Pharmaceutical patent life-cycle management after KSR v. teleflex

Food and Drug Law Journal

Volumn 63, Issue 1, 2008, Pages 275-320

  Furrow, Michael Enzo ^a  

^a Fitzpatrick Cella Harper and Scinto   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT;

DRUG DEVELOPMENT; DRUG FORMULATION; DRUG INDUSTRY; DRUG LEGISLATION; DRUG STRUCTURE; ECONOMIC ASPECT; JURISPRUDENCE; KSR INTERNATIONAL; LIFE CYCLE; PHARMACEUTICS; PRESCRIPTION; REVIEW; STEREOISOMERISM; TELEFLEX INCORPORATION;

BIOTECHNOLOGY; DRUG INDUSTRY; FORECASTING; HISTORY, 20TH CENTURY; HUMANS; LEGISLATION, DRUG; PATENTS AS TOPIC; SUPREME COURT DECISIONS; UNITED STATES;

EID: 40549138827     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (276)

1. See generally George Kurian, ed., A Historical Guide to the U.S. Government (New York: Oxford University Press, 1998) (provides a historical account of the Food and Drug Laws). Also, see FDA website at http://www.fda.gov/oc/history/historyoffda/default.htm (provides summaries of important events and laws in FDA history).
2. See generally Gerald J. Mossinghoff, Overview of the Hatch-Waxman Act and Its Impact on the Drug Development Process, 54 FOOD & DRUG L.J. 187 (1999) (provides an overview of the Hatch-Waxman Act and the legislative history thereof);
3. and S.Hrg. 107-1081, "Generic Pharmaceuticals: Marketplace Access and Consumer Issues," April 23, 2002, Prepared statement of Dr. Greg Glover, M.D., J.D., Pharmaceutical Research and Manufacturers of America, p. 49 (discusses the impact of the Hatch-Waxman Act upon the innovator drug industry).
4. See, e.g., Saying No to Penelope - Father Seeks Experimental Cancer Drug, but a Biotech Firm Says Risk is Too High, THE WALL STREET JOURNAL, May 1, 2007, A1.
5. See Kaiser Family Foundation, "Impact of Direct-to-Consumer Advertising on Prescription Drug Spending," http://www.kff.org/rxdrugs/ upload/Impact-of-Direct-to-Consumer-Advertising-on-Prescription-Drug-Spending- Summary-of-Findings.pdf;
6. Jun Ma, Randall S. Stafford, Iain M. Cockburn, and Stan Finkelstein, Statistical Analysis of the Magnitude and Composition of Drug Promotion in the United States in 1998, 25 CLINICAL THERAPEUTICS 1503 (2004);
7. P. Villanueva, S. Piero, J. Librero, and I. Pereiro, Accuracy of Pharmaceutical Advertisements in Medical Journals, 361 LANCET 27 (2003);
8. and M. G. Ziegler, P. Lews, and B. C. Singer, The Accuracy of Drug Information from Pharmaceutical Sales Representatives, 274 JAMA 1267 (1995);
9. also see http://nofreelunch.org/requiredbias.htm.
10. See, e.g., "Oxfam America, The US Must Stop Blocking Access to HIV/AIDS Drugs" (July 10 2003), available at http://www.oxfamamerica. org/newsandpublications/press_releases/archive2003/art5658.html;
11. Alicia Ely Yamin, Not Just a Tragedy: Access to Medications as a Right Under International Law, 21 BOS. U. INT'L. L.J. 325 (2003);
12. Michael Kremer, Pharmaceuticals and the Developing World, 16 J. ECON. PERSP. 67 (2002);
13. James Hookway and Nicholas Zamiska, Thai Showdown Spotlights Threat to Drug Patents, THE WALL STREET JOURNAL, April 24, 2007, at A1;
14. Alastair Stewart, Brazil Moves to Break Merck AIDS Drug Patent, THE WALL STREET JOURNAL, May 5, 2007, at B6;
15. and A Gathering Storm, THE ECONOMIST, June 9-15, 2007, at 71.
16. See Edwin Mansfield, Patents and Innovation: An Empirical Study, 2 MANAGEMENT SCI. 32 (Feb. 1986) (60 percent of pharmaceuticals developed and 65 percent of pharmaceuticals introduced into the U.S. would not have been developed or introduced absent patent protection).
17. KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727.
18. See, e.g., Michael Burdon and Kristie Sloper, The Art of Using Secondary Patents to Improve Protection, INTERNATIONAL JOURNAL OF MEDICAL MARKETING Vol. 3, No. 3, 226 (2003);
19. and Perry, Greg, J. GENERIC MEDICINES Vol. 1, No. 1, 4-5 at 5, Oct. 2003.
20. Hotchkiss v. Greenwood, 52 U.S. 248 (1851); Great Atlantic & Pacific Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147 (1950); Graham v. John Deere Co., 383 US 1 (1966); U.S. v. Adams, 383 U.S. 39 (1966); Anderson's-Black Rock v. Pavement Co., 396 U.S. 57 (1969); and Sakraida v. Ag Pro, Inc., 425 U.S. 273 (1976).
21. See, e.g., Michael A. Heller and Rebecca S. Eisenberg, Can Patents Deter Innovation? The Anti-commons in Biomedical Research, 280 SCI. 698 (1998);
22. Michael A. Heller, The Tragedy of the Anticommons: Property in the Transition from Marx to Markets, 111 HARV. L. REV. 621 (1998);
23. Garret Hardin, Tragedy of the Commons, 162 SCI. 1243 (1968);
24. and James Buchanan and Yong J. Yoon, Symmetric Tragedies: Commons and Anticommons, 43 J.L. & ECON. 1 (2000).
25. For some recent discussion of the potentially changing innovator business model, see Beyond the pill - Drug firms are casting about for new business models, THE ECONOMIST, October 25, 2007;
26. Jeanne Whalen, Prescription-Drug Sales Growth Is Expected to Slow, THE WALL STREET JOURNAL, November 1, 2007 at A12;
27. and Curtis R. Chong and David J. Sullivan Jr., New uses for old drugs, 448 NATURE 645, (2007).
