Acorda Therapeutics, Inc. v. Roxane Labs., Inc.

• Decision Date: 31 March 2017
• Docket Number: Civil Action No. 14-882-LPS (CONSOLIDATED)
• Parties: ACORDA THERAPEUTICS, INC., et al. Plaintiffs, v. ROXANE LABORATORIES, INC., et al. Defendants.
• Court: U.S. District Court — District of Delaware

ACORDA THERAPEUTICS, INC., et al. Plaintiffs,
v.
ROXANE LABORATORIES, INC., et al. Defendants.

Civil Action No. 14-882-LPS (CONSOLIDATED)

UNITED STATES DISTRICT COURT FOR THE DISTRICT OF DELAWARE

March 31, 2017

Jack B. Blumenfeld, Maryellen Noreika, MORRIS, NICHOLS, ARSHT & TUNNELL LLP, Wilmington, DE
Aaron Stiefel, Daniel P. Di Napoli, Jeffrey Martin, David Harris, Philip Smithback, Stephanie M. Piper, ARNOLD & PORTER KAYE SCHOLER LLP, New York, NY
Sylvia M. Becker, ARNOLD & PORTER KAYE SCHOLER LLP, Washington, DC
Soumitra Deka, ARNOLD & PORTER KAYE SCHOLER LLP, Palo Alto, CA
Jane Wasman, Anthony Michael, ACORDA THERAPEUTICS, INC., Ardsley, NY

Attorneys for Plaintiffs.

John C. Phillips, Jr., Megan C. Haney, PHILLIPS, GOLDMAN, MCLAUGHLIN, & HALL, P.A., Wilmington, DE
Charles B. Klein, WINSTON & STRAWN LLP, Washington, DC
George C. Lombardi, Samuel S. Park, Bryce A. Cooper, Reid Smith, WINSTON & STRAWN LLP, Chicago, IL

Attorneys for Defendants Apotex Corp., Apotex, Inc., Teva Pharmaceuticals USA Inc., and Roxane Laboratories, Inc.

Richard K. Herrmann, Mary B. Matterer, MORRIS JAMES LLP, Wilmington, DE
Robert L. Florence, Karen L. Carroll, Michael L. Binns, PARKER POE ADAMS & BERNSTEIN LLP, Atlanta, GA
Melanie Black Dubis, Catherine R.L. Lawson, Christopher M. Thomas, PARKER POE ADAMS & BERNSTEIN LLP, Raleigh, NC

Attorneys for Defendant Mylan Pharmaceuticals Inc.

MEMORANDUM OPINION

March 31, 2017
Wilmington, Delaware

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STARK, U.S. District Judge:

Acorda Therapeutics, Inc. and Alkermes Pharma Ireland Limited ("Plaintiffs") allege that Apotex Corp., Apotex Inc., Mylan Pharmaceuticals Inc., Roxane Laboratories, Inc., and Teva Pharmaceuticals, USA, Inc. ("Defendants") infringe several United States Patents. Patent No. 5,540,938 (the "'938 patent" or the "Elan Patent") relates to the use of a sustained-release formulation of 4-AP, administered once or twice daily, to treat neurological diseases including multiple sclerosis ("MS"). Patent Nos. 8,007,826 (the "'826 patent"), 8,663,685 (the "'685 patent"), 8,354,437 (the "'437 patent"), and 8,440,703 (the "'703 patent") (collectively, the "Acorda Patents") relate to the use of 10 mg sustained-release formulations of 4-AP to treat walking impairments in individuals with MS.

The Court adopted stipulated constructions for certain claim terms in the patents-in-suit. (D.I. 187, 193) With respect to disputed claim terms, the Court held a claim construction hearing on March 7, 2016 and issued an opinion and order on March 16, 2016. (D.I. 195, 196) In September 2016, the Court held a four-day bench trial. (See D.I. 266-69) ("Tr.") The parties have submitted a Statement of Uncontested Facts ("SUF") (D.I. 252-1 Ex. 1) and their competing versions of proposed findings of fact (D.I. 262, 263). They have also submitted extensive post-trial briefing, which concluded with supplemental letter briefs filed on March 6, 2017. (D.I. 265, 272, 273, 274, 278, 279)¹

Pursuant to Federal Rule of Civil Procedure 52(a), and after having considered the entire

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record in this case and the applicable law, the Court concludes that: (1) Defendants have stipulated that their proposed products infringe the asserted claims of the patents-in-suit; (2) Defendants have failed to prove by clear and convincing evidence that the asserted claims of the Elan Patent are invalid for obviousness; and (3) Defendants have proven by clear and convincing evidence that the asserted claims of the Acorda Patents are invalid for obviousness. The Court's findings of fact and conclusions of law are set forth in detail below.

FINDINGS OF FACT

This section contains the Court's findings of fact ("FF") on disputes raised by the parties during trial, as well as facts to which the parties have stipulated. Certain findings of fact are also provided in connection with the Court's conclusions of law.

