claimed invention therefore depends upon conception and reduction to practice. Hybritech Inc.
v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1376 (Fed. Cir. 1986); Price v. Symsek, 988 F.2d
1187, 1190 (Fed. Cir. 1993).
ANALYSIS
I.
Here, Actavis, bears the burden of proving by clear and convincing evidence that the
asserted claims 11 and 12 of the ’151 patent are invalid. Actavis advances the position that claim
11 is invalid because it is inherently anticipated by the EP ’938 reference, and claim 12 is

26

inherently obvious in view of the EP ’938 reference. However, Actavis’ invalidity defenses stand
only if the EP ’938 reference is in fact a prior art reference.
The EP ’938 reference is a prior art reference to the ’151 patent under pre-AIA 35 U.S.C.
§ 102(a) if the invention recited in claims 11 and 12 was “patented or described in a printed
publication in this or a foreign country, before the invention thereof by the applicant for patent.”
See prior law or pre-AIA 35 U.S.C. § 102(a). The claimed ‘invention’ depends upon conception
and reduction to practice. Hybritech Inc., 802 F.2d at 1376; see also Perfect Surgical Techniques,
Inc. v. Olympus Am., Inc., 841 F.3d 1004, 1015 (Fed Cir. 2016).
A pre-AIA 35 U.S.C. § 102(a) reference, unlike a pre-AIA 35 U.S.C. § 102(b) reference,
can be antedated, and thereby render the reference not a prior art reference. (See MPEP 715
“Swearing Behind a Reference – Affidavit or Declaration under 37 C.F.R. 1.131(a)”9); see also In
re Steed, 802 F.3d at 1316.
In the instant matter, Merck argued that the EP ’938 reference is not prior art because the
inventive concepts recited in claims 11 and 12 of the ’151 patent were conceived and diligently
reduced to practice on April 14, 1993, which is prior to the publication of the EP ’938 reference
(May 5, 1993). Consequently, rendering Actavis’ defenses futile. See Pl.’s FoF at ¶ 2110.
Accordingly, the Court now determines whether the earliest filing date of the ’151 patent,
December 21, 1993, can be perfected back to April 14, 1993.

9
See MPEP 715—“To antedate a reference or activity that qualifies as prior art under pre-AIA 35 U.S.C. §
102(a) and not under pre-AIA 35 U.S.C. § 102(b), e.g., where the prior art date under pre-AIA 35 U.S.C. §
102(a) of the patent, the publication or activity used to reject the claim(s) is less than 1 year prior to
applicant’s or patent owner’s effective filing date.
10
  At this reference, Merck argued that since “Actavis’s inherent anticipation and obviousness defenses
are based on its contention that EP ‘938 is prior art, both of Actavis’s defenses fail if the Court finds that
EP ‘938 is not prior art, and the Court need not address any other issue.” 

27

II.
The parties agree that the subject matter of claims 11 and 12 of the ’151 patent is
sufficiently supported by the earlier filing date of the PCT application filed on December 20, 1994;
and the U.S. patent application ’083, filed on December 21, 1993, pursuant to MPEP 211.05(B).11
(See generally JX 2; JX 2.0023-26; JX 2.0054-58; JX 2.0090-91; JX 3; JX 3.0023-26; JX 3.0056).
For the Court to determine that the claimed subject matter of claims 11 and 12 antedates
the EP ’938 reference, a pre-AIA 35 U.S.C. § 102(a) reference, Merck has the burden to show that
the inventive concepts directed to posaconazole, as recited in claim 11, and the pharmaceutical
composition, recited in claim 12, were in-fact—(i) conceived prior to the publication date the EP
’938 reference, and (ii) diligently reduced to practice soon thereafter. In re Steed, 802 F.3d at 1316;
see also Mahurkar v. C.R. Bard, 79 F.3d 1572, 1576-77 (Fed. Cir. 1996). With respect to
‘conception,’ only those inventions conceived are granted patent protection that are directed to
patent eligible subject matter. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 134 S.Ct. 2347, 2350 (2014).
A.

PATENTABILITY & CONCEPTION

It is important to note the interplay between patentability and invention. Under the U.S.
patent laws, only those inventions are patentable, or granted patent protection, that are directed to,

11
See MPEP 211.05(B): Sufficiency of Disclosure in Prior-Filed Application. Claiming the Benefit of
Nonprovisional Applications (“A continuation-in-part application may include matter not disclosed in the
prior-filed application. See MPEP § 201.08. Only the claims of the continuation-in-part application that are
disclosed in the manner provided by 35 U.S.C. 112(a) in the prior-filed application are entitled to the benefit
of the filing date of the prior-filed application. If there is a continuous chain of copending nonprovisional
applications, each copending application must disclose the claimed invention of the later-filed application
in the manner provided by 35 U.S.C. 112(a) in order for the later-filed application to be entitled to the
benefit of the earliest filing date.”).