28. Nick Timiraos, Businesses Battle Over Patent Laws, WALL STREET JOURNAL, June 9, 2007 at A7.
29. See Carl Shapiro, Navigating the Patent Thicket: Cross Licenses, Patent Pools, and Standard Setting, in 1 INNOVATION POLICY AND THE ECONOMY 119, 119 (A. Jaffe et al. eds., MIT Press Journals, 2001).
30. This account of the history of the pharmaceutical industry is adapted generally from: Charles G. Smith, The Process of New Drug Discovery and Development, INFORMA HEALTH CARE, 2006;
31. Pharmaceutical Innovation: Revolutionizing Human Health, Ralph Landau, Basil Achilladelis, and Alexander Scriabine., eds., THE CHEMICAL HERITAGE FOUNDATION SERIES IN INNOVATION AND ENTREPRENEURSHIP, Chemical Heritage Press, 1999;
32. John Taylor and Peter Kennewell, MODERN MEDICINAL CHEMISTRY at 5-21 (1993);
33. and Miles Weatherall, IN SEARCH OF A CURE: A HISTORY OF PHARMACEUTICAL DISCOVERY, (1990).
34. See, e.g., Michael Strong, FDA Policy and Regulation of Stereoisomers: Paradigm Shift and the Future of Safer, More Effective Drugs, 54 FOOD DRUG L.J. 463, 463 (1999).
35. See, e.g., Bowden, Mary Ellen, PHARMACEUTICAL ACHIEVERS, Philadelphia: Chemical Heritage Foundation, 2003.
36. Richard A. Epstein, Overdose, How Excessive Government Regulation Stifles Pharmaceutical Innovation, Yale University Press, 2006, Chapter 1 at 7.
37. Id. at rear cover.
38. See, e.g., Alisa Opar, Bad bugs need more drugs, 6(12) NATURE REVIEWS DRUG DISCOVERY 2007 at 943;
39. and Robert Lee Hotz, Evolution at Work: Watching Bacteria Grow Drug Resistant, WALL STREET JOURNAL, June 8, 2007 at B1.
40. See, e.g., Christopher F. Higgins, Multiple molecular mechanisms for multidrug resistance transporters, 446 NATURE 749 (2007).
41. For a discussion of how mismanagement of disease via arguably irresponsible infection treatment practices may have exacerbated the drug resistance problem with respect to antibiotics, see Robert Bud, PENICILLIN: TRIUMPH AND TRAGEDY, Oxford University Press, 2007.
42. Much of the following account of the early history of the Food and Drug Laws are adapted from: the FDA website at http://www.fda.gov/oc/history/ historyoffda/default.htm;and in certain places, from A HISTORICAL GUIDE TO THE U.S. GOVERNMENT, George Kurian, ed., Oxford University Press, 1998.
43. See, e.g., Michael Strong, FDA Policy and Regulation of Stereoisomers: Paradigm Shift and the Future of Safer, More Effective Drugs, 54 FOOD DRUG L.J. 463, 463 (1999).
44. Federal Food and Drugs Act of 1906 (the "Wiley Act"), Pub. L. No. 59-384, 34 Stat. 768 (1906), 21 U.S.C. Sec 1-15 (1934), (repealed in 1938 by 21 U.S.C. Sec 329 (a)).
45. http://www.fda.gov/oc/history/historyoffda/section2.html.
46. Pub. L. No. 75-717, 52 Stat. 1040 (1938) (codified as amended 21 U.S.C. §§ 301 et seq.).
47. The Durham-Humphrey Amendment of 1951 codified FDA regulations, providing clarification as to what constituted a prescription versus an over-the-counter medication.
48. Pub. L. No. 87-781, 76 Stat. 780 (codified at 21 U.S.C. §§ 321, 331-32, 348, 351-53, 355, 357-60, 372, 374, 376, 381).
49. 21 U.S.C § 321(p)(1) defines a "new drug" (in part) as "any drug the composition of which is such that such drug is not generally recognized, among experts qualified by the scientific training and experience to evaluate the safety of drugs, as safe for use under the conditions prescribed, recommended or suggested in the labeling thereof...."
50. 21 C.F.R. § 312.23.
51. th ed. 2001).
52. See, e.g., Richard J. Findlay, Originator Drug Development, 54 FOOD & DRUG L.J. 227, 227 (1999).
53. 37 C.F.R. § 312.21.
54. 37 C.F.R. § 312.21(a).
55. 37 C.F.R. § 312.21(b). See also, Sharona Hoffman, A Proposal for Federal Legislation to Address Health Insurance Coverage for Experimental and Investigational Treatments, 78 OR. L. REV. 203, 234 (1999). For terminal patients, such as those who participate in oncology trials, if patients showed positive results during phase I trials, even if the drug overall fails the trials and is not pursued, often these patients are granted "compassionate use" and are not taken off the drug.
56. 21 C.F.R. § 312(c). See also, John Patrick Dillman, Prescription Drug Approval and Terminal Diseases: Desperate Times Require Desperate Measures, 44 VAND. L. REV. 925, 929 (1991).
57. 21 C.F.R. §§ 314.50 and 314.100(a).
58. DiMasi, J.A. et al. The Price of Innovation: New Estimates of Drug Development Costs, JOURNAL OF HEALTH ECONOMICS 22 (2003): 151-185.
59. Id.
60. DiMasi, J.A., New Drug Development in the United States from 1963 to 1999, CLINICAL PHARMACOLOGY AND THERAPEUTICS 69, no. 5 (2001): 286-296.
61. Common estimates range from $800 million to $1.7 billion per drug, although the $800 million figure is outdated at this point. See, e.g., Allison Ladd, Integra v. Merck: Effects on the Cost and Innovation of New Drug Products, 13 J.L. & POL'Y 311, 311 (2005).
62. Roche Products, Inc. v. Bolar Pharmaceutical Co., 733 F.2d 858 (Fed. Cir. 1984)
63. See H.R. Rep. No. 98-857, Part I at 17 (1984), reprinted in 1984 U.S.C.C.A.N. 2647, 2650. Also see Gilston, The Generic Patent Compromise, MED. ADVERTISING NEWS, Apr. 30, 1984, at 16-17.
64. Pub. L. No. 98-417, 98 Stat. 1585 (codified at 15 U.S.C. §§ 68b-68c, 70b (1994); 21 U.S.C. §§ 301 note, 355, 360cc (1994); 28 U.S.C. § 2201 (1994); 35 U.S.C. §§ 156, 271, 282 (1994)).