A. The Parties

i. Plaintiffs

1. Plaintiff Acorda Therapeutics, Inc. ("Acorda") is a corporation organized and existing under the laws of the State of Delaware, having a principal place of business at 420 Saw Mill River Road, Ardsley, New York 10502. (SUF ¶ 1)

2. Plaintiff Alkermes Pharma Ireland Limited ("Alkermes") is an Irish corporation having a principal place of business at Connaught House, 1 Burlington Road, Dublin 4, Ireland. (SUF ¶ 2)

3. Plaintiffs have standing with respect to each of Plaintiffs' claims asserted against Defendants. (D.I. 254 ¶ 9)

ii. Defendants

4. Defendant Apotex Corp. (together with Apotex, Inc., "Apotex") is a corporation

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organized and existing under the laws of the State of Delaware, having a principal place of business at 2400 North Commerce Parkway, Suite 400, Weston, Florida 33326. (SUF ¶ 3)

5. Defendant Apotex Inc. is a corporation organized and existing under the laws of Canada, having its principal place of business at 150 Signet Drive, Toronto, Ontario M9L 1T9, Canada. (SUF ¶ 4)²

6. Defendant Mylan Pharmaceuticals Inc. ("Mylan") is a corporation organized and existing under the laws of the State of West Virginia, having a principal place of business at 781 Chestnut Ridge Road, Morgantown, West Virginia 26505. (SUF ¶ 5)

7. Defendant Roxane Laboratories, Inc. ("Roxane") is a corporation organized and existing under the laws of the State of Nevada, having a principal place of business at 1809 Wilson Road, Columbus, Ohio 43228. (SUF ¶ 6)

8. Defendant Teva Pharmaceuticals USA, Inc. ("Teva") is a corporation organized and existing under the laws of the State of Delaware, having a principal place of business at 1090 Horsham Road, North Wales, Pennsylvania 19454. (SUF ¶ 7)

B. Multiple Sclerosis

9. Multiple Sclerosis ("MS") is a chronic disease of the neuroimmunological system. (Peroutka Tr. at 52-53)³ MS causes a loss of myelin, the fatty material that insulates many of the nerves in the central nervous system. (Peroutka Tr. at 53-54; see also Lublin Tr. at 392) This

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loss of myelin is called demyelination. (Peroutka Tr. at 52-53; Lublin Tr. at 392)

10. Demyelination slows or blocks the movement of nerve impulses along the nerve, resulting in diminished coordination of nervous system signals. (Lublin Tr. at 392; Goodman Tr. at 432-33) This disruption results in a wide variety of symptoms affecting a range of body parts and systems. (Lublin Tr. at 392) The symptoms of MS may include walking impairment, visual difficulty, fatigue, bladder dysfunction, tingling or pain, sexual dysfunctions, balance problems, and cognitive changes. (Id.; Peroutka Tr. at 55; Goodman Tr. at 433)

11. Weakness in the legs and/or alterations in walking are among the most common symptoms of MS. (Peroutka Tr. at 55; Goodman Tr. at 432) Roughly 50-75% of MS patients experience difficulty walking. (Peroutka Tr. at 55)

12. MS may also cause brain scarring, which can lead to permanent symptoms and make MS patients susceptible to seizures or convulsions. (Goodman Tr. at 430-31, 442)

13. There is substantial variability in how MS manifests itself both among different patients and within a single patient over time. (Goodman Tr. at 431-32, 434-36; Peroutka Tr. at 121) Any particular patient's symptoms may vary on a day-to-day, or even hour-to-hour, basis. (Goodman Tr. at 435-36; Peroutka Tr. at 121-22)

C. Treating MS

14. There is presently no known cure for MS. (Peroutka Tr. at 53-54)

15. Current treatments for MS fall into two categories: (1) the use of disease-modifying agents, which alter the course of the disease and lessen the chance that a patient's condition deteriorates; and (2) therapies that attempt to alleviate the individual symptoms of MS, to improve a patient's quality of life. (Lublin Tr. at 393-94)

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16. Designing and interpreting the results of clinical trials for MS therapies is complex because the wide variety of MS symptoms makes it difficult to select clinical endpoints (i.e., measures of efficacy) and leads to mixed results. (Goodman Tr. at 436-37) In particular, it can be difficult to determine whether changes in symptoms result from the treatment being tested, from independent changes in the course of the disease, or from day-to-day variability in symptoms. (Id. at 436-38)

17. Placebo effect is also a problem in analyzing results of MS trials. (Lublin Tr. at 401-05) Placebo effect is an improvement in symptoms among test subjects who do not receive a drug. (See id. at 412; Goodman Tr. at 468-69)

18. There are a number of methods for assessing the disease state of a patient with MS. Some measures consist of numerical scales designed to interpret patients' subjective assessment of particular symptoms - such as fatigue or walking - or their condition in general. (Goodman Tr. at 455, 481, 518-19) Other measures, such as timed walking tests, provide objective, quantitative indications of results. (Lublin Tr. at 394)

19. In addition to tests that measure clinically manifested symptoms, other tests directly assess nerve impulse transmission. For example, researchers and clinicians can measure subclinical visually evoked potentials ("VEP") to detect the speed of nerve impulse transmissions. (JTX-0065;⁴ Lublin Tr. at 394-96) Research established in the 1970s that VEP could serve as a valuable test in the early diagnosis of MS. (JTX-0065; Lublin Tr. at 395-97) By the 1980s and 1990s, VEP was also being used in conjunction with clinical metrics as a measure

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of therapeutic efficacy in clinical trials. (JTX-0025) VEP is an especially useful tool because it is not susceptible to placebo effect. (Lublin Tr. at 401-05)

D. Ampyra®

20. Acorda holds an FDA-approved New Drug Application ("NDA"), No. 022250, for the use of 10 mg dalfampridine extended release tablets to improve walking in patients with MS. (D.I. 1 ¶ 30; SUF ¶ 8) Acorda markets the approved drug product under the registered name Ampyra®. (D.I. 1 ¶ 30; SUF ¶ 8)

21. Dalfampridine, also known as fampridine, 4-Aminopyridine, or "4-AP," is the active ingredient in Ampyra®. Ampyra® was the first FDA-approved use of 4-AP. (SUF ¶ 9, 68)

22. The FDA approved...