abstract. Antibodies constitute a staggering $145 billion annual market—an amount projected to almost double by 2026. Consequently, patents covering antibodies are among the most valuable in the patent system. But antibody patents are being struck down left and right, victims of the Federal Circuit’s recent shift to strengthen two doctrinal areas of patent law: enablement and the written description requirement. For each, the Federal Circuit has heightened requirements that patentees disclose or teach how to make and use the “full scope” of their inventions.

There are good reasons to be skeptical of the Federal Circuit’s attack on genus claims in chemistry generally. But it seems to be a particular problem for antibodies. Applying the Federal Circuit’s reinvigorated written description and enablement requirements to antibodies and their chemical structure fits poorly with the science underlying the molecules themselves. Immune-receptor production, a semi-random and galactically expansive process, produces antibodies that are startlingly different in both structure and function. There is no way to describe genus claims to antibodies that satisfy the court’s current tests. The science simply doesn’t allow it. At the same time, this change in the Federal Circuit’s jurisprudence is a legitimate reaction to some of the problems with the long-standing (and long-permitted) practice of claiming antibodies in functional terms. Functional claiming can lead to overbroad patents that stifle future innovation, as it has done in the software industry. Perhaps the Federal Circuit is wary of a similar result in biotechnology. Fortunately, we think there is a middle ground. A new (or, really, quite old) form of patent-claim drafting would give inventors effective control over true substitutes without giving them the power to block real improvements: means-plus-function claims and infringement by the equivalents. Those doctrines limit patentees to claiming only the specific structural features of antibodies they both possessed and described, but also entitle them to assert their patents against antibodies with equivalent functions but different structural characteristics. If the economics of intellectual property center on balancing a need for protection beyond the literal invention with a desire to allow improvements, this seems a step in the right—or, at least in a doctrinally permissible and economically sensible—direction.

Whether patentees go for such a solution remains to be seen. Recent empirical evidence on antibody claims has yet to document such a shift. Patent attorneys may need to get over their historical reluctance to writing their claims in such a fashion. Our solution won’t give patentees everything they want. But they just might find it gives them what they need.

authors. William H. Neukom Professor of Law, Stanford Law School, Partner, Durie Tangri LLP; Professor of Law, College of Law, Professor of Medicine, Carle Illinois College of Medicine, Professor, European Union Center, Affiliate, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Permanent Visiting Professor, Centre for Advanced Studies in Biomedical Innovation Law, University of Copenhagen Faculty of Law. The authors wish to thank Robert Bohrer, Dan L. Burk, Bernard Chao, Paul R. Gugliuzza, Rose Hagan, Matthew Herder, Timothy R. Holbrook, Christopher M. Holman, Dmitry Karshtedt, Rachel Moodie, Lisa Larrimore Ouellette, Arti K. Rai, Rachel E. Sachs, Joshua D. Sarnoff, Brenda M. Simon, John R. Thomas, S. Sean Tu, Timothy A. Worrall, and participants at Biolawlapalooza 4.2, PatCon10, the Bay Area IP Professors conference, the Intellectual Property Scholars Conference, and Temple University Beasley School of Law’s Issues in Patent Law class.

Introduction

Antibodies are the backbone of modern biotechnology. They are the workhorses of molecular-biology research, the principal component in numerous diagnostic tests, and the heart of both the immunity provided by COVID-19 vaccines and of the single most effective COVID therapy.1 Long before “antibodies” became a household word during the COVID-19 pandemic, engineered antibodies were central to many of the most important and most valuable medical tests and therapies of the past thirty years.2 Annual revenue from just the top ten best-selling antibody drugs in 2019 reached $79.1 billion—almost double that of the global market for movies and music, combined.3

Patent law has long given antibodies broad protection, allowing an inventor who identifies an antibody that targets a particular antigen of interest to claim ownership over not just the particular antibody they developed, but over a genus of antibodies attracted to the same antigen.4 An inventor who created an antibody that bound to, say, tumor necrosis factor alpha (TNF-α)—the basis of three of the six top-selling antibody therapies—could claim that antibody and almost all other antibodies that bound to it.5 In part, this claim practice was one of necessity. Unlike typical “small-molecule” drugs, scientists had long identified antibodies not by their precise molecular structure but by what they did.6 Indeed, characterizing antibodies atom by atom was both impractical and pointless—akin to describing a fighter jet by listing every nut and bolt.7 “Functional claiming,” the ownership of “any device that performs [a] function,” was not only permitted but a norm for antibody patents.8 The form of patent claims thus followed their function.

