In Re '318 Patent Infringement Litigation ( 2009 )

United States Court of Appeals for the Federal Circuit
2008-1594, 2009-1070
IN RE ‘318 PATENT INFRINGEMENT LITIGATION
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JANSSEN PHARMACEUTICA N.V., JANSSEN L.P.,
and SYNAPTECH, INC.,
Plaintiffs-Appellants,
v.
TEVA PHARMACEUTICALS USA, INC. and TEVA PHARMACEUTICAL INDUSTRIES, LTD.,
Defendants,
and
MYLAN PHARMACEUTICALS, INC. and MYLAN LABORATORIES, INC.,
Defendants-Appellees,
and
DR. REDDY’S LABORATORIES, INC. and DR. REDDY’S LABORATORIES, LTD.,
Defendants,
and
BARR LABORATORIES, INC.,
Defendant-Appellee,
and
PUREPAC PHARMACEUTICAL CO. and ACTAVIS GROUP,
Defendants,
and
ALPHAPHARM PTY LTD.,
Defendant-Appellee.
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2009-1088
JANSSEN PHARMACEUTICA, N.V., JANSSEN, L.P.,
ORTHO-MCNEIL NEUROLOGICS, INC., and SYNAPTECH, INC.,
Plaintiffs-Appellants,
v.
BARR LABORATORIES, INC., and BARR PHARMACEUTICALS, INC.,
Defendants-Appellees.
George F. Pappas, Covington & Burling LLP, of Washington, DC, argued for all
plaintiffs-appellants. With him on the brief for Janssen Pharmaceutica, N.V., et al. were
Christopher N. Sipes and Kurt G. Calia. Of counsel on the brief for plaintiff-appellant
Synaptech, Inc. were Edward V. Filardi and Rachel Blitzer, Skadden, Arps, Slate,
Meagher & Flom LLP, of New York, New York.
William A. Rakoczy, Rakoczy Molino Mazzochi Siwik LLP, of Chicago, Illinois,
argued for defendants-appellees Mylan Pharmaceuticals, Inc., Mylan Laboratories, Inc.,
and Alphapharm Pty Ltd. With him on the brief for defendants-appellees Mylan
Pharmaceuticals, Inc., et al. were Christine J. Siwik and Amy D. Brody; Mona Gupta,
Alan H. Bernstein, James J. Kozuch, and William C. Youngblood, Caesar Rivise
Bernstein Cohen & Pokotilow, Ltd., of Philadelphia, Pennsylvania, for defendant-
appellee Alphapharm Pty Ltd.
George C. Lombardi, Winston & Strawn LLP, of Chicago, Illinois, argued for
defendant-appellee Barr Laboratories, et al. With him on the brief were Taras A.
Gracey, Lynn M. Ulrich, Ryanne L. Easley and William P. Ferranti. Of counsel was
Steven J. Winger.
Appealed from: United States District Court for the District of New Jersey
Judge Joel A. Pisano
Appealed from: United States District Court for the District of Delaware
Judge Sue L. Robinson
United States Court of Appeals for the Federal Circuit
2008-1594, 2009-1070
IN RE ’318 PATENT INFRINGEMENT LITIGATION
---------------------------------------------------------------------------
JANSSEN PHARMACEUTICA N.V., JANSSEN L.P.,
and SYNAPTECH, INC.,
Plaintiffs-Appellants,
v.
TEVA PHARMACEUTICALS USA, INC. and TEVA PHARMACEUTICAL INDUSTRIES,
LTD.,
Defendants,
and
MYLAN PHARMACEUTICALS, INC. and MYLAN LABORATORIES, INC.,
Defendants-Appellees,
and
DR. REDDY’S LABORATORIES, INC. and DR. REDDY’S LABORATORIES, LTD.,
Defendants,
and
BARR LABORATORIES, INC.,
Defendant-Appellee,
and
PUREPAC PHARMACEUTICAL CO. and ACTAVIS GROUP,
Defendants,
and
ALPHAPHARM PTY LTD.,
Defendant-Appellee.
Appeals from the United States District Court for the District of Delaware, in
consolidated case nos. 05-CV-356, 05-CV-371, 05-CV-380, 05-CV-381, 05-CV-382,
05-CV-420, and 05-CV-451, Judge Sue L. Robinson.
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2009-1088
JANSSEN PHARMACEUTICA, N.V., JANSSEN, L.P.,
ORTHO-MCNEIL NEUROLOGICS, INC., and SYNAPTECH, INC.,
Plaintiffs-Appellants,
v.
BARR LABORATORIES, INC. and BARR PHARMACEUTICALS, INC.,
Defendants-Appellees.
Appeal from the United States District Court for the District of New Jersey in case no.
06-CV-3008, Judge Joel A. Pisano.
___________________________
DECIDED: September 25, 2009
___________________________
Before MAYER, GAJARSA, and DYK, Circuit Judges.
Opinion for the court filed by Circuit Judge DYK. Dissenting opinion filed by Circuit
Judge GAJARSA.
DYK, Circuit Judge.
Janssen Pharmaceutica N.V., Janssen L.P., and Synaptech, Inc. (“Janssen”),
appeal from a final judgment of the United States District Court for the District of
Delaware. After a bench trial, the district court determined that the claims of U.S.
2008-1594, 2009-1070, -1088 2
Patent No. 4,663,318 (“the ’318 patent”) were invalid for lack of enablement. In re ’318
Patent Infringement Litig., 578 F. Supp. 2d 711, 737 (D. Del. 2008). We affirm.
