Pfizer Inc. v. Teva Pharmaceuticals U.S.A., Inc. (882 F. Supp. 2d 643, 2012)

United States District Court for the District of Delaware 2012-07-19

Food and Drugs Indians Patents

Citations

Full opinion text

MEMORANDUM

GREGORY M. SLEET, Chief Judge.

I. INTRODUCTION

In this consolidated patent infringement action, plaintiffs Pfizer Inc., Warner-Lambert Company, L.L.C., C.P. Pharmaceuticals International C.V., and Northwestern University (collectively, “the plaintiffs”) allege that pharmaceutical products proposed by defendants Actavis Elizabeth, L.L.C., Actavis, Inc., Alphapharm Pty. Ltd., Mylan Pharmaceuticals, Inc., Cobalt Laboratories, Inc., Lupin Ltd., Sandoz, Inc., Sun Pharma Global, Inc., Sun Pharmaceutical Industries, Ltd., Sun Pharmaceutical Industries, Inc., Teva Pharmaceuticals U.S.A., Inc., Teva Pharmaceutical Industries, Ltd., Wockhardt Limited, and Wockhardt U.S.A., L.L.C. (collectively, “the defendants”) infringe the asserted claims of the patents-in-suit. (D.I. 1.) The court held a nine-day bench trial in this matter on October 11 through October 21, 2011. (D.I. 362-370.) Presently before the court are the parties’ post-trial Findings of Fact and Conclusions of Law concerning the validity of the patents-in-suit and whether the defendants’ proposed products infringe the patents-in-suit. (D.I. 349-353.)

Pursuant to Federal Rule of Civil Procedure 52(a), and after having considered the entire record in this case and the applicable law, the court concludes that: (1) the asserted claims of the patents-in-suit are not invalid due to obviousness; (2) the asserted claims of the patents-in-suit are not invalid due to anticipation; (3) the asserted claims of the '819 and '175 Patents are entitled to a November 27, 1990 priority filing date; (4) the asserted claims of the '819 Patent are not invalid for written description; (5) the asserted claims of the '819 Patent are not invalid due to improper inventorship; (6) the defendants’ proposed products do not literally infringe claims 1 and 4 of the '819 Patent; (7) the defendants’ proposed products infringe claims 1 and 4 of the '819 Patent under the doctrine of equivalents; (8) the '819 and '876 Patents’ term extensions are not invalid under 35 U.S.C. § 156; and (9) each of the parties’ Rule 52(c) motions are granted in part and denied in part. These findings of fact and conclusions of law are set forth in further detail below.

II. FINDINGS OF FACT

A. The Parties

1. Plaintiff Pfizer Inc. (“Pfizer”) is a corporation organized and existing under the laws of the State of Delaware, having a place of business at 235 East 42nd Street, New York, New York 10017.

2. Plaintiff Warner-Lambert L.L.C. (“Warner-Lambert”) is a limited liability company organized and existing under the laws of the State of Delaware, having a place of business at 235 East 42nd Street, New York, New York 10017. Pfizer Inc. is the ultimate parent of Warner-Lambert Company L.L.C.

3. Plaintiff C.P. Pharmaceuticals International C.V. (“CPPI CV”) is a limited partnership organized under the laws of the Netherlands, having its registered seat in Rotterdam, and is represented by its general partners, Pfizer Manufacturing L.L.C., a limited liability company organized under the laws of the State of Delaware and having a place of business at 235 East 42nd Street, New York, New York 10017 and Pfizer Production L.L.C., a limited liability company organized under the laws of the State of Delaware, and having a place of business at 235 East 42nd Street, New York, New York 10017, jointly acting, each in its capacity as a general partner for and on behalf of CPPI CV. Pfizer Inc. is a limited partner of and is the ultimate parent of all other partners of CPPI CV.

4. Plaintiff Northwestern University (“Northwestern”) is an Illinois corporation, having its principal place of business at 633 Clark Street, Evanston, Illinois.

5. Defendant Actavis Elizabeth L.L.C. is a limited liability company organized and existing under the laws of the State of Delaware, having a principal place of business at 200 Elmora Avenue, Elizabeth, New Jersey. Actavis Elizabeth L.L.C. is a wholly owned subsidiary and agent of defendant Actavis, Inc.

6. Defendant Actavis, Inc. (together with Actavis Elizabeth L.L.C., “Actavis”) is a corporation organized and existing under the laws of the State of Delaware, having a principal place of business at 60 Columbia Road, Building B, Morristown, New Jersey.

7. Defendant Alphapharm Pty. Ltd. (“Alphapharm”) is a corporation organized and existing under the laws of Australia, having a principal place of business at Chase Building 2, Wentworth Park Road, Glebe, NSW 2037, Australia.

8. 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.

9. Defendant Cobalt Laboratories, Inc. is a corporation organized and existing under the laws of the State of Delaware, having a principal place of business at 24840 South Tamiami Trail, Ste. 1, Bonita Springs, Florida.

10. Defendant Cobalt Pharmaceuticals, Inc. (together with Cobalt Laboratories, Inc., “Cobalt”), a sister company of Cobalt Laboratories, Inc., is a corporation organized and existing under the laws of Canada having a principal place of business at 6500 Kitmat Road, Mississauga, Ontario, Canada.

11. Defendant Lupin Ltd. is a company organized and existing under the laws of India, having a principal place of business at Laxmi Towers, B Wing, Bandra Kurla Complex, Bandra (East), Mumbai, Maharashtra 400 051, India.

12. Defendant Lupin Pharmaceuticals, Inc. (together with Lupin Ltd., “Lupin”) is a corporation organized and existing under the laws of the State of Virginia, having a principal place of business at 111 South Calvert Street, Ste. 2150, Baltimore, Maryland. Lupin Pharmaceuticals, Inc. is a wholly-owned subsidiary of Lupin Ltd.

13. Defendant Sandoz, Inc. (“Sandoz”) is a corporation organized and existing under the laws of the State of Colorado, having a principal place of business at 506 Carnegie Center, Ste. 400, Princeton, New Jersey.

14. Defendant Sun Pharma Global, Inc. is a company organized and existing under the laws of the British Virgin Islands, having a principal place of business at Akara Building, 24 De Castro Street, Wilkhams Clay 1 Road, Town Tartola, British Virgin Islands. Sun Pharma Global Inc. is a wholly-owned subsidiary of defendant Sun Pharmaceutical Industries Ltd.

15. Defendant Sun Pharma Industries Ltd. is a company organized and existing under the laws of India, having a principal place of business at Acme Plaza, Andheri Kurla Road, Andheri East, Mumbai 400 059, India.

16. Defendant Sun Pharmaceutical Industries, Inc. (together with Sun Pharma Global, Inc. and Sun Pharma Industries Ltd., “Sun Pharma”) is a company organized and existing under the laws of the State of Michigan, having a principal place of business at 270 Prospect Plains Road, Cranbury, New Jersey 08512. Sun Pharmaceutical Industries, Inc. is a wholly owned subsidiary of defendant Sun Pharmaceutical Industries, Ltd.

17. Defendant Teva Pharmaceutical Industries, Ltd. (“Teva Ltd.” and. together with Teva Pharmaceuticals U.S.A., Inc., “Teva”) is a corporation organized and existing under the laws of Israel, having a principal place of business at 5 Basel Street, Petach Tikva 49131, Israel.