28

“any new and useful process, machine, manufacture, or composition of matter, or any new and
useful improvement thereof.”12
“Conception is the touchstone of inventorship,” and it is the “formation in the mind of the
inventor, of a definite and permanent idea of the complete and operative invention as it is hereafter
to be applied in practice.” Burroughs Wellcome Co. v. Barr Labs., Inc., 40 F.3d 1223
(Fed.Cir.1994). An inventor conceives of an invention upon formation of “a definite and
permanent idea of the complete and operative invention.” Hybritech, 802 F.2d at 1376.
Establishing conception requires evidence that the inventor actually made the invention
and understood the invention to have the features that comprise the inventive subject matter at
issue. Invitrogen,Corp. v. Clontech Laboratories, Inc., 429 F.3d 1052, 1064 (Fed. Cir. 2005). That
is, the inventor must form a definite and permanent idea of the complete and operable invention to
establish conception. Bosies v. Benedict, 27 F.3d 539, 543 (Fed. Cir. 1994).
Generally, for conception, the inventor must have a specific idea, or particular solution
firmly in mind; however, chemical compounds have an even more stringent conception rule. For
example, in one case, the Federal Circuit divided conception for chemical compounds into two
parts—(i) the idea of a structure or formula of the chemical compound; and (ii) the possession of
an operative method of making or synthesizing the same. Oka v. Yousefeyh, 849 F.2d 581, 583
(Fed. Cir. 1988) (internal citations omitted); see also Fina Oil & Chem. Co. v. Ewen, 123 F.3d
1466, 1473 (Fed.Cir.1997); Falana v. Kent State Univ., 669 F.3d 1349, 1357 (Fed. Cir. 2012)

12

At first glance, the observation of a metabolite in the mouse may be a natural phenomenon
that is not subject to patentability; but neither party argued same. It appears the synthesizing of the
compound and developing it into a useful product is patentable. Molecular Pathology v. Myriad Genetics,
Inc., 133 S.Ct. 2107, 2116 (2013).

29

(“Conception of a chemical compound requires knowledge of both the specific chemical structure
of the compound and an operative method of making it.”).
“The idea of a structure or formula of the chemical compound”
In Oka, the Federal Circuit cited to Townsend v. Smith, 36 F.2d 292, 295 (CCPA13 1929)
to further elaborate on this two prong test to determine ‘conception.’ The Court noted that the first
prong is “‘the directing conception’ and may be defined as the idea or conception that a certain
desired result may be obtained by following a particular general plan. The directing conception is
often referred to as the inventive concept, thought or idea.” Oka, 849 F.2d at 583. That is,
“[c]onception does not occur unless one has a mental picture of the structure of the chemical, or is
able to define it by its method of preparation, its physical or chemical properties, or whatever
characteristics sufficiently distinguish it.” Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927
F.2d 1200, 1206 (Fed. Cir. 1991).
On April 14, 1993, Dr. Pramanik configured the chemical structure in his notebook of
Metabolite A after reviewing the mass spectra provided by mass spectrometrist Dr. Heimark. (See
JX 7.0001; see also Part D of the Introduction Section). In his configuration of the chemical
structure (SCH 51048 Metabolite), Dr. Pramanik provided substantial detail and specificity of the
SCH 51048 metabolite. That is, Dr. Pramanik drew out—(i) all the components of the azole core,
(ii) all the components of the piperazine linker, (iii) all the components of a side chain; and (iv)
where the side chain is attached to the piperazine linker.
In the azole core and the piperazine linker, Dr. Pramanik was specific with respect to the
bonds (single or double bonds) between the different chemical elements (i.e., Nitrogen (N),
Fluorine (F), Oxygen (O), Hydrogen (H), and Carbon (C)) that formed the azole core and the

13

CCPA refers to the former Court (U.S. Court of Customs and Patent Appeals) which was reconstituted into
the United States Court of Appeals for the Federal Circuit. 96 Stat. 25 (1982).

