Integra Lifesciences I, Ltd. v. Merck KGaA

496 F.3d 1334, 83 U.S.P.Q. 2d (BNA) 1673, 2007 U.S. App. LEXIS 17930, 2007 WL 2142878
CourtCourt of Appeals for the Federal Circuit
DecidedJuly 27, 2007
Docket2002-1052, 2002-1065
StatusPublished
Cited by15 cases

This text of 496 F.3d 1334 (Integra Lifesciences I, Ltd. v. Merck KGaA) is published on Counsel Stack Legal Research, covering Court of Appeals for the Federal Circuit primary law. Counsel Stack provides free access to over 12 million legal documents including statutes, case law, regulations, and constitutions.

Bluebook
Integra Lifesciences I, Ltd. v. Merck KGaA, 496 F.3d 1334, 83 U.S.P.Q. 2d (BNA) 1673, 2007 U.S. App. LEXIS 17930, 2007 WL 2142878 (Fed. Cir. 2007).

Opinions

[1336]*1336Opinion for the court filed by Circuit Judge NEWMAN. Dissenting-in-part and concurring-in-part opinion filed by Circuit Judge RADER.

NEWMAN, Circuit Judge.

This case returns to us upon vacatur by the Supreme Court of the judgment of the the Court’s statutory construction of 35 U.S.C. § 271(e)(1).1 We received further briefing and argument, and now reverse the district court’s judgment of infringement.

BACKGROUND

Reference is made to the prior opinions, see n. 1, for the history of this case, discussion of the science, and the issues and arguments raised at earlier stages of the litigation. The five patents in suit, owned by Integra Life Sciences Corporation, relate to certain peptides that contain the RGD sequence of amino acids, viz. the contiguous sequence of arginine (R), glycine (G), and aspartic acid (D) within a peptide chain. The patented inventions are described as demonstrating various cell interactions with the extracellular peptide matrix, including ways of promoting cell attachment, blocking cell attachment, and disrupting cell attachment. The validity of the Integra patents was sustained at trial but for one claim, and is not here at issue.

In activities preceding this litigation, Merck KGaA (a German company) and Scripps Research Institute were collaborating in research related to studies that Dr. David Cheresh and others at Scripps were conducting on the inhibition of an-giogenesis.2 The development and growth of undesired blood vessels is a factor in several diseases, including solid tumor cancers, diabetic retinopathy, and rheumatoid arthritis. Dr. Cheresh, in the course of research using monoclonal antibodies, had discovered that angiogenesis is affected by blocking the ct^ integrin cell surface receptors on endothelial cells, thereby depriving the cells of blood. In 1994 Dr. Cheresh evaluated a cyclic RGD peptide that was provided by Merck, and found that it was effective in inhibiting angiogen-esis. Merck and Scripps then entered into a sponsorship agreement directed to the goal of progressing, within three years, to clinical trials with human subjects. Clinical trials require the prior approval of the Food and Drug Administration, which is obtained through the mechanism of an In-vestigational New Drug (IND) application in accordance with FDA Regulations.

During the collaboration with Merck, Dr. Cheresh and others at Scripps conducted the experiments here charged with infringement. As the work proceeded they studied the efficacy, mechanism of action, pharmacology, pharmacokinetics, and safety of three structurally related RGD peptides. The collaborators duly selected the peptide designated EMD 121974 as having optimum properties for development. In October 1998 the National Cancer Institute agreed to sponsor clinical trials for EMD 121974.

In 1996 Integra sued Merck, Scripps, and Dr. Cheresh for infringement of one or more of the five Integra patents, reportedly after failed negotiations. In the district court two principal defenses were presented: first, that the early scientific [1337]*1337studies at Scripps on RGD peptides are not subject to patent infringement, based on the common law research exemption; and second, that the ensuing studies were conducted in furtherance of drug development and the projected clinical trials, and are exempt from infringement under the FDA Exemption (or “safe harbor”) established by 35 U.S.C. § 271(e)(1):

35 U.S.C. § 271(e)(1). 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 ... 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.

As to the first defense, the district court ruled that all but one of the experiments conducted by Dr. Cheresh before 1995, that is, his initial studies of angiogenesis inhibition by the first cyclic RGD peptide provided by Merck (designated EMD 66203), were of the nature of basic scientific research and within the common law research exemption. No appeal was taken from this ruling, and these early experiments are not included in the subject matter charged with infringement. Although in the district court Scripps had argued that at least some of the ensuing studies were also shielded from infringement by the common law research exemption, this argument was not presented on appeal to the Federal Circuit or the Supreme Court, and is not at issue.

As to the second defense, the district court submitted to the jury the question of whether the challenged activities were protected by the FDA Exemption. The court instructed the jury as follows:

Merck contends that it does not infringe or induce the infringement of any of the patents-in-suit, based upon the Food and Drug Administration or “FDA” Exemption. To prevail on this defense, Merck must prove by a preponderance of the evidence that it would be objectively reasonable for a party in Merck’s and Scripps’ situation to believe that there was a decent prospect that the accused activities would contribute, relatively directly, to the generation of the kinds of information that are likely to be relevant in the processes by which the FDA would decide whether to approve the product in question.
Each of the accused activities must be evaluated separately to determine whether the exemption applies.
Merck does not need to show that the information gathered from a particular activity was actually submitted to the FDA.

Neither side assigned error to this instruction, although Merck objected to the verdict form which grouped the accused activities such that if any one experiment were found not entitled to the FDA Exemption, infringement could be found by the jury. Although the parties continue to argue about this aspect, it is mooted by the Court’s rulings and our conclusion in light thereof.

At the trial both sides presented expert testimony concerning the FDA Exemption, and argued theory, fact, and application of § 271(e)(1). Integra’s position was that the FDA Exemption did not apply to the Scripps experiments or to most of them. Some of the experiments were with RGD peptides that were not the subject of an IND application, and Integra presented opinion testimony that most or all of the experiments could not be the basis of an IND application because the work did not conform to the Good Laboratory Practices protocols of the FDA, and in all events that the FDA Exemption at the IND stage applies only to studies of safety for administration to human subjects and thus did [1338]*1338not include the majority of the experiments, which concerned the properties and mode of action but not the safety of the candidate angiogenesis inhibitor.

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Integra Lifesciences I, Ltd. v. Merck KGaA
496 F.3d 1334 (Federal Circuit, 2007)

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496 F.3d 1334, 83 U.S.P.Q. 2d (BNA) 1673, 2007 U.S. App. LEXIS 17930, 2007 WL 2142878, Counsel Stack Legal Research, https://law.counselstack.com/opinion/integra-lifesciences-i-ltd-v-merck-kgaa-cafc-2007.