BACKGROUND
Janssen’s ’318 patent claims a method for treating Alzheimer’s disease with
galanthamine. Claim 1 is representative. It claims “[a] method of treating Alzheimer’s
disease and related dementias which comprises administering to a patient suffering
from such a disease a therapeutically effective amount of galanthamine or a
pharmaceutically-acceptable acid addition salt thereof.” ‘318 patent col.3 ll.6–10. 1 The
application for the ’318 patent was filed on January 15, 1986, by Dr. Bonnie Davis, the
claimed inventor.
Alzheimer’s disease is a form of progressive dementia in which memory and
mental abilities steadily decline. At the time of the ’318 patent’s application in early
1986, researchers had observed a correlation between Alzheimer’s disease symptoms
and a reduced level of the neurotransmitter acetylcholine in the brain. During
neurotransmission, acetylcholine is released by a transmitting neuron and binds to
receptors on a receiving neuron. The two main types of acetylcholine receptors are
nicotinic receptors and muscarinic receptors. Nicotinic and muscarinic receptors are
present in neurons in both the central nervous system (which includes the brain and
spinal cord) and the peripheral nervous system (which connects the central nervous
system to muscles and organs).
In early 1986, many researchers focused primarily on the importance of central
1
The six additional claims in the ’318 patent claim the administration of
galantamine orally, parenterally, or intracerebroventricularly in various dosage ranges.
2008-1594, 2009-1070, -1088 3
nervous system muscarinic receptors in developing treatments for Alzheimer’s disease.
At that time, galanthamine (also spelled “galantamine”), a small molecule compound,
was known to inhibit acetylcholinesterase, an enzyme that breaks down acetylcholine.
Acetylcholinesterase inhibitors like galantamine increase the amount of acetylcholine
available for binding to muscarinic or nicotinic receptors.
The specification for the ’318 patent was only just over one page in length, and it
provided almost no basis for its stated conclusion that it was possible to administer “an
effective Alzheimer’s disease cognitively-enhancing amount of galanthamine.” Id. col.1
ll.47–48. The specification provided short summaries of six scientific papers in which
galantamine had been administered to humans or animals. 2 The specification
summarized the first paper as showing that administering galantamine with the drug
2
The specification stated:
Galanthamine and acid addition salts thereof have, for many years,
been known to have anticholinesterase properties. Cozanitis in
Anaesthesia 29 163–8 (1974) describes the effect of galanthamine
hydrobromide on plasma cortisol of patients receiving relaxant
anaesthesia and Cozanitis et al in Acta Anesth. Scand. 24:166–168
(1980) describe the effect of galanthamine on plasma ACTH values during
anaethesia. These studies showed an increase in both plasma cortisol and
plasma ACTH when galanthamine was administered to patients together
with atropine.
Il’yuchenok et al (Chemical Abstracts 70 36296K describe the
appearance of θ-rhythm on an electroencephalogram when galanthamine
is administered intravenously to rabbits.
Increase in short-term memory in dogs by use of galanthamine is
described by Krauz in Chemical Abstracts 81 72615Z.
The antagonistic effect of galanthamine to scopolamine-induced
amnesia in rats is described by Chaplygina et al in Chemical Abstracts 86
115157Z, and in Zhurnal Vysshei Nervnoi Deiatelnosti imeni P. Pavlova
(MOSKVA) 26:1091-1093, 1976.
‘318 patent col.1 ll.11–33.
2008-1594, 2009-1070, -1088 4
atropine to humans under anesthesia raised blood levels of the hormone cortisol, and
the second paper as showing that administering galantamine and atropine together
during anesthesia also raised levels of adrenocorticotropic hormone (“ACTH”) in
humans. See id. col.1 ll.13–21. There was no explanation of the significance of
increasing cortisol or ACTH levels, but it was known to those skilled in the art in early
1986 that the production of cortisol and ACTH was controlled by the central nervous
system rather than the peripheral nervous system, and that the studies thus suggested
that galantamine was able to cross the blood-brain barrier and have effects within the
brain.
The specification then provided brief summaries of four scientific papers
reporting brain effects and positive effects on memory from administering galantamine
to animals. See id. col.1 ll.22–33. The first paper concluded that galantamine
intravenously administered to rabbits affected brain wave activity. The second paper
concluded that galantamine increased short-term memory in dogs. The third and fourth
papers concluded that galantamine reversed amnesia in rats that had been induced by
administering the drug scopolamine. The specification did not suggest that such
scopolamine-induced amnesia was similar to Alzheimer’s disease. The specification did
not provide analysis or insight connecting the results of any of these six studies to
galantamine’s potential to treat Alzheimer’s disease in humans.
The specification noted that another prior art scientific paper described an animal
testing model for replicating in animals the acetylcholine deficit and other effects of
2008-1594, 2009-1070, -1088 5
Alzheimer’s disease. 3 The specification agreed that acetylcholine deficiency in animals
is a “good animal model for Alzheimer’s disease in humans” because the deficiency
produces “[n]umerous behavioral deficits, including the inability to learn and retain new
information.” Id. col.2 ll.50–52. The specification cited the prior art for the conclusion
that “[d]rugs that can normalize these abnormalities would have a reasonable
expectation of efficacy in Alzheimer’s disease.” Id. col.2 ll.52–54. However, the
specification did not refer to any then-existing animal test results involving the
administration of galantamine in connection with this animal model of Alzheimer’s
disease.
In April 1986 an examiner at the United States Patent and Trademark Office
(“PTO”) rejected the claims in the ’318 patent’s application for indefiniteness and
obviousness. The examiner found the patent application’s claim of a method of
“diagnosing” Alzheimer’s disease to be indefinite, because diagnosing “has nothing to
do with treating” and because the claims thus “fail[ed] to particularly point out and
distinctly claim the subject matter which applicant regards as the invention.” J.A. 4108.