30

piperazine linker. Additionally, he unambiguously noted the bond orientation; drawing dashed
lines in the azole core to represent accurate three-dimensional configuration. The dashed lines
depict bonds extending toward the reader, and the solid wedge-shaped lines depict bonds extending
away from the reader. (See Def.’s Br. at 4-5; D.I. 162). And, lastly, with respect to the hydroxyl
group, OH, in the side chain, he was specific to connect it to a particular location of the piperazine
linker.
Dr. Pramanik discussed his findings with Drs. Giri and Saksena the very same day, April
14, 1993. In this meeting, it was determined that there are seven possibilities for the chemical
structure, which included two primary alcohols, four secondary alcohols, and one tertiary alcohol.
(See Pl.’s FoF at ¶¶ 121-124). The tertiary alcohol was quickly ruled out during this meeting, and
they collectively decided to synthesize and test each of the six alcohols to determine which one of
the six had antifungal activity. (See Pl.’s FoF at ¶ 127; citing Trans. at 476:13-20 (Saksena);
1145:21—1146:2 (Giri); and 1337:25—1338:2 (Glick)).
During this meeting on April 14, 1993, Drs. Giri and Saksena (inventors of the ’151 patent)
had conceived of the chemical structure or formula of a potential antifungal drug that would result
in posaconazole. In other words, Schering perceived that the OH, or hydroxyl group, was included
in the side chain that was attached to the piperazine linker. And, wherein one of the six possible
configurations constituted the chemical structure of posaconazole. (See Pl.’s FoF at ¶ 180). All
that was required hereon was to perform testing to determine which stereoisomer would provide
activity against fungal agents, both in vivo and in vitro, and thereby be developed into a marketable
drug.
Moreover, Actavis agrees that the structure of posaconazole was conceived on April 14,
1993. (See Def.’s FoF at ¶ 23 (citing Trans. at 412:7-10 (Pramanik); “[t]here is no dispute that it

31

was Dr. Pramanik, not named inventors Dr. Saksena or Dr. Giri, who first conceived of the
structure of posaconazole”); see also Def.’s Br. at 4-5)14. Accordingly, the Court finds that the
chemical structure or formula of the chemical compound posaconazole, was perceived on April
14, 1993 as memorialized in Dr. Pramanik’s lab notebook.
In Oka, the Federal Circuit, again citing to Townsend, noted that the second part of
conception is “the selection of the means for effectively carrying out the directing conception.”
Oka, 849 F.2d at 583. That is, the inventor must show it had an operative method of making or
synthesizing the compound. The Court noted that when “a method of making a compound with
conventional techniques is a matter of routine knowledge among those skilled in the art, [in which
case] the compound has been deemed to have been conceived when it was described, and the
question of whether the conceiver was in possession of a method of making it is simply not raised.”
Id.; see also Burroughs Wellcome Co., 40 F.3d at 1230.
In other words, ‘operable route’ can be shown by satisfying either an objective standard or
a subjective standard. The subjective standard requires a showing of independent, corroborated
evidence that the inventors actually possessed an operative method of making the chemical
compound. Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1171-72 (Fed. Cir. 2006). Whereas,
the objective standard requires a showing of evidence that “a method of making the compound
with conventional techniques [was] a matter of routine knowledge among those skilled in the art.”
Oka, 849 F.2d at 583-84; see also Def.’s Reply at ¶¶ 12-30; Pl.’s Reply at ¶¶ 12-33). From a
review of the evidence, the Court finds that Merck has shown the subjective standard has been
met15.

14

The argument of improper inventorship of the ’151 patent pursuant to pre-AIA 35 U.S.C. § 102(f)
is not raised as a defense in the invalidity contentions. 
15

Where there is no corroborated evidence one can demonstrate that the inventor actually possessed
an operative route to produce a compound, by showing that “method of making a compound with

32

With respect to the subjective standard, because conception is a mental act, courts require
corroborating evidence, such as contemporaneous documentation testimony, which would enable
a POSA to make the invention. Burroughs Wellcome, 40 F.3d at 1228.
The requirement of independent knowledge remains key to the corroboration inquiry, and
such corroboration “must not depend solely on the inventor himself.” See Reese v. Hurst, 661 F.2d
1222, 1225 (CCPA 1981). “Independent corroboration may consist of testimony of a witness,
other than the inventor, to the actual reduction to practice or it may consist of evidence of
surrounding facts and circumstances independent of information received from the inventor.” Id.
One consequence of the independence requirement is that the testimony of one co-inventor cannot
be used to help corroborate the testimony of another. Lacks Indus. v. McKechnie Vehicle
Components USA, Inc., 322 F.3d 1335, 1350 (Fed. Cir. 2003).
Nevertheless, “[t]he law does not impose an impossible standard of ‘independence’ on
corroborative evidence by requiring that every point of a reduction to practice be corroborated by
evidence having a source totally independent of the inventor....” Cooper v. Goldfarb, 154 F.3d
1321, 1330 (Fed. Cir. 1998) (internal quotations omitted). Similarly, “it is not necessary to produce