18. Defendant Teva Pharmaceuticals U.S.A., Inc. (“Teva U.S.A.” and, together with Teva Pharmaceutical Industries, Ltd., “Teva”) is a Delaware corporation having a principal place of business at 1090 Hors: ham Road, North Wales, Pennsylvania 19454.

19. Defendant Wockhardt Limited is a company organized and existing under the laws of India, having a principal place of business at Wockhardt Towers, Bandra Kurla Complex, Bandra East, Mumbai, 400 511, India.

20. Defendant Wockhardt U.S.A., L.L.C. (together with Wockhardt Limited, “Wockhardt”) is a limited liability company organized and existing under the laws of the State of Delaware, having a place of business at 20 Waterview Boulevard, Parsippany, New Jersey 07054. Wockhardt U.S.A., L.L.C. is a'wholly-owned subsidiary and agent of defendant Wockhardt Limited.

B. Background

21. 4-amino-3-(2-methylpropyl) butanoic acid is also known as “3-isobutylGABA” or “3IBG” and is used to treat seizures:

22. 3-isobutylGABA is a chiral compound: it exists in two different mirror-image orientations in space, called “enantiomers.” 3-isobutylGABA has the structure of gamma-arnino butyric acid (“GABA”), with a four-carbon isobutyl group added to the molecule in the “3-position,”

23. A 50:50 mixture of enantiomers is called a “racemate” or a “racemic mixture.”

24. Chemists distinguish between enantiomers by assigning an “R” or “S” prefix to the compound name depending on the “priorities of the substituents around the [chiral] carbon atom:” These prefixes allow a chemist to immediately understand the three-dimensional structure of each enantiomer.

25. Chemists also designate enantiomers as (+) or (-) depending on the direction in which the enantiomer rotates polarized light, which is an inherent property of each enantiomer.

26. S-( + )^-amino-3-(2-methylpropyl) butanoic acid (hereinafter, “S-3-isobutyl-GABA”) is the S-enantiomer of 3-isobutyl-GABA, which is generally known as “pregabalin” and is the active ingredient in the product at issue, Lyrica®.

27. Pfizer, itself and through its wholly owned subsidiary, CPPI CV, holds approved New Drug Application (“NDA”) Nos. 21-446, 21-723, and 21-724 for pregabalin capsules in 25, 50, 75, 100, 150, 200, 225, and 300 mg dosage strengths, which Pfizer sells under the trade name Lyrica®.

28. Pfizer also holds NDA No. 22-488 for pregabalin oral solution containing 20 mg/mL of pregabalin.

29. Lyrica® is approved by the United States Food and Drug Administration (the “FDA”) for adjunctive therapy of partial onset seizures, as well as for the treatment of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia.

30. The FDA first approved Lyrica® in December 2004 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy and post herpetic neuralgia.

31. In June 2005, the FDA approved Lyrica® as adjunctive therapy for the treatment of partial onset seizures and, in June 2007, the FDA approved Lyrica® for the treatment of fibromyalgia.

32. Pursuant to 21 U.S.C. § 355(b)(1) and attendant FDA regulations, U.S. Patent Nos. 6,197,819 (“the '819 Patent”), 5,563,-175 (“the '175 Patent”), and 6,001,876 (“the '876 Patent”), as well as U.S. Reissued Patent No. RE 41,920 (“the RE '920 Patent”) are listed in the FDA publication, “Approved Drag Products with Therapeutic Equivalence Evaluations” (the “Orange Book”), with respect to Lyrica®. The RE '920 Patent is a reissue of the '876 Patent.

C. The Patents-in-Suit

27. The '819 Patent issued on March 6, 2001 and is entitled “Gamma Amino Butyric Acid Analogs and Optical Isomers.” The '819 Patent lists two inventors, Dr. Richard Silverman and Dr. Ryszard Andruszkiewicz.

28. Northwestern holds title to the '819 Patent, and has granted Warner-Lambert an exclusive license to the Patent.

29. The '819 Patent claims priority to the following applications: U.S. Patent Application No. 07/618,692 (“Initial Application” or “the '692 application”), filed on November 27, 1990; U.S. Patent Application No. 07/886,080 (“First CIP” or “the '080 application”), filed on May 20,1992 as a “continuation-in-part” of the Initial Application; U.S. Patent Application No. 08/064,285 (“Second CIP” or “the '285 application”), filed on May 18,1993 as a “continuation-in-part” of the First CIP; and U.S. Patent Application No. 08/420,905 (“Final Application” or “the '905 application”), filed on April 11, 1995 as a “continuation” of the Second CIP.

30. The '175 Patent issued on October 8, 1996 and is entitled “GABA and L-Glutamic Acid Analogs For Antiseizure Treatment.”

31. On February 22, 2005, the United States Patent and Trademark Office (“the PTO”) issued a Certificate of Correction naming Richard B. Silverman, Ryszard Andruszkiewicz, and Po-Wai Yuen as inventors of the '175 Patent.

32. Northwestern holds title to the '175 Patent, and has granted Warner-Lambert an exclusive license to the Patent,

33. On March 1, 2011, the PTO issued a Certification of Correction, correcting the “Related Application Data” field on the '175 Patent to read “Divisional of Ser. No. 08/420,905, filed Apr. 11, 1995.” With this correction, the '175 Patent claims priority to the '692 application, filed on November 27, 1990, through the '080, '285, and '905 applications.

34. The '876 patent issued on December 14, 1999 and is entitled “Isobutyl GABA and Its Derivatives for the Treatment of Pain.” The sole inventor of the '876 Patent, Dr. Lakhbir Singh, assigned it to Warner-Lambert, which held title to the '876 Patent.

35. On November 9, 2007, Warner-Lambert filed Application No. 11/983,750 with the PTO, seeking reissue of the '876 Patent and, on November 9, 2010, the PTO reissued the '876 Patent as the RE '920 Patent.

36. At the time of its reissue, the RE '920 Patent was assigned to Warner-Lambert and Warner-Lambert continues to hold title to the RE '920 Patent.

37. The RE '920 Patent claims priority to U.S. Provisional Application No. 60/022,-337, filed July 24,1996.

38. On February 25, 2005, Pfizer applied for patent term extensions under 35 U.S.C. § 156 for the '819 Patent and for its '876 Patent (ultimately reissued as the RE '920 Patent), in view of the FDA’s approval of two of its NDAs related to Lyrica®. Pfizer stated in its application that because the FDA approved the two Lyrica® NDAs on the same day, both patents were entitled to extensions under the statute. The PTO agreed and extended the term of both patents through December 30, 2018.

1. The Asserted Claims

39. The plaintiffs are asserting claims 1, 2, and 4 of the '819 Patent against all defendants.

40. The plaintiffs are asserting claim 1 of the '175 Patent against defendants Actavis, Cobalt, Lupin, and Sun (collectively, “the '175 Patent defendants”).

41. The plaintiffs are asserting that: (1) Actavis’ ANDA No. 91-025 infringes claims 2, 5, 13, 15-17, 19-22, and 24-25 of the RE '920 Patent; (2) Alphapharm and Mylan’s ANDA No. 91-228 infringes claims 2, 5, 13, 15-17, 19-22, and 24-25 of the RE '920 Patent; (3) Lupin’s ANDA Nos. 91-040 and 201989 infringe claims 2, 5, 13, 15-17, 19-22, and 24-25 of the RE '920 Patent; (4) Sandoz’s ANDA No. 91-229 infringes claims 2, 5, 13, 16, 17, 19-22, and 24 of the RE '920 Patent; and (5) Teva’s ANDA Nos. 91-219 and 91-224 infringe claims 2, 5, 13, 16-17, 19-22, and 24 of the RE '920 Patent.

i.'819 Patent, Claim 1

42. Claim 1 of the '819 Patent claims: “[a] compound of the formula (S)-( + )^t-amino-3-(2-methylpropyl) butanoic acid as a single optical isomer.”