The examiner also found the patent application’s claim of a method of treating
3
The specification of the ’318 patent stated:
The following test provides a good animal model for Alzheimer’s
disease in humans: A selective lesion is placed in a subcortical nucleus
(nucleus basalis of Meynert) with a resultant cortical cholinergic [i.e.,
acetylcholine] deficiency, similar in magnitude to that seen in early to
moderate stage Alzheimer’s disease. Numerous behavioral deficits,
including the inability to learn and retain new information, characterizes
this lesion. Drugs that can normalize these abnormalities would have a
reasonable expectation of efficacy in Alzheimer’s disease. Haroutunian, V,
Kanof P, Davis, KL: Pharmacological alleviations of cholinergic-lesion-
induced memory defects in rats. Life Sciences 37:945-952, 1985.
‘318 patent col.2 ll.45–57.
2008-1594, 2009-1070, -1088 6
Alzheimer’s disease obvious—in light of the animal studies cited in the specification
describing the use of galantamine to treat scopolamine-induced amnesia and in
improving short-term memory. The examiner did not reject the application for lack of
enablement.
In September 1986 the applicant, Dr. Davis, responded to the examiner’s
indefiniteness rejection by narrowing the claim language, deleting the words “and
diagnosing” from the original application’s claim of “[a] method of treating and
diagnosing Alzheimer’s disease.” Dr. Davis responded to the obviousness rejection by
explaining that, because the brains of the animals in the studies cited in the
specification were “normal” (rather than having “physiological changes” similar to
Alzheimer’s disease), the studies were conducted under “circumstances having no
relevance to Alzheimer’s disease,” and that it thus would be “baseless” to predict from
such studies that galantamine would be useful to treat Alzheimer’s disease. J.A. 4407.
In addition, Dr. Davis responded by stating that “experiments [are] underway
using animal models which are expected to show that treatment with galanthamine does
result in an improvement in the condition of those suffering from Alzheimer’s disease,”
and that it was “expected that data from this experimental work will be available in two
to three months and will be submitted to the Examiner promptly thereafter.” J.A. 4405.
The ’318 patent issued on May 5, 1987. Dr. Davis did not learn the results of the animal
testing experiments—which suggested that galantamine could be a promising
Alzheimer’s disease treatment—until July 1987, after the ’318 patent had issued. These
studies required several months and considerable effort by researchers at the Johns
Hopkins University under the supervision of Dr. Joseph T. Coyle. No such testing
2008-1594, 2009-1070, -1088 7
results were ever submitted to the PTO.
After the ’318 patent issued in May 1987, Dr. Davis licensed the patent in
November 1995 to Janssen. In February 2001 Janssen received approval from the
Food and Drug Administration (“FDA”) for using galantamine to treat mild to moderate
Alzheimer’s disease.
In February 2005 several generic drug manufacturers filed abbreviated new drug
applications (“ANDAs”) and so-called “Paragraph IV” certifications with the FDA, and
Janssen sued each manufacturer for infringing the ’318 patent. 4 The actions were
consolidated, the defendants conceded infringement of claims 1 and 4 of the ‘318
patent, and a bench trial was held in May 2007 on the invalidity issues of anticipation,
obviousness, and enablement.
The district court found that the ’318 patent was neither anticipated nor obvious.
However, the district court concluded that the ’318 patent was invalid for lack of
enablement on two distinct grounds. The district court found that the specification did
not demonstrate utility because relevant animal testing experiments were “not finished
. . . by the time the ’318 patent was allowed” and the specification provided only
“minimal disclosure” of utility. ’318 Patent Infringement Litig., 578 F. Supp. 2d at 723,
735; see also id. at 736–37 & n.39. The district court alternatively found that the
specification and claims did not “teach one of skill in the art how to use the claimed
method” because the application “only surmise[d] how the claimed method could be
used” without providing sufficient galantamine dosage information. Id. at 736. The
4
A Paragraph IV certification “is defined as an act of infringement for
litigation purposes.” Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1078 (Fed. Cir.
2008); see 21 U.S.C. § 355(j)(2)(A)(vii)(IV); 35 U.S.C. § 271(e).
2008-1594, 2009-1070, -1088 8
district court entered judgment in favor of the defendants that the ’318 patent was
invalid for lack of enablement.
Janssen timely appealed. We have jurisdiction under 28 U.S.C. §§ 1291 and
1295(a)(1).
DISCUSSION
Enablement is a question of law we review without deference. Invitrogen Corp.
v. Clontech Labs., Inc., 429 F.3d 1052, 1070 (Fed. Cir. 2005). We review the factual
issues underlying enablement for clear error. Enzo Biochem, Inc. v. Calgene, Inc., 188
F.3d 1362, 1369 (Fed. Cir. 1999).
The enablement requirement is stated in 35 U.S.C. § 112. 5 Enablement is
determined as of the effective filing date of the patent’s application. Plant Genetic Sys.,
N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339 (Fed. Cir. 2003).
Enablement is closely related to the requirement for utility. 6 As we noted in
5
The statute states:
The specification shall contain a written description of the invention,
and of the manner and process of making and using it, in such full, clear,
concise, and exact terms as to enable any person skilled in the art to
which it pertains, or with which it is most nearly connected, to make and
use the same, and shall set forth the best mode contemplated by the
inventor of carrying out his invention.
35 U.S.C. § 112, ¶ 1 (emphases added).
6
The utility requirement is stated in 35 U.S.C. § 101:
Whoever invents or discovers any new and useful process,
machine, manufacture, or composition of matter, or any new and useful
improvement thereof, may obtain a patent therefor, subject to the
conditions and requirements of this title.
