Detailed Table of Contents

Detailed Table of Contents Foreword... vii Preface... ix vii Summary Table of Contents... xi ix I. Introduction 1. Introduction to Pharmaceutical Patents... 3 3 I. The Drug Patent Debate... 4 II. Overview of the Patent Law... 5 III. Overview of the Marketing Approval Process... 6 IV. A Brief History of Pharmaceutical Patent Law and Food and Drug Law... 9 4 A. Roche v. Bolar... 9 B. The Hatch-Waxman Act... 12 1. The Statutory Experimental Use Exception... 13 2. Abbreviated New Drug Applications... 14 3. Certifications for Orange Book-Listed Patents... 15 4. Patent Infringement Proceedings... 16 5. Patent Term Extension... 18 6. Marketing Exclusivities... 18 7. Generic Exclusivity... 19 8. The Impact of the Hatch-Waxman Act... 19 C. The Generic Animal Drug and Patent Term Restoration Act... 20 D. The Prescription Drug User Fee Act... 20 E. The Uruguay Round Agreements Act of 1995... 21 F. The FDA Modernization Act... 21 G. The American Inventors Protection Act of 1999... 22 H. The 2002 FTC Study... 22 xi

xii Pharmaceutical Patent Law 2014 Supp. I. The 2003 FDA Regulations... 23 J. The Medicare Prescription Drug, Improvement, and Modernization Act of 2003... 24 1. Single 30-Month Stay... 24 2. Notice of Applications... 24 3. Counterclaim for Patent De-Listing... 25 4. Declaratory Judgment Actions... 25 5. Generic Exclusivity... 25 6. Notice of Agreements... 26 K. The Biologics Price Competition and Innovation Act... 26 L. The Leahy-Smith America Invents Act [New Topic]... 4 M. Additional Legislation in the 113th Congress [New Topic]... 5 II. Patent Acquisition 2. Patent Eligibility... 29 11 I. Basic Concepts... 29 II. Product and Process Claims... 30 11 A. Abstract Ideas... 31 11 B. Products of Nature... 33 12 C. Living Inventions... 36 D. Process Claims for New Uses... 39 III. Types of Pharmaceutical Patent Claims... 39 14 A. Drug Substances... 40 B. Formulations... 40 C. Chemical Intermediates... 41 D. Metabolites and Prodrugs... 41 E. Crystals and Polymorphs... 43 F. Isomers... 44 G. Salts... 45 H. Combination Therapies... 45 I. Methods of Using... 46 J. Methods of Making... 47 K. Methods of Diagnosis... 47 14 L. Kits [New Topic]... 20 IV. Methods of Medical Treatment... 52 3. Utility... 57 23 II. Moral Utility... 60 III. Practical Utility... 64 IV. Practical Utility for Pharmaceutical Patents... 67 A. Brenner v. Manson... 68

Detailed Table of Contents xiii B. Leading Case Law of the Court of Customs and Patent Appeals... 70 C. Early Case Law of the Federal Circuit... 72 D. The 1995 PTO Utility Examination Guidelines 73 E. The 2001 PTO Utility Examination Guidelines 75 F. In re Fisher... 77 V. Recurring Issues... 80 A. Safety and Efficacy Considerations... 80 B. Structural Similarity to Compounds With an Established Utility... 84 C. In Vitro and In Vivo Tests... 85 D. Human Clinical Data... 88 E. Chemical Intermediates... 90 F. Inoperable Species Within a Genus... 91 G. Assertions of Multiple Utilities... 91 H. The Utility Requirement in Adversarial Proceedings... 92 I. The Utility Requirement and Priority Applications... 95 4. Novelty... 97 25 I. Introduction... 97 25 II. Anticipation... 100 A. Genus and Species... 101 B. The Enablement Requirement... 107 III. Inherency... 109 28 IV. The 35 U.S.C. 102(b) Statutory Bar... 123 29 A. Public Use Under 35 U.S.C. 102(b)... 124 31 B. On Sale Under 35 U.S.C. 102(b)... 128 C. In This Country... 132 33 D. Experimental Use... 134 E. Patents... 139 F. Printed Publications... 140 V. Abandonment Under 35 U.S.C. 102(c)... 142 33 VI. Delayed U.S. Filing Under 35 U.S.C. 102(d)... 143 33 VII. Prior Invention Under 35 U.S.C. 102(a)... 145 33 VIII. Prior Invention Under 35 U.S.C. 102(g)... 149 34 A. Prior Art Under 35 U.S.C. 102(g)... 152 B. Priority Under 35 U.S.C. 102(g)... 153 C. Inventive Activity in Foreign Countries... 153 D. Conception... 155 34 E. Reduction to Practice... 156 F. Diligence... 158 G. Corroboration... 160 H. Patent Award to the Second Inventor... 163