43. The court has construed the term “(S)-( + )-4-amino-3-(2-methylpropyl) butanoic acid as a single optical isomer,” as used in claim 1, to mean 4-arnino-3-(2-methylpropyl) butanoic acid “in single (S)- ( + ) isomer form only, free of the R-(-) isomer form.”

ii. '819 Patent, Claim 2

44. Claim 2 of the '819 Patent claims “4-amino-3-(2-methylpropyl) butanoic acid, or a pharmaceutically acceptable salt thereof.”

45. The court has construed the term “4-amino-3-(2-methylpropyl) butanoic acid” in claim 2 to cover “the chemical compound 4-amino-3-(2-methylpropyl) butanoic acid ... without limitation as to sterochemical form.”

iii. '819 Patent, Claim 4

46. Claim 4 of the '819 Patent claims “[a] pharmaceutical composition comprising a compound [of] any one of claims 1 or 3, together with a pharmaceutically acceptable carrier.”

iv. '175 Patent, Claim 1

47. Claim 1 of the '175 Patent claims “[a] method of treating a patient having seizure disorders which comprises administering to said patient an effective amount of a substantially pure compound of the formula (S)-( + )-4-amino-3-(2-methylpropyl) butanoic acid.”

48. The parties have construed “substantially pure” in claim 1 of the '175 Patent to mean “the compound [ (S)-( + )-4-3-(2-me-thylpropyl) butanoic acid] containing primarily the (S)-(+)enantiomer.”

v.RE '920 Patent, Claim 2

49. Claim 2 of the RE '920 Patent reads: “[a] method for treating pain comprising administering a therapeutically effective amount of [pregabalin], or a pharmaceutically acceptable salt thereof, ... to a mammal in need of said treatment.”

vi.RE '920 Patent, Claim 5

50. Claim 5 reads: “[a] method according to claim 2 wherein the pain treated is neuropathic pain.”

vii. RE ’920 Patent, Claim 13

51. Claim 13 reads: “[a] method according to claim 2 wherein the pain treated is acute herpetic and postherpetic pain.”

viii. RE '920 Patent, Claim 15

52. Claim 15 reads: “[a] method according to claim 2 wherein the pain treated is idiopathic pain.”

ix. RE '920 Patent, Claim 16

53. Claim 16 reads: “[a] method for treating pain comprising administering a therapeutically effective amount of [pregabalin], or a pharmaceutically acceptable salt thereof, to a human in need of said treatment.”

x. RE '920 Patent, Claim 17

54. Claim 17 reads: “[a] method according to claim 16 wherein the compound administered is [pregabalin].”

xi. RE '920 Patent, Claim 19

55. Claim 19 reads: “[a] method according to claim 17 wherein the pain treated is chronic pain.”

xii. RE '920 Patent, Claim 20

56. Claim 20 reads: “[a] method according to claim 17 wherein the pain treated is selected from the group consisting of inflammatory pain, neuropathic pain, cancer pain, postoperative pain, and idiopathic pain.”

xiii. RE '920 Patent, Claim 21

57. Claim 21 reads: “[a] method according to claim 17 wherein the pain treated is neuropathic pain.”

xiv. RE '920 Patent, Claim 22

58. Claim 22 reads: “[a] method according to claim 17 wherein the pain treated is diabetic neuropathic pain.”

xv. RE '920 Patent, Claim 24

59. Claim 24 reads: “[a] method according to claim 17 wherein the pain treated is postherpetic pain.”

xvi. RE '920 Patent, Claim 25

60. Claim 25 reads: “[a] method according to claim 17 wherein the pain treated is fibromyalgia pain.”

2. The Accused Products

i. ANDA No. 91-025 Submitted by Actavis

61. Actavis submitted Abbreviated New Drug Application (“ANDA”) No. 91-025 (“Actavis’ ANDA”) to the FDA on December 30, 2008, pursuant to 21 U.S.C. § 355®, seeking approval to market pregabalin capsules in 25, 50, 75,100,150, 200, 225, and 300 mg dosage strengths (“Actavis’ Proposed Product”).

62. Actavis’ ANDA refers to and relies upon the Lyrica® NDAs and contains data that, according to Actavis, demonstrates the bioequivalence of Actavis’ Proposed Product and Lyrica®.

63. Actavis included certifications in its ANDA, pursuant to 21 U.S.C. § 355®(2)(A)(vii)(IV), that the '819, '876, and '175 Patents are invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Actavis’ Proposed Product.

64. On March 26, 2009, Actavis sent its Paragraph IV certifications to the plaintiffs, providing its asserted factual and legal bases for its contentions that the '819, '876, and '175 Patents are not infringed and are invalid or unenforceable.

65. In response to Actavis’ Notice, on April 29, 2009, the plaintiffs brought suit against Actavis for infringement of the '819, '876, and '175 Patents, pursuant to 35 U.S.C. § 271(e)(2)(A).

66. On December 29, 2010, after the RE '920 Patent issued, Actavis sent another Notice of its Paragraph IV certification with asserted factual and legal bases for non-infringement and invalidity. The plaintiffs thereafter amended their complaint against Actavis to include claims for infringement of the '819, RE '920, and '175 Patents.

67. The plaintiffs have asserted infringement of claims 1, 2, and 4 of the '819 Patent, claim 1 of the '175 Patent, and claims 2, 5, 13, 15-17, 19-22, and 24-25 of the RE '920 Patent, against Actavis.

ii. ANDA No. 91-228 Submitted by Alphapharm & Mylan

68. Alphapharm submitted ANDA No. 91-228 to the FDA on December 30, 2008, pursuant to 21 U.S.C. § 355(j), seeking approval to market pregabalin capsules in 25, 50, 75, 100, 150, 200, 225, and 300 mg dosage strengths (“Alphapharm’s Proposed Product” or “Mylan’s Proposed Product”). Alphapharm designated Mylan as its U.S. agent for pregabalin ANDA No. 91-228 (hereinafter, “Mylan’s ANDA”).

69. Mylan’s ANDA refers to and relies upon the Lyrica® NDAs and contains data that, according to Alphapharm and Mylan, demonstrates the bioequivalence of the generic product of Mylan’s Proposed Product and Lyrica®.

70. Mylan’s ANDA includes a certification, pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV), that the '876 Patent is invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Mylan’s Proposed Product.

71. On April 29, 2009, the plaintiffs filed suit against Alphapharm and Mylan for infringement of the '876 Patent, pursuant to 25 U.S.C. § 271(e)(2)(A).

72. On March 1, 2010, Alphapharm filed a revised Patent Certification with the FDA and amended Mylan’s ANDA to include a certification, pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV), that the '819 Patent is invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Mylan’s Proposed Product.

73. On March 12, 2010, the plaintiffs sued Alphapharm and Mylan for infringement of the '819 Patent, pursuant to 35 U.S.C. § 271(e)(2)(A).

74. On January 26, 2011, after the RE '920 Patent issued, the plaintiffs amended their complaint against Alphapharm and Mylan to include claims for infringement of the RE '920 Patent.