65. See, e.g., Vannevar Bush, "Science: The Endless Frontier, a Report to the President on a Program for Postwar Scientific Research," (Nat'l Science Foundation 1960) (1945), available at http://www.nsf.gov/ about/history/nsf50/vbush1945jsp.
66. 149 Cong. Rec. S15582, S15584 (Nov. 25, 2003) (remarks of Sen. Kennedy, Medicare Prescription Drug, Improvement, and Modernization Act of 2003).
67. FDA considered "such retesting to be unnecessary and wasteful because the drug [had] already been determined to be safe and effective. Moreover, such retesting is unethical because it requires that some sick patients take placebos and be denied treatment known to be effective." See H.R. Rep. No. 98-857, Part I at 16 (1984), reprinted in 1984 U.S.C.C.A.N. 2647, 2649.
68. In actuality, each applicant who submits a substantially complete ANDA with a "Paragraph IV Certification" (discussed infra) on the same day is eligible for the same exclusivity period. See generally, Jaeger, Kathleen, America's generic pharmaceutical industry: Opportunities and challenges in 2006 and beyond, J. GENERIC MED. Vol. 4, No. 1, 15, Oct. 2006, at 17-18.
69. 21 U.S.C. § 355(b)(1). FDA's listing regulations interpret "drug" to be "drug product" and define "drug product" as "a finished dosage form, for example, a tablet, capsule, solution, etc., that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients." 21 C.F.R. §§ 314.53(b) (the "listing regulation") and 210.3(4). Also see Pfizer, Inc. v. FDA, 753 F. Supp. 171 (D. Md. 1990) for judicial affirmation of FDA's interpretation of the Code.
70. 21 C.F.R. § 314.53(b).
71. 21 C.F.R. § 210.3(4).
72. 21 U.S.C. § 355(j)(7)(A).
73. 21 U.S.C. § 355(j)(2)(A)(iv).
74. Richard R. Abood, PHARMACY PRACTICE AND THE LAW, at 70, Jones and Bartlett Publishers, 2003.
75. Elizabeth Stotland Weiswasser & Scott D. Danzis, The Hatch-Waxman Act: History, Structure, and Legacy, 71 ANTITRUST L.J. 585, 591 (2003).
76. 21 U.S.C. § 355(j)(2)(B), and 35 U.S.C. § 271(e)(2).
77. 35 U.S.C. § 282.
78. Although the patent holder and the NDA filer are often the same person, this is not always the case. The Hatch-Waxman Amendments require that all patents that claim the drug described in an NDA must be listed in the Orange Book. Occasionally, this requires an NDA filer to list a patent that it does not own. Furthermore, a detailed statement of the factual and legal basis for the assertion of invalidity or non-infringement must be provided to the patent holder.
79. 21 U.S.C. § 355(j)(5)(B)(iii).
80. Id.
81. Federal Trade Commission, "Generic Drug Entry Prior to Patent Expiration, An FTC Study" at 39 (July 2002) ("FTC Study"), available at http://www.ftc.gov/os/2002/07/genericdrugstudy.pdf.
82. FTC Study at 40, supra at footnote 60.
83. 21 C.F.R. § 314.53(f). For two court cases upholding this requirement, see aaiPharma v. Thompson, 2002 WL 1473429 (4th Cir. 2002); Watson Pharmaceuticals v. Henney, Civil Action No. 00-3516 (D. Md. Jan. 17, 2001).
84. 59 Fed. Reg. 50338, 50343 (Oct. 3, 1994) ("FDA does not have the expertise to review patent information. The agency believes that its resources would be better utilized in reviewing applications rather than reviewing patent claims."); Abbreviated New Drug Application Regulations, 54 Fed. Reg. 28872, 28910 (1989) ("In deciding whether a claim of patent infringement could reasonably be asserted...the agency will defer to the information submitted by the NDA applicant.").
85. Medicare Act § 1101(2)(A), codified at 21 U.S.C. § 355(j)(5)(B)(iii). The statutory changes supercede FDA regulations limiting 30-month stays of approval of ANDAs, codified at 21 C.F.R. 314.52(a)(3) and 21 C.F.R. 314.95(a)(3). Federal Register, Vol. 69, No 47 (3/10/04) 11309.
86. Medicare Act §1101(a)-(b), codified at § 355(j)(B); (b)(3).
87. th Cir. 1999) (Posner, C.J). Also see, e.g., Malcolm Gladwell, High Prices: How to Think About Prescription Drugs, NEW YORKER, October 25, 2004, at 86.
88. FTC Study, supra at footnote 60.
89. Breda Lund, Generic Industry Experiencing A Golden Age, GENERIC LINE, Vol. 24, No. 14, July 25, 2007, at 12;
90. Patricia M. Danzon and Michael F. Furukawa, "Prices And Availability Of Pharmaceuticals: Evidence From Nine Countries, Health Affairs," Web Exclusive, at W3-525, available at http://content.healthaffairs.org/ webexclusives (2004);
91. Jaeger, Kathleen. America ' s generic pharmaceutical industry: Opportunities and challenges in 2006 and beyond, J. GENERIC MEDICINES Vol. 4, No. 1, 15-22, at 15, Oct. 2006.
92. Tuttle, Edward; Parece, Andrew; and Hector, Anne. Your Patent is About to Expire. What Now?, PHARMACEUTICAL EXECUTIVE, NOV. 2004, 88-98, at 88.
93. See, e.g., Congressional Budget Office, "How Increased Competition from Generic Drugs has Affected Prices and Returns in the Pharmaceutical Industry," at 40-41 (July 1998). Also see Pharmaceutical Research and Manufacturers of America (PhRMA), Delivering on the Promise of Pharmaceutical Innovation: The Need to Maintain Strong and Predictable Intellectual Property Rights, White Paper Submitted to the FTC, at ii, 27 (Washington, DC: PhRMA, 2002).
94. For earlier work in the area, see Henry G. Grabowski and John M. Vernon, Returns to R&D on New Drug Introductions in the 1980s, 13 J. HEALTH ECON. 383, 389 (1994).
95. For recent calculations, suggesting that the pharmaceutical period of effective patent-derived market exclusivity may be as low as nine years, see Richard A. Epstein, OVERDOSE. HOW EXCESSIVE GOVERNMENT REGULATION STIFLES PHARMACEUTICAL INNOVATION, Yale University Press, 2006, Chapter 7, fn 9.
