Court Opinion

ID: 8407896
Source: CourtListenerOpinion
Date Created: 2022-11-02 16:36:33.152513+00
Date Added: 2024-06-11T16:47:31.090144
License: Public Domain

PAULINE NEWMAN, Circuit Judge,
concurring in part, dissenting in part.
This case raises a question of the nature and application of the common law research exemption, an exemption from infringement that arose in judge-made law almost two centuries ago, and that recently has come into sharper focus. Its correct treatment can affect research institutions, research-dependent industry, and scientific progress.
The question is whether, and to what extent, the patentee’s permission is re*873quired in order to study that which is patented. For the Scripps/Merck research, the panel majority holds that all of the activity at Scripps during 1995-1998 was “discovery-based research” and that there is no right to conduct such research, under either the common law research exemption or the statutory immunity established in 35 U.S.C. § 271(e)(1). However, neither law nor policy requires that conclusion, and both law and policy have long required a different conclusion in implementation of the purpose of the patent system.
The purpose of a patent system is not only to provide a financial incentive to create new knowledge and bring it to public benefit through new products; it also serves to add to the body of published scientific/technologic knowledge. The requirement of disclosure of the details of patented inventions facilitates further knowledge and understanding of what was done by the patentee, and may lead to further technologic advance. The right to conduct research to achieve such knowledge need not, and should not, await expiration of the patent. That is not the law, and it would be a practice impossible to administer. Yet today the court disapproves and essentially eliminates the common law research exemption. This change of law is ill-suited to today’s research-founded, technology-based economy. I must, respectfully, dissent.

A. The Scripps/Merck Activities

The research on which Scripps and Merck collaborated was directed to studies of certain peptide components of fi-bronectin, containing a chain of the three amino acids arginine (R), glycine (G), and aspartic acid (D). The scientists who founded Integra’s predecessor, co-plaintiff Telios, discovered that peptides containing this RGD sequence had potential use in promoting wound healing and prosthesis adhesion, and obtained patents on various RGD peptide compositions and methods; however, the Telios scientists were unable to develop a viable commercial product, and eventually sold the patents to Integra.
Merck KgaA of Germany began funding research at Scripps in 1988, after Dr. Cheresh of Scripps had identified a monoclonal antibody, designated LM609, having activity as an inhibitor of integrin5 activity. The collaboration was enlarged in 1995 with increased funding by Merck, after Dr. Cheresh discovered that a Merck-provided peptide designated EMD66203, having the sequence c(RGDfV),6 inhibits new blood vessel growth by interaction with a specific integ-rin. In this collaboration, cyclic RGD peptides of various structures and composition7 were synthesized and studied, as knowledge was gained concerning their chemical and biological properties and the effects of changes in their structure. It was discovered that the cyclic peptide structure solved certain problems that had *874been experienced with the Telios linear RGD peptides, and that some products have anti-angiogenic properties, of interest for treatment of such diseases as cancer, macular degeneration, rheumatoid arthritis, and others. “Angiogenic” refers to the process of generating new blood vessels, a process essential to tumor growth. As summarized by Merck, Dr. Cheresh testified that the purpose of the research was to “(1) assess the potential efficacy of the peptides as therapeutic agents; (2) discover the mechanism of action of the peptides; and (3) shed light on histopathology, toxicology, circulation, diffusion, and half-life of the peptides in the bloodstream.” Brief at 15. The ultimate goal of the research was undisputed: it was to find a product that would be sufficiently effective in the treatment of angiogenic disease that it could be developed and brought to market for this purpose.
The record describes modifications in the structure of RGD-containing peptides and investigations of their properties in the Scripps/Merck collaboration, including: receptor binding assays to investigate the efficacy and specificity of structural change; angiogenesis/chick CAM assays for inhibition of blood vessel formation in chick embryos when vessel growth is artificially induced, to study the mechanism of action, pharmacokinetics, and other properties; angio-matrigel experiments to investigate inhibition of artificially induced vascularization in mice; cell adhesion assays by spectrophotometric measurement of inhibition of cell attachment to protein, to provide information about mechanisms, efficacy, and other properties; chemotaxis studies to determine the effect of various peptides on cell migration over extracellular matrix fibers; use of chick embryos to obtain pharmacokinetic data; fluorescent-activated cell sorting to study the effect on the receptor-ligand binding reaction, to aid in understanding mechanisms of activity; vascularization of the retina and induced arthritis of the joints, studied with mice and rabbits; chick CAM assays to study angiogenesis associated with tumor transplantation and growth in chick embryos; and tumor growth in SCID-mice or nude mice, including studies of mechanism, pharmacology, and pharmacokinetics.
As this research progressed, so did the scientific understanding of these peptide products and their mode of action. In 1997 Scripps/Merck selected the peptide designated EMD 121974 and having the amino acid sequence c(RGDf-NMeV) as the most promising product thus far, although they continued to synthesize and evaluate further modifications of the peptides. In 1998 an Investigatory New Drug application for EMD 121974 was filed with the Food and Drug Administration.
The panel majority describes all of this activity as “discovery-based research,” and holds that it is subject to neither a common law research exemption nor the “safe harbor” of § 271(e)(1). I cannot agree. In my view, either the common law research exemption or the development associated with § 271(e)(1) immunity embraces all of these activities.