75. On March 30, 2011, Mylan notified Pfizer and Warner-Lambert that Mylan had filed an amended certification with the FDA to include a certification, pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV), that the RE '920 Patent is invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Mylan’s Proposed Product.

76. The plaintiffs have asserted infringement of claims 1, 2, and 4 of the '819 Patent and claims 2, 5, 13, 15-17, 19-22, and 24-25 of the RE '920 Patent against Alphapharm and Mylan.

77. On March 21, 2011, Alphapharm and Mylan timely filed a Motion for Leave to File an Amended Answer, Defenses, and Counterclaims to the Amended Complaint to add an affirmative defense and counterclaim based on inequitable conduct.

iii. ANDA No. 91-221 Submitted by Cobalt

78. Cobalt submitted ANDA No. 91-221 (“Cobalt’s ANDA”) to the FDA, pursuant to 21 U.S.C. § 355(j), seeking approval to market pregabalin capsules in 25, 50, 75, 100, 150, 200, 225, and 300 mg dosage strengths (“Cobalt’s Proposed. Product”).

79. Cobalt’s ANDA refers to and relies upon the Lyrica® NDAs and contains data that, according to Cobalt, demonstrates the bioequivalence of Cobalt’s Proposed Product and Lyrica®.

80. Cobalt included certifications in its ANDA, pursuant to 21 U.S.C. § 355Cj)(2)(A)(vii)(rVr), that the '819 Patent and the '175 Patent are invalid, unenforceable, or will not be infringed by the commercial, manufacture, use, or sale of Cobalt’s Proposed Product.

81. On April 29, 2009, the plaintiffs filed suit against Cobalt alleging infringement of the '819 and '175 Patents, pursuant to 35 U.S.C. § 271(e)(2)(A).

82. The plaintiffs have asserted infringement of claims 1, 2, and 4 of the '819 Patent and claim 1 of the '175 Patent against Cobalt.

iv. ANDA Nos. 91-040 & 201989 Submitted by Lupin

83. Lupin submitted ANDA No. 91-040 (“Lupin’s Capsule ANDA”) to the FDA, pursuant to 21 U.S.C. § 355(j), seeking approval to market pregabalin capsules in 25, 50, 75, 100, 150, 200, 225, and 300 mg dosage strengths (“Lupin’s Proposed Capsule Product”).

84. Lupin included certifications in its Capsule ANDA, pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV), that the '819 Patent and the '175 Patent are invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Lu-pin’s Proposed Capsule Product,

85. On April 29, 2009, the plaintiffs sued Lupin for infringement of the '819 and the '175 Patents, pursuant to 35 U.S.C. § 271(e)(2)(A), based on Lupin’s Capsule ANDA.

86. On May 20, 2009, the plaintiffs filed an amended complaint asserting infringement of only the '819 and '175 Patents, pursuant to 35 U.S.C. § 271(e)(2)(A), based on Lupin’s Capsule ANDA.

87. By letter dated August 31, 2010, Lu-pin informed the plaintiffs that it had submitted ANDA No. 201989 (“Lupin’s OS ANDA” and, together with Lupin’s Capsule ANDA, “Lupin’s ANDAs”) to the FDA, pursuant to 21 U.S.C. § 355Q), seeking approval to market pregabalin oral solution, 20 mg/mL dosage strength (“Lu-pin’s Proposed OS Product” and, together with Lupin’s Proposed Capsule Product, “Lupin’s Proposed Products”).

88. Lupin included certifications in its OS ANDA, pursuant to 21 U.S.C. § 355Cj)(2)(A)(vii)(IV), that the '819, '876, and '175 Patents are invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Lu-pin’s Proposed OS Product.

89. On October 6, 2011, the plaintiffs sued Lupin for infringement of the '819, '876, and '175 Patents, pursuant to 35 U.S.C. § 271(e)(2)(A), based on Lupin’s OS ANDA.

90. On June 2, 2011, after the RE '920 Patent issued, the plaintiffs amended their complaint against Lupin to include claims for infringement of the '819, RE '920, and '175 Patents based on Lupin’s OS ANDA.

91. The plaintiffs have asserted infringement of claims 1, 2, and 4 of the '819 Patent, claim 1 of the '175 Patent, and claims 2, 5, 13, 15-17, 19-22, and 24-25 of the RE '920 Patent, against Lupin.

v. ANDA No. 91-229 Submitted by Sandoz

92. Sandoz filed ANDA No. 91-229 (“Sandoz’s ANDA”) with the FDA, pursuant to 21 U.S.C. § 335®, on December 20, 2008, seeking approval to market 25, 50, 75, 100, 150, 200, 225, and 300 mg dosage capsules (“Sandoz’s Proposed Product”).

93. Sandoz’s ANDA refers to and relies upon the Lyrica® NDAs and contains data that, according to Sandoz, demonstrates the bioequivalence of Sandoz’s Proposed Product and Lyrica®.

94. Sandoz included certifications in its ANDA, pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV), that the '819, '876, and '175 Patents are invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of San-doz’s Proposed Product.

95. On April 29, 2009, the plaintiffs sued Sandoz for infringement of the '819, '876, and '175 Patents, pursuant to 35 U.S.C. § 271(e)(2)(A).

96. On March 9, 2011, after the RE '920 Patent issued, the plaintiffs amended their complaint against Sandoz to include claims of infringement of the '819 and RE '920 Patents, and to drop the claims for infringement of the '175 Patent.

97. The Section viii statement in the November 12, 2010 Certification indicated that Sandoz is not seeking approval for the treatment of seizure disorder and fibromyalgia. Concurrent with the November 12, 2010 Patent Certification, Sandoz submitted an amended label in which all references to seizure disorder and fibromyalgia (or idiopathic pain) were deleted.

98. On March 30, 2011, Sandoz submitted a second revised Paragraph IV Patent Certification with the FDA indicating that the claims of the '876, '819, and RE '920 Patents are invalid, unenforceable, and/or will not be infringed by the manufacture, use, or sale of the Sandoz pregabalin capsules; excepting where uses for which Sandoz is not presently seeking approval under Section viii.

99. The March 30, 2011, revised Patent Certification contained a Section viii statement that Sandoz “is not presently seeking approval” for uses for fibromyalgia in connection with the '876 and RE '920 Patents.

100. The plaintiffs have asserted infringement of claims 1, 2, and 4 of the '819 Patent and claims 2, 5, 13, 15-17, 19-22, and 24 of the RE '920 Patent against Sandoz. The plaintiffs withdraw without prejudice all allegations of infringement of claims 15 and 25 of the RE '920 Patent against Sandoz in view of Sandoz’s proposed label amendment associated with ANDA No. 91-229, which does not indicate treatment of fibromyalgia. The plaintiffs reserve the right to reassert claims 15 or 25 of the RE '920 Patent if Sandoz amends the label associated with ANDA No. 91-229 to indicate treatment of fibromyalgia before the RE '920 Patent expires. San-doz reserves the right to raise any defense should the plaintiffs reassert claims 15 or 25 of the RE '920 Patent in the future, but Sandoz would not contest the reassertion of those claims on any basis related to the plaintiffs’ agreement to withdraw them now.

101. On March 21, 2011, Sandoz filed a motion to request leave to file amended affirmative defenses and counterclaims of inequitable conduct in its Answer to the plaintiffs’ amended complaint.

