In 2003 Court of Appeals for the Federal Circuit (CAFC) narrowly interpreted the safe harbor statute that permits a drug manufacturer to perform potentially infringing experiments needed to obtain FDA approval without incurring liability for patent infringement.  Integra LifeSciences I, Ltd. v. Merck KGaA, 331 F.3d 860 (Fed. Cir. June 6, 2003) [PDF] (Interpreting 35 U.S.C. §271(e)(1)). In January 2005, the Supreme Court granted certiorari in the case and will hear the appeal on April 20.  Cert. granted, No. 03-1237 (U.S. Jan. 7, 2005).  The question revolves around what types of experiments are ‘safe’ from liability under the statute. 

The party and amicus briefs are summarized below Of course, the length of individual summaries below does not indicate my view of that brief — in fact, my view is often that the length of an argument has an inverse relationship with the quality of the argument. 

Merck’s substantive brief was filed on February 15. I split Merck’s arguments into two categories.

1. The Law: The FDA exemption covering any “use . . . reasonably related to the development and submission of information” to the FDA should be interpreted broadly.  Merck argues that any research that is “directed at developing information relevant to an IND application” should fall under the 271(e)(1) safe harbor.
2. The Facts: The allegedly infringing experiments in this case falls under the safe harbor statute because (i) it was reasonably believed that the compound was a viable drug candidate and (ii) the experiments produced information that is considered in an IND application.

You can download the Merck KGaA brief here [pdf].

Brief of the United States in Support of Merck: The government has already played an important role in this case by filing a brief in support of Merck’s petition for cert.  Now, the Government has filed it brief on the merits.  Essentially, the U.S. argues that the statutory exemption should protect “all activities that are undertaken in the course of attempting to develop a particular drug and are reasonably related to the development of the types of information that would be relevant to an INDA or NDA.”

1. The exemption should apply to pre-clinical studies.
2. The exemption should begin to apply once research “progresses beyond basic research and begins efforts to develop a particular drug.”

The Government brief also discusses the research tool market, saying that the CAFC “erred by artificially narrowing the statutory exemption in an effort to protect research tools.”  According to the Government, it is unclear whether the statute even applies to research tools. 

You can download the Government brief here [pdf].

AIPLA’s Amicus Brief:  The AIPLA brief is officially in support of neither party.  However, the brief makes the argument that the Federal Circuit erred on both the facts and the law.  Here is a summary of some of the AIPLA arguments:

1. Limiting the safe harbor protection to only (i) clinical tests that are (ii) related only to the exact drug for which FDA approval is ultimately sought would leave the statute much too narrow.
2. The road to FDA approval involves much more than clinical tests.  The Federal Circuit payed too little attention to the FDA regulatory scheme in its decision.
3. The earliest stage of experiments do not fall under the safe harbor statute.  The brief notes, for instance, that high-throughput screening of drugs for potential activity should not fall within the safe harbor.
4. Finally, the Supreme Court should not weigh-in on the common-law experimental use exception.  [NOTE: Although I understand the AIPLA’s legal reasoning on this point, I do not understand their motivation.  If not now, when will the Court look at the common-law experimental use exception]

William McGeveran at Foley Hoag was kind enough to supply a copy of the AIPLA brief.  You can download the AIPLA brief here [pdf].

Eli Lilly, Wyeth & Merck as Amicus in Support of Merck: The three big drug manufacturers submitted an eloquently written brief that makes strong practical points:

Virtually Every Experiment is Reasonably Related to FDA Approval: Because the length, risks and costs of innovative drug development are so great, every activity in the development process has a purpose and a clear rationale. Each is designed to generate information that ultimately goes into the decision of whether a potential new drug will progress to the next hurdle. Each is aimed at the same ultimate goal: to gain FDA approval. . . . Innovative new drug development, thus, resembles a funnel. Just as a funnel is widest at the top, so too the early phases of drug development involve many more potential drugs than eventually emerge. The narrowing of the funnel represents the winnowing of less attractive potential new drugs. Blocking the funnel at any point cuts off the entire flow of new drugs. The Federal Circuit in its 1993 decision blocked the funnel.

The decision enables patent holders to prevent others from entering, or moving down the funnel. As a result, drug development will slow and its costs will mount in what is already a lengthy, high risk, high cost process; patients will be deprived of timely access to new, safer, more effective drugs; the entry of generic equivalents will be delayed; promising drugs to treat unmet medical needs will never be developed; and drug development activities along with valuable American jobs will be exported to countries having more favorable legal environments.

You can download the brief here [pdf].