B. The Common Law Research Exemption

The common law research exemption is a limited exception to the patentee’s unrestricted right to exclude. Its jurisprudential origin is with Justice Story, who stated in Whittemore v. Cutter, 29 Fed. Cas. 1120, 1121 (C.C.D.Mass.1813) (No. 17,600), that
it could never have been the intention of the legislature to punish a man who constructed such a machine merely for philosophical experiments,8 or for the *875purpose of ascertaining the sufficiency of the machine to produce its described effects.
Again in Sawin v. Guild, 21 Fed. Cas. 554 (C.C.D.Mass.1818) (No. 12,391) Justice Story distinguished
the making with an intent to use for profit, and not for the mere purpose of philosophical experiment, or to ascertain the verity and exactness of the specification.
The few judicial decisions on this issue have applied the research exemption when no commercial purpose was demonstrated for the research. See, e.g., Chesterfield v. United States, 141 Ct.Cl. 838, 159 F.Supp. 371 (1958) (experimentation by the United States did not infringe the patent); Ruth v. Stearns-Roger Manufacturing Co., 13 F.Supp. 697 (D.Colo.1935) (patent not infringed when the Colorado School of Mines cut up and studied the patented machines).
The majority’s prohibition of all research into patented subject matter is as impractical as it is incorrect. The information contained in patents is a major source of scientific as well as technologic knowledge. Indeed, in many areas of technology, technical information is not published outside of patent documents. A rule that this information cannot be investigated without permission of the patentee is belied by the routine appearance of improvements on patented subject matter, as well as the rapid evolution of improvements on concepts that are patented.
The subject matter of patents may be studied in order to understand it, or to improve upon it, or to find a new use for it, or to modify or “design around” it. Were such research subject to prohibition by the patentee the advancement of technology would stop, for the first patentee in the field could bar not only patent-protected competition, but all research that might lead to such competition, as well as barring improvement or challenge or avoidance of patented technology. Today’s accelerated technological advance is based in large part on knowledge of the details of patented inventions and how they are made and used. Prohibition of research into such knowledge cannot be squared with the framework of the patent law.
The patent statute requires full disclosure of the invention, including details of enabling experiments and technical drawings and best modes and preferred embodiments, even commercial sources of special components. Such details would be idle and purposeless if this information cannot be used for 17-20 years. Indeed, there would be little value in the requirement of the patent law that patented information must be removed from secrecy in consideration of the patent right to exclude, if the information is then placed on ice and protected from further study and research investigation. To the contrary, the patent system both contemplates and facilitates research into patented subject matter, whether the purpose is scientific understanding or evaluation or comparison or improvement. Such activities are integral to the advance of technology.
In the framework of United States patent law there is no obligation that the patentee use the invention; the obligation is to disclose it and describe it and to provide enabling detail whereby it can be duplicated without undue experimentation. The patentee’s permission is not required whenever a patented device or molecule is *876made or modified or investigated. Study of patented information is essential to the creation of new knowledge, thereby achieving further scientific and technologic progress.
Of course, the common law exemption is not unlimited. Indeed, it is a narrow exemption, for it must preserve the paten-tee’s incentive to innovate, an incentive secured only by the right to exclude. It is the patentee who opened the door by providing the initial knowledge, without which there would be nothing to improve. Setting the boundaries of a common law exemption requires careful understanding of the mechanisms of the creation, development, and use of technical knowledge, and of today’s complexity of interactions among invention and the innovating fruits of invention. It is the initial inventor whose rights must receive primary consideration in an effective patent law, for the public interest starts with the threshold invention. However, while that threshold invention may (as here) exact tribute from or enjoin commercial and pre-commercial activity, the patent does not bar all research that precedes such activity.
I do not here undertake to define the boundaries of the research exemption for all purposes and all activities, other than to observe that there is a generally recognized distinction between “research” and “development,” as a matter of scale, creativity, resource allocation, and often the level of scientific/engineering skill needed for the project; this distinction may serve as a useful divider, applicable in most situations. Like “fair use” in copyright law,9 the great variety of possible facts may occasionally raise dispute as to particular cases. However, also like fair use, in most cases it will be clear whether the exemption applies. Indeed, the question of boundary does not arise for the Scripps/ Merck research here at issue, for the statutory immunity of § 271(e)(1) takes effect wherever the research exemption ends, as I discuss in Part C, post.