102. On April 5, 2011, the plaintiffs responded to Sandoz’s March 21, 2011 motion, stating that they did not oppose the motion.

vi. ANDA No. 91-157 Submitted by Sun Pharma

103. Sun Pharma submitted ANDA No. 91-157 (“Sun’s ANDA”) to the FDA, pursuant to 21 U.S.C. § 355(j), seeking approval to market pregabalin capsules in 25, 50, 75, 100, 150, 200, 225, and 300 mg dosage strengths (“Sun Pharma’s Proposed Product”).

104. Sun Pharma’s ANDA refers to and relies upon the Lyrica® NDAs and contains data that, according to Sun, demonstrates the bioequivalence of Sun Pharma’s Proposed Product with Lyrica®.

105. Sun Pharma included certifications in its ANDA, pursuant to 21 U.S.C, § 355Cj)(2)(A)(vii)(IV), that the '819 Patent is invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Sun’s Proposed Product.

106. On April 29, 2009, the plaintiffs sued Sun Pharma for infringement of the '819 Patent, pursuant to 35 U.S.C. § 271(e)(2)(A).

107. Pfizer and Northwestern received from Sun Pharma a letter, dated May 26, 2009, stating that Sun Pharma had included a certification in Sun Pharma’s ANDA, pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV), that the '175 Patent is invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Sun Pharma’s Proposed Product.

108. On June 15, 2009, the plaintiffs amended their complaint against Sun Pharma to include claims for infringement of the '175 Patent, pursuant to 35 U.S.C. § 271(e)(2)(A).

109. In January 2011, Sun Pharma sent samples of Sun Pharma’s Proposed Product to SSCI (a division of Aptuit, Inc.) in West Lafayette, Indiana. SSCI received the samples.

110. The plaintiffs have asserted infringement of claims 1, 2, and 4 of the '819 Patent and claim 1 of the '175 Patent against Sun Pharma.

vii. ANDA Nos. 91-219 & 91-224 Submitted by Teva

111. Teva USA submitted ANDA Nos. 91-219 and 91-224 (collectively, “Teva’s ANDAs”) to the FDA, pursuant to 21 U.S.C. § 355(j), seeking approval to market pregabalin capsules in 25, 50, 75, 100, 150, 200, 225, and 300 mg dosage strengths (“Teva’s Proposed Product”).

112. Teva USA included certifications in its ANDAs, pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV), that the '819 and. '876 Patents are invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Teva’s Proposed Product.

113. On April 29, 2009, the plaintiffs sued Teva for infringement of the '819 and '876 Patents, pursuant to 35 U.S.C. § 271(e)(2)(A).

114. On January 20, 2011, after the RE '920 Patent issued, the plaintiffs amended their complaint against Teva to include claims for infringement of the '819 and RE '920 Patents.

115. On January 25, 2011, Teva USA filed a Patent Amendment to ANDAs Nos. 91-219 and 91-224, which included certifications pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV), that the '819 and RE '920 Patents are invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Teva’s Proposed Product.

116. The plaintiffs have asserted infringement of claims 1, 2, and 4 of the '819 Patent and claims 2, 5, 13, 16-17, 19-22, and 24 of the RE '920 Patent against Teva.

viii. ANDA No. 91-222 Submitted by Wockhardt

117. Wockhardt submitted ANDA No. 91-222 (“Wockhardt’s ANDA”) to the FDA, pursuant to 21 U.S.C. § 355(j), seeking approval to market pregabalin capsules in 25, 50, 75, 100, 150, 200, 225, 300 mg dosage strengths (“Wockhardt’s Proposed Product”).

118. Wockhardt’s ANDA refers to and relies upon the Lyriea® NDAs and contains data that, according to Wockhardt, demonstrates the bioequivalence of Wockhardt’s Proposed Product and Lyriea®.

119. Wockhardt included certifications in its ANDA, pursuant to 21 U.S.C, § 355(j)(2)(A)(vii)(IV). that the '819 Patent is invalid, unenforceable, or will not be infringed, by the commercial manufacture, use, or sale of Wockhardt’s Proposed Product,

120. On April 29, 2009, the plaintiffs sued Wockhardt for infringement of the '819 Patent, pursuant to 35 U.S.C. 271(e)(2)(A).

121. The plaintiffs have asserted infringement of claims 1, 2, and 4 of the '819 Patent against Wockhardt.

D. Procedural History

122. The plaintiffs filed their complaint for patent infringement against Actavis (09-cv-311), Alphapharm (09-cv-308), Cobalt (09-cv-315), Mylan (09-CV-308), Lu-pin (09-cv-309), Sandoz (09-CV-310), Sun Pharma (09-CV-313), Teva (09-CV-307), and Wockhardt (09-CV-312) on April 29, 2009.

123. The parties filed a stipulation to consolidate the above-listed actions under case number 09-cv-307 on September 3, 2009. (D.I. 14.) The court approved the parties’ consolidation stipulation on September 4, 2009. (D.I. 15.)

124. The plaintiffs filed a complaint for patent infringement against Lupin on October 6, 2010 (10-cv-853). This action was consolidated with the 09-cv-307 action on April 12, 2011.

125. The plaintiffs filed an amended complaint against: Actavis on January 6, 2011 (D.I. 151); Teva on January 21, 2011 (D.I. 159); Alphapharm and Mylan on February 1, 2011 (D.I. 164); and Sandoz on March 15,2011 (D.I. 211).

126. The court held a nine-day bench trial in this matter on October 11 through October 21, 2011. (D.I. 362-370.)

127. On October 11, 2011, the first day of trial, the parties stipulated that: (1) to the extent the court finds the claim valid and enforceable, the defendants’ respective ANDAs are covered by claim 2 of the '819 Patent under the court’s claim construction; (2) to the extent the court finds it valid and enforceable, defendants Aetavis, Cobalt, Lupin, and Sun Pharma’s respective ANDAs are covered by claim 1 of the '175 Patent; (3) to the extent the court finds the claims valid and enforceable, defendants Actavis, Alphapharm, Mylan, Lupin, and leva’s respective ANDAs, as directed to post-herpetic neuralgia, are covered by claims 2, 5, 16-17, 19-21, and 24 of the RE '920 Patent; (4) to the extent the court finds the claims valid and enforceable, defendants Actavis, Alphapharm, Mylan, Lupin, and Leva’s respective ANDAs, as directed to diabetic neuropathy, are covered by claims 2, 5, 16-17, and 19-22 of the RE '920 Patent; (5) to the extent the court finds the claims valid and enforceable, defendants Actavis, Alphapharm, Mylan, and Lupin’s respective ANDAs, as directed to fibromyalgia, are covered by claims 2, 16-17, 19, and 25 of the RE '920 Patent; and (6) each of the foregoing individual patent claims shall automatically convert to a final judgment of infringement of the respective claim by each applicable defendant upon a final judgment of validity and enforceability regarding the particular claim. (D.I. 335.) To this end, should the court find that the asserted claims of the patents-in-suit are valid and enforceable, the defendants stipulate to infringement.