conventional techniques is a matter of routine knowledge among those skilled in the art.” Oka, 849 F.2d
at 583. This is an objective test that looks to the knowledge of “those skilled in the art”—i.e., public
information available to POSA. Creative Compounds, LLC v. Starmark Labs., 651 F.3d 1303, 1312-13
(Fed. Cir. 2011); Falana v. Kent State Univ., 669 F.3d 1349, 1358 (Fed. Cir. 2012) (equating the
“routine” nature of a synthesis with the “basic exercise of normal skill expected of one skilled in the art”).
Merck attempts to show same by arguing a POSA would have had the knowledge to make
posaconazole, in particular posaconazole’s azole core. (See Pl.’s FoF at ¶ 169; see also Def.’s FoF at ¶ 46
(citing Trans. at 702:19—703:2 (Dolle) (“A [POSA] would have known how to synthesize that left hand
piece […] That is the basis of a patent by Schering-Plough a couple of years earlier, I believe we referred
to it here as the ’676 patent.”); see also Trans. at 705:21-25 (Dolle) (“The piperazine core was wellknown in the prior art [in 1993].”).
Here, the Court refrains from delving into the objective inquiry as to whether “method of making
a compound with conventional techniques is a matter of routine knowledge among those skilled in the
art.” Oka, 849 F.2d at 583. Merck’s burden was to satisfy either the objective standard or the subjective
standard. Id.; see also Medichem, S.A., 437 F.3d at 1171-72. As discussed herein, there is sufficient
independent, corroborating evidence showing that the inventors of the ’151 patent actually possessed an
operative method of making the subject matter of claims 11 and 12.

33

an actual over-the-shoulder observer. Rather, sufficient circumstantial evidence of an independent
nature can satisfy the corroboration requirement.” Id.
Here, Actavis argues that Merck has presented no corroborated evidence that the inventors
actually possessed an operative method of synthesizing posaconazole on April 14, 1993. In a
nutshell, Actavis argues the following—(i) testimony of inventors Drs. Giri and Saksena is
insufficient as a matter of law to support its contention that inventors actually possessed an
operable method of making posaconazole. (see Def.’s Reply at ¶ 26); (ii) the synthesis
contemplated by the inventors on April 14, 1993, was of SCH-55801 (a racemic mixture), and not
posaconazole itself—the subject matter of claim 11 (id. at ¶ 28); (iii) Dr. Bennett, and not Mr.
Lovey, performed the first synthesis of posaconazole in August 1993 (id. at ¶ 29); (iv) prosecution
history of the ’151 patent dictates that the inventors limited the claim scope of claim 11 to a specific
compound with specific stereochemistry, i.e., the single posaconazole stereoisomer (id. at ¶ 30);
and (v) the racemic mixtures made by Mr. Lovey did not contain any posaconazole, as testified by
Mr. Lovey on one occasion, but who testified differently on another. (id. at ¶ 31).
Actavis provides Dr. Glick’s testimony that more than routine skill and conventional
techniques are required to synthesize posaconazole. (See Def.’s FoF at ¶ 37 (citing Trans. at
511:23—512:12 (Saksena); 1302:24—1303:22 (Glick)). Dr. Glick testified that posaconazole is a
large, complex molecule, which is further complicated by the presence of four stereocenters. And
because of its size and complexity, the synthesizing of posaconazole requires twenty-six (26)
separate chemical reactions, as shown below—

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(Id. at ¶ 38).
Dr. Glick further testified that it took Schering scientists years of experimental work, and
numerous failures, before they could configure out a way to synthesize the posaconazole
compound. (Id. at ¶ 39). One part that was particularly challenging was synthesizing the azole core
(“28R”), which contained the weakest step in the entire sequence because the problems with
synthesizing the azole core just did not go away. (Id. at ¶ 40 (citing “Schering’s President’s Award
for Scientific/Technical Achievement” (the “Nomination Memo”) (JX 44.0016-18)).
The Nomination Memo seeks an internal Schering award for the work that the Schering
scientists did in the antifungal program for over a decade, starting in the 1980s with their synthesis
of analogs based on ketoconazole, to their development of the tetrahydrafuran family of triazole
compounds in the early 1990s. (See Pl.’s FoF at ¶ 145). Prior to May 5, 1993, the chemistry that
Schering had developed, which is described in the Nomination Memo, had not been published and
not available to a POSA on April 14, 1993. (See Def.’s FoF at ¶ 42).
With respect to the side chain, Dr. Glick testified that making the side chain and attaching
the same to the piperazine linker would have been much easier, and even routine, for a POSA. (Id.
at ¶ 48 (citing Trans. at 1304:19—1305:2, 1305:12—1306:14, 1309:12-14)).
35

