GRUNENTHAL GMBH, ASSERTIO THERAPEUTICS, INC., Plaintiffs-Cross-Appellants
ALKEM LABORATORIES LIMITED, HIKMA PHARMACEUTICALS INTERNATIONAL LIMITED, HIKMA PHARMACEUTICALS USA INC., Defendants-Appellants ACTAVIS ELIZABETH LLC, Defendant-Appellee
ACTAVIS LABORATORIES UT, INC., Defendant
Appeals from the United States District Court for the
District of New Jersey in Nos. 2:13-cv-04507-CCC-MF,
2:15-cv-06797-CCC-MF, Judge Claire C. Cecchi.
Michael Sitzman, Gibson, Dunn & Crutcher LLP, San
Francisco, CA, argued for all plaintiffs-cross-appellants.
Plaintiff-cross-appellant Assertio Therapeutics, Inc. also
represented by Jaysen Chung; Christine Ranney, Denver, CO;
Timothy P. Best, Los Angeles, CA.
A. Wadler, Finnegan, Henderson, Farabow, Garrett &
Dunner, LLP, Washington, DC, for plaintiff-cross-appellant
Grunenthal GmbH. Also represented by Krista E. Bianco.
Michael E. Joffre, Sterne Kessler Goldstein & Fox, PLLC,
Washington, DC, argued for defendant-appellee. Also
represented by William H. Milliken.
J. Gajarsa, Latham & Watkins LLP, Washington, DC, argued
for defendants-appellants Hikma Pharmaceuticals International
Limited, Hikma Pharmaceuticals USA Inc. Also represented by
Kenneth G. Schuler, Chicago, IL; Gregory Sobolski, San
T. Aly, Schiff Hardin, Chicago, IL, argued for
defendant-appellant Alkem Laboratories Limited. Also
represented by Cindy Ahn, Jason Harp, Neil Lloyd; Ahmed M.T.
Riaz, New York, NY.
Reyna, Taranto, and Chen, Circuit Judges.
Laboratories Limited, Hikma Pharmaceuticals International
Limited, and Hikma Pharmaceuticals USA Inc. appeal the
judgment of the district court that U.S. Patent No. 7, 994,
364 is not invalid for obviousness or lack of utility.
Grünenthal GmbH and Assertio Therapeutics, Inc.,
formerly Depomed, Inc., cross-appeal the finding that Hikma
Pharmaceuticals International Limited, Hikma Pharmaceuticals
USA Inc., and Actavis Elizabeth LLC do not infringe U.S.
Patent No. 8, 536, 130. Because the district court did not
err in its conclusions, we affirm.
Patents at Issue
GmbH ("Grünenthal") is the assignee of U.S.
Patent Nos. 7, 994, 364 ("the '364 patent") and
8, 536, 130 ("the '130 patent"). Assertio
Therapeutics, Inc., formerly Depomed, Inc.
("Depomed"), is an exclusive licensee of both
patents. Each patent is listed in the U.S. Food and Drug
Administration's ("FDA") Approved Drug
Products with Therapeutic Equivalence Evaluations (the
"Orange Book") for NUCYNTA® ER
(extended release), a tapentadol hydrochloride tablet. J.A.
52853, 52856. The '364 patent is directed to the Form A
polymorph of the chemical compound tapentadol
hydrochloride and a method of treating pain and/or urinary
incontinence. See '364 patent, Abstract;
id. col. 18 l. 66-col. 19 l. 4. The '364 patent
states that Form A "is very stable at ambient conditions
and therefore useful for producing a pharmaceutical
composition." Id. col. 1 ll. 63-67. The
asserted claims of the '364 patent, claims 1, 2, 3, and
25, recite various X-ray powder diffraction (XRPD) patterns.
See, e.g., id. col. 18 l. 65-col. 19 l. 4.
XRPD is a method for measuring the X-rays scattered by a
polycrystalline sample as a function of scattering angle.
Each polymorph has a unique XRPD.
'130 patent describes a method of using tapentadol and
tapentadol hydrochloride for the treatment of polyneuropathic
pain. Polyneuropathic pain is a type of pain caused by damage
to multiple nerves. In contrast, mononeuropathic pain is pain
associated with damage to a single nerve.
of the '130 patent is directed to the method of treating
"polyneuropathic pain" with tapentadol or "a
pharmaceutically acceptable salt thereof," i.e.,
tapentadol hydrochloride. '130 patent, col. 18 ll. 2-7.