128. The defendants do not stipulate to infringement of claims 1 and 4 of the '819 Patent.

III. DISCUSSION AND CONCLUSIONS OF LAW

The court has subject matter over this matter pursuant to 28 U.S.C. §§ 1331, 1338, and 2201. Venue is proper in this court under 28 U.S.C. §§ 1391 and 1400(b). After having considered the entire record in this case, the substantial evidence in the record, the parties’ post-trial submissions, and the applicable law, the court concludes that: (1) the asserted claims of the patents-in-suit are not invalid due to obviousness; (2) the asserted claims of the patents-in-suit are not invalid due to anticipation; (3) the asserted claims of the '819 and '175 Patents are entitled to a November 27, 1990 priority filing date; (4) the asserted claims of the '819 Patent are not invalid for written description; (5) the asserted claims of the '819 Patent are not invalid due to improper inventorship; (6) the defendants’ proposed products do not literally infringe claims 1 and 4 of the '819 Patent; (7) the defendants’ proposed products infringe claims 1 and 4 of the '819 Patent under the doctrine of equivalents; (8) the '819 and '876 Patents’ term extensions are not invalid under 35 U.S.C. § 156; and (9) each of the parties’ Rule 52(c) motions are granted in part and denied in part. The court’s discussion of its findings of fact and conclusions of law are set forth in further detail below.

A. Obviousness

The defendants challenge the validity of many of the asserted claims as obvious in light of the prior art. Specifically, the defendants assert that claim 2 of the '819 Patent and each of the asserted claims of the RE '920 Patent are invalid for obviousness under 35 U.S.C. § 103. The court finds, for the reasons that follow, that the defendants have failed to establish, by clear and convincing evidence, that the asserted claims of the patents-in-suit are, in fact, obvious.

1. The Legal Standard

35 U.S.C. § 103(a) provides that a patent may not be obtained “if differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious to a person having ordinary skill in the art.” 35 U.S.C. § 103(a). Obviousness is a question of law that is predicated on several factual inquiries. See Richardson-Vicks v. Upjohn Co., 122 F.3d 1476, 1479 (Fed.Cir.1997). Specifically, the trier of fact is tasked with assessing four considerations: (1) the scope and content of the prior art; (2) the level of ordinary skill in the art; (3) the differences between the claimed subject matter and the prior art; and (4) secondary considerations of non-obviousness, such as commercial success, long felt but unmet need, failure of others, acquiescence of others in the industry that the patent is valid, and unexpected results. See Graham v. John Deere Co., 383 U.S. 1, 17-18, 86 S.Ct. 684, 15 L.Ed.2d 545 (1966).

A party seeking to challenge the validity of a patent based on obviousness must demonstrate by “clear and convincing evidence” that the invention described in the patent would have been obvious to a person of ordinary skill in the art at the time the invention was made. Importantly, in determining what would have been obvious to one of ordinary skill in the art, the use of hindsight is not permitted. See KSR Intern. Co. v. Teleflex, Inc., 550 U.S. 398, 421, 127 S.Ct. 1727, 167 L.Ed.2d 705 (2007) (cautioning the trier of fact against “the distortion caused by hindsight bias” and “arguments reliant upon ex post reasoning” in assessing obviousness). In KSR, the Supreme Court rejected ridged application of the principle that there should be an explicit “teaching, suggestion, or motivation” in the prior art, the nature of the problem, or the knowledge of a person having ordinary skill in the art, in order to find obviousness. See KSR, 550 U.S. at 415, 127 S.Ct. 1727. The KSR Court acknowledged, however, the importance of identifying “ ‘a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does’ in an obviousness determination.” Takeda Chem. Indus. v. Alphapharm Pty. Ltd., 492 F.3d 1350, 1356-57 (Fed.Cir.2007) (quoting KSR, 550 U.S. at 418, 127 S.Ct. 1727).

“Obviousness does not require absolute predictability of success,” but, rather, requires “a reasonable expectation of success.” See Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1165 (Fed.Cir.2006) (quoting In re O’Farrell, 853 F.2d 894, 903-04 (Fed.Cir.1988)). To this end, obviousness “cannot be avoided simply by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed.Cir.2007). Moreover, while the Federal Circuit has noted that pharmaceuticals can be an “unpredictable art” to the extent that results may be unexpected, it also recognizes that, per KSR, evidence of a “finite number of identified, predictable solutions” or alternatives “might support an inference of obviousness.” See Eisai Co. Ltd. v. Dr. Reddy’s Labs. Ltd., 533 F.3d 1353, 1359 (Fed.Cir.2008).

The Federal Circuit has also clarified that, where the patented invention in question is a chemical compound, a court’s assessment of “differences between the claim subject matter and the prior art” will involve examination of the compound and its properties, which are “inseparable.” See Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1087 (Fed.Cir.2008). “In this examination, the challenger initially bears the burden of proving a prima facie case of obviousness by showing: (1) that there is structural similarity between the claimed compound and the prior art “lead compound,” which one skilled in the art would have selected for further research; and (2) that there was some reason in the art to make the “specific molecular modifications” to the lead compound necessary to arrive at the claimed compound.” Takeda Chem. Indus. Ltd., 492 F.3d at 1356-57. If the challenger fails to prove by clear and. convincing evidence both that a person of ordinary skill in the art would have selected the alleged lead compound for further research, and that the prior art suggested the specific modifications needed to make the claimed invention, then the compound is not obvious. See id. at 1360. However, even if the challenger is able to establish the prima facie case of obviousness, the patentee may rebut it with evidence of “some superior property or advantage that a person of ordinary skill in the relevant art would have found surprising or unexpected.” See Procter & Gamble v. Teva Pharms. USA, Inc., 566 F.3d 989, 994 (Fed.Cir.2009).

2. The Level of Ordinary Skill in the Art

With regard to the asserted claims of the '819 Patent, a person of ordinary skill in the art would be a scientist with a Ph.D. in organic or medicinal chemistry with at least two years of experience in the synthesis of organic compounds or, alternatively, a master’s degree in the same fields with at least five years of experience in organic synthesis. (D.I. 349 at 24 (citing Tr. at 1171:16-1172:1 (Roush)).) A person of ordinary skill in the art with respect to the RE '920 Patent would be a physician trained in a clinical specialty focused on neuropathic pain management with drugs. (D.I. 353 at 18 (citing Tr. at 1396:3-8 (Loeser)).) The parties agree and the court concludes that the plaintiffs and defendants’ definitions of a person of ordinary skill in the art do not differ in a meaningful way. (Id.; D.I. 353 at 9 (citing Tr. at 790:1-16 (Kupferberg); Tr. at 1284:24-1285:14 (White)).)

Moreover, the court concludes, with respect to the '819 Patent, that, for the reasons stated more fully in Section III.D, November 27, 1990, the filing date of the Initial Application that issued as the '819 Patent, is appropriate and is the date at which the level of ordinary skill in the art should be assessed. The defendants’ expert, Dr. Kupferberg, conducted his analysis of the prior art as of November 1990 and, therefore, his conclusions evaluate the prior art up to and including the appropriate priority date. (Id. (citing Tr. at 789:20-790:16 (Kupferberg)).) The court also finds, and the parties do not contest, that July 24, 1996 is the appropriate priority filing and prior art date for the RE '920 Patent. The court, therefore, assesses the parties’ obviousness arguments in light of these findings. For the purpose of clarity, the court examines the defendants’ arguments with respect to the '819 Patent and RE '920 Patent separately below.