96. See, e.g., Voet, Martin, A., The Generic Challenge: Understanding Patents, FDA and Pharmaceutical Life-Cycle Management, Brown Walker Press, Boca Raton, Florida, USA, 2005.
97. 35 U.S.C. § 271(a).
98. 35 U.S.C. § 154.
99. 35 U.S.C. § 151.
100. 35 U.S.C. § 101.
101. Id.
102. 35 U.S.C. § 102.
103. 35 U.S.C. § 103.
104. 35 U.S.C. § 112.
105. U.S. Patent No. 5,054,552, covering Aciphex®.
106. See "Changes To Practice for Continued Examination Filings, Patent Applications Containing Patentably Indistinct Claims, and Examination of Claims in Patent Applications." 72 Fed. Reg. 46716-47843 (Aug. 21,2007). These Final Rules revise the rules of practice in patent applications relating to continuing applications, requests for continued examination, and for the examination of claims in patent applications.
107. See Pharmaceutical Salts: Properties, Selection and Use, P. Heinrich Stahl & Camille G. Wermuth, eds., 2002.
108. th ed. 2001).
109. See, e.g, E.J. Ariens, Stereochemistry, a Basis for Sophisticated Nonsense in Pharmacokinetics and Clinical Pharmacology, 26 EUR. J. CLINICAL PHARMACOLOGY 663 (1984), and references therein.
110. Stephen C. Stinson, Counting on Chiral Drugs, CHEM. & ENG. NEWS SPECIAL REPORT, Vol. 76, No. 38, 1 (1998).
111. See discussions in Forest Laboratories, Inc. v. Ivax Pharmaceuticals, 438 F.Supp.2d 479, 493 (D.Del 2006) and Pfizer Inc. v. Ranbaxy Laboratories Ltd., 405 F.Supp.2d 495 517 (D.Del. 2005).
112. See, e.g., In re Doyle, 293 F.3d 1355, 1356 (Fed. Cir. 2002).
113. See discussion in Michael Strong, FDA Policy and Regulation of Stereoisomers: Paradigm Shift and the Future of Safer, More Effective Drugs, 54 FOOD DRUG L.J. 463 (1999).
114. It should be noted that the enantiomers are known to interconvert to some extent in vivo, so the teratogenic effects cannot completely be avoided.
115. Patent protection for the 1:1 mixture of enantiomers (the "racemate"), which was sold under the brand name Celexa, expired in 2003.
116. The '712 patent was originally set to expire on June 8, 2009; however, with a patent term extension of 827 days, and an additional six-month extension for investigating pediatric indications, generic versions of the Lexapro® products covered by the '712 patent are precluded from being marketed in the United States until March 13, 2012.
117. th ed. 1999).
118. See, e.g., Joel Bernstein, Polymorphism and Patents from a Chemist's Point of View, Chapter 14 in POLYMORPHISM: IN THE PHARMACEUTICAL INDUSTRY, edited by Rolf Hilfiker, Wiley-VCH Verlag GmbH& Co. KGaA, Weinheim, 2006 at p. 367: "In general, new crystal forms can be patented without showing unexpected properties, since one of ordinary skill cannot predict the structure, properties or method of preparation of that crystal form prior to its discovery." Also see, In re Irani, 427 F.2d 806 (C.C.P.A. 1970). While the issue of non-obviousness may not merit discussion here, other areas of polymorph patent jurisprudence are in some dispute right now. For example, compare Glaxo, Inc. v. Novopharm Ltd., 830 F. Supp. 871, 876-77 (E.D.N.C. 1993), aff'd Glaxo Inc. v. Novopharm Ltd., 52 F.3d 1043, 1047-48 (Fed. Cir.), cert. denied, 133 L. Ed. 2d 424, 116 S. Ct. 516 (1995), with SmithKline Beecham Corp. v. Apotex Corp. 403 F.3d 1331 (Fed. Cir. 2005).
119. See, e.g., Nandita G. Das and Sudip K. Das, Controlled-Release of Oral Dosage Forms, FORMULATION, FILL & FINISH, 10 (2003);
120. Drug Delivery Technologies-Innovations and Market Challenges, SCRIP REPORTS (PJB Publications Ltd., 2003);
121. W.H. Helfand and D.L.Cowen, Evolution of Pharmaceutical Oral Dosage Forms, PHARM HIST. 25, 3-18 (1983);
122. and R. Löbenberg and G.L. Amidon, Modern Bioavailability, Bioequivalence and Biopharmaceutics Classification system. New Scientific Approaches to International Regulatory Standards, 50 EUR. J. PHARM. BIOPHARM. 3-12 (2000).
123. For an overview of such technologies, see Charles Chiao and Joseph Robinson, Sustained-Release Drug Delivery Systems, Chapter 94 in THE SCIENCE AND PHARMACY, Mack Publishing Company, Eaton Pennsylvania, 1995.
124. Wyllie, Michael, G. Evergreening: there's life in the old drug yet. 2005 BJU INTL. 95, 1359-1360.
125. Also see, Andersson K-E, Wyllie M.G., Ejaculatory dysfunction: why all -blockers are not equal. BJU INTL. 2003; 92: 876-7;
126. and David Bradley, Finding New Formulas for Pharma Success, 6 NATURE REVIEWS DRUG DISCOVERY 423 (2007).
127. See, e.g., Stenson, Jacqueline. "Report questions generic antidepressant. ConsumerLab.com finds cheaper drug may not work the same as brand," last viewed October 13, 2007 at http://www.msnbc.msn.com/id/ 21142869.
128. Commercial formulations of Ditropan XL are sold as the racemate. The (R)-enantiomer is a more potent anticholinergic than either the racemate or the (S)-enantiomer, which is essentially without anticholinergic activity at the doses used in clinical practice. However despite the potency advantage, (R)-oxybutynin administered alone offers little or no clinical benefit above and beyond the racemic mixture.
129. See, e.g., Cabri, W. and Di Fabio, R., From Bench to Market, THE EVOLUTION OF CHEMICAL SYNTHESIS, Oxford University Press, 2000, particularly chapter 11, section 2.1 The Biological Hypothesis.
