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

Filing 118

MEMORANDUM & ORDER denying without prejudice 89 Motion for Partial Summary Judgment. Signed by Judge Peter G. Sheridan on 3/6/2017. (mmh)

UNITEDD STATES DISTRICT COURT
FOR THE DISTRICT OF NEW JERSEY

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

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

MEMORANDUM
&
ORDER

SHERIDAN, U.S.D.J.
This matter comes before the Court on plaintiff Merck Sharp & Dohme Corp.’s (“Merck”)
motion for partial summary judgment on defendant Actavis Laboratories FL, Inc., Andrx Corp.,
and Actavis Pharma, Inc.’s (collectively “Actavis”) inherent anticipation defense to claim 12 of
U.S. Pat. 5,661,151 (the “’151 patent”) (see Dkt. No. 89). The ’151 patent is directed to synthesis
and clinical use of an antifungal compound, posaconazole, which is used for treating and/or
preventing fungal infections.
Merck argues that because claim 12 is directed to a “pharmaceutical composition,” instead
of a “compound,” the aforementioned claim cannot be inherently anticipated by the prior art
reference, European Patent Application 0539938 A1 (“EP ’938”), as a matter of law. In response,
Actavis asserts that—(i) the compound (compound IIc) disclosed in the EP ’938 reference is
“extremely close” to the posaconazole compound in the ’151 patent; and (ii) the Court should not
undertake an inherent anticipation analysis until the claim terms “pharmaceutically acceptable
carrier” and “pharmaceutical composition” are construed in a Markman hearing.
Based on the arguments presented on the record, intrinsic and extrinsic evidence submitted
before the Court, the Court denies Merck’s partial summary judgment motion as being premature.

BACKGROUND
The ’151 Patent

I.

The ’151 patent, entitled “Tetrahydrofuran Antifungals,” issued on August 26, 1997, to
Saksena, et al., and assigned to Schering Corporation, has a potential earliest priority date of
December 21, 1993.1 The ’151 patent is generally directed to the synthesis and clinical use of the
antifungal compound, posaconazole, which is used to treat fungal infections. (see abstract of the
’151 patent). In its background section, the ’151 patent cites to prior art reference EP ’938 as
disclosing a group of antifungal compounds which have a “C1-C10 alkyl” side chain groups. (see
Actavis’ Invalidity Contentions, p. 5, citing the ’151 patent, col. 2:10-17; Dkt. No. 89-4).
The ’151 patent discloses that compounds represented by formula I exhibit broad spectrum
antifungal activity against human and animal pathogens. The antifungal compounds of formula I
and pharmaceutical compositions are expected to exhibit anti-allergic, anti-inflammatory and
immunomodulating activities. The pharmaceutical composition also contains a fungicidally
effective amount of other antifungal compounds such as cell wall active compound. (Id. at col. 56,
ll. 40-55).
Further, the pharmaceutical compositions disclosed may be adapted for any mode of
administration e.g., for oral, parenteral, e.g., SC, IM. IV and IP, topical or vaginal administration
or by inhalation (orally or intranasally). Such 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
compositions include solid or liquid compositions for oral administration such as tablets, capsules,

The ’151 patent is a continuation-in-part of PCT/US94/14236, Dec. 20, 1994, which is a continuation-in-part of Ser.
No. 171,083, Dec. 21, 1993. (see Manual of Patent Examining Procedure (“MPEP”) 1895.01; 35 U.S.C. § 365(c)
(“Pursuant to 35 U.S.C. 365(c), a regular national application filed under 35 U.S.C. 111(a) and 37 CFR 1.53(b) [] may
claim benefit of the filing date of an international application which designates the United States.”))
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pills, powders, granules, solutions, suppositories, troches, lozenges, suspensions or emulsions. (Id.
at col. 57, ll. 40-50).
With regards to “pharmaceutically acceptable carrier,” the ’151 patent discloses that a solid
carrier can be one or more substances that may act as, for example, diluents, flavoring agents,
solubilizers, or encapsulating material. Whereas, the carrier can also be a finely divided solid
which is in admixture with the finely divided active compound. (Id. at col. 57, ll. 45-55).
Lastly, the ‘151 patent includes a total of 13 claims, wherein claims 1 and 11 are in
independent form. Claim 11 recites a compound which is represented by a chemical formula, and
claim 12 is directed to a pharmaceutical composition that depends from claim 11.
II.