(emphases added).
2008-1594, 2009-1070, -1088 9
Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1358 (Fed. Cir. 1999),
The enablement requirement of 35 U.S.C. § 112, ¶ 1 requires that the
specification adequately discloses to one skilled in the relevant art how to
make, or in the case of a process, how to carry out, the claimed invention
without undue experimentation. The utility requirement of 35 U.S.C. § 101mandates that any patentable invention be useful and, accordingly, the
subject matter of the claim must be operable. If a patent claim fails to
meet the utility requirement because it is not useful or operative, then it
also fails to meet the how-to-use aspect of the enablement requirement.
(emphasis added, citations and footnote omitted). See also 3 Donald A. Chisum,
Chisum on Patents § 7.03(6) (2007). The Supreme Court in Brenner v. Manson, 383
U.S. 519 (1966), discussing the utility requirement, stated that inventions must have
“substantial utility” and “specific benefit exist[ing] in currently available form.” Id. at 534–
35.
The utility requirement prevents mere ideas from being patented. As we noted in
Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997), “[p]atent
protection is granted in return for an enabling disclosure of an invention, not for vague
intimations of general ideas that may or may not be workable. . . . Tossing out the mere
germ of an idea does not constitute enabling disclosure.” See also In re Fisher, 421
F.3d 1365, 1373 (Fed. Cir. 2005) (inventions fail to meet the utility requirement if their
“asserted uses represent merely hypothetical possibilities, objectives which the claimed
[inventions] . . . could possibly achieve, but none for which they have been used in the
real world”).
The utility requirement also prevents the patenting of a mere research proposal
or an invention that is simply an object of research. Again as the Supreme Court stated
in Brenner, “a patent is not a hunting license. It is not a reward for the search, but
compensation for its successful conclusion.” 383 U.S. at 536. A process or product
2008-1594, 2009-1070, -1088 10
“which either has no known use or is useful only in the sense that it may be an object of
scientific research” is not patentable. Id. at 535. As we observed in Fisher, inventions
do not meet the utility requirement if they are “objects upon which scientific research
could be performed with no assurance that anything useful will be discovered in the
end.” 421 F.3d at 1373. Allowing ideas, research proposals, or objects only of research
to be patented has the potential to give priority to the wrong party and to “confer power
to block off whole areas of scientific development, without compensating benefit to the
public.” Brenner, 383 U.S. at 534 (footnote omitted).
Typically, patent applications claiming new methods of treatment are supported
by test results. But it is clear that testing need not be conducted by the inventor. In
addition, human trials are not required for a therapeutic invention to be patentable. Our
predecessor court, the United States Court of Customs and Patent Appeals, held in In
re Krimmel that patent applications need not “prove that compounds or other materials
which [the applicant] is claiming, and which [the applicant] has stated are useful for
‘pharmaceutical applications’ are safe, effective, and reliable for use with humans.” 292
F.2d 948, 954 (CCPA 1961). As we observed in In re Brana, “[w]ere we to require
Phase II testing [human trials] in order to prove utility, the associated costs would
prevent many companies from obtaining patent protection on promising new inventions,
thereby eliminating an incentive to pursue . . . potential cures.” 51 F.3d 1560, 1568
(Fed. Cir. 1995); see also Scott v. Finney, 34 F.3d 1058, 1063–64 (Fed. Cir. 1994).
We have held that results from animal tests or in vitro experiments 7 may be
7
“In vitro” experiments are performed in artificial environments outside
living organisms (such as in a test tube or culture media), while “in vivo” experiments
are performed within living organisms. Brana, 51 F.3d at 1562 n.3; Cross v. Iizuka,
2008-1594, 2009-1070, -1088 11
sufficient to satisfy the utility requirement. Our predecessor court held in Krimmel that
animal tests showing that a new nonobvious compound “exhibits some useful
pharmaceutical property” are sufficient to demonstrate utility. 292 F.2d at 953. We
noted in Cross v. Iizuka that “[w]e perceive no insurmountable difficulty, under
appropriate circumstances, in finding that the first link in the screening chain, in vitro
testing, may establish a practical utility for the [pharmaceutical] compound in question”
in order for a patent to issue. 753 F.2d 1040, 1051 (Fed. Cir. 1985). We concluded that
in vitro test results for a claimed pharmaceutical compound, combined with animal test
results for a structurally similar compound, showed “a reasonable correlation between
the disclosed in vitro utility and an in vivo activity, and therefore a rigorous correlation is
not necessary where the disclosure of pharmacological activity is reasonable based
upon the probative evidence.” Id. at 1050.
In this case, however, neither in vitro test results nor animal test results involving
the use of galantamine to treat Alzheimer’s-like conditions were provided. The results
from the ’318 patent’s proposed animal tests of galantamine for treating symptoms of
Alzheimer’s disease were not available at the time of the application, and the district
court properly held that they could not be used to establish enablement. 8
753 F.2d 1040, 1043 n.6 (Fed. Cir. 1985).
8
In Brana we held that the patent applicants had established the utility of
claimed therapeutic compounds by presenting in vitro test results and evidence of
structural similarity between the claimed and prior art compounds when filing the
application. 51 F.3d at 1566. The applicants also submitted animal testing results for
the claimed compounds to the PTO after the filing date, but our finding of enablement
did not depend on these post-application test results. In Brana, moreover, unlike the
present case, the testing was submitted to the PTO during prosecution. Id. at 1567.
2008-1594, 2009-1070, -1088 12
Nor does Janssen contend that the prior art animal testing summarized in the
’318 patent application’s specification established utility. Indeed, both in responding to
the examiner’s obviousness rejection and in responding to the obviousness defense at
trial, the inventor (Dr. Davis) and Janssen’s witnesses explicitly stated that the utility of
the invention could not be inferred from the prior art testing described in the application.