Claim 2 is directed to the method of treating polyneuropathic
pain using "a hydrochloric salt" of tapentadol,
i.e., tapentadol hydrochloride. Id. col. 18 ll.
Prior Art References
are two different polymorphs of tapentadol hydrochloride:
Form A and Form B. Form B of tapentadol hydrochloride was
known in the art and previously disclosed in U.S. Patent No.
6, 248, 737 ("the '737 patent"), also assigned
to Grünenthal. See '364 patent, col. 1 ll.
58-63. The '737 patent discloses a number of compounds,
including tapentadol hydrochloride, intended to have an
analgesic effect suitable for the treatment of pain. See,
e.g., '737 patent, col. 1 l. 52-col. 2 l. 36;
id., Example 25, col. 20 ll. 1- 20. Specifically,
Example 25 of the '737 patent discloses the steps for
synthesizing tapentadol hydrochloride. The '737 patent
states that tapentadol hydrochloride was crystallized, but it
does not describe the resulting crystal structure, nor does
it discuss polymorphs.
known in the art at the time of filing was the concept of
polymorph screening, which is the practice of characterizing
all crystal forms of a chemical compound. A 1995 article by
Byrn et al. ("Byrn") "describes a
conceptual approach to the characterization of pharmaceutical
solids," including a flow chart describing investigative
steps to determine whether polymorphs are possible. J.A.
57372-73. Byrn does not outline a particular method to
definitively test for polymorphism. Instead, it provides a
decision tree outlining, among other things, different ways
to gain additional information about whether polymorphs exist
for a particular chemical compound and lists various
analytical tests to identify polymorphs. J.A. 57373.
determine whether polymorphs are possible, Byrn lists a
number of solvents to be used in recrystallizing the
substance in question. The listed solvents are water,
methanol, ethanol, propanol, isopropanol, acetone,
acetonitrile, ethyl acetate, and hexane. Id. Other
variables such as temperature, concentration, agitation, and
pH could affect the solids produced by recrystallization with
these various solvents. Id., Figure 1. This case
focuses on the extent and limits of what the disclosure in
Byrn teaches about discovering polymorphs, if any, of a known
compound, and ultimately, whether a skilled artisan would
reasonably expect the recrystallization of tapentadol
hydrochloride to result in any polymorph, let alone one with
the physical properties of Form A.
Proceedings in District Court
and Depomed (collectively, "Cross-Appellants")
brought suit against Alkem Laboratories Limited
("Alkem"), Hikma Pharmaceuticals International
Lim-ited,  Hikma Pharmaceuticals USA Inc.
(collectively, "Hikma"), and Actavis Elizabeth LLC
("Actavis"),  alleging infringement of the '364
and '130 patents stemming from their respective
Abbreviated New Drug Application ("ANDA") filings
seeking to market generic versions of immediate and extended
release tapentadol hydrochloride tablets. All defendants
subsequently stipulated to infringement of the '364
patent. Alkem and Hikma challenged the validity of the
'364 and '130 patents.
bench trial, the district court concluded that Alkem
infringes the '130 patent, but that Actavis and Hikma do
not. In re Depomed Patent Litig., No.
13-cv-4507-CCC-MF, 2016 WL 7163647, at *2 (D.N.J. Sept. 30,
2016) ("Depomed Litigation"). The district
court also determined that the '364 patent is not invalid
as obvious, that the '130 patent is not invalid as
anticipated, and that the '130 patent is not invalid due
to obviousness-type double patenting in light of U.S. Patent
No. RE39, 593. Id.
and Hikma each appeal different aspects of the district
court's invalidity rulings. Grünenthal and Depomed
collectively appeal the district court's finding of
noninfringement of the '130 patent. We have jurisdiction
under 28 U.S.C. § 1295(a)(1).
Hikma's argument on appeal is made in the alternative and
many of its arguments become moot should we hold Hikma does
not infringe the '130 patent. Therefore, we will first
address Cross-Appellants' arguments regarding
noninfringement. We will then address Alkem's appeal of
the finding that the '364 patent is not invalid as
obvious and Hikma's challenge to the utility and validity
of the '130 patent.
begin with a discussion of Grünenthal and Depomed's
cross-appeal. Because neither Hikma's nor Ac-tavis's
proposed label is indicated to treat polyneuropathic pain,
and the case made by Grünenthal and Depomed for indirect
infringement depended on the proposed label indications, we
agree with the trial court that Hikma and Ac-tavis ...