The EP ’938 Reference
The EP ’938 reference, which was published on May 5, 1993, is a prior art reference to the

’151 patent under pre-AIA (America Invents Act) 35 U.S.C. § 102(a).2 The EP ’938 reference
discloses the synthesis, formulation and use of several azole class antifungal agents, which are
used to treat systematic fungal infections, especially Aspergillus and Candida infections. (see EP
’938 at p. 3, ll. 1-25).
EP ’938 discloses that preferred antifungal compounds represented by formulas IIa, IIb and
IIc are more active orally against Aspergillus flavus pulmonary infections in an in vivo mouse
model than itraconzale, fluconzale and saperconazole. (Id. at p. 8, ll. 10-15). The antifungal
compounds of formula I and pharmaceutical compositions of this invention are expected to exhibit
anti-allergic, anti-inflammatory and immunomodulating activities, broad spectrum anti-infective
activity, e.g., antibacterial, anti-protozoal and anti-helminthic activities. The present invention

See MPEP 2132.01(I) (“A prima facie case is made out under pre-AIA 35 U.S.C. 102(a) if, within 1 year of the
filing date, the invention, or an obvious variant thereof, is described in a “printed publication” whose authorship
differs in any way from the inventive entity unless it is stated within the publication itself that the publication is
describing the applicant’s work.” (internal citations omitted))
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also provides a composition for treating or preventing fungal infections comprising an antifungal
effective amount of a compound represented by formula I or a pharmaceutically acceptable salt
thereof, and a pharmaceutically acceptable carrier or diluent. (Id. at p. 15, ll. 5-10). Further, EP
’938 discloses that the pharmaceutical compositions may be adapted for oral, parenteral, topical
or vaginal administration. They 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 compositions include solid or
liquid compositions for oral administration such as, for example, tablets, capsules or pills. (Id. at
p. 16, ll. 20-25).
To prepare a pharmaceutical composition, a pharmaceutically acceptable carrier, e.g.,
hydroxypropyl-β-cyclodextrin, may be admixed in water together with an antifungal effective
amount of a drug. (Id. at p. 16, ll. 50-55).
III.

Actavis’s Expert Reports
Dr. Gary D. Glick, PH.D., expert for Actavis, asserts in his report that claim 12 of the ’151

patent, under the plain and ordinary meaning of “pharmaceutically acceptable carrier,” is
inherently anticipated by the disclosure of EP ’938 reference because the formation of
posaconazole in mice occurs in the presence of a pharmaceutically acceptable carrier. (“Glick’s
Report” at ¶ 1; see Dkt. No. 104). Dr. Glick states that EP ’938 discloses several experiments in
which compound IIc was administered to mice and hamsters in order to treat fungal infections.
And, even though EP ’938 does not provide quantitative results for compound IIc, it states that
compound IIc was used in the same animal models and gives qualitative results for those
experiments. (Id. at ¶ 90). In relying on a secondary reference (‘Nomeir 2008’), Dr. Glick contends
that the amount of posaconazole present in the blood would be considered an antifungal effective

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amount due to (i) posaconazole’s known antifungal activity; and (ii) the disclosure of this
secondary reference (Nomier 2008), which states that the formation of secondary alcohol
metabolites in vivo resulted in a prolongation of the antifungal activity. (Id. at ¶ 99).
Further, Dr. Glick states in his opinion a person of ordinary skill in the art would have
understood as of 1993 that blood, and components of blood, e.g., water or sale, are
‘pharmaceutically acceptable carrier[s].’ (Id. at ¶ 101). Lastly, in his reply, Dr. Glick states that
because posaconazole was formed within the mice together with at least one pharmaceutically
acceptable carrier, claim 12 is inherently anticipated by EP ’938.
Next, in Dr. Paul R. Ortiz De Montellano, PH.D, also an expert for Actavis, contends that
when a certain compound disclosed by EP ’938, e.g., Compound IIc or SCH-51048, is dosed to
male CF-1 mice, according to the method described therein, posaconazole is inevitably formed via
metabolism. (“Monetllano’s Report” at ¶ 3-4; see Dkt. No. 104). In his report, Dr. Monetllano
provides the findings of his experiment conducted on parent drug compound (SCH-51048), which
is incubated with liver microsomes prepared from a target male (a male CF-1 mice). (Id. at ¶ 21).
Based on his laboratory experiments, which were conducted at the University of California at San
Francisco, Dr. Monetlano concluded that data collected demonstrated that posaconazole was
formed when SCH-51048 is incubated in vitro with liver microsomes prepared from male CF-1
mice. (Id. at ¶ 42).
IV.

