Amy Kapczynski

Is Bayh-Dole Good for Developing Countries?: Lessons From the US Experience

The US Bayh-Dole Act encourages university patenting of inventions arising from publicly funded research. Lessons from three decades of US experience serve as a cautionary tale for those countries that may choose to emulate Bayh-Dole.

Polymorphs and Prodrugs and Salts (Oh My!): An Empirical Analysis of 'Secondary' Pharmaceutical Patents

Background While there has been much discussion by policymakers and stakeholders about the effects of “secondary patents” on the pharmaceutical industry, there is no empirical evidence on their prevalence or determinants. Characterizing the landscape of secondary patents is important in light of recent court decisions in the U.S. that may make them more difficult to obtain, and for developing countries considering restrictions on secondary patents. Methodology/Principal Findings We read the claims of the 1304 Orange Book listed patents on all new molecular entities approved in the U.S. between 1988 and 2005, and coded the patents as including chemical compound claims (claims covering the active molecule itself) and/or one of several types of secondary claims. We distinguish between patents with any secondary claims, and those with only secondary claims and no chemical compound claims (“independent” secondary patents). We find that secondary claims are common in the pharmaceutical industry. We also show that independent secondary patents tend to be filed and issued later than chemical compound patents, and are also more likely to be filed after the drug is approved. When present, independent formulation patents add an average of 6.5 years of patent life (95% C.I.: 5.9 to 7.3 years), independent method of use patents add 7.4 years (95% C.I.: 6.4 to 8.4 years), and independent patents on polymorphs, isomers, prodrug, ester, and/or salt claims add 6.3 years (95% C.I.: 5.3 to 7.3 years). We also provide evidence that late-filed independent secondary patents are more common for higher sales drugs. Conclusions/Significance Policies and court decisions affecting secondary patenting are likely to have a significant impact on the pharmaceutical industry. Secondary patents provide substantial additional patent life in the pharmaceutical industry, at least nominally. Evidence that they are also more common for best-selling drugs is consistent with accounts of active “life cycle management” or “evergreening” of patent portfolios in the industry.

Harmonization and its Discontents: A Case Study of TRIPS Implementation in India's Pharmaceutical Sector

In 2005, India amended its patent law to provide product patents on medicines, to comply with the WTO’s TRIPS Agreement. In order to mitigate the impact on access to medicines, India at the same time adopted an expansive menu of flexibilities in its patent law. Reviewing these important flexibilities, some of which are entirely novel, this article argues that at a formal level TRIPS leaves developing countries far more policy space than is commonly recognized. But while TRIPS as a formal matter cannot produce deep harmonization, it nonetheless channels a strong harmonizing force, because it inserts countries into a transnational circuit that fills in the gaps in the Agreement and that works against the use of TRIPS flexibilities. Limits on administrative resources, the influence of transnational legal networks, and the threat of unilateral retaliation from high-protection jurisdictions all make it difficult for countries like India to implement an autonomous vision of patent law. The paper also identifies compensating strategies that may facilitate the effective use of TRIPS flexibilities, responding to the transnationalized pressures that TRIPS implementation sets up. I call these strategies fragmentation, mimicry, and counter-harmonization. As I demonstrate, counter-harmonization shows the most promise for developing countries, because it offers countries safety in numbers, can lower the administrative costs of implementing an alternative patent law, and can generate a transnational legal counterculture. Lastly, the paper engages with the literature about the implications of the legalization of the global trading regime. The case study offered here suggests that legalization cannot simply be identified, as some prominent trade law scholars have argued, with the substitution of politics for principle, and with the leveling of power differences between states. It also suggests a new perspective on the debate over whether the WTO has a “constitutional” form, and if so, what this means. To date, those who claim a constitutional nature for the WTO have identified that nature with a move beyond politics. The analysis offered here suggests that if the WTO has a constitutional nature, it lies in its capacity to mobilize and channel, rather than to suppress or transcend, political disagreement.

Engineered in India — Patent Law 2.0

Indias Supreme Court ruling in Novartis v. Union of India adopting a strict interpretation of the countrys new patent law represents a step toward a “patent law 2.0” that may help ensure access to medicines and align drug innovation with public health needs.

The Trans-Pacific Partnership — Is It Bad for Your Health?

Several leaked chapters of the Trans-Pacific Partnership Agreement indicate that it could have a substantial effect on health, largely by increasing the costs of medications in both low-income and high-income countries.

Commentary: Innovation Policy for a New Era

This commentary offers a response to the Sonderholm, Bird, and Flynn et al. articles, and argues that the current innovation crisis requires more ambitious approaches, as well as a serious consideration of alternative mechanisms for R&D such as prizes.