In opposition, Merck contends that Dr. Giri, Dr. Saksena, and Mr. Lovey had extensive
experience working on related antifungal compounds, including ones with an azole core and
piperazine links prior to April 14, 1993, as they were skilled chemists. (See Pl.’s FoF at ¶¶ 136137). Antifungal compounds that included an azole core and a piperazine linker. In support, Merck
relies on Dr. Giri’s testimony which is corroborated by internal Schering documents (i.e., the
Nomination Memo), and Dr. Giri’s history of working on compounds like posaconazole. (Id. at ¶
144).
Merck purports that when the inventors of the ’151 patent conceived the structure of
posaconazole on April 14, 1993, they already knew how to make SCH-51048, since they disclosed
the same on October 28, 1992 (filing date of the EP ‘938 reference), and they had extensive
experience working on similar compounds. (Id. at ¶¶ 136-137). The EP ’938 reference is a
contemporaneous disclosure corroborating that the inventors knew how to make the azole core and
the piperazine linker. The lack of publication of the EP ‘938 reference is immaterial to inventor’s
state of mind.
The Court finds Merck’s arguments persuasive that on April 14, 1993, there was substantial
corroborating evidence, such as contemporaneous documentation and testimony, to show that the
inventors of the ’151 patent had an ‘operable route’ to synthesizing posaconazole.
The inventors of the ’151 patent already knew how to make the azole core and piperazine
linker as of April 14, 1993. This is evidenced by the fact that—(i) Compound IIc or SCH-51048
and posaconazole of the ’151 patent have the same azole core and piperazine linker, the two most
complicated components of posaconazole as testified by Dr. Glick, (ii) the EP ’938 reference
shares the same inventors as the ’151 patent (i.e., Dr. Saksena, Ashit Ganguly and Mr. Lovey),
although different inventive entity, which was assigned to Schering; and (iii) the EP ’938 reference

36

discloses how to synthesize the azole core and the piperazine linker. (See Pl.’s FoF at ¶¶ 135-138).
That is, the fact that Schering scientists experimented with drugs involving antifungal drugs for
number of years, shows strong corroborating evidence that the inventors of the ’151 patent had the
knowledge, familiarity and understanding to synthesize the azole core and the piperazine linker
prior to the filing of the EP ’938 reference in 1992. Combining this with the years of experimental
work by Schering, there is substantial corroborative evidence that inventors of the ’151 patent had
the operative route or method of making posaconazole on April 14, 1993. Moreover, Schering
scientists had the knowledge of such synthesis for years, but it may not have become available to
the rest of the scientific community until May 5, 1993 (the publication date of the EP ’938
reference).
The years of work done by Schering in developing antifungal drugs is evidenced by the
Nomination memo. This memo shows that Dr. Giri, Dr. Saksena, and Mr. Lovey, among others,
were familiar with the synthesis of the azole core and the piperazine linker, as they had made them
during the course of the antifungal program. (See Pl.’s FoF at ¶ 145).
The Nomination memo addresses the problems with conventional drugs for treating
antifungal activity, and what were the objectives of achieving a novel antifungal agent with broadspectrum activity. (See JX 44.0002-0004). Further, the memo notes that, interestingly, SCH-51048
was found to be more active in vivo than its counterpart analog. Consequently, existing efforts
were redirected in support of SCH-51048. (Id. at 44.0017-18).
Schering scientists experienced synthetic problems in formulating SCH-51048, which
required an extremely challenging and novel chemistry to make the azole core (“28R”). (Id.). And,
because no examples existed in the literature for formulating the same, Schering scientists
undertook two approaches. The first approach was not promising; however, the second approach

37

was ‘close to a breakthrough’ (Id. at 44.0020). The second approach required numerous chemical
reactions, as outlined in Schemes VII & VIII, to achieve the desired chemical structure. (Id. at
44.22-25). The memo concludes by stating the following—
“We have described here a significant effort leading to the discovery of Sch 51048,
a potent antifungal agent in advanced stages of preclinical development. Its
excellent broad spectrum activity (P.O.) and superiority over most existing
(synthetic) antifungal agents has been confirmed by our outside investigators. Sch
51048 is by far the best compound in the prophylactic treatment protocol against
Candida infection model. We believe this has placed Schering-Plough well ahead
of our competition.”
(Id. at 44.0034).
The Nomination memo provides corroborative evidence to Dr. Giri’s testimony that he,
and other Schering scientists, knew how to synthesize the six alcohols, including posaconazole, on
April 14, 1993. Furthermore, having this knowledge in hand, Drs. Giri and Saksena were able to
direct Mr. Lovey with the synthetic steps to make the racemates or racemic mixtures. As discussed
above, Mr. Lovey’s five-step synthesis of SCH-55801, which started on April 26, 1993 and
completed by May 26, 1993, included—(i) dihydroxylation of 2-pentene (step 1); (ii) protection
of 2,3-pentanediol (step 2); (iii) sulfonation of SEM protected 2,3 pentanediol (step 3); (iv)
coupling of triazole core (step 4); and (v) deprotection to remove SEM protecting group, yielding
posaconazole and its enantiomer (step 5). (See PX 1010; Pl.’s FoF at ¶ 182-183).
Dr. Giri, Dr. Saksena, and Mr. Lovey had the general plan or the operable route in hand
that constituted the method of making posaconazole. However, Actavis raises an interesting
argument that what Mr. Lovey synthesized on May 26, 1993, is not posaconazole, the subject
matter of claim 11. Instead, Mr. Lovey’s synthesis was a racemic mixture, which did not include
pure posaconazole, the subject matter of claim 11. (See Def.’s Reply at ¶¶ 23-24).