Claim Construction
Pursuant to L. Pat. R. 4.3, the parties submitted a Joint Claim Construction and Prehearing

Statement to the Court on July 27, 2016. In their joint claim construction brief, the parties disputed
the meaning of the claim terms “pharmaceutically acceptable carrier” and “pharmaceutical

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composition,” as recited in claim 12. In particular, the parties asserted that the aforementioned
claim terms should be construed as follows:

(See First Amended Joint Claim Construction and Prehearing Statement; Dkt. No. 53-1).
However, in Merck’s response to statement of material facts not in dispute pursuant to local
rule 56.1, Merck stipulates Actavis’s position that the claim terms “pharmaceutically acceptable
carrier” and “pharmaceutical composition,” as recited in claim 12, can be understood in accord
with its plain meaning and, accordingly “requires no construction.” (See Merck’s Response to
Material Facts, “Fact No. 1” and “Fact No. 3;” Dkt. No. 109-1). As such, for purposes of this
motion, Merck concedes and adopts Actavis’s interpretation of the aforementioned claim terms.
(See Merck’s Reply Br. at 7).
LEGAL STANDARD
Fed. R. Civ. P. 56
Summary judgment is appropriate under Fed. R. Civ. P. 56(c) when the moving party
demonstrates that there is no genuine issue of material fact and the evidence establishes the moving
party’s entitlement to judgment as a matter of law. Celotex Corp. v. Catrett, 477 U.S. 317, 32223 (1986). A factual dispute is genuine if a reasonable jury could return a verdict for the non6

movant, and it is material if, under the substantive law, it would affect the outcome of the suit.
Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 248 (1986).
In considering a motion for summary judgment, a district court may not make credibility
determinations or engage in any weighing of the evidence; instead, the non-moving party’s
evidence “is to be believed and all justifiable inferences are to be drawn in his favor.” Marino v.
Indus. Crating Co., 358 F.3d 241, 247 (3d Cir. 2004) (quoting Anderson, 477 U.S. at 255).
Once the moving party has satisfied its initial burden, the party opposing the motion must
establish that a genuine issue as to a material fact exists. Jersey Cent. Power & Light Co. v. Lacey
Twp., 772 F.2d 1103, 1109 (3d Cir. 1985). The party opposing the motion for summary judgment
cannot rest on mere allegations and instead must present actual evidence that creates a genuine
issue as to a material fact for trial. Anderson, 477 U.S. at 248; Siegel Transfer, Inc. v. Carrier
Express, Inc., 54 F.3d 1125, 1130-31 (3d Cir. 1995). “[U]nsupported allegations . . . and pleadings
are insufficient to repel summary judgment.” Schoch v. First Fidelity Bancorp., 912 F.2d 654,
657 (3d Cir. 1990); see also Fed. R. Civ. P. 56(e) (requiring nonmoving party to Aset forth specific
facts showing that there is a genuine issue for trial”).
Moreover, only disputes over facts that might affect the outcome of the lawsuit under
governing law will preclude the entry of summary judgment. Anderson, 477 U.S. at 247-48. If a
court determines, Aafter drawing all inferences in favor of [the non-moving party], and making all
credibility determinations in his favor “that no reasonable jury could find for him, summary
judgment is appropriate.” Alevras v. Tacopina, 226 Fed. App’x. 222, 227 (3d Cir. 2007).

