In re '318 Patent Infringement Litigation

• Decision Date: 25 September 2009
• Docket Number: No. 2009-1088.,No. 2009-1070.,No. 2008-1594.,2008-1594.,2009-1070.,2009-1088.
• Citation: 583 F.3d 1317
• Parties: 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. 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.
• Court: U.S. Court of Appeals — Federal Circuit

583 F.3d 1317

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.

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.

No. 2008-1594.

No. 2009-1070.

No. 2009-1088.

United States Court of Appeals, Federal Circuit.

September 25, 2009.

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, NY.

William A. Rakoczy, Rakoczy Molino Mazzochi Siwik LLP, of Chicago, IL, 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, IL, 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.

Before MAYER, GAJARSA, and DYK, Circuit Judges.

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. 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 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 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 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 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 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.

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