NYIPLA Amicus Brief in Support of Merck: The New York Intellectual Property Law Association is filing an Amicus brief.  (The Brief is available here [pdf] ). The NYIPLA’s conclusions parallel many of those outlined by the AIPLA.  For instance, the NYIPLA argues that the statutory safe harbor was construed too narrowly and that the experiments performed in this case were “reasonably related” to the process of FDA approval.

Additionally, the NYIPLA presents a nuanced statutory construction argument that is derived from Professor Janice Mueller’s recent paper on the Experimental Use Exception (56 Baylor L. Rev. 101 (2004)).

1. The Federal Circuit misused a de minimis maxim to narrowly construe the safe harbor statute.
2. The statutory FDA exemption arises from Article 1, Section 8 of the Constitution and from the economic principles echoed in numerous Supreme Court cases. See, e.g., Universal Oil Products Co. v. Globe Oil & Refining Co., 322 U.S. 471, 484 (1944). These first principles indicate that the statute should be given a broader interpretation.

Thanks to David Ryan at Fitzpatrick Cella for providing a copy of the brief.

Amicus Brief for PhRMA in Support of Merck: PhRMA is an association of the largest drug development companies in the U.S. Last year PhRMA members spent $38 billion on drug development and have been responsible for almost all innovative new medicines approved during the last ten years. According to PhRMA’s brief, the CAFC 2003 decision in this case “represents a direct and substantial threat to future drug development.” The brief argues that pre-clinical testing is an essential part of drug development and an FDA requirement.

Download the PhRMA brief here [pdf].

Amicus Briefs of Professors Rochelle Dreyfuss, John Duffy, Arti Rai and Katherine Strandburg:  The professors argue that the Court should not determine the reach of the common-law experimental use exception in this case. And, in fact, the brief asks that a clear disclaimer be placed in the Supreme Court opinion so that the opinion cannot be used by the Federal Circuit to decide issues on experimental use. In the professors’ view, the disclaimer may encourage litigants to bring the common-law issue to the Supreme Court. Of note, the professors find no “generally applicable relationship between the coverage of” the common-law experimental use exception and the statutory safe harbor.

You can download the Professors’ Brief Here [pdf]. Thanks to Professor Strandburg at DePaul for providing a copy of the brief.

Amicus Brief of The Bar Association of the District of Columbia (BADC): According to the BADC, regardless of a statutory safe harbor under 271(e)(1), the allegedly infringing “development activities are of the type that have traditionally been excluded from infringement liability under the common law experimental use exemption. . . .Failure to recognize this important exemption to infringement will deter research in the United States and encourage companies to conduct their research and development off-shore.”

You can download the BADC Brief Here [pdf]. Thanks to Susan Dadio at Burns Doane for providing a copy of the brief. Lynn Eccleston is the counsel of record.

Brief of EON LABS as Amicus Curiae in Support of Merck KGaA: Shashank Upadhye, VP and Counsel at the Generic Manufacturer Eon Labs has submitted a brief that explicitly supports Merck’s position.

1. The statute discusses “reasonably related . . . information.”  Logically, exemption applies to any information that the FDA would normally request or that it mandates be submitted. For instance, the FDA has promulgated regulations that mandate certain pre-clinical or screening information be submitted.
2. Generic drug companies often engage in the same kind of screening activities that Merck KGaA did in order to find a bio-equivalent product. This activity is shielded.

Eon also provides a nice description of the two most common types of drug research covered by the safe harbor regime: (i) testing and information collection on brand new drugs and proving safety and efficaciousness; and (ii) testing and information collection related to approving a generic bio-equivalent version of a preapproved drug.  Eon argues that the Federal Circuit erred by fixating on policy of safe harbor applying to generic drugs only.

You can download the EON Labs brief here [PDF].

Brief of the Consumer Project and the EFF as Amicus Curiae in Support of Merck KGaA: The consumer brief, filed by professor Joshua Sarnoff, makes the compelling argument that Section 271(e) and the common law experimental use exception provide overlapping protection. Sarnoff asks the Court to “confirm that Congress intended a broad experimental use exception to promote the progress of science and technology.”

It is critically important that the Court take this opportunity to correct the Federal Circuit’s improperly narrow interpretations of the experimental use exception in Roche, Embrex, Madey, and this case. This is likely to be the best (and, given the chill these cases exert, may be the only foreseeable) opportunity to set the historic and statutory record straight and to explain how Section 271(e) and Section 271(a) and its experimental use exception relate to each other.

You can download the Consumer/EFF brief here [pdf].