The Scripps/Merck activities that are here challenged took place during the collaboration outlined in Part A ante. Were all research using RGD peptides prohibited until the Integra/Telios patents expired, not even the patent owner would benefit, for the patented products had failed in Telios’ hands, leaving the patents valueless until Scripps and Merck made their discoveries • as to the cyclic peptides and their anti-angiogenic properties. The panel majority states that because the Scripps/ Merck research had the goal of curing cancer and commercializing the cure, this purpose moved the research outside of any common law exemption. However, an ultimate goal or hope of profit from successful research should not eliminate the exemption. The better rule is to recognize the exemption for research conducted in order to understand or improve upon or modify the patented subject matter, whatever the ultimate goal. That is how the patent system has always worked: the patent is infringed by and bars activity associated with development and commercialization of infringing subject matter, but the research itself is not prohibited, nor is comparison of the patented subject matter with improved technology or with designs whose purpose is to avoid the patent.
*877C. Immunity Under § 271(e)(1); Damages
§ 271(e)(1). It shall not be an act of infringement to make, use, [sell or import] ... 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.
The panel majority holds that the 35 U.S.C. § 271(e)(1) “safe harbor” does not apply to federal registration of pioneering new drugs like the Scripps/Merck products here at issue, but only to registration of generic copies of drugs for which the patent is about to expire. I agree as to the origin of § 271(e)(1). However, the statute has been interpreted as of broader scope, see Eli Lilly & Co. v. Medtronic Inc., 496 U.S. 661, 110 S.Ct. 2683, 110 L.Ed.2d 605 (1990), and the parties accept that § 271(e)(1) applies to Merck’s filing of the Investigatory New Drug application for EMD 121974. This issue was not raised at trial.
The majority also holds that none of the research by Scripps/Merck qualifies for § 271(e)(1) immunity because the research was directed to “discovery,” not to federal registration. I agree that “the § 271(e)(1) safe harbor [does not] reach back down the chain of experimentation to embrace development and identification of new drugs.” Maj. op. at 865-66. However, the territory that the Scripps/Merck research traversed, from laboratory experimentation to development of data for submission to the FDA, was either exempt exploratory research, or was immunized by § 271(e)(1). It would be strange to create an intervening kind of limbo, between exploratory research subject to exemption, and the FDA statutory immunity, where the patent is infringed and the activity can be prohibited. That would defeat the purposes of both exemptions; the law does not favor such an illogical outcome.
After a product loses the § 271(e)(1) protection, it is subject to the full force of any adversely held patents. That aspect is not here in dispute, but it is relevant to the damages verdict, not appropriately treated in the majority opinion.
If the question of damages is remanded, as the panel majority holds, my colleagues go too far in counseling the parties as to how to present their case. The “hypothetical negotiation” is no more than a convenience in estimating value, not a compulsory economic standard, and surely not one that requires appellate speculation as to when the parties might have hypothetically negotiated, requiring retrial. The presentation of evidence on damages was extensive, and included evidence that well supported a jury verdict that included a license. Our appellate role is to decide whether the jury verdict was supported by substantial evidence as presented at trial, not to rewrite the trial script as we might have tuned it to our taste. See Brooktree Corp. v. Advanced Micro Devices, Inc., 977 F.2d 1555, 1570, 24 USPQ2d 1401, 1411 (Fed.Cir.1992) (when there is sufficient evidence to support the jury verdict in light of the entire record, the verdict must stand unless the evidence permits only one reasonable conclusion.) The damages verdict is readily sustainable if construed to include a license for the remaining two to three years of patent life. The evidence before the jury well supports the magnitude of the damages award. I would affirm the verdict on that basis.
D. The Research Exemption and Research Tools
The panel majority states that acceptance of a common law research exemption would eliminate patents on “research tools.” That is a misperception. There is *878a fundamental distinction between research into the science and technology disclosed in patents, and the use in research of patented products or methods, the so-called “research tools.”
A research tool is a product or method whose purpose is use in the conduct of research, whether the tool is an analytical balance, an assay kit, a laser device (as in Madey v. Duke University),10 or a biochemical method such as the PCR (polymerase chain reaction). It is as subject to the patent right as is any other device or method, whether it is used to conduct research or for any other purpose. Use of an existing tool in one’s research is quite different from study of the tool itself.
My colleagues on this panel appear to view the Integra patents as for a “research tool.” That is a misdefinition. The RGD-containing peptides of the Integra patents are not a “tool” used in research, but simply new compositions having certain biological properties. The Scripps/Merck syntheses and evaluations of new RGD peptides were not use of the Integra products as a research tool.
The majority states that this issue is not before us, that “the district court did not instruct the jury” on the question. However, the question was before the district court, who held that the common law exemption applied to one Scripps experiment in 1994, but to nothing else. The issue was before the district court, and counsel explained at oral argument that they were not pressing this argument “in part because of a very recent case.” Since the question was fundamental to resolution of this case, it cannot be ignored.
Conclusion
I do not attempt to resolve, for all technologies and circumstances, the application of the research exemption or the point at which research into patented technology loses the immunity that the common law has always provided. However, the basic research here performed was within the common law research exemption, and the development shielded by § 271(e)(1) took up where the research exemption left off. Thus the accused activities were either exempt from or immune from infringement.