Promotion of Drugs for Off-label Uses: The US Food and Drug Administration at a Crossroads

Since 1962, the US Food and Drug Administration (FDA) has required companies to establish, with adequate and well-controlled clinical trials, a drug’s safety and efficacy for each intended use and has prohibited the “offlabel” promotion of drugs. For companies to market an approved medicine for new indications, they must first conduct trials and submit data to establish safety and efficacy, as was the case for the initial approval. The FDA’s approach to off-label promotion is in jeopardy, however. In response to recent US Supreme Court decisions strengthening First Amendment protection for companies, the pharmaceutical industry has framed offlabel marketing as a free speech right. Drug companies have won several important court cases that have weakened the FDA’s authority to regulate off-label marketing. Although the legal issue—whether the FDA’s restrictions on off-label marketing are unconstitutional— remains unresolved, the agency has initiated a comprehensive review of its approach to off-label marketing. On November 9 and 10, 2016, the FDA will convene a public hearing to address “its regulations and policies governing firms’ communications about unapproved uses of approved/cleared medical products.”1 The Food, Drug, and Cosmetic Act grants the FDA the authority to approve drugs for specific indications and to prohibit the sale of “misbranded” drugs. When used for a new condition or population, a drug’s riskbenefit ratio may change, or new safety considerations may emerge. By requiring studies before permitting marketing of new uses, the FDA gives companies incentives to produce the needed evidence for sound medical decisions. Off-label uses can be clinically appropriate, and physicians are free to prescribe medicines off-label. To help facilitate well-informed decisions, the FDA has created safe harbors that allow companies to communicate about potential new uses with physicians. Under current FDA guidance, drug companies may respond to unsolicited questions from physicians and proactively circulate peer-reviewed journal articles about off-label uses if the articles are based on adequate and wellcontrolled studies.2,3 Recently, companies have begun to challenge this framework for communicating with clinicians about offlabel uses of drugs. Some have argued that more extensive marketing is not merely good policy, but a constitutionally protected right. In a watershed 2012 case, United States v Caronia, the US Court of Appeals for the Second Circuit in New York sided with the industry. In that case, a pharmaceutical detailer had promoted sodium oxybate (Xyrem), approved to treat narcolepsy, for off-label uses, including chronic pain, and a jury convicted him of misbranding the drug. In a 2 to 1 decision, the appellate court vacated the conviction on First Amendment grounds.4 The court ruled that the government could not prosecute the detailer simply for making off-label promotional statements, but was also careful not to entirely strike down the FDA’s authority to regulate off-label promotion. It suggested that the FDA might have prevailed if it had treated promotional speech merely as evidence of criminal conduct (namely, the selling of a misbranded drug) and not as criminal itself. This draws on a well-established rule that the use of speech as evidence to prove criminal conduct does not violate, or even implicate, the First Amendment. This rule in fact sustains the FDA’s authority to forbid the marketing of entirely unapproved drugs. A company that markets an unapproved drug cannot defend its actions by arguing that its treatment claims are constitutionally protected speech.5 In 2015, a US district court in Manhattan went beyond Caronia, in a case involving Amarin Pharmaceuticals.6 The trial judge concluded that drug companies have a First Amendment right to market any off-label use to physicians as long their statements are not false or misleading.7 The judge barred the FDA from using such promotional statements as evidence of misbranding, effectively rejecting the legal argument that was left open by the Caronia case. On this logic, once a drug is approved for any indication, it can be promoted to physicians for any use as long as a judge, not the FDA, views the marketing to be truthful and nonmisleading. But judges are not experts in trial design, pharmaceutical regulation, or the evaluation of medical evidence, and the effects of drugs cannot be known unless they are carefully studied. The Amarin decision invites a world where companies no longer pursue broad clinical indications for new drugs but instead seek the narrowest possible indication for approval and then market the drug for any new use for which there is some evidence, no matter how weak. Companies would no longer have to conduct rigorous trials and submit, to the FDA, data demonstrating the safety and efficacy of new uses. Such an approach would compromise the future evidence base for medicines, expose patients to a greater risk of adverse events, and increase pharmaceutical spending without evidence that the expenditures would help improve patients’ health.8 VIEWPOINT

Pediatric Exclusivity and Regulatory Authority: Implications of Amgen v HHS

In May 2017, the US Food and Drug Administration (FDA) denied a 6-month extension of market exclusivity for Sensipar (cinacalcet), a drug manufactured by Amgen to manage hypercalcemia, common among patients with end-stage renal disease who are undergoing dialysis. The FDA determined that Amgen’s pediatric studies had been conducted inadequately and had provided inconclusive safety data. Amgen brought a lawsuit, Amgen v HHS (US Department of Health and Human Services), to challenge the denial.1 If Amgen prevails, it can delay generic competition for 6 months for a drug that generated

Innovation Sticks: The Limited Case for Penalizing Failures to Innovate

1.24 billion of revenue in 2016.2 More broadly, a decision favoring Amgen could diminish the FDA’s ability to encourage clinically meaningful pediatric studies and thus undermine the purpose of Congress in offering patent extensions to reward pediatric research.

Legal Challenges to State Drug Pricing Laws

When policymakers and academics think about designing optimal innovation incentives, they almost exclusively limit their considerations to alternative types of reward incentives. But in this article, we show that under specific circumstances innovation sticks – potential penalties for failure to innovate – can play a valuable role in our innovation policy, either alone or in conjunction with innovation carrots. What’s more, we provide examples of several innovation sticks that already have been used with apparent success, including the Federal Corporate Average Fuel Economy (CAFE) standards. Finally, we apply our approach to a new area to which we think innovation sticks may be well-suited: the problem of car fatalities. Our model suggests that a relatively simple system of yardstick penalties could help reduce national auto fatalities by as much 20%, simply by bringing laggard entities (companies and states) up to the median.