Things have changed. In the laboratory, it is now easier to identify the physical sequence of a newly discovered antibody.9 But at the U.S. Court of Appeals for the Federal Circuit, no antibody patent in over a decade has survived a challenge based on overbreadth and inadequate disclosure,10 with the court regularly throwing out billion-dollar jury verdicts in favor of those patents.11 Mainly, the patents have fallen victim to patent law’s “written description” requirement, the doctrine that requires patentees to disclose “enough” examples of what they invented to show a “person having ordinary skill in the art” (a PHOSITA, or a reasonable expert) that the inventor was in possession of the invention.12 That doctrine is intended to prevent a patentee from “gun jumping”—filing for a patent application before they have actually nailed down the invention.13 Emboldened, perhaps, by this expansion of the written description doctrine, the Federal Circuit has also invalidated antibody patents on the related doctrinal ground of enablement, even though the technology is now easier to find and apply.14

Because the written description doctrine prevents inventors from filing patent applications too early, the doctrine has long operated with the conceit that the more knowledge a PHOSITA possesses about the field, the less a patent must show to demonstrate possession of that invention.15 With antibodies, however, a paradox has emerged. In the early days of the industry, when scientists often knew little about the precise molecular and genetic structures of antibodies and lacked tools to easily find them, the law permitted broad patents covering any antibody that bound to a particular target with a certain specificity; identifying those characteristics was the only practical way to describe newly discovered antibodies.16 Now that scientists understand the chemical structure of antibodies better—including an appreciation for just how genetically diverse antibodies are, even those that bind to a single target—functional patent claims to antibodies’ antigens are routinely being held invalid for failing the enablement or written description doctrines.17 Today, scientists know that the discovery of one or even dozens of antibodies that bind to a particular target with a particular specificity doesn’t exclude the possibility that many other antibodies with different structures do the same.18 Instead of requiring scientists to disclose more information when their colleagues start out knowing less, patent law now requires them to disclose more information about each invention when their colleagues know more. This development cuts against patent law’s precept that “there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement.”19 We call this the antibody patent paradox.

The antibody patent paradox may be part of a broader shift in patent doctrine, what one of us has called “the death of genus claims.”20 Or it may be an extension of the concerns about the abuse of functional claiming in other areas like software.21 Or it could be the result of trying to fit one of the most complex biological molecules we know in the single, convoluted sentence that is a patent claim.22 Or perhaps it is simply the result of a circumstance in which the more we learn, the more we learn what we don’t know.23 We explore all of these possibilities.24

Regardless of the explanation, the antibody patent paradox lies at the heart of several critical questions in patent policy: how broad patent claims should be to encourage invention; whether patent law is and should be technology-specific; and how we accommodate follow-on innovation after an initial, pioneering disclosure.25 If we get those questions wrong, we could end up with a second paradox—how the patent-fueled success of antibody technology made it impossible to get the very kinds of patents that drove innovation in the first place. As a matter of innovation policy, we think the end of functional antibody claims is a problem, but the likely effects on innovation are complicated. We suggest some possible middle ground that might save narrower antibody genus claims.

In Part I, we explain the science of antibodies, how it has changed, and why antibodies are so complex. In Part II, we discuss the parallel history of the law, beginning with broad protection for functional antibody claims and ending with the current period of hostility to antibody patents. Part III considers several possible explanations for this shift, none of which are completely satisfactory. In Part IV, we explain how the antibody patent paradox is central to many of the current policy debates in patent law, and we offer some guidance as to how to resolve the paradox. We conclude by suggesting broader implications for the written description doctrine and patent claims for other complex technologies.