. “Integrin” refers to a family of cell surface receptors.

. In this nomenclature L isomers of amino acids are represented by their single letter codes in capital letters (R= arginine, G=glycine, D=aspartic acid). The "f” represents the D isomer of phenylalanine. "NMeV,” appearing infra, represents the N-methyl derivative of valine. The "c” means that the sequence is cyclic.

. Also at issue in this litigation was whether the Integra patents cover the cyclic RGD peptides that were produced and investigated by Scripps/Merck. On this close question of infringement I would affirm the district court, as does the panel majority, for there was extensive evidence at trial, including the (conflicting) advice of experts, supporting the district court's findings.

. By "philosophical” experiments Justice Story was referring to "natural philosophy,” the *875term then used for what we today call "science.” For example, in the volume on Classification of Subjects of Inventions Adopted by the United States Patent Office, January 1, 1868 (GPO 1868), the section headed "Philosophical Instruments—Class XXV” lists "Philosophical Apparatus, Scales, Measures, and Instruments of Precision.”

. The research exemption has been compared to "fair use,” which was also a creation of Justice Story, in Folsom v. Marsh, 9 Fed. Cas. 342 (C.C.D.Mass.1841) (No. 4901). The House Report drew this analogy in discussing 35 U.S.C. '271(e)(1), stating: "Just as we have recognized the doctrine of fair use in copyright, it is appropriate to create a similar mechanism in the patent law. That is all this bill does.” H.R.Rep. No. 98-857 at 30 (1984), reprinted in 1984 USCCAN 2714.

. Madey v. Duke University, 307 F.3d 1351 (Fed.Cir.2002) concerned the use of a patented laser device for the purpose for which it was made, not research into understanding or improving the design or operation of the machine. The facts of Madey v. Duke do not invoke the common law research exemption, despite the broad statement in that opinion. I do not disagree with that decision on its facts; I disagree only with its sweeping dictum, and its failure to distinguish between investigation into patented things, as has always been permitted, and investigation using patented things, as has never been permitted.