The Biotechnology Industry Organization (BIO) filed in support of neither party: According to BIO, this “is not a case about whether Section 271(e)(1) is limited to generic drugs and/or required regulatory activity. Instead, it is a case about whether the particular animal and in vitro studies at issue are “reasonably related to the development and submission of information” for regulatory approval and therefore non-infringing under Section 271(e)(1).”

BIO makes four specific arguments:

1. Section 271(e)(1) is not limited to generic drugs.
2. Section 271(e)(1) is not limited to required regulatory activity.
3. Section 271(e)(1) protects “reasonably related” testing activities.
4. Section 271(e)(1)’s “reasonably related” inquiry must be fact-based. For instance, if a researcher pursues more safety information than what Federal regulators require, the researcher should not be punished for being careful.

Finally, BIO makes the practical point that even the potential for an errant application of Integra could have a great and adverse impact on many avenues of research and funding critical to BIO members. You can download the BIO brief here [pdf].

Amicus Brief for Sepracor in Support of Merck: Michael Dzwonczyk at Sughrue assisted with the Sepracor brief.  He also provided a copy of the brief for Patently-O and the following summary [slightly edited]:

The brief for amicus Sepracor takes the position that the federal circuit misinterpreted the scope of the exemption under §271(e)(1) by suggesting that the statutory immunity is limited to clinical activities in furtherance of FDA approval of a generic version of a commercialized drug. Notwithstanding the Supreme Court’s reliance in Eli Lilly on the public policies underlying the Hatch-Waxman Act that the §271(e)(1) infringement exemption and §156 patent term extension remedy symmetrical, yet opposing, patent term distortions imposed by the FDA regulatory process, the scope of the immunity conferred by §271(e)(1) is not limited to subject matter also encompassed by §156, which is far narrower in scope.  Because FDA routinely requires pre-clinical data in evaluating INDs and NDAs, activities directed to generating this data should be exempt under §271(e)(1).

You can download Sepracor’s brief here [pdf].

AARP in Support of Merck: The AARP’s brief argues that the Federal Circuit mistakenly focused on generic drug approval rather and mistakenly omitted a discussion of how the statute provides a safe harbor for the development of innovative drugs as well.  As would be expected, AARP also argues that a narrow exemption delays medical advancement and increases the costs of prescription drugs.

The Federal Circuit’s unwillingness to allow a broader experimental use exemption to patent infringement as Congress intended will lead to delay of medical advances by hampering the free exchange of scientific knowledge and by postponing competition beyond the patent term. The costs for prescription drugs, which already are so high as to prohibit many people from accessing their benefits, will be driven even higher.

You can download the AARP Brief Here [pdf]. Thanks to Sarah Lens Lock, author of the brief, for providing the PDF copy. 

Genentech and Biogen Idec in Support of Merck: The Biologic companies bring out the important point that drug development of biologics is quite different than that of chemically-synthesized drugs, and that those differences alters the FDA approval process.  The conclusion is that, perhaps even more than traditional chemical drugs, the FDA requires an incredible amount of pre-clinical research before a new biologic will be approved.

You can download the Biologics Brief here [PDF].  Thanks to Raymond Arner for providing a copy of the brief.

Integra LifeScience’s Brief on the Merits: In their brief, respondents Integra and the Burnham Institute attempt to shift the direction of the argument away from whether certain experimental activities may fall within the scope of FDA requirements to an examination of Merck’s activities and whether they were taken recklessly.

[Merck] did not proceed with caution in the face of patent rights held by [Integra].  This case did not arise from a decision by Merck to perform experiments designed to satisfy FDA regulatory requirements. . . This case arose from Merck’s reckless decision to hire [Scripps] to embark on a basic research program to search for new drugs

Integra also asks the High Court to dismiss the case for lack of controversy.  “Given that the parties agree that the District Court’s jury instruction applied the correct legal standard, and given that Merck did not seek a sufficiency of the evidence review of the jury’s verdict in its petition for certiorari, there is essentially no controversy for this Court to adjudicate.

Finally, in an attempt to lessen the perceived importance of the case, Integra argues that companies who “seek a safe harbor under the FDA Exemption for preclinical work in their own laboratories in compliance with FDA regulations have nothing to fear. . . . Merck’s problems in this case are of its own making and are unique to it.”

Benitec Australia’s brief in support of Integra: Benitec argues that the safe harbor does not extend to “identifying, characterizing and developing new drugs.” Such a right would interfere substantially and selectively with the rights of certain patentees and undermines the fundamental principles of the patent system.

Interestingly, the counsel for Benitec (in support of Integra) is the same as for BIO (in support of neither party).