The response of the inventor, Dr. Davis, to the examiner’s obviousness rejection stated,
with regard to studies cited in the specification showing galantamine’s ability to reverse
scopolamine-induced amnesia in normal rats, that “[n]othing in this teaching leads to an
expectation of utility against Alzheimer’s disease.” J.A. 4409. The response of Dr.
Davis also stated that “predict[ing] that galanthamine would be useful in treating
Alzheimer’s disease just because it has been reported [in the prior art studies cited in
the specification] to have an effect on memory in circumstances having no relevance to
Alzheimer’s disease” would be “as baseless as a prediction that impaired eyesight due
to diabetes would respond to devices (eyeglasses) or treatments (eye exercises) known
to improve the vision of normal persons.” J.A. 4407. Janssen’s other expert Dr.
Raskind testified that studying a compound’s effects on scopolamine-induced amnesia
“ignores the whole other [nicotinic] part that’s damaged in Alzheimer’s disease” and thus
“doesn’t mimic Alzheimer’s disease.” J.A. 9301–02. The district court agreed, finding,
for example, that the utility of galantamine in treating scopolamine-induced amnesia did
not establish galantamine’s utility in treating Alzheimer’s disease. See ’318 Patent
Infringement Litig., 578 F. Supp. 2d at 731 (“[S]copolamine[’s] . . . usefulness as a
model for [Alzheimer’s disease] research has limitations. . . . [A] person of skill in the art
2008-1594, 2009-1070, -1088 13
would not have a reasonable expectation of success for using a drug that worked for
scopolamine-induced delirium to treat [Alzheimer’s disease].”).
However, Janssen argues that in some circumstances utility may be established
without testing the proposed treatment in the claimed environment or a sufficiently
similar or predictive environment; that is, Janssen argues that utility may be established
by analytic reasoning. Although no case has been called to our attention where utility
was established simply by analytic reasoning, 9 the PTO’s Manual of Patent Examining
Procedure (“MPEP”) has recognized that “arguments or reasoning” may be used to
establish an invention’s therapeutic utility. 10
Janssen goes on to argue that the specification here establishes utility by
analytic reasoning. Relying on trial testimony, Janssen reasons that the selection and
description of the prior art tests, while not directly pertinent, “set[] forth the evidence
from existing studies demonstrating galantamine’s effects on central nicotinic as well as
muscarinic receptors and connect[ed] it to a model for Alzheimer’s therapy rendering
9
Cases cited by Janssen did not involve patents that relied solely on
analysis to establish utility. See, e.g., Brana, 51 F.3d at 1565–66 (holding that patent
applicants had established the utility of claimed therapeutic compounds by presenting in
vitro test results and evidence of structural similarity to therapeutically useful
compounds); Atlas Powder Co. v. E.I. Dupont de Nemours & Co., 750 F.2d 1569, 1576–
77 (Fed. Cir. 1984) (upholding a district court’s judgment of enablement because the
examples in the specification “were based on actual experiments”).
10
As stated in the MPEP, establishing “a reasonable correlation between” a
compound’s activity and its asserted therapeutic use may involve “statistically relevant
data documenting the activity of a compound or composition, arguments or reasoning,
documentary evidence (e.g., articles in scientific journals), or any combination thereof.”
MPEP § 2107.03 (8th ed., Rev. 7, July 2008). See also Fisher, 421 F.3d at 1372 (“The
MPEP and [PTO Utility] Guidelines are not binding on this court, but may be given
judicial notice to the extent they do not conflict with the statute.” (quotation marks
omitted)).
2008-1594, 2009-1070, -1088 14
those effects therapeutically relevant.” Janssen Reply Br. 17 n.2. Janssen asserts that
the prior art tests summarized in the specification would lead one skilled in the art to
infer that galantamine affected the ability of acetylcholine to bind to both nicotinic and
muscarinic receptors in the brain. Janssen also asserts that the animal tests proposed
in the specification as a model for Alzheimer’s disease would further lead one skilled in
the art to infer that the model’s method of impairing brain acetylcholine availability would
allow both muscarinic and nicotinic effects to be observed. Janssen thus argues that
because nicotinic receptors in the brain are involved with the ability to learn, the
specification suggested that galantamine could have beneficial effects on learning
(unlike prior art treatments, which had primarily affected muscarinic receptors). These
insights, however, are nowhere described in the specification. Nor was there evidence
that someone skilled in the art would infer galantamine’s utility from the specification,
even if such inferences could substitute for an explicit description of utility.
Janssen relies on the testimony of its expert Dr. Coyle, the scientist who later
supervised the performance of the animal studies suggested in the specification. He
testified that the specification “connected the dots” for galantamine as a potential
Alzheimer’s disease treatment, listing the “dots” as “[g]alanthamine in humans safe and
well tolerated[,] [c]holinesterase inhibitor, selective nicotinic effects, and very modest
muscarinic receptor side effects.” J.A. 9057–58. This testimony of Dr. Coyle on which
Janssen relies, however, characterized the use of galantamine to treat Alzheimer’s
disease as “a proposal that connected the dots that raised very interesting questions
and worth the effort to check it out in a model in which . . . both nicotinic and muscarinic
2008-1594, 2009-1070, -1088 15
receptors would come into play.” Id. (emphases added). 11 Similarly, agreement by
another of Janssen’s expert witnesses, Dr. Raskind, that a person of ordinary skill in the
art in early 1986 would have viewed the “invention as set forth in the patent as
scientifically grounded” falls far short of demonstrating that a person of ordinary skill in
the art would have recognized that the specification conveyed the required assertion of
a credible utility. J.A. 9305. In fact, the inventor’s own testimony reveals that an
ordinarily skilled artisan would not have viewed the patent’s disclosure as describing the
utility of galantamine as a treatment for Alzheimer’s disease: “[W]hen I submitted this
patent, I certainly wasn’t sure, and a lot of other people weren’t sure that cholinesterase
inhibitors[, a category of agents that includes galantamine,] would ever work.” J.A.