xiv Pharmaceutical Patent Law 2014 Supp. IX. Disclosure in U.S. Patent Applications Under 35 U.S.C. 102(e)... 167 X. Derivation Under 35 U.S.C. 102(f)... 170 35 5. Nonobviousness... 173 37 I. Introduction... 174 II. Prior Art for Nonobviousness... 174 38 A. Section 102 as the Source of Prior Art... 174 B. 35 U.S.C. 103(c)(1)... 175 C. The CREATE Act... 177 38 III. The Nonobviousness Inquiry... 178 38 A. The Historical Standard of Invention... 178 B. The Modern Standard of Nonobviousness... 180 38 C. The Person of Ordinary Skill in the Art... 192 D. The Prima Facie Case of Obviousness... 195 E. Obvious to Try... 196 42 IV. The Secondary Considerations... 198 42 A. Commercial Success... 200 43 B. Copying... 203 C. Licenses... 204 D. Long-Felt Need... 205 E. Praise and Skepticism... 205 F. Prior Failures of Others... 206 G. Unexpected Results... 208 V. Structural Similarities as Evidence of Obviousness... 209 A. Introduction... 209 B. Homologues... 218 1. Adjacent Homologues... 218 2. Ring Expansion and Contraction... 220 3. Remote Homologues... 222 C. Isomers... 223 1. Structural Isomerism... 223 a. Position Isomerism... 223 b. Tautomers... 225 c. Stereoisomers... 226 2. Bioisomerism... 233 D. Esters... 234 1. Prior Art Alcohols... 235 2. Prior Art Free Acids... 236 E. Analogs... 237 VI. Product and Process Claims... 237 6. The Patent Instrument... 241 45 I. Enablement... 243 45 A. Basic Concepts... 243 45 B. Working and Prophetic Examples... 250

Detailed Table of Contents xv C. Exhibits and Biological Samples... 251 II. Best Mode... 252 47 III. Written Description... 256 A. New Matter... 256 B. Originally Filed Claims... 260 IV. The Claims... 263 49 A. Basic Claim Drafting... 264 1. The Preamble... 264 2. The Transition Phrase... 267 3. The Body... 270 B. Claim Formats... 271 1. Dependent Claims... 271 2. Markush Claims... 272 3. Product-by-Process Claims... 274 4. Jepson Claims... 276 5. Functional Claims... 278 6. Skuballa Claims... 281 7. First Medical Use and Swiss-Style Claims... 282 C. Definiteness... 284 49 7. Patent Acquisition Procedures... 289 51 I. Fundamentals of Patent Prosecution... 290 52 A. Preparation of Applications... 290 52 B. Provisional Applications... 291 C. Examination of Applications... 292 D. Continuing Applications... 294 E. The Restriction Requirement and Divisional Applications... 295 F. Publication of Applications... 296 G. Petition and Appeal... 298 H. Invention Secrecy Orders... 298 II. Other PTO Proceedings... 299 53 A. Interferences... 299 B. Protests... 301 53 C. Citation of Prior Art... 301 55 D. Public Use Proceedings... 302 III. Post-Grant Proceedings... 302 55 A. Certificates of Correction... 303 B. Disclaimers... 303 C. Reissue... 303 D. Reexamination... 306 55 1. Ex Parte Reexamination... 307 2. Inter Partes Reexamination... 308 E. Intervening Rights... 309 F. Supplemental Examination [New Topic]... 58 IV. Abuses of Patent Acquisition Procedures... 310 60