3. The '819 Patent: The Scope and Content of the Prior Art and Differences Between the Claimed Subject Matter and the Prior Art

As noted, the defendants contend that claim 2 of the '819 Patent is invalid as obvious. Claim 2 of the '819 Patent recites 3-isobutyIGABA, which the court has construed to include individual isomers (i.e., S-3-isobutylGABA and R-3-isobutyl-GAJ3A), racemic mixtures, and non-racemic mixtures having unequal proportions of isomers, because the claim does not limit as to stereochemical form. At trial, the defendants focused their obviousness argument on the assertion that the PTO Examiner was incorrect in deciding, during prosecution of the '819 Patent, that comparative data overcame a rejection that the structure of 3-isobutylGABA was prima facie obvious based on the disclosure of homologous compounds in three prior art references: Fish, Shashoua, and Colonge. (D.I. 353 at 8 (citing Tr. at 794:13-18, 796:10-797:2, 800:11-805:25, 806:25-807:10, 812:4-815:16 (Kupferberg); DTX-820; DTX-1767; DTX-2406; DTX-2408)). Specifically, the defendants’ expert, Dr. Kupferberg, testified that the anticonvulsant test data the plaintiffs submitted in the application and in declarations filed under 37 CFR § 1.132 relied on “flawed procedures” and were “imprecise” and/or “meaningless.” (Id., (citing Tr. at 791:20-792:4, 819:10-24, 849:1-12 (Kupferberg); DTX-836).) For the reasons that follow, the court finds that the defendants have failed to show, by clear and convincing evidence, that claim 2 of the '819 Patent is obvious in light of the prior art as of November 27,1990.

a. Prior Art Addressing the Use of 3-isobutylGABA to Improve Seizure Treatment

In response to the defendants’ arguments, the plaintiffs assert that the defendants did not introduce any evidence to support why a person of ordinary skill in the art in 1990 would have identified 3-isobutylGABA as an anticonvulsant treatment, other than to show that certain “homologous compounds were known to have anticonvulsant activity” and that homologous series “should have similar properties.” (Id. (citing Tr. at 789:20-25, 791:240, 806:6-807:10 (Kupferberg)).) The court agrees and concludes that the evidence presented is insufficient to show clearly and convincingly that skilled artisans would have known to select 3-isobu-tylGABA in November 1990 based simply on the fact that it is a homologous compound.

Specifically, the plaintiffs’ experts, Drs. White and Bazil, explained, in testimony the court finds credible, that identifying improved anticonvulsant drugs in 1990 was a complicated and unpredictable and was largely conducted through trial and error. (Id. (citing Tr. at 1277:18-1278:1 (White); Tr. at 1612:23-1615:2 (Bazil)).) In fact, by 1990 only one drug, vigabatrin, had been successfully developed by targeting a mechanism known to be related to epilepsy. (Id. at 10 (citing Tr. at 1276:18-1277:17 (White)).) Dr. White further testified that anticonvulsant drug discovery remains unpredictable today. Indeed, while almost 34,000 investigational drugs have been tested as potential anticonvulsants as part of an NIH screening program at the University of Utah, only fifteen new drugs have been approved in the United States for seizure treatment since 1993. (Id. (citing Tr. at 1269:18-1270:11 (White); Tr. at 851:15-852:4 (Kupferberg)).).

Moreover, the defendants did not identify any teachings from the Colonge, Fish, and Shashoua references, which, individually or combined, would have directed one of skill in the art to select 3-isobutylGA-BA. Specifically, and as the plaintiffs correctly note, the defendants did not point to any evidence in the prior art indicating that a particular compound or class of compounds, including alkyl-substituted GABA analogs, abroad class of compounds including 3-isobutylGABA, would improve anti-seizure treatment. (Id.) The defendants also failed to identify any teachings as of the filing date that would have directed a skilled artisan to substitute with an isobutyl group, as opposed to any other alkyl group, in the event that alkyl-substituted GABA-analogs were selected. (Id.)

In view of the foregoing and, in particular, in consideration of the unpredictability of anticonvulsant drag discovery and the absence of information detailing what structures were important for anticonvulsant activity in 1990, the court finds that the prior' art did not direct skilled artisans to select 3-isobutylGABA or to anticipate its anticonvulsant activity.

b. Prior Art Addressing 3-isobutyIGA-BA’s Anticonvulsant Activity Compared to Homologous Compounds

In support of their argument that the superiority of 3-isobutylGABA was known in the art in 1990, the defendants cite the testimony of their expert, Dr. Kupferberg, for the proposition that Dr. Taylor’s declarations to the PTO regarding 3-isobutyl-GABA’s superiority were based on “unreliable” and/or “meaningless” data. The court disagrees. During prosecution of the '819 Patent, the applicants submitted two declarations by Dr. Taylor, pursuant to 37 CFR § 1.132, and, based at least in part on these declarations, the Examiner concluded that 3-isobutylGABA’s anticonvulsant activity was unexpectedly superior to compounds identified in the prior art. PTX7A. Dr. Taylor, a pharmacologist at ParkeDavis who supervised preelinical screening of new anticonvulsant drug candidates, summarized in his declarations the preclinical anticonvulsant test data for 3-isobutyl-GABA as well as its closest prior art analogs and provided ED50 values for the data. (D.I. 353 at 11 (citing Tr. at 965:6— 967:12 (Taylor)).) In light of the testimony adduced at trial, the court finds the data underlying Dr. Taylor’s declarations and his conclusions reliable.

Specifically, Dr. Taylor’s declarations explained how the estimated and calculated ED50 values were derived and referenced the data underlying their findings. The plaintiffs note that this data was already known to the Examiner because it was included in Table 2 of the original application that resulted in the '819 Patent. (Id. (citing Tr. at 1295:16-1296:19 (White)).) Dr. White, an expert who has supervised the screening of over 34,000 investigational drugs during his twenty-five years at the Anticonvulsant Screening Program at the University of Utah, testified that Dr. Taylor’s underlying testing was appropriate, including the time point chosen, the number of animals tested, and the decision not to determine the time-to-peak effect for each compound — all decisions the defendants challenge as undermining the reliability of his data and conclusions. (Id. (citing Tr. at. 1269:5-1271:12, 1295:16-1296:19, 1297:4-22, 1297:23-1299:8, 1299:9-16, 1300:2-9 (White)).) In consideration of the record before it and the testimony of Drs. Taylor and White, which the court finds credible, the court concludes that Dr. Taylor’s testing and summary of the Table 2 data in his declarations did not rely on flawed procedures and was, in fact, appropriate. (Id. at 12 (citing Tr. at 1296:17-1297:3, 1299:17-1300:1 (White)).)

Dr. Taylor explained in his declarations and confirmed at trial that the data in Table 2 of the original application demonstrates that 3-isobutylGABA is “clearly superior to other compounds.” (Id. (citing Tr. at 1288:8, 1286:22-1290:6 (White); Tr. at 984:11-986:11 (Taylor)).) Dr. Taylor reached this conclusion for three reasons. First, the data showed a dose-dependent anticonvulsant effect, which is considered in the art a critical pharmacological attribute. (Id. (citing Tr. at 1289:9-13 (White)).) Second, the data also showed that 3-isobu-tylGABA was substantially more potent than the other compounds to which it was compared. (Id. (citing Tr. at 1289:18-22 (White)).) Third, while many of the tested compounds did not protect one hundred-percent of the animals tested at any dose, 3-isobutylGABA successfully protected all of the animals, indicating that it had. “good efficacy.” (Id. (citing Tr. at 1289:14-17, 1289:23-1290:2 (White)).) In sum, Drs. Taylor and White testified that the data outlined confirmed that 3-isobutylGABA was unexpectedly and significantly superi- or to 3-isopropylGABA and that, per Dr. White, “anyone looking at this kind of data would consider that isobutylGABA would be clearly superior to isopropyl.” (Id. (citing Tr. at 1292:23-1294:23 (White)).) Dr. Taylor further testified that 3-isobutylGA-BA even “stood out [from] most of the compounds that [he] had ever screened in [his] laboratory.” (Id. (citing Tr. at 985:16-986:5 (Taylor); Tr. at 892:22-893:23 (Silverman)).)