8747; see ’318 Patent Infringement Litig., 578 F. Supp. 2d at 736.
Thus, at the end of the day, the specification, even read in the light of the
knowledge of those skilled in the art, does no more than state a hypothesis and propose
testing to determine the accuracy of that hypothesis. That is not sufficient. See
Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1325 (Fed. Cir. 2005) (“If
mere plausibility were the test for enablement under section 112, applicants could
obtain patent rights to ‘inventions’ consisting of little more than respectable guesses as
to the likelihood of their success. When one of the guesses later proved true, the
11
Janssen also relies on conclusory testimony by defendants’ witness Dr.
Levey to establish that the specification demonstrated utility. See J.A. 8329–30 (Dr.
Levey agreeing that “the idea of using galanthamine as a treatment[] for Alzheimer’s
disease in 1986 [was a] scientifically reasonable judgment”). The testimony by
defendants’ witness Dr. Levey was in support of an obviousness defense and was not
credited by the district court, and Dr. Levey testified that if the district court rejected his
opinion that the ’318 patent was obvious, then it was his opinion that the patent was not
enabled. See J.A. 8248, 8253.
2008-1594, 2009-1070, -1088 16
‘inventor’ would be rewarded the spoils instead of the party who demonstrated that the
method actually worked. That scenario is not consistent with the statutory requirement
that the inventor enable an invention rather than merely proposing an unproved
hypothesis.”).
The ’318 patent’s description of using galantamine to treat Alzheimer’s disease
thus does not satisfy the enablement requirement because the ’318 patent’s application
did not establish utility. 12
CONCLUSION
For the foregoing reasons, the decision of the district court is affirmed.
AFFIRMED
12
Under circumstances where the record would not support a finding of
utility, the absence of findings by the district court on the issue of whether a person
skilled in the art could infer galantamine’s utility from the selected prior art described in
the ’318 patent’s specification is not error. Where disputed factual findings are
irrelevant, it is not error not to make them. See 28 U.S.C. § 2111 (“On the hearing of
any appeal . . . the court shall give judgment after an examination of the record without
regard to errors or defects which do not affect the substantial rights of the parties.”);
Sampson v. Murray, 415 U.S. 61, 87 n.58 (1974) (“Admittedly, the District Court did not
comply with Fed. Rule Civ. Proc. 52(a), but we do not think that we are thereby
foreclosed from examining the record to determine if sufficient allegations or sufficient
evidence supports the issuance of injunctive relief.”); Baxter Healthcare Corp. v.
Spectramed, Inc., 49 F.3d 1575, 1582 (Fed. Cir. 1995) (declining to remand because
“[o]n appeal we are free to examine the record to determine whether the facts support
the judgment”); Consol. Aluminum Corp. v. Foseco Int’l Ltd., 910 F.2d 804, 814 (Fed.
Cir. 1990) (“[R]emand should not be a matter of rote in every case in which findings and
reason are not expressly set forth. An appellate court need not close its eyes to the
record where, as in this case, there is a way clearly open to affirm the district court’s
action.”); see also Jenkens & Gilchrist v. Groia & Co., 542 F.3d 114, 119 (5th Cir. 2008)
(“[A] remand is not necessary if the record would not support a finding . . . and if such a
finding would be deemed clearly erroneous had it been made.” (quotation marks
omitted)); United States v. $242,484.00, 389 F.3d 1149, 1154 (11th Cir. 2004) (“We can
and have decided appeals on the merits where the district court has not even entered
any findings on each separate factual issue so long as a complete understanding of the
issues is possible.” (quotation marks omitted)).
2008-1594, 2009-1070, -1088 17
COSTS
No costs.
2008-1594, 2009-1070, -1088 18
United States Court of Appeals for the Federal Circuit
2008-1594, 2009-1070
IN RE ’318 PATENT INFRINGEMENT LITIGATION
---------------------------------------------------------------------------
JANSSEN PHARMACEUTICA N.V., JANSSEN L.P.,
and SYNAPTECH, INC.,
Plaintiffs-Appellants,
v.
TEVA PHARMACEUTICALS USA, INC. and TEVA PHARMACEUTICAL INDUSTRIES,
LTD.,
Defendants,
and
MYLAN PHARMACEUTICALS, INC. and MYLAN LABORATORIES, INC.,
Defendants-Appellees,
and
DR. REDDY’S LABORATORIES, INC. and DR. REDDY’S LABORATORIES, LTD.,
Defendants,
and
BARR LABORATORIES, INC.,
Defendant-Appellee,
and
PUREPAC PHARMACEUTICAL CO. and ACTAVIS GROUP,
Defendants,
and
ALPHAPHARM PTY LTD.,
Defendant-Appellee.
Appeals from the United States District Court for the District of Delaware, in
consolidated case nos. 05-CV-356, 05-CV-371, 05-CV-380, 05-CV-381, 05-CV-382,
05-CV-420 and 05-CV-451, Judge Sue L. Robinson.
---------------------------------------------------------------------------
2009-1088
JANSSEN PHARMACEUTICA, N.V., JANSSEN, L.P.,
ORTHO-MCNEIL NEUROLOGICS, INC., and SYNAPTECH, INC.,
Plaintiffs-Appellants,
v.