130. See Raytheon Co. v. Roper Corp., 724 F.2d 951 (Fed. Cir. 1983); Ex parte Lanham 121 USPQ 223 (Pat. Off. Bd. App. 1958).
131. See generally Thomas A Faunce, Global Intellectual Property Protection of 'Innovative' Pharmaceuticals, Chapter 7 in GLOBALIZATION AND HEALTH: CHALLENGES FOR BIOETHICS AND HEALTH LAW, Belinda Bennett and George F. Tommosy Eds., Springer 2005.
132. Eggles ton, Richard; Bruce, Lindsay, Maximizing profitability through commercially successful implementation of over-the-counter switches, J. GENERIC MEDICINES Vol. 1, No. 1, 13-20, at 16, Oct. 2003;
133. and Tuttle, Edward; Parece, Andrew; and Hector, Anne, Your Patent is About to Expire. What Now?, PHARMACEUTICAL EXECUTIVE, NOV. 2004, 88-98, at 90.
134. See, e.g., James D. Veltrop and Chad A. Landmon, The Impact of a Brand Generic Launch on the Recovery of Patent Damages, 23 IPL NEWSLETTER NO. 4, p. 1 (2005).
135. Weissman, Robert, The Face of Big Pharma's Failure. Victory and Betrayal: The Evergreen Patent System, Pharmaceutical Company Tactics to Extend Patent Protections, MULTINATIONAL MONITOR, Vol. 23, No. 6, June 2002.
136. Perry, Greg. J. GENERIC MEDICINES Vol. 1, No. 1, 4-5, at 5, Oct. 2003.
137. See, e.g., Reuters Business Insight (2001): Achieving market dominance through reformulation: A strategic insight, Datamonitor, London, UK;
138. and Wyllie, Michael, G, Evergreening: there's life in the old drug yet, 2005 BJU INTL. 95, 1359-1360, at 1359.
139. See, e.g., John P. Walsh, Wesley M. Cohen, and Ashish Arora, Working Through the Patent Problem, 299 SCI. 1021 (2003).
140. See, e.g., Thomas H. Lee, Me-Too Products - Friend or Foe? 360 NEW ENG. J. MED. 211, (January 15, 2004) ("Me-too products reflect and create competition among drug and device manufacturers, and that competition is also a powerful driver of better quality and lower cost.").
141. See, e.g., Malcolm Gladwell, High Prices: How to Think About Prescription Drugs, NEW YORKER, October 25, 2004, at 86.
142. Dep't of Health & Human Services., Nat'l Insts. of Health, "A Plan to Ensure Taxpayers Interests Are Protected," July 2001, http://www.nih.gov/news/070101wyden.htm. Also see http://www.phrma.org/ index.php?option=com_content&task=view&id=382&Itemid=118.
143. 35 U.S.C. § 103(a).
144. Graham v. John Deere Co., 383 US 1 (1966).
145. Id. at 17.
146. Id. at 17-18.
147. See, e.g., Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006). ("a reference that 'teaches away' from a given combination may negate a motivation to modify the prior art to meet the claimed invention.")
148. Loom Co. v. Higgins, 105 U. S. 580, 591 (1881).
149. Potts v. Creager, 155 U.S. 597, 607-08 (1895).
150. Expanded Metal Co. v. Bradford, 214 U.S. 366, 381 (1909).
151. See, e.g., Giles S. Rich, Laying the Ghost of the Invention Requirement, 1 AIPLA Q.J. 26, 34 (1972); In re Kahn, 441 F.3d 977, 986 (Fed. Cir. 2006) ["The motivation-suggestion-teaching requirement protects against the entry of hindsight into the obviousness analysis, a problem which § 103 was meant to confront. See 35 U.S.C. § 103 (stating that obviousness must be assessed at the time the invention was made)"] (internal quotations omitted); and Alza Corp. v. Mylan Labs., Inc., 464 F.3d 1286, 1290 (Fed. Cir. 2006) (the suggestion test "prevent[s] statutorily proscribed hindsight reasoning when determining the obviousness of an invention.").
152. See, e.g., discussion in In re Kahn, 441 F.3d 977, 986-987 (Fed. Cir. 2006).
153. st Century" 90 National Research Council (2004) available at http://www.nap.edu/html/patentsystem/0309089107.pdf.
154. Decided, April 30, 2007 in KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727.
155. See, e.g., Glynn S. Lunney, Jr., E-Obviousness, 7 MICH. TELECOM. & TECH. L. REV. 363, 412 (2001).
156. Compare, e.g., Brief For Amicus Curiae Computer & Communications Industry Association In Support Of Petitioner with Brief Of Amicus Curiae Pharmaceutical Research And Manufacturers Of America In Support Of Respondents.
157. See, e.g., Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1361-1365 (Fed. Cir. 2007).
158. See, e.g., "Laying the Ghost of the Invention Requirement," supra at footnote 119.
159. See, e.g., Grain Processing Corp., 840 F.2d 902, 907 (Fed. Cir. 1988) ("Care must be taken to avoid hindsight reconstruction by using 'the patent in suit as a guide through the maze of prior art references, combining the right references in the right way so as to achieve the result of the claims in suit.")
160. See e.g., Brief For Petitioners ("[I]n the Federal Circuit's view, the undisputed prior art of record did not render the Respondents' claimed invention unpatentable under § 103(a), because Petitioner had not gone further and proved, beyond genuine dispute and by clear and convincing evidence, that there was a suggestion or motivation to combine the teachings of Asano with an electronic control in the particular manner claimed by claim 4 of the Engelgau patent". Internal quotations and references omitted.).
161. See, e.g., the opinion of the CAFC in Teleflex, Inc. v. KSR Int'l Co., 119 Fed. Appx. 282, at 288 (Fed. Cir. 2005) ("Under our case law, whether based on the nature of the problem to be solved, the express teachings of the prior art, or the knowledge of one of ordinary skill in the art, the district court was required to make specific findings as to whether there was a suggestion or motivation to combine the teachings of Asano with an electronic control in the particular manner claimed by claim 4 of the '565 patent.")
