Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc.

TEVA PHARMACEUTICALS USA, INC., et al., Plaintiffs,

v.SANDOZ, INC., et al., Defendants.

TEVA PHARMACEUTICALS USA, INC., et al., Plaintiffs,

v.MYLAN PHARMACEUTICALS INC., et al., Defendants.

08 Civ. 7611

09 Civ. 8824

UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF NEW YORK

Dated: June 22, 2012

(BSJ)(AJP)

(BSJ)(AJP)

Opinion and Order

BARBARA S. JONES

UNITED STATES DISTRICT JUDGE

TABLE OF CONTENTS

INTRODUCTION...................................................6

I. The Parties...............................................7

A. Teva....................................................8

B. Sandoz ..................................................8

C. Mylan...................................................8

II. The Patents-in-Suit.......................................9

A. Overview................................................9

B. Copaxone® - Teva NDA...................................14

C. Sandoz's and Momenta's ANDA............................15

D. Mylan and Natco ANDA...................................17

III. Procedural History and Claim Construction .............. 18

A. July 2011 Inequitable Conduct Trial ....................20

i. Teva's Witnesses......................................20ii. Defendants' Witnesses.................................22

B. September 2011 Infringement and Invalidity Trial ....... 22

i. Teva's Witnesses......................................23

ii. Mylan's Witnesses.....................................26

iii. Sandoz's Witnesses....................................28

iv. Witnesses Testifying by Deposition....................29

IV. The Patents-in-Suit and the Patent Claims at Issue ....... 30

A. Molecular Weight Claim Limitations ..................... 31

i. Average Molecular Weight Limitations..................31

ii. Molar Fraction Limitations............................32

iii. Predetermined Molecular Weight Profile Limitations .... 34

B. Process Limitations ....................................34

C. Treatment of Multiple Sclerosis ........................35

D. Pharmaceutical Composition ............................. 36

V. Copolymer-1 and Multiple Sclerosis ....................... 36

A. Multiple Sclerosis: The Disease ....................... 36

B. The Weismann Scientists' Discovery of Copolymer-1 ...... 38

C. Teva's Agreement with Weizmann .........................43

D. Discovery of the Process for Achieving Low Molecular Weight Copolymer-1 ..................................... 51

VI. Background on Polypeptide Chemistry, Synthesis, Analytical Testing..................................................52

A. Polypeptide Chemistry .................................. 52

B. Synthesis of Copolymer-1 ...............................53

C. Size Exclusion Chromatography ..........................56

D. Level of Ordinary Skill in the Art .....................66

DISCUSSION....................................................68

I. Infringement.............................................68

A. General Principles ..................................... 68

B. Findings of Fact as to Mylan ...........................71

i. Mylan's ANDA Product ..................................71

ii. Amino Acid Composition ................................72

iii. Molecular Weight ...................................... 73

iv. Mylan's Manufacturing Process .........................77

v. ANDA Process..........................................79vi. Mylan's ANDA Product Label............................84

C. Conclusions of Law as to Mylan's Product ...............84

i. Mylan's Proposed Product Infringes Each of the Asserted Claims because Mylan's Product is Copolymer-1.........85

ii. The Reason for Mylan's Molar Ratio is Irrelevant to the Infringement Analysis................................100

iii. The Doctrine of Equivalents..........................103

iv. Mylan's Product Meets the Molecular Weight Limitations..

.....................................................109

1) Average Molecular Weight Limitations ................ 109

2) Copolymer-1 Molar Fraction Limitations .............. 110

3) TFA Copolymer-1 Molar Fraction Limitations .......... 111

v. Mylan's Process Meets the Process Limitations........111

vi. Mylan Meets the Treatment Limitations................113

vii. Mylan Infringes All Asserted Claims .................. 114

D. Findings of Fact as to Sandoz .........................115

i. Sandoz's ANDA Product and its Active Ingredient......115

1) Amino Acid Composition..............................115

2) Molecular Weight .................................... 116

ii. Sandoz's Manufacturing Process.......................119

iii. Sandoz's ANDA Product Label .......................... 128

E. Conclusions of Law as to Sandoz's Product .............128

i. Sandoz's Proposed Product Infringes Each of the Asserted Claims because Sandoz's Product is Copolymer-1.......128

ii. Sandoz's Product Meets the Molecular Weight Limitations. .....................................................131