BARR LABORATORIES, INC. and BARR PHARMACEUTICALS, INC.,
Defendants-Appellees.
Appeal from the United States District Court for the District of New Jersey in case no.
06-CV-3008, Judge Joel A. Pisano.
GAJARSA, Circuit Judge, dissenting.
I respectfully dissent from the majority’s affirmance because the district court did
not undertake the required legal analysis to determine whether an ordinarily skilled
artisan reading the patent would understand it to reveal a credible utility for the
invention. In addition, the district court failed to make the factual findings necessary to
support the ultimate legal conclusion regarding enablement. See Koito Mfg. Co. v.
Turn-Key-Tech, LLC, 381 F.3d 1142, 1149 (Fed. Cir. 2004) (“Enablement is a matter of
law that we review without deference; however, this Court reviews the factual
underpinnings of enablement for substantial evidence.”). Thus, I would vacate the
2008-1594, 2009-1070, -1088 2
judgment of non-enablement and remand for the district court to make the required
factual findings and to perform the necessary legal analysis in the first instance.
The parties do not dispute that Dr. Davis’s insight regarding galantamine’s utility
for treating Alzheimer’s Disease (AD) was correct; later animal studies and human
clinical trials proved and confirmed galantamine’s effectiveness. The relevant question
here is whether, at the time Dr. Davis filed her application, the patent’s written
description would have credibly revealed to an ordinarily skilled artisan galantamine’s
utility for AD treatment. See In re Cortright, 165 F.3d 1353, 1356 (Fed. Cir. 1999)
(noting that the patent’s written description must “illuminate a credible utility” to meet the
enablement requirement). The district court failed to answer that question. Instead, the
district court reasoned:
Dr. Davis did not receive any confirming data until after the
’318 patent was allowed. In view of the prior art disclosures
regarding the flaws of physostigmine [a compound
chemically similar to galantamine] in AD treatment,
discussed previously in the context of obviousness, it does
not follow that a person of ordinary skill in the art, reading
the ’318 patent, would have recognized that galanthamine
would be effective in treating AD in the absence of any
experimental proof. Put another way, since plaintiffs rely
exclusively on the prior art to establish enablement, the court
agrees with defendants that the ’318 patent cannot both be
non-obvious and enabled.
In re ’318 Patent Infringement Litig., 578 F. Supp. 2d 711, 736 (D. Del. 2008) (citation
and footnote omitted) (“District Court Decision”).
The district court’s reasoning is flawed. In general terms, an inventor may look at
the prior art differently than those before her, arrive at a novel and nonobvious insight,
and submit a patent application that compiles the prior art findings that led her to the
insight in such a way as to render obvious in hindsight what was wholly nonobvious at
2008-1594, 2009-1070, -1088 3
the time she filed her application. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 420
(2007) (“The question is not whether the combination was obvious to the patentee but
whether the combination was obvious to a person with ordinary skill in the art.”); Grain
Processing Corp. v. Am. Maize-Products Co., 840 F.2d 902, 907 (Fed. Cir. 1988) (In
considering obviousness, “[c]are must be taken to avoid hindsight reconstruction by
using ‘the patent in suit as a guide through the maze of prior art references, combining
the right references in the right way so as to achieve the result of the claims in suit.’”
(quoting Orthopedic Equip. Co. v. United States, 702 F.2d 1005, 1012 (Fed. Cir.
1983))). As a result, the proper focus when assessing enablement is on what is
disclosed in the patent, not what is taught in the prior art. See In re Ziegler, 992 F.2d
1197, 1201 (Fed. Cir. 1993) (“The how to use prong of section 112 incorporates as a
matter of law the requirement of 35 U.S.C. § 101 that the specification disclose as a
matter of fact a practical utility for the invention.” (emphases added)). In terms of the
present case, if Dr. Davis used her unique neuroendocrine perspective to examine the
prior art and arrive at a novel insight about galantamine based on selected prior art
findings, then the invention may be nonobvious; and if her patent disclosed those
selected findings in such a manner that a person of ordinary skill would credit her insight
regarding galantamine’s utility, then the invention is enabled.
Unfortunately, the district court committed error here by focusing generally on
what the prior art does or does not teach—the primary factual consideration underlying
obviousness—while neglecting to consider what the patent text discloses to an
ordinarily skilled artisan—the primary factual consideration underlying enablement.
Specifically, although the ’381 patent describes particular findings from six prior art
2008-1594, 2009-1070, -1088 4
publications, the district court noted only one such publication, see District Court
Decision, 578 F. Supp. 2d at 722, and did not determine how one of ordinary skill would
understand those cited findings, either independently or in combination with one
another. Thus, it is clear that the district court failed to focus on the necessary
underlying factual findings required to ascertain how an ordinarily skilled artisan would
understand the text of the patent for the purpose of establishing utility and thus
enablement. Under the district court’s erroneous approach, a court can invalidate for
lack of enablement a patent claim to a nonobvious combination of prior art elements
without ever considering what the patent actually discloses to one of ordinary skill in the
art. That is contrary to law.
Nor was the district court’s error harmless. See Majority Op. at 17 n.12.