162. See e.g., In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006) ("A suggestion, teaching or motivation to combine the relevant prior art teachings does not have to be found explicitly in the prior art."); Dystar Textilfarben GmbH v. C.H. Patrick Co., 464 F.3d 1356, 1361 (Fed. Cir. 2006) ("In contrast to the characterization of some commentators, the suggestion test is not a rigid categorical rule. The motivation need not be found in the references sought to be combined, but may be found in any number of sources, including common knowledge, the prior art as a whole, or the nature of the problem itself."); Ormco Corp. v. Align Tech., Inc., 463 F.3d 1299, 1307 (Fed. Cir. 2006) (quoting In re Kahn, above); Alza Corp. v. Mylan Labs., Inc., 464 F.3d 1286, 1291 (Fed. Cir. 2006) ("There is flexibility in our obviousness jurisprudence because a motivation may be found implicitly in the prior art. We do not have a rigid test that requires an actual teaching to combine before concluding that one of ordinary skill in the art would know to combine references."); and references cited therein.
163. See, e.g., Brief For Amicus Curiae Computer & Communications Industry Association In Support Of Petitioner.
164. See, e.g., Patently Obvious, THE WALL STREET JOURNAL, May 3, 2007.
165. Teleflex, Inc. v. KSR Int'l Co., 119 Fed. Appx. 282, 290 (Fed. Cir. 2005) ("[I]n granting summary judgment in favor of KSR, the district court erred as a matter of law by applying an incomplete teaching-suggestion-motivation test to its obviousness determination. The correct standard requires a court to make specific findings showing a teaching, suggestion or motivation to combine prior art teachings in the particular manner claimed by the patent at issue.").
166. In the KSR opinion, the phrase "common sense" is used 9 times.
167. Transcripts can be downloaded from the Supreme Court website at http://www.supremecourtus.gov/oral_arguments/argument_transcripts.html. Page references are to the PDF version of the document available thereat.
168. Id. at 51.
169. Id. at 6.
170. Mandel, Gregory, Patently Non-Obvious: Empirical Demonstration that the Hindsight Bias Renders Patent Decisions Irrational, OHIO STATE LAW JOURNAL, Vol. 67, p. 1391, 2006, 1st Annual Conference on Empirical Legal Studies.
171. Mandel, Gregory, Patently Non-Obvious II: Experimental Study on the Hindsight Issue Before the Supreme Court in KSR v. Teleflex, YALE JOURNAL OF LAW & TECHNOLOGY, Vol. 9, No. 1, 2007.
172. Mandel, Gregory, "KSR v. Teleflex: A Tale Full of Sound and Fury, Signifying Little?" http://www.patentlyo.com/patent/2007/05/ ksr_v_teleflex_.html#more. Last accessed online, May 8, 2007.
173. Id.
174. Id.
175. See, e.g., In re Dembiczak, 175 F.3d 994, 999 (Fed. Cir. 1999) ("combining prior art references without evidence of such a suggestion, teaching or motivation simply takes the inventor's disclosure as a blueprint for piecing together the prior art to defeat patentability - the essence of hindsight.").
176. See, e.g., Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1465 (Fed. Cir. 2007) (stating that "obvious to try" may not be enough to find an advance obvious, but that "absolute predictability of success is not required".)
177. Oral Arguments at 41.
178. See slip opinion 04-1350 (2007) at 8.
179. Id.
180. Id. at 17.
181. As mentioned above, the Supreme Court used the phrase "common sense" nine times in its opinion.
182. See slip opinion 04-1350 (2007) at 8 (emphasis added).
183. Id. at 10.
184. Id. at 7.
185. Id.
186. Id. at 6 (emphasis added).
187. Id. at 9.
188. Id. at 16-18 (emphasis added).
189. Id. at 5.
190. Id. at 15.
191. See, e.g., Margaret A. Focarino, Deputy Commissioner for Patent Operations, Memorandum: "Supreme Court Decision on KSR Int'l., Co. v. Teleflex, Inc.," May 3, 2007. The flexibility is likely to lead to an increase in the filing of declarations and of appeals to the Board of Patent Appeals and Interferences following § 103 rejections, see, e.g., Peter Zura, "Does Dystar Provide the First Glimpse Into a Post-KSR World?" Peter Zura's 271 Patent Blog, May 2, 2007, last accessed online May 3, 2007 at http://271patent.blogspot.com/2007/05/does-dystar-provide-first-glimpse-into. html.
192. Harries v. Air King Products Co., 183 F.2d 158, 162 (2d Cir. 1950).
193. Slip opinion 04-1350 (2007) at 15.
194. Id. at 11. ["We note the Court of Appeals has since elaborated a broader conception of the TSM test than was applied in the instant matter...The extent to which they may describe an analysis more consistent with our earlier precedents and our decision here is a matter for the Court of Appeals to consider in its future cases." Citing Dystar Textilfarben GmbH v. C.H. Patrick Co., 464 F.3d 1356, 1361 (Fed. Cir. 2006) and Alza Corp. v. Mylan Labs., Inc., 464 F.3d 1286, 1291 (Fed. Cir. 2006)]
195. See slip opinion 04-1350 (2007) at 17.
196. Compare, e.g., Brief For Amicus Curiae Computer & Communications Industry Association In Support Of Petitioner with Brief Of Amicus Curiae Pharmaceutical Research And Manufacturers Of America In Support Of Respondents.
197. "The presence or absence of a motivation to combine references in an obviousness determination is a pure question of fact," In re Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000); accord Winner Int'l Royalty Corp. v. Wang, 202 F.3d 1340, 1348 (Fed. Cir. 2000), as is the presence or absence of a "reasonable expectation of success" from making such a combination, Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006).
198. See slip opinion 04-1350 (2007) at 14.
199. Id. at 7, citing In re Kahn, 441 F.3d 977 (Fed. Cir. 2006).
200. For an early blog post that clearly highlights this seeming clairvoyance, see Peter Zura, "Does Dystar Provide the First Glimpse Into a Post-KSR World?" Peter Zura's 271 Patent Blog, May 2, 2007, last accessed online May 3, 2007 at http://271patent.blogspot.com/2007/05/does-dystar- provide-first-glimpse-into.html. Judge Rader, discussing the decision in Leapfrog Enters, v. Fisher-Price, Inc., 2007 U.S. App. LEXIS 10912 (Fed. Cir. 2007) at a recent CIP Forum in Sweden, confirmed that the court felt that its jurisprudence in existence just prior to the KSR decision would not need any "great changes." Furthermore, he told delegates that the opinion in Leapfrog had actually been written before the Supreme Court's decision was handed down and "did not require one iota of change." See Joff Wild, Federal Circuit Judge Reveals KSR Secret, I NTELLECTUAL ASSET MANAGEMENT MAGAZINE, May 21, 2007, accessed online May 22, 2007 at http://www.iam-magazine.com/blog/ Detail.aspx?g=b53c64ee-fc33-455e-b760-cdc9d9059474.