In view of the foregoing, the court concludes that the data in Dr. Taylor’s declarations and Table 2 of the original application, demonstrate the unexpected superiority of 3-isobutyIGABA and its (S)-3-isobutylGABA over the closest pri- or art analogs, including 3-isopropylGA-BA and other structurally close compounds not in the prior art. (Id. at 12-13 (citing Tr. at 1286:22-1291:6, 1292:23-1294:23 (White)).) In particular, the court finds the data presented to the Examiner and the comparisons between compounds made in the declarations to be reliable and agrees that it demonstrates that 3-isobutylGABA was unexpectedly and significantly superior to the prior art compounds. (Id. at 13 (citing Tr. at 1296:20-1300:9 (White)).) Thus, based in part on the data summarized in the declarations, the court agrees with the plaintiffs that the Examiner properly concluded that 3-isobutylGABA’s- unexpected superiority over the prior art was sufficient to rebut any prima, facie case of obviousness.

4. The '819 Patent: Secondary Considerations

In addition to the findings outlined above, the court also finds that the plaintiffs have presented evidence of secondary considerations sufficient to rebut a prima facie case of obviousness. The court examines these secondary considerations-namely, unexpected results, long felt but unmet need, commercial success, and industry recognition-separately below.

a. Unexpected Beneficial Properties

The plaintiffs maintain that 3-isobutyl-GABA’s “unexpected superiority derived from its unexpected inherent properties” and, as a result, that persons of skill in the art would not have anticipated its beneficial properties. In support of this contention, the plaintiffs note that 3-isobutylGA-BA binds to what was a then-unknown binding site in the brain, is able to cross into the brain by active transport, and is able to treat chronic pain — characteristics that were unknown to the inventors and those of ordinary skill in the art. Specifically, per the testimony of Dr. Silverman, he and Dr. Andruszkiewicz initially believed that the series of 3-alkylGABA analogs they synthesized, including 3-isobutyl-GABA, could be improved anticonvulsant agents because they activated an enzyme known as glutamate decarboxylase (“GAD”), which produces gamma aminobutanoic acid. (“GABA”), a compound preventing seizures. (D.I. 353 at 13-14 (citing Tr. at 869:19-875:24, 884:6-885:20 (Silver-man)).) 3-isobutylGABA, however, was one of the weaker GAD-activators that they synthesized, which made it surprising to the inventors that 3-isobutylGABA was the most potent anticonvulsant of those compounds in vivo. (Id. (citing Tr. at 892:22-893:23 (Silverman)).)

Notably, the inventors ultimately discovered that 3-isobutylGABA’s anticonvulsant activity was not attributed to activating GAD or inactivating GABA-aminotransferase (“GABA-AT”), the other enzyme the inventors targeted in their research, but by antagonizing a calcium channel in the brain, which indirectly leads to increased GABA levels and decreased seizures. (Id. at 14 (citing Tr. at 905:11-906:11 (Silver-man)).) Dr. Silverman testified that this mechanism of action was completely unexpected in 1990.(/a!.) The inventors were also surprised to learn that, of all the 3-alkylGABA analogs they synthesized, only 3-isobutylGABA bound with high affinity to the specific channel binding cite. (Id. (citing Tr. at 1412:2-11 (Enna)).)

In addition, the inventors explained that 3-isobutylGABA’s ability to pass through the blood brain barrier was unexpected, as compared to other analogs, and rendered this compound potentially more effective than other anticonvulsants. (Id. (citing Tr. at 874:19-23 (Silverman)).) Specifically, and as Dr. Silverman described, while anticonvulsant agents must enter the brain to be effective, amino acids like GABA are generally unable to cross the barrier. (Id. (citing Tr. at 874:13-875:15, 877:9-878:11 (Silverman)).) Dr. Silverman speculated that GABA analogs with lipophilic substituents might be “greasy” enough to pass the blood brain barrier, but was “skeptical” that 3-isobutylGABA would enter the brain without further modification of its structure to increase its lipophilicity. (Id. (citing Tr. at 889:3-890:4 (Silverman)).) The inventors were, therefore, surprised to discover that 3-isobutylGABA passed through the blood brain barrier without additional modifications. (Id. (citing Tr. at 906:12-907:5 (Silverman)).) The inventors learned that 3 — isobutylGABA passes through the barrier via an unanticipated mechanism — active transport via the “System L” transporter for the amino acid leucine, which is not normally associated with alkyl or gamma amino acids. (Id. at 15 (citing Tr. at 906:12-907:5 (Silverman)).)

Finally, the inventors learned that 3-isobutylGABA also possesses a number of surprising and beneficial pharmacokinetic properties. First, unlike most amino acids, which are “metabolized and excreted very readily,” 3-isobutylGABA is not readily broken down into metabolites when ingested and, therefore, is “excreted intact.” (Id. at 15 (citing Tr. at 907:6-11 (Silverman)).) Second, 3-isobutylGABA is ninety-percent orally bioavailable, meaning that ninety-percent of an oral dose is absorbed into and distributed throughout the body. To this end, it does not interact with potassium channels to cause arrhythmia or with enzymes in the liver to cause negative drug-drug interactions. (Id. (citing Tr. at 907:14-17 (Silverman)).) Third. 3-isobutylGABA was shown to display linear pharmacokinetics, such that as dosage is increased, the amount absorbed in the intestines increases proportionally.

In view of the foregoing and in consideration of Drs. Silverman’s testimony, which the court finds credible, the court concludes that the inventors and persons of skill in the art would not have expected 3-isobutylGABA to possess the beneficial properties and attributes detailed above. Thus, the court finds that the plaintiffs have produced evidence sufficient to show this secondary consideration and to support the court’s conclusion that the asserted claim of the patent-in-suit is not obvious.

b. Long Felt, Unmet Need

The plaintiffs contend that, as of the early 1990s, there was a long felt need for anticonvulsants that had a linear pharmacokinetic profile, did not have significant protein binding, induce hepatic enzymes, or interact with other drugs, would prove effective in patients who were refractory to other anticonvulsants, and were not associated with the significant side effects common to many anticonvulsants at the time. (D.I. 353 at 15 (citing Tr. at 1615:3-1618:10 (Bazil.)).) In support of this argument, the plaintiffs note that, in the 1990s, many anticonvulsants were associated with increased liver metabolism, because they induced hepatic enzymes, which could result in adverse side effects. (Id. at 16 (citing Tr. at 1615:22-1616:8 (Bazil)).) For instance, levels of warfarin, which is used to reduce blood clotting, may be reduced from increased liver metabolism and could cause a heart attack or stroke. (Id. (citing Tr. at 1615:22-1616:16 (Bazil)).) 3-isobutyl-GABA, however, is not known to metabolize in the liver and, as a result, largely eliminates problems associated with drug interaction because its metabolization does not affect any other drug. Tr. at 1618:16-3619:9 (Bazil).

The plaintif