xvi Pharmaceutical Patent Law 2014 Supp. A. Double Patenting... 311 60 1. Basic Principles... 311 60 2. Double Patenting and the Restriction Requirement... 317 3. Two-Way Double Patenting... 319 B. Inequitable Conduct... 320 62 C. Misjoinder or Nonjoinder of Inventors... 337 D. Prosecution Laches... 340 8. Duration of Rights... 343 69 I. Fundamentals of Patent Term... 343 II. Maintenance Fees... 345 III. The Patent Term Guarantee Act... 345 IV. Specialized Legislation... 346 V. The Hatch-Waxman Act... 346 69 A. Eligible Patents... 347 1. Drug Products... 347 2. Combination Therapies... 352 3. Metabolites... 353 4. Stereoisomers... 354 5. Medical Devices... 355 6. Patents Subject to a Terminal Disclaimer... 357 B. Application for Term Extension... 358 69 1. Time Limit for Filing... 358 69 2. Identity of the Applicant... 361 3. Contents... 361 4. Review of the Application... 362 5. Interim Extensions... 363 6. Strategic Considerations... 364 C. Period of Extension... 364 D. Limitation Upon Scope of Rights... 366 III. Marketing Approval Procedures 9. The FDA Drug Approval Process... 371 67 I. Marketing Approval for Innovative Drugs... 371 A. Preclinical Investigations... 372 B. Investigational New Drug Applications... 373 1. Phase I Investigations... 373 2. Phase II Investigations... 374 3. Phase III Investigations... 374 4. Treatment INDs... 374 5. Screening INDs... 375 C. New Drug Applications... 375 D. Postmarketing Surveillance / Phase IV Investigations... 376

Detailed Table of Contents xvii II. Marketing Approval for Generic Drugs... 376 67 A. FDA Practices Prior to Hatch-Waxman... 377 B. Abbreviated New Drug Applications... 378 C. Section 505(b)(2) Applications... 380 D. Patent Certifications... 382 E. Section viii Statements... 383 67 F. Thirty-Month Stay of Marketing Approval... 388 72 1. Multiple 30-Month Stays... 391 72 2. Judicial Modification of the 30-Month Period... 393 III. Antibiotics... 398 10. The Orange Book... 401 75 I. Overview of the Orange Book... 401 II. Patents Appropriate for Orange Book Listing... 403 A. The Hatch-Waxman Act... 403 B. FDA Regulations... 409 1. General Rules... 409 2. Polymorph Patents... 412 3. Product-by-Process Patents... 413 C. Third-Party Patents... 413 III. The Timing of Patent Listings... 415 IV. Orange Book Listing Disputes... 416 75 A. The Role of the FDA... 417 B. De-listing Litigation Prior to the MMA... 418 1. Efforts by Generic Firms to De-list... 418 2. De-listing by Brand Name Firms... 422 C. De-listing Litigation Under the MMA... 425 75 1. Efforts by Generic Firms to De-list... 425 75 2. De-listing by Brand Name Firms... 429 D. FTC Enforcement... 430 11. Marketing Exclusivities... 431 87 I. Marketing Exclusivity Concepts... 431 II. New Chemical Entity Exclusivity... 432 87 III. New Clinical Study Exclusivity... 435 88 IV. Generic Marketing Exclusivity... 437 90 A. Basic Concepts... 437 B. Pre-MMA Standards... 439 1. Entitlement... 439 2. Timing of Notice... 445 3. Commencement of the 180-Day Period... 446 4. Separate Exclusivities for Distinct Dosages and Strengths... 448 5. Patent-by-Patent Approach... 448 6. Relationship to Pediatric Exclusivity... 450 7. Transferability... 450

xviii Pharmaceutical Patent Law 2014 Supp. C. Standards Under the MMA... 451 90 1. Entitlement... 451 2. Forfeiture... 451 90 3. Timing of Notice... 454 4. Commencement of the 180-Day Period... 454 5. Product-by-Product Approach... 455 D. Unresolved Issues... 455 93 1. Authorized Generics... 455 93 2. Award of Exclusivity for Judgments of Noninfringement... 460 V. Pediatric Marketing Exclusivity... 460 VI. Orphan Drug Marketing Exclusivity... 463 VII. Infectious Disease Products [New Topic]... 93 IV. Infringement 12. Scope of Patent Rights... 469 97 I. Basic Concepts... 470 98 A. Direct Infringement... 470 B. Indirect Infringement... 472 98 1. Active Inducement... 473 98 2. Contributory Infringement... 474 3. Deepsouth and 35 U.S.C. 271(f)... 477 4. Bioconversion as Infringement... 477 C. Process Patents... 479 1. The Process Patent Amendments Act... 479 2. Screening Methods... 482 D. Government Infringers... 483 1. The Federal Government... 484 2. The Bayh-Dole Act... 487 3. State and Local Governments... 489 II. Infringement Under the Hatch-Waxman Act... 491 103 A. Patent Implications of ANDAs and Section 505(b)(2) Applications... 491 103 B. Notification of a Paragraph IV Certification... 493 C. Offers of Confidential Access... 494 D. Biobatch Data Versus the ANDA Specification... 494 108 E. Generic Submissions for Unapproved Uses... 497 109 III. Patent Litigation... 499 111 A. Subject Matter Jurisdiction... 499 B. Supplemental Jurisdiction... 501 C. Personal Jurisdiction... 502