201. Recall slip opinion 04-13 50 (2007) at 11, ["We note the Court of Appeals has since elaborated a broader conception of the TSM test than was applied in the instant matter...The extent to which they may describe an analysis more consistent with our earlier precedents and our decision here is a matter for the Court of Appeals to consider in its future cases." Citing Dystar Textilfarben GmbH v. C.H. Patrick Co., 464 F.3d 1356, 1361 (Fed. Cir. 2006) and Alza Corp. v. Mylan Labs., Inc., 464 F.3d 1286, 1291 (Fed. Cir. 2006)].
202. Dystar Textilfarben GmbH v. C.H. Patrick Co., 464 F.3d 1356, 1361 (Fed. Cir. 2006).
203. Id. at 1367.
204. Id. at 1368.
205. I.e., patents claiming Pfizer's Norvasc®, Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir. 2007); Astra's Prilosec®, Astra Aktiebolag v. Andrx Pharms., Inc. (In re Omeprazole Patent Litig.), 2007 U.S. App. LEXIS 9233 (Fed. Cir. 2007); Aventis's Rilutek®, Impax Labs., Inc. v. Aventis Pharms., Inc., 468 F.3d 1366 (Fed. Cir. 2006); Abbott's Ultane®, Abbott Labs. v. Baxter Pharm. Prods., 471 F.3d 1363 (Fed. Cir. 2006); DyStar's dyeing process, Dystar Textilfarben GmbH v. C.H. Patrick Co., 464 F.3d 1356 (Fed. Cir. 2006); Alza's Ditropan XL®, Alza Corp. v. Mylan Labs., Inc., 464 F.3d 1286 (Fed. Cir. 2006); Align Technology's orthodontics treatment, Ormco Corp. v. Align Tech., Inc., 463 F.3d 1299 (Fed. Cir. 2006); and Leonard Kahn's reading machine for the blind, In re Kahn, 441 F.3d 977 (Fed. Cir. 2006).
206. The Dynamics of Obviousness, THE PATENT PROSPECTOR, posted online, May 14,2007, accessed online at http://www.patenthawk.eom/blog/2007/05/the_dynamics_of_obviousness.html#more.
207. For other accounts of the negative impact of KSR on patentability generally, see Jesse Greenspan, KSR Leads To Increase In Obviousness Invalidations, IP LAW 360, Oct. 26, 2007;
208. and Thinning the Patent Thicket, THE PATENT PROSPECTOR, posted online, Oct. 20, 2007.
209. See, e.g., The Dynamics of Obviousness, THE PATENT PROSPECTOR, posted online, May 14, 2007, accessed online at http://www.patenthawk.com/blog/2007/05/the_dynamics_of_obviousness. html#more.
210. Slip opinion 04-1350 (2007) at 10 (emphasis added).
211. Id. at 6 (emphasis added).
212. See, e.g., Gillette Co. v. S.C. Johnson & Son, Inc., 919 F.2d 720, 725 (Fed. Cir. 1990) ("we have consistently held that 'obvious to try' is not to be equated with obviousness"). Also see In re Tomlinson, 53 C.C.P.A. 1421, 363 F.2d 928, 931 (CCPA 1966) ("there is usually an element of 'obviousness to try' in any research endeavor, that...is not undertaken with complete blindness but rather with some semblance of a chance of success"). For a recent discussion, see Harold C. Wegner, "Post-KSR Treatment of 'Problems' in the Background of the Invention" last accessed June 15, 2007 at http://www.patenthawk. com/blog_docs/070613_PostKSRChemicalObviousness.pdf.
213. See, e.g., Richard A. Epstein, "Flexible Patent Law... and Its Achilles Heel," The Wall Street Journal, Friday, May 11, 2007;
214. and Calvert D. Crary, "The Impact of KSR v. Teleflex on the Pharmaceutical Industry," Litigation Notes, May 2, 2007, accessed online at http://www.litigationnotes.com.
215. Seema Singh, "India's Generic Drug Run - Indian companies see an opening for generic drugs in U.S.," Red Herring, May 15, 2007, last accessed online May 19, 2007 at http://www.redherring.com/Article.aspx?a= 22284&hed=India%e2%80%99s+Generic+Drug+Run#.
216. In re Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990) (en banc).
217. Id. at 692; see also In re Wilder, 563 F.2d 457, 460 (C.C.P.A. 1977) ("[O]ne who claims a compound, per se, which is structurally similar to a prior art compound must rebut the presumed expectation that the structurally similar compounds have similar properties.").
218. See, e.g., discussion in Yamanouchi Pharm. Co. v. Danbury Pharmacal, Inc., 231 F.3d 1339, at 1343 ff. (Fed. Cir. 2000).
219. No. 07-1021 (Fed. Cir. 2007),
220. See discussion in Janssen Pharmaceutica N.V. v. Mylan Pharms., Inc., 456 F. Supp. 2d 644, at 655-656 (D.N.J. 2006).
221. Audio recordings of the oral arguments are available online at http://www.cafc.uscourts.gov/oralarguments/mp3/07-1021.mp3.
222. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1367 (Fed.Cir. 2007) (emphasis added).
223. Takeda Chemical Industries v. Alphapharm Pty, 492 F.3d 1350, 1361 (Fed.Cir. 2007) citing In re Grabiak, 769 F.2d 729, 731 (Fed.Cir. 1985).
224. Id. at 1356.
225. Arguably, within this framework, there may still be some room for KSR-related jurisprudence in determinations of motivation or expectation of success. See, e.g., Altana Phama AG v. Teva Pharmaceuticals USA, Inc., 2007 WL 2688917 (D.N.J. 2007) (In the context of a motion seeking a preliminary injunction to prevent the sale of a generic, stating, "[w]hen Bryson's teachings are combined with the structure of compound 12 and combined with Dr. Sachs's teachings, Defendants have raised a substantial question that this combination was at the very least obvious to try and that such would lead to a predictable variation of compound 12, i.e., a compound with better pH5 stability.").
226. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir. 2007).
227. See id. at 1364.
228. Id. at 1365.
229. Id. at 1368, (internal citation and quotations omitted; emphasis added) (citing Dystar Textilfarben GmbH v. C.H. Patrick Co., 464 F.3d 1356 (Fed. Cir. 2006) and Merck & Co. v. Biocraft Laboratories, Inc., 874 F.2d 804 (Fed. Cir. 1989).
230. Id. at 1371 (emphasis added) (citing Dystar Textilfarben GmbH v. C.H. Patrick Co., 464 F.3d 1356 (Fed. Cir. 2006)).
231. See slip opinion 04-1350 (2007) at 10.
232. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1367 (Fed. Cir. 2007).
233. Id. (citation omitted).
234. Id. (citation omitted).
235. See the three dissenting opinions of Judges Newman, Lourie, and Rader to the denial of rehearing en banc, Pfizer, Inc. v. Apotex, Inc., 2007 U.S. App. LEXIS 11886 (Fed. Cir. 2007).
236. As the court in Pfizer v. Apotex noted, "[u]ndue dependence on mechanical application of a few maxims of law, such as 'obvious to try,' that have no bearing on the facts certainly invites error as decisions on obviousness must be narrowly tailored to the facts of each individual case." 480 F.3d 1366.
237. See, e.g., In re Anthony, 414 F.2d 1383, 1386 (C.C.P.A. 1969) (footnote omitted); also see, In re Adamson, 275 F.2d 952 (C.C.P.A. 1960). For a related historical source, see In re Merz, 97 F.2d 599, 601 (C.C.P.A. 1938) (holding, prior to the enactment of § 103, that an applicant "is not entitled to a patent on [an] article which after being produced has a greater degree of purity than the product produced by former methods" unless the purification results in "properties and characteristics which were different in kind from those of the known product rather than in degree.")
238. See discussion in Forest Laboratories, Inc. v. Ivax Pharmaceuticals, 438 F.Supp.2d 479, 492-96 (D.Del. 2006) and references therein.
239. 2007 WL 2482122; 2007 US.App.LEXIS 21165 (Fed. Cir. 2007).
240. Aventis v. Lupin, 2007 WL 2593791, at 12 (Fed. Cir. 2007).
241. Id.
242. Aventis v. Lupin, at 11.
243. Id.
244. See discussions in Forest Laboratories, Inc. v. Ivax Pharmaceuticals, 438 F.Supp.2d 479, 493 (D.Del 2006) and Pfizer Inc. v. Ranbaxy Laboratories Ltd., 405 F.Supp.2d 495 517 (D.Del. 2005).
245. Id.
246. Forest Laboratories, Inc. v. Ivax Pharmaceuticals, 438 F.Supp.2d 479, 493 (D.Del 2006).
247. For an alternative viewpoint, see, e.g., Brian D. Coggio and Steven N. Hird, The Patentability of Drug Enantiomers, 190 N.J.L.J. 51, October 1, 2007.
248. 464 F.3d at 1367. This quote from DyStar implicitly addressed the arguments in KSR that were under review at the time. It was quoted by the CAFC in Pfizer v. Apotex in the context of debunking Pfizer's argument that "obvious to try" was insufficient to satisfy the expectation of success. 480 F.3d at 1366.
249. Id.
250. Alza Corp. v. Mylan Labs., Inc., 464 F.3d 1286, 1290 (Fed. Cir. 2006).
251. Id.
252. Alza Corp. v. Mylan Labs., Inc., 388 F. Supp. 2d 717 (N.D. W.Va. 2005).
253. Id. at 739.
254. Id.
255. Alza Corp. v. Mylan Labs., Inc., 464 F.3d 1286, 1294 (Fed. Cir. 2006).
256. Id. at 1293-1294.
257. Id. at 1294.
258. Id.
259. Id.
260. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir. 2007).
261. Forest Labs., Inc. v. Ivax Pharms., Inc., 438 F. Supp. 2d 479 (D. Del 2006).
262. Knoll Pharms. Co. v. Teva Pharms. USA, Inc., 2002 U.S. Dist. LEXIS 17201 (N.D. Ill, 2002).
263. Id. at 17240.
264. Id. at 17206.
265. Knoll Pharms. Co. v. Teva Pharms. USA, Inc., 367 F.3d 1381 (Fed. Cir. 2004).
266. For one of the early perspectives on the effect of KSR on pharmaceutical patentability, see Calvert D. Crary, The Impact of KSR v. Teleflex on the Pharmaceutical Industry, LITIGATION NOTES, May 2, 2007, accessed online at http://www.litigationnotes.com.
267. See, e.g., "World pharmaceutical market to cross $900 billion by 2008," Research Studies-Business Communications Company, Inc., March 12, 2004.
268. See list of programs at https://www.pparx.org/ ViewCompanies.php.
269. th Cir. 1999) (Posner, C.J.)
270. PATENT TRADEMARK & COPYRIGHT JOURNAL, Volume: 73 Number: 1797, December 08, 2006. http://ipcenter.bna.com/pic2/ip.nsf/id/BNAP-6WAK96?OpenDocument.
271. See, e.g., 149 Cong. Rec. S15582, S15584 (Nov. 25, 2003) (remarks of Sen. Kennedy, Medicare Prescription Drug, Improvement, and Modernization Act of 2003).
272. DiMasi, J.A., Hansen, R.W., and Grabowski, H.G., 22 J. HEALTH ECON. 151 (2003);
273. Reichert, J.M. and Milne, C.P., 9 AM. J. THER. 543 (2002).
274. S.Hrg. 107-1081. Generic Pharmaceuticals: Marketplace Access and Consumer Issues, April 23, 2002. Prepared statement of Dr. Greg Glover, M.D., J.D., Pharmaceutical Research and Manufacturers of America, p. 49. For some recent life-expectancy figures, see Frank R. Lichtenberg, Yes, New Drugs Save Lives, THE WASHINGTON POST Wednesday, July 11, 2007; Page A15.
275. Id.
276. See Kevin Murphy and Robert Topel, Diminishing Returns?: The Costs and Benefits of Improving Health, 46 PERSPS. BIOLOGY MED. S108, S108 (Supp. 2003).