Innovation vs. Evasion: Clarifying Patent Rights in Second-Generation Genes and Proteins

Berkeley Technology Law Journal, Feb 2014

By Antony L. Ryan and Roger G. Brooks, Published on 09/01/02

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Innovation vs. Evasion: Clarifying Patent Rights in Second-Generation Genes and Proteins

BERKELEY TECHNOLOGY LAW JOURNAL Antony L Ryant andRoger G. Brookl "Protein engineering" enables molecular biologists to create modified proteins with properties different from those found in nature. These "second generation" proteins present both promise and peril for the biotechnology industry. On the one hand, an increasing number of pharmaceutical products contain modified proteins, many with important clinical advantages. These innovative products should not be blocked by patents on the natural gene or protein. On the other hand, companies can now create modified proteins that behave no differently from the patented analogs in their competitors' products. This threatens to make gene and protein patents so easy to evade as to render them almost meaningless. SECOND-GENERATION GENES AND PROTEINS TABLE OF CONTENTS I. INTRODUCTION The recent sequencing of the human genome has generated considerable debate over the patentability of naturally occurring human genes. The issue has received attention at the highest political levels,1 and the United States Patent and Trademark Office (PTO) has reacted by issuing new guidelines for the review of patents on genes. 2 But the remarkable scientific accomplishment represented by the Human Genome Project is just the first step toward clinical application of that knowledge. At the outset, medical breakthroughs will require the identification and characterization of the proteins expressed by human genes.3 Going further, in some cases scientists will be able to create modified proteins with properties superior to those of their naturally occurring analogs. This process of "protein engineering" involves altering the nucleotide sequence of the gene so it expresses a protein with a different amino acid sequence, which in turn may alter the protein's properties. 4 Such "second generation" proteins are an important and growing segment of the biopharmaceutical market, and in some cases may yield important clinical advantages over their natural analogs. The potential utility and value of these engineered proteins raises a question less visible than the patentability of human genes, but scarcely less important for the pharmaceutical industry: whether gene and protein patents, once issued, will cover variant genes and proteins that differ slightly in their nucleotide or amino acid sequence. On the one hand, such dominance would be undesirable if it impeded the development of clinically superior second-generation proteins. On the other hand, the increasing ease of protein engineering raises the spectre that all gene and protein patents could be easily evaded by making slight variations to the nucleotide or amino acid sequence. Thus, defining a clear and sensible boundary as to when a natural-sequence patent may dominate second-generation analogs will be critical to pharmaceutical companies' continuing ability to invest in the development of recombinant DNA products. That boundary, however, is not yet clear. The issue generally arises in two ways. First, the discoverer of a natural sequence may apply for a patent that encompasses analogs within its literal claim scope--either by claiming all genes or proteins with a certain structural similarity or by claiming sequences based on the protein's function. Once issued, such a broad patent can be challenged in infringement litigation for lack of enablement or written description. Second, the holder of a narrower patent to the natural sequence may claim that the secondgeneration gene or protein, although outside the literal claim scope, infringes the patent under the doctrine of equivalents. At present, it is unclear how courts will decide whether the two gene or protein sequences are equivalent. The difficulties often created when radically new technology is forced into existing patent-law categories are here compounded by the fact that some of the underlying patent law doctrines have recently become unsettled. Earlier this year, in Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co.,5 the Supreme Court upheld the doctrine of equivalents by rejecting the Federal Circuit's expansive application of prosecution history estoppel, which threatened to preclude any finding of equivalence for most 4. For background on protein engineering, see Part II below. 5. 535 U