1) Average Molecular Weight Limitations ................ 131

2) Sandoz's Proposed Post-Trial Claim Construction..... 132

3) Copolymer-1 Molar Fraction Limitations .............. 136

4) TFA Copolymer-1 Molar Fraction Limitations .......... 137

iii. Sandoz's Process Meets the Process Limitations ...... 137

iv. Sandoz's Viscometer Process Meets the Test Reaction Limitations..........................................138

v. Sandoz Meets the Treatment Limitations...............141

vi. Sandoz Infringes All of the Asserted Claims..........143

II. INVALIDITY DEFENSES ..................................... 143

A. Best Mode.............................................143

i. General Principles...................................144

ii. The Use of Phenol to Pre-treat HBr/Acetic Acid....... 146

iii. The Level of Bromo tyro sine Impurity..................153

iv. The Patents' Lack of Disclosure Regarding Phenol Is Not a Best Mode Violation................................156

v. The Patents' Lack of Disclosure Regarding a "Low Bromotyrosine" Content of Copolymer-1 Is Not a Best Mode Violation............................................158

B. Inequitable Conduct ................................... 160

i. General Principles...................................160

ii. The Decision to File the '037 Application............162

iii. The Relevant Contents of the '037 Application........165

iv. The April 1994 Data Table............................167

v. The April 1994 Data Table Is Consistent with Example 2 . . .....................................................171

vi. Example 2 Is Representative of Teva's Toxicity Data as a Whole................................................173

vii. The Patent Office Was Aware That Not All High Molecular Weight Copolymer-1 Batches Were Toxic................175

viii. Dr. Pinchasi's Views on the RBL Degranulation Test... 176

ix. Professor Arnon Believed the RBL Degranulation Test To Be a Reliable Screening Test for Toxicity............179

x. The RBL Degranulation Test Described in the Patent Is a Well-Accepted Test in the Scientific Community.......181

xi. The Patent Office Knew About the Reproducibility of the RBL Degranulation Test...............................183

xii. The April 1994 Data Table and the RBL Degranulation Information Were Not Material........................184

xiii. Defendants Failed to Establish that Dr. Pinchasi Intended to Deceive the PTO..........................186

C. Lack of Enablement....................................188

i. General Principles...................................188

ii. A Person of Ordinary Skill...........................190

iii. Self-Standards.......................................191

iv. Universal Calibration................................205

v. Teva's Experimentation with Copolymyer-1.............207

vi. Self-Standards.......................................210vii. Universal Calibration...............................217

viii. In re Wands Factors.................................222

ix. The Patents-in-Suit Provided Sufficient Direction or Guidance............................................225

D. INDEFINITENESS........................................228

i. General Principles...................................228

ii. None of the Asserted Claims Are Indefinite...........229

E. OBVIOUSNESS...........................................231

i. General Principles...................................232

ii. The Scope and Content of the Prior Art...............234

1) The "550 Patent.....................................234

2) EP "620 Patent Application..........................236

3) The Teitelbaum 1971 Article and 1974 Abstract ....... 237

4) Prior Art Regarding the Use of HBr/acetic Acid To Achieve Desired Molecular Weight .................... 238

iii. Secondary Considerations of Non-obviousness .......... 243

iv. The Prior Art Does Not Teach Copolymer-1 Compositions with the Claimed Average Molecular Weight Characteristics......................................247

v. There Is No "Overlap" in Average Molecular Weight Ranges or Molar Fraction Limitations........................250

vi. The Defendants Have Not Demonstrated Evidence of Any Reason or Motive to Alter the Molecular Weight of Copolymer-1..........................................256

vii. The Claimed Ranges Do Not "Abut" the Prior Art.......258

viii. The Prior Art "Taught Away" from Molecular Weights in the Claimed Ranges.................................260

ix. The Claimed Weight Characteristics of the Patents-in-Suit Are Not Obvious.................................261

x. The Claimed Process for Making Copolymer-1 in HBr/Acetic Acid Is Not Obvious..................................263

xi. Secondary Considerations of Non-obviousness..........269

1) Commercial Success .................................. 269

2) Long-felt, Unmet Need...............................271

3) Failure of Others...................................273

4) Unexpected Results .................................. 274

5) Copying.............................................277

CONCLUSION...................................................278

INTRODUCTION

This case involves the Drug Price Competition and Patent Term...