Detailed Table of Contents xix 1. General Principles... 502 2. Implications of the Hatch-Waxman Act... 503 D. Venue... 504 E. Declaratory Judgment... 505 111 1. General Principles... 505 2. Declaratory Judgment Actions in the Hatch-Waxman Framework... 508 111 F. The Availability of Jury Trials Under the Hatch-Waxman Act... 518 IV. Infringement Defenses... 520 A. Invalidity and Unenforceability... 520 B. Issue Preclusion... 521 C. Laches and Estoppel... 522 D. Licenses... 523 1. Basic Concepts... 523 2. Licensee and Assignor Estoppel... 526 3. Implied Licenses... 528 4. Shop Rights... 530 E. Prior User Rights... 532 V. Remedies... 535 A. General Principles... 535 1. Injunctions... 535 2. Compensatory Damages... 540 a. Reasonable Royalties... 540 b. Lost Profits... 542 i. But For Causation... 543 ii. Proximate Causation... 546 iii. The Entire Market Value Rule... 547 3. Marking... 549 4. Provisional Rights... 551 5. Enhanced Damages... 551 B. Remedies Under the Hatch-Waxman Act... 555 1. Remedies Available for Infringing Generic Applications... 555 2. Generic Filings as Willful Infringements.. 555 C. Implications of Generic Market Entry During Patent Litigation... 557 13. Claim Interpretation and the Doctrine of Equivalents. 559 115 I. Claim Interpretation... 559 A. Basic Concepts... 559 B. Markman v. Westview Instruments... 560 C. Canons of Claim Construction... 563 D. Dictionaries, the Specification, and the Phillips Case... 566 E. Representative Claim Construction Cases... 571

xx Pharmaceutical Patent Law 2014 Supp. II. The Doctrine of Equivalents... 580 115 A. Basic Concepts... 580 115 1. Graver Tank and the Function-Way-Result Standard... 581 2. Warner-Jenkinson and the Insubstantial Differences Standard... 584 115 3. Functional Equivalents... 586 B. Limitations on the Doctrine of Equivalents... 587 117 1. The All Elements Rule... 587 2. Prior Art Limitations... 592 3. Prosecution History Estoppel... 596 117 4. The Public Dedication Doctrine... 604 C. The Reverse Doctrine of Equivalents... 608 14. Parallel Importation... 611 121 I. Introduction... 611 II. FDA Practices With Respect to Importing Prescription Drugs... 612 121 A. The Prescription Drug Marketing Act of 1987. 612 B. The MEDS Act of 2000... 614 C. The MMA of 2003... 615 D. Reform Proposals... 616 121 III. Patent Implications of Parallel Importation... 617 A. The Exhaustion Doctrine... 617 B. International Exhaustion... 618 C. Reform Proposals... 621 D. Potential Legal Issues... 622 1. The Takings Clause... 622 2. State and Local Governments... 627 3. The TRIPS Agreement... 629 4. Free Trade Agreements... 630 5. Label Licenses... 633 15. The Experimental Use Privilege... 635 123 I. The Common Law Experimental Use Privilege... 637 A. Origins of the Experimental Use Privilege... 637 B. Cases Upholding the Privilege... 640 C. Experimental Use as a Matter of Remedies... 642 D. Cases Rejecting the Experimental Use Privilege... 644 E. The Common Law Experimental Use Privilege in Pharmaceutical Cases... 649 F. The Common Law Experimental Use Privilege in Academic Settings... 650 G. Experimental Use Policy... 655