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ANALYSIS
I.
A patent is anticipated, and hence invalid, if a single prior art reference discloses each
limitation of a claimed invention. See 35 U.S.C. § 102; Lewmar Marine, Inc. v. Barient, Inc., 827
F.2d 744, 747 (Fed. Cir. 1987). More specifically, “invalidity by anticipation 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) (emphasis added).
“[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 single anticipating
reference.” Schering Corp. v. Geneva Pharms., Inc., 339 F.3d 1373, 1377 (Fed. Cir. 2003).
Inherent anticipation does not require recognition of the missing characteristic by the inventor or
persons of ordinary skill in the art; the characteristic need only be a “necessary consequence” of
practicing the invention claimed in the prior art. Id. (quoting Mehl/Biophile Int'l Corp. v.
Milgraum, 192 F.3d 1362, 1366 (Fed. Cir. 1999)).
“[A]nticipation by inherent disclosure is appropriate only when the reference discloses
prior art that must necessarily include the unstated limitation....”. Transclean Corp. v. Bridgewood
Servs., Inc., 290 F.3d 1364, 1373 (Fed. Cir. 2002). “Inherency, however, may not be established
by probabilities or possibilities. The mere fact that a certain thing may result from a given set of
circumstances is not sufficient.” Cont'l Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1269 (Fed.
Cir. 1991) (internal quotation marks and citations omitted).

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To prove inherent anticipation, a party must show that, though a feature of the invention is
not explicitly disclosed in the prior art, it “necessarily and inevitably” flows from practice of the
prior art. See Schering Corp., 339 F.3d at 1379. “Inherent anticipation requires that the missing
descriptive material is ‘necessarily present,’ not merely probably or possibly present, in the prior
art.” Trintec Indus., Inc. v. Top-U.S.A. Corp., 295 F.3d 1292, 1295 (Fed. Cir. 2002). Therefore, if
the teachings of the prior art can be practiced in a way that yields a product lacking the allegedly
inherent property, the prior art in question does not inherently anticipate. Glaxo Inc. v. Novopharm
Ltd., 52 F.3d 1043, 1047-48 (Fed. Cir. 1995) (finding no inherent anticipation where testing
evidence demonstrated that the prior art example could yield crystals of either the claimed
polymorph or a different polymorph).
II.
In the instant matter, in support of its motion, Merck relies upon the Federal Circuit case,
Schering Corp. v. Geneva Pharmaceuticals, 339 F.3d 1373 (Fed. Cir. 2003), and argues that EP
’938 does not inherently anticipate the pharmaceutical composition claim 12 because the Federal
Circuit in Schering Corp. carved out a “safe harbor” provision for claims directed to
pharmaceutical compositions, as opposed to compounds. (Merck’s Br. at 6-7, Dkt. No. 89-1;
Merck’s Reply Br. at 2-4, Dkt. No. 109). In response, Actavis argues that claim 12 is inherently
anticipated by EP ’938 because the compound disclosed in this reference forms into the compound
of posaconazole upon metabolizing, which is the compound recited in claim 12.
In particular, Actavis argues that Compound IIc of EP ’938 (i.e., the compound) is
“extremely close” to posaconazole (i.e., the metabolite) of claim 12 (or the chemical formula
shown in claim 11). Actavis notes that the only chemical difference is the “presence of a hydroxyl
group at the C-2 position of the alykyl side chain of compound IIc.”

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(Actavis’s Opp. at 3; see Dkt. No. 104; footnote 4 notes that “Merck acknowledges that compound
IIc is the same as Schering’s SCH-51048; also see Actavis’s Invalidity Contentions, Dkt. No. 894; also see Montellano’s Report). As such, Actavis maintains the position that claim 12 is
inherently anticipated by EP ’938.
Claim 12 recites as follows:
12. A pharmaceutically composition for treating or preventing a fungal infection
comprising an antifungally effective amount of the compound of claim 11 together
with a pharmaceutically acceptable carrier therefor.
The Court notes that claim 12 is dependent of claim 11 because it relates back to another claim
from which it depends. And, claim 12 comprises of the following elements—(i) pharmaceutical
composition; (ii) an antifungal effective amount; (iii) of the compound of claim 11; and (iv) with
a pharmaceutically acceptable carrier. The Court recognizes and notes that the EP ’938 reference
discloses compounds of formula I and pharmaceutical compositions, which exhibit anti-allergic,
anti-inflammatory and immunomodulating activities. And, these compositions comprise an
antifungal effective amount of a compound represented by formula I or a pharmaceutically
acceptable salt and a pharmaceutically acceptable carrier or diluent. (see EP ’938, p. 8, ll. 10-15
and p. 15, ll. 5-10). However, the key inquiry lies on whether formula I of EP ’938 (i.e., the
compound) is the same as the compound of claim 11 when metabolized.