38

Actavis also notes that Mr. Lovey stated in one of his depositions that he did not make
posaconazole, but in other depositions he noted that he had posaconazole in a racemic mixture.
Further, in support of its argument, Actavis cites to the inventors’ statements made during the
prosecution of the ’151 patent, where inventors stated that claim 11 may cover the single
stereoisomer posaconazole and not a racemic mixture containing posaconazole and one or more
other stereoisomers. (Id. at ¶ 24; citing DTX-27_205). However, Actavis does not dispute that Mr.
Lovey was asked to make posaconazole as a 1:1 mixture with the R,R isomer (i.e., SCH-55801).
(See Pl.’s Reply at ¶ 18 (citing Def.’s FoF at ¶ 26)).
Merck agrees that in the course of making this amendment, the applicants stated that the
claims have been amended “to cover a specific compound with specific stereochemistry.” (See
Pl.’s Reply at ¶ 33; citing DTX 27_025). However, Merck notes that claim 11 does not restrict the
claim to posaconazole in a pure form. And, as such, a racemic mixture that contains posaconazole
could potentially read on claim 11. (Id. at ¶ 33).
Actavis’ argument that claim 11 is directed to ‘pure’ posaconazole, and in turn avoids a
racemic mixture that includes posaconazole is unpersuasive. Granted, statements made by the
Applicant to the Patent Office characterizing his or her invention may give rise to prosecution
disclaimer, which is part of the intrinsic evidence. Hockerson-Halberstadt, Inc. v. Avia Group
Int’l, Inc., 222 F.3d 951, 957 (Fed. Cir. 2000); see also Phillips v. AWH Corp., 415 F.3d 1303,
1313 (Fed. Cir. 2005). However, here, fair reading of the statement does not limit scope of claim
11 to only ‘pure’ posaconazole. Moreover, and more importantly, the corroborative evidence of
the contemporaneous disclosure of the EP ’938 reference indicating the inventors knew how to
make the azole core and the piperazine linker, demonstrates that specific instructions on how to
synthesize the different alcohols was within the minds of the inventors on April 14, 1993.

39

Applicants’ statement that the amended claim 11 “covers a specific compound with
specific stereochemistry,” does not exclude a racemic mixture, such as SCH-55801, because such
formulation includes a specific compound (i.e., posaconazole and an isomer) with specific
stereochemistry (i.e., S,S and R,R). As shown below, SCH-55801 has a specific compound and
specific stereochemistry that is different from the other racemic mixtures such as SCH-55803, for
example.

(See Pl.’s FoF at ¶ 180). As such, the Court notes that claim 11 covers both, a pure posaconazole
compound and a racemic mixture that includes posaconazole.
Accordingly, based on the foregoing reasons, the Court is satisfied that Merck met its
burden of producing independent, corroborated evidence, which shows that the inventors of the
’151 patent actually possessed an operative method of making the subject matter recited in claims
11 and 12.
Accordingly, the Court finds that Merck has satisfied the subjective inquiry by showing
that there was independent, corroborating evidence available to the inventors on April 14, 1993,
40

such that they had an ‘operable route’ or method of synthesizing posaconazole and a
pharmaceutical composition containing the same.
In conclusion, with respect to the ‘conception’ inquiry, the Court finds that the inventors
of the ’151 patent—(i) had the idea of a structure or formula of posaconazole and pharmaceutical
composition containing the same on April 14, 1993, and (ii) the possession of an operative method
of making or synthesizing the same was also present on April 14, 1993.
B.

DILIGENTLY REDUCING TO PRACTICE
i.