Detailed Table of Contents xxi II. The Statutory Experimental Use Privilege... 659 124 A. Introduction to 35 U.S.C. 271(e)(1)... 659 1. Roche v. Bolar... 659 2. The Hatch-Waxman Act... 662 3. Basic Analytical Framework... 663 B. Application of 35 U.S.C. 271(e)(1)... 659 124 1. Manufacture... 659 2. Preclinical Trials... 670 3. Clinical Trials... 673 4. Other Product Testing... 674 5. Sales... 675 6. Displays and Demonstrations... 676 7. Publications and Promotions... 677 8. Foreign Patenting and Regulatory Approval... 678 9. Medical Devices... 679 10. Research Tools... 684 11. Importation... 687 12. Post-Marketing Activity [New Section]... 124 16. Antitrust Considerations... 689 129 I. Introduction... 689 II. Notice of Patent Settlements... 691 III. Judicial Treatment of Reverse Payment Settlements... 692 129 A. Sixth Circuit... 692 B. Eleventh Circuit... 695 C. Second Circuit... 701 D. Federal Circuit... 707 E. Concluding Observations... 708 V. International and Comparative Aspects 17. International and Comparative Patent Law... 715 135 I. The Paris Convention... 717 A. National Treatment... 717 B. Independence of Patents... 717 C. International Priority... 718 D. Benefits of Paris Convention Priority... 719 E. Limitations of the Paris Convention... 722 II. The Patent Cooperation Treaty... 723 III. Foreign Filing Licenses... 724 IV. Regional Agreements... 725 A. NAFTA... 725 B. Other Regional Agreements... 726

xxii Pharmaceutical Patent Law 2014 Supp. V. The TRIPS Agreement... 727 A. National Treatment and Most-Favored-Nation Status... 728 B. Minimum Standards of Protection... 728 C. Compulsory Licenses... 730 1. TRIPS Agreement Article 31... 730 2. The Doha Declaration... 731 D. Other Provisions... 733 E. Effective Dates... 734 1. Pipeline Protection... 735 2. Exclusive Marketing Rights... 736 F. Dispute Settlement... 736 1. India Pharmaceutical Products... 737 2. Canada Pharmaceutical Products... 739 G. Debate on the TRIPS Agreement... 741 VI. Free Trade Agreements... 742 A. Patent Term Restoration... 742 B. Data Exclusivity... 742 C. Confidential Status of Experimental Data... 743 D. Accelerated Generic Marketing Approval... 743 E. Experimental Use Privilege... 744 F. Parallel Importation... 744 G. Implications... 745 VII. Comparative Patent Law... 745 136 A. Deferred Examination... 746 B. Experimental Use Privilege... 746 C. Grace Period... 748 D. Methods of Medical Treatment... 748 E. Oppositions... 749 F. Patent Validity as an Infringement Defense... 749 G. Priority Principle... 750 H. Publication of Pending Applications... 750 I. Patentable Subject Matter... 751 J. The Promise of the Patent Doctrine [New Topic]... 136 18. International and Comparative Data Protection Law... 753 139 I. International Data Protection Standards... 755 A. The TRIPS Agreement... 755 1. Basic Principles... 755 2. Eligible Data... 756 3. Protection Against Unfair Commercial Use... 757 4. Protection Against Disclosure... 760 B. Free Trade Agreements... 761

Detailed Table of Contents xxiii II. Comparative Law... 763 139 A. European Union Data Protection Law... 763 1. Introduction... 764 2. The Pre-2005 6/10 Formula... 764 3. 2005 and Beyond: The 8+2+1 Formula... 765 4. Orphan Drugs... 766 5. The Pediatric Testing Incentive... 767 B. European Supplementary Protection Certificates... 767 139 C. Japan... 768 141 VI. Biologics 19. Follow-On Biologics... 771 145 I. Introduction... 771 145 II. The Regulatory Pathway... 774 A. Biosimilars... 774 B. Interchangeable Biologics... 774 C. The Role of the FDA... 774 III. Marketing Exclusivities and Data Protection... 775 A. Brand-Name Products... 775 B. First Interchangeable Products... 776 IV. Patent Dispute Resolution... 777 V. Observations and Potential Issues... 781 Appendices List of Documents Included on CD-ROM... 783 The Leahy-Smith America Invents Act... 147 Table of Cases... 787 205 Index... 815 About the Author... 829 209