Vaccinex brief in support of Integra: Vaccinex makes the important policy point that patented research tools are essential to the development of new drugs.  Without patent protection, the development of future tools is at substantial risk. As a rule, Vaccinex argues that the exemption extends “only to infringing activities that are ‘solely for uses reasonably related to the development and submission of information’ to the FDA.”

Applera and ISIS brief in support of Integra: Applera argues that from a textual statutory construction, that the plain meaning of section 271(e)(1) limits the exemption to uses that are “solely for the purposes of regulatory approval,” and that the Petitioner’s interpretation of the meaning treats the word “solely” as mere surplusage.

The statute provides that the exemption applies to making, using, and selling “a patented invention . . . solely for uses reasonably related to development” for FDA approval 

Applera’s argument is that the sole pupose of the invention should be for uses related to FDA approval while Merck argues that solely applies to the infringing act.

Invitrogen et al. brief in support of Integra:  The research tool makers request a ruling from the Court that expressly states that the 271(e) safe harbor does not extend to patented research tools. 

WARF brief in support of Integra: Among other arguments, WARF outlines its position that the Federal Circuit’s decision effectively thwarts the purposes of the Bayh-Dole Act.

STATUTE: The primary statute relevant to this proceeding is the FDA exemption, found at 35 U.S.C. § 271(e)(1) (2000):

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention (other than a new animal drug or veterinary biological product (as those terms are used in the Federal Food, Drug, and Cosmetic Act and the Act of March 4, 1913) which is primarily manufactured using recombinant DNA, recombinant RNA, hybridoma technology, or other process involving site specific genetic manipulation techniques) solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.

Also at issue are various statutory provisions and regulations governing the FDA: 21 U.S.C. § 355 (2000 & Supp. 2001); 21 C.F.R. §§ 58.3, 312.22-312.23, 314.50 (2004).

Links:

• Federal Circuit’s Opinion in Merck v. Integra
• Government brief requesting cert [PDF]
• Cert granted [Question Presented]

Briefs on the Merits:

• In Support of Merck:

• Brief by Petitioner Merck KGaA
• NY Intellectual Property Law Association’s Brief
• EON Labs Brief
• AARP Brief
• Amicus Brief for the Consumer Project and the Electronic Frontier Foundation (EFF)
• PhRMA Amicus Brief
• Amicus Brief for Sepracor
• Brief of Genentech and Biogen Idec
• Brief for the United States Government
• Brief of Amici Curiae Eli Lilly, Wyeth, and Pfizer

• Professors’ Amicus Brief
• AIPLA Amicus Brief
• Bar Association of the District of Columbia (BADC) Brief
• San Diego Intellectual Property Law Association (SDIPLA) Brief
• Biotechnology Industry Organization (BIO) Brief

• Brief by Respondent Integra
• Benitec Amicus Brief
• Vaccinex Amicus Brief
• Applera and Isis Amicus Brief
• Invitrogen Amicus Brief
• WARF Amicus Brief

Reference Material:

• John F. Duffy, Harmony and Diversity in Global Patent Law, 17 Berkeley Tech. L. J. 685 (2002).
• John F. Duffy, Rethinking the Prospect Theory of Patents, 71 U. Chi. L. Rev. 439 (2004).
• Rochelle Dreyfuss, Protecting the Public Domain of Science: Has the Time for an Experimental Use Defense Arrived?, 46 Ariz. L. Rev. 457 (2004).
• Rebecca S. Eisenberg, Patents and the Progress of Science: Exclusive Rights and Experimental Use, 56 U. Chi. L. Rev. 1017 (1989).
• Janice M. Mueller, The Evanescent Experimental Use Exception from United States Patent Infringement Liability: Implications for University/Nonprofit Research and Development, 56 BAYLOR L. REV. 917 (2004).
• Katherine J. Strandburg, What Does the Public Get? Experimental Use and the Patent Bargain, 2004 Wisc. L. Rev. (2004).
• Noonan, Greenfield, and Zuhn, Paradise Lost: The Uncertain Future of Research Tool Patents, 15 INTELL. PROP. & TECH. L.J. 1 (2003).
• Richard Epstein and Bruce Kuhlik, Is There a Biomedical Anticommons?, Regulation, Summer 2004.

• Shashank Upadhye, Understanding Patent Infringement Under 35 U.S.C. 271(e): The Collisions Between Patent, Medical Device, and Drug Laws, 17(1) Santa Clara Comp. & High Tech. L.J. 1, 23 2000)(available at http://www.lordbissell.com/Newsstand/UPIUSUpadhye-1999.pdf).