REDUCTION TO PRACTICE

There are two types of reduction to practice—(i) constructively, by filing a patent
application; and (ii) actually, by building and testing a physical embodiment of the invention. If
the inventor relies on a constructive reduction to practice, the filed application must fully disclose
the invention. Travis v. Baker, 137 F.3d 109, 111 (CCPA 1943); Hybritech, 802 F.2d 1367, 1376
(Fed. Cir. 1986). Whereas, an actual reduction to practice must show that the invention works for
its intended purpose in the actual environment of its use. Scott v. Finney, 34 F.3d 1058, 1062 (Fed.
Cir. 1994).
In Scott, the Court explained:
“the testing requirement depends on the facts of each case, with the court guided
by a common sense approach in weighing the sufficiency of the testing. Reduction
to practice does not require that the invention, when tested, be in a commercially
satisfactory stage of development. Testing need not show utility beyond a
possibility of failure, but only utility beyond a probability of failure. When
reviewing the sufficiency of evidence of reduction to practice, this court applies a
reasonableness standard.”
Scott, 34 F.3d at 1061-62 (quotations and citations omitted).
On some occasions conception and reduction to practice occur simultaneously. Alpert v.
Slatin, 305 F.2d 891, 894 (CCPA 1962); Amgen, Inc., 927 F.2d at 1207. “[I]n some unpredictable

41

areas of chemistry and biology, there is no conception until the invention has been reduced to
practice.” MacMillan v. Moffett, 432 F.2d 1237, 1234-40, 167 USPQ 550, 552-553 (CCPA 1970).
Here, the constructive reduction to practice of the subject matter recited in claims 11 and
12 was accomplished on December 21, 1993, the filing date of the earliest parent application from
which the patent application of the ’151 patent claims priority. As such, the constructive reduction
to practice took place on December 21, 1993.
Whereas actual reduction to practice of claim 11 took place on April 14, 1993, when
inventors of the ’151 patent discovered the hydroxyl or OH group on the side chain of metabolite
A. This hydroxyl group was missing from the parent compound, Compound IIc or SCH 51048.
The Court finds that the reduction to practice of posaconazole was envisioned on April 14, 1993,
but some further testing and analysis was required on part of Schering’s scientists to determine
and confirm which one of the six alcohols had adequate antifungal activity such that it could be
commercially used. Although such further testing and analysis is not a requirement for showing
actual reduction to practice. (Scott, 34 F.3d at 1061-62). It was a prudent practice to confirm same
through more in depth analysis.
Accordingly, the Court finds that the subject matter recited in claim 11 was actually
reduced to practice on April 14, 1993.
With respect to claim 12, which depends from claim 11, it requires a pharmaceutical
composition comprising an antifungally effective amount of the posaconazole compound of claim
11 with a pharmaceutically acceptable carrier. In the Markman opinion, the Court defined
“pharmaceutical composition” to mean—“formulation of at least one active ingredient with a
substance or collection of substances capable of being combined with the at least one active
ingredient;” and “pharmaceutically acceptable carrier” to mean—“substance or collection of

42

substances capable of being combined with an active ingredient that is suitable for use in contact
with the tissues of mammals for purposes of a therapeutic treatment in the mammals under
anticipated exposure conditions.” (See Memorandum & Order at p. 19; D.I. 164) As such, the
subject matter of claim 12 requires that the composition consisting of posaconazole is suitable for
use in contact with the tissues of mammals in order to provide a therapeutic treatment in the
mammals under anticipated exposure conditions.
Since the inventors of the ’151 patent were not certain that the posaconazole compound
conceived on April 14, 1993, can be used for its intended purpose in the actual environment of its
use, which is for treating antifungal activity and commercializing the same, further testing and
analysis was required. Scott, 34 F.3d 1058.
It is necessary to decide when the actual reduction to practice occurred. The Court finds
that on April 14, 1993, Mr. Lovey was tasked by Dr. Giri and Dr. Saksena to synthesize the racemic
mixture containing posaconazole and its corresponding (R,R) stereoisomer. (See Def.’s FoF at ¶
26). Mr. Lovey employed a five-step synthesis of SCH-55801 starting on April 26, 1993, and
completed the work by May 26, 1993. With respect to synthesizing pure posaconazole compound,
SCH-56592, Dr. Bennett began his synthesis of pure posaconazole on June 30, 1993, and
completed the synthesis on August 20, 1993. (Pl.’s FoF at ¶¶ 161-164).
Since claim 11, which is incorporated in claim 12, applies to both—(i) a racemic mixture
that contains posaconazole; and (ii) pure posaconazole—both dates, May 26, 1993 and August 20,
1993, apply as to the actual reduction to practice of the subject matter recited in claim 12.
The Court recognizes that the aforementioned two dates occur after the publication date of
the EP ’938 reference (May 5, 1993). Merck has shown by substantial evidence that prior to the
May 5, 1993 publication date of the EP ’938 reference, that the reduction to practice at a later date

43

is coupled with due diligence (discussed below) from the conception date of April 14, 1993. (See
MPEP 715 “Swearing Behind a Reference – Affidavit or Declaration under 37 CFR 1.131(a). See
also Rieser v. Williams, 225 F.2d 419, 423 (CCPA 1958)
Accordingly, the Court determines that the subject matter recited in claim 12 was actually
reduced to practice on May 26, 1993 and August 20, 1993.
ii.

DILIGENCE

While diligence naturally depends on the factual circumstances, it requires persistent work
from conception to reduction to practice. The diligence relates to reasonable “attorney-diligence”
and “engineering-diligence.” Keizer v. Bradley, 270 F.2d 396, 397 (CCPA 1959). Once the
invention has been conceived, the patent holder must show reasonable diligence from just prior to
the competing reference’s effective date until the date of the invention’s reduction to practice.
Perfect Surgical, 841 F.3d at 1007 (citing Monsanto Co. v. Mycogen Plant Sci., Inc., 261 F.3d
1356, 1363 (Fed. Cir. 2001)). “The party chargeable with diligence must account for the entire
period during which diligence is required.” Gould v. Schawlow, 363 F.2d 908 (CCPA 1966)
(Merely stating that there were no weeks or months that the invention was not worked on is not
enough).
Here, with respect to claim 11, diligence is not an issue because posaconazole was
conceived and simultaneously reduced to practice on April 14, 1993. Whereas, with respect to
claim 12, the Court finds that Schering was diligent in reducing to practice the subject matter of
claim 12. Based on the evidence presented before the Court, there were no gaps in the record that
would allow one to question diligence on part of the inventors of the ’151 patent.
For example, Mr. Lovey’s five-step synthesis of SCH 55801 started on April 26, 1993, and
was completed by May 26, 1993. (See Pl.’s FoF at ¶ 154). Similarly, Dr. Bennett began his

44

synthesis of pure posaconazole on June 30, 1993, and completed the synthesis on August 20, 1993.
(Id. at ¶ 161).
Actavis raises concerns that inventors of the ’151 patent were not diligent because they
were not focused specifically on posaconazole. Instead, the inventors were simply just concerned
about synthesizing and testing numerous compounds, which did not include posaconazole. (Def.’s
FoF at ¶¶ 48-50). The Court does not find Actavis’ arguments persuasive because by its own
admission it agrees that Dr. Pramanik identified posaconazole as a potential active metabolite of
SCH 51048. (See Def.’s Br. at 4-5). This was taken under consideration by Dr. Giri and Dr.
Saksena, senior chemists in charge of the antifungal program, who immediately delegated tasks to
Mr. Lovey to synthesize the racemic mixtures. (Def.’s FoF at ¶¶ 25-26). From thereon out, Mr.
Lovey synthesized racemic mixtures on May 26, 1993, and Dr. Bennett’s synthesis of pure
posaconazole on June 30, 1993. Merck has shown that reasonable diligence was undertaken from
the date of conception, April 14, 1993, to reduction to practice—May 26, 1993 (racemic mixtures)
and August 20, 1993 (pure posaconazole).
Accordingly, the Court determines that the inventors of the ’151 patent were diligent in
reducing to practice the subject matter recited in claim 12.
III.
The Court finds that Merck has successfully met its burden in establishing that the
inventors of the ’151 patent conceived the subject matter recited in claims 11 and 12 on April 14,
1993, and diligently reduced the inventions to practice soon thereafter.
Because the EP ’9387 reference is a pre-AIA 35 U.S.C. § 102(a) reference, and not a §
102(b) reference, Merck can successfully antedate this reference and render it not a prior art

45

reference. See In re Steed, 802 F.3d at 1316; see also MPEP 715 “Swearing Behind a Reference –
Affidavit or Declaration under 37 C.F.R. 1.131(a).”
As such, since the Court finds that Merck can successfully antedate the EP ’938 reference,
Actavis’ both invalidity contentions—(i) inherent anticipation under pre-AIA 35 U.S.C. § 102(a)
with respect to claim 11; and (ii) obviousness under pre-AIA 35 U.S.C. § 103(a) with respect to
claim 12, lack merit.
ORDER
IT IS on this 28th day of September, 2017,
ORDERED that claim 11 of the 5,661,151 (“the ’151 patent”) patent is not invalid under
pre-AIA 35 U.S.C. § 102(a); and it is further
ORDERED that claim 12 of the ’151 patent is not invalid under pre-AIA 35 U.S.C. §
103(a).

s/Peter G. Sheridan
PETER G. SHERIDAN, U.S.D.J.

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