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In Schering Corp. v. Geneva Pharmaceuticals, the Federal Circuit noted that use of
loratadine, a compound, of U.S. Pat. 4,282,233 (the “’ 233 patent”) infringed claims 1 and 3 of the
4,659,716 (the “’716 patent”), which covered a metabolite DCL, if the compound (i.e., loratadine)
is metabolized to form the metabolite (i.e., DCL) upon ingestion by a person. Schering Corp., 339
F.3d at 1380. The record showed that the metabolite of the prior art, loratadine, is the same
compound as the claimed invention. Id. As such, the Federal Circuit held that DCL, as recited in
claims 1 and 3 of the ’716 patent, was inherently anticipated by the compound disclosed in the
’233 patent. Id.
However, the Court in Schering Corp. further noted that a “skilled patent drafter [] might
fashion a claim to cover the metabolite in a way that avoids anticipation.” For example, the Court
noted that the metabolite may be claimed as a pharmaceutical composition (e.g., with a
pharmaceutically acceptable carrier). Id. at 1381. The Court reasoned that claiming the metabolite
in such a fashion would avoid inherent anticipation by a prior art reference because the prior art
would not “provide an enabling disclosure to anticipate such claims […] [as] the ’233 patent does
not disclose isolation of DCL.” Id. at 1381.
The Court recognizes and appreciates the distinction between “pharmaceutical
composition,” recited in claim 12, and “compound,” recited in claim 11. The Court notes that
Federal Circuit in Schering Corp. indicated that a prior art reference may inherently anticipate a
compound but not necessarily anticipate a pharmaceutical composition because the prior art
reference may not provide an “enabling disclosure to anticipate such [pharmaceutical composition]
claims because […] the [reference] does not disclose isolation of [the compound].” Id. at 1381. As
such, based on this “safe harbor” provision set forth in Schering Corp., claim 12 of the ’151 patent
may not be inherently anticipated by the EP ’938 reference.

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However, the current dispositive motion for partial summary judgment is made by Merck
prior to construing the claim terms “pharmaceutically acceptable carrier” and “pharmaceutical
composition,” recited in claim 12. Although local patent rules do not prevent a party from bringing
dispositive motions prior to the Markman hearing, it has generally been the practice that claims of
a patent are construed prior to delving into, for example, anticipation, obviousness, or infringement
analysis. Ricoh Co., Ltd. v. Katun Corp., 486 F. Supp. 2d 395, 406 (D.N.J. 2007) (“Claim
construction is distinct from, and a prerequisite to, an anticipation analysis.”). In the instant matter,
the Court does not have the benefit of a technical tutorial generally presented during a Markman
hearing to construe the aforementioned claim terms to determine whether the EP ’938 reference
anticipates claim 12 of the ’156 patent.
The Court notes that Merck has stipulated to Actavis’s position that the aforementioned
claim terms are to be understood in accord with its plain meaning and, accordingly “requires no
construction.” (see Merck’s Response to Material Facts, “Fact No. 1” and “Fact No. 3;” Dkt. No.
109-1). However, the parties have not agreed upon the claim construction of what constitutes
“plain meaning” with regards to the aforementioned terms. As such, it is best to complete the claim
construction of the aforementioned claim terms before performing an anticipation analysis.
Accordingly, the Court finds Merck’s dispositive motion for partial summary judgment
against Actavis’s inherently anticipated defense to claim 12 of the ’151 patent is premature.

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ORDER
IT IS on this 6th day of March, 2017,
ORDERED that Plaintiff’s motion for partial summary judgment motion (see Dkt. No. 89)
pursuant to Fed. R. Civ. P. 56(c) is DENIED without prejudice.

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

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