Because the district court failed to make the required fact-findings, which stemmed from
its erroneous legal analysis, the majority must engage in extensive appellate fact-finding
in order to affirm the district court’s judgment. It is improper for an appellate court to
become the fact-finder. This court cannot presume to have the skills of the ordinary
artisan and cannot substitute its weighing of the evidence and factual conclusions for
those of the fact-finder. According to the majority, even though the district court failed to
make the appropriate findings or conduct the proper legal analysis, we need not vacate
here because “the record would not support a finding of utility.” Id. I respectfully
disagree. The record clearly includes evidence that may support a finding of utility,
2008-1594, 2009-1070, -1088 5
which the majority discounts in order to reach its erroneous conclusion. 1 For example,
Janssen provided evidence indicating that the specific findings recited in the patent, as
understood by one of ordinary skill in the art, disclose the following: (1) galantamine
administration increases blood cortisol levels and plasma acetylcholine when
muscarinic function is blocked, an indication that galantamine increases the function of
central nicotinic receptors, J.A. 8906–07; J.A. 9296–97; J.A. 9302–03; (2) galantamine
can cross into the brain and affect brain function, J.A. 9298; J.A. 9303; (3) galantamine
also has muscarinic effects in the brain, as indicated by its ability to improve memory in
1
In particular, the majority discounts both the disclosures made in the ’318
patent specification and the value of the post-filing test results offered to support a
finding of credible utility. In so doing, the majority attempts to distinguish this court’s
decision in In re Brana, 51 F.3d 1560 (Fed. Cir. 1995). See Majority Op. at 12 n.8. I do
not believe a distinction may so readily be made. Rather, as here, evidence of post-
filing test results was presented to support a finding of utility. That evidence, the court
found, “alone should have been sufficient to satisfy applicants’ burden [even assuming
the PTO had met its initial burden, thereby shifting the burden to applicants].” Brana,
51 F.3d at 1567. The majority’s claim that “unlike the present case, the testing [in
Brana] was submitted to the PTO during prosecution” is misleading. The appeal in
Brana was taken from the Board of Patent Appeals to this court during prosecution of a
patent application. And thus the Brana panel could not possibly have intended to
provide for a distinction between test results offered to support the credible utility of an
otherwise enabling disclosure pre– and post–patent issuance.
Moreover, the majority’s relentless focus on the need for timely test results as
evidence of utility appears to conflate credible utility in the context of enablement, at
issue here, with the notion of reduction to practice, which is not at issue. See, e.g.,
Majority Op. at 13 (“[N]o case has been called to our attention where utility was
established simply by analytic reasoning [without testing].”). Such a conflation risks the
introduction of an actual reduction-to-practice requirement into patent law, contrary to
more than a century of settled precedent. See The Telephone Cases, 126 U.S. 1, 536
(1888) (“The law does not require that a discoverer or inventor, in order to get a patent
for a process, must have succeeded in bringing his art to the highest degree of
perfection; it is enough if he describes his method with sufficient clearness and
precision to enable those skilled in the matter to understand what the process is, and if
he points out some practicable way of putting it into operation.”). To reiterate: the
question here is whether the written description of the ’318 patent would have
illuminated to a person of ordinary skill in the art a credible utility, not whether actual
utility was in fact demonstrated.
2008-1594, 2009-1070, -1088 6
animals that have been administered scopolamine (a muscarinic receptor blocker) to
induce amnesia, J.A. 8250; J.A. 8963; J.A. 9298–99; and (4) the patent discloses the
importance of nicotinic receptors in AD by describing an animal model for AD that
includes muscarinic and nicotinic receptors, J.A. 9302. Thus, one of ordinary skill—
having the relevant background knowledge and reading the patent text at the time the
application was filed—may have understood the patent to disclose the importance of
nicotinic receptors in AD intervention and galantamine’s promising effects on nicotinic
function and memory, such that she would recognize in the patent text galantamine’s
credible utility as an AD treatment. Moreover, the defendants’ expert agreed that “[a]
person in 1986 reading the patent would believe that galanthamine would be a
treatment for Alzheimer’s Disease.” J.A. 8327. Although the defendants’ expert gave
that testimony in support of his assertion that the claims are obvious, see Majority Op.
at 15 n.11, the testimony is nonetheless evidence that may support a finding for the
patentee on enablement. Because there is evidence of record that supports a
conclusion that the ’318 patent claims are not invalid, it is inappropriate for this court to
weigh the evidence and make contrary factual findings, especially in the absence of any
consideration by the district court of numerous prior art references that were specifically
discussed in the patent. Thus, in my judgment the district court’s failure to make the
necessary findings and conduct the proper legal analysis is reversible error. We should
remand to the district court for it to make the appropriate factual findings instead of
weighing the evidence ourselves.
Finally, I disagree with the majority opinion’s emphasis on the sufficiency of the
evidence presented by Janssen. As both parties’ correctly note, the question before us
2008-1594, 2009-1070, -1088 7
is “whether the defendants have shown, by clear and convincing evidence, that the
patent’s marshalling of evidence from the technical literature of galantamine’s effects,
combined with its model for Alzheimer’s therapy, is not sufficient for a skilled artisan to
believe the invention’s utility.” Appellant’s Br. at 27; Appellee’s Br. at 29. That is a
correct articulation of the question presented on appeal because, unlike many of the
cases upon which the majority and district court rely, the claims in dispute here are
issued patent claims, and are thus presumed valid. Yet, the majority fails to establish
the defendants’ burden and instead focuses almost exclusively on the sufficiency of
Janssen’s showing and the merit of Janssen’s arguments. See, e.g., Majority Op. at
15–16 (“Similarly, [the testimony of Janssen’s expert witness, Dr. Raskind] falls far short
of demonstrating that a person of ordinary skill in the art would have recognized that the
specification conveyed the required showing of utility.”). That focus is improper.
Because the district court erred as a matter of law and failed to make certain required
factual findings, we cannot defer to the district court’s legal conclusion or fact-findings,
and thus, it is particularly problematic for the majority to require Janssen to demonstrate
on appeal that its patent is valid.
For the foregoing reasons, I respectfully dissent from the majority’s decision.
2008-1594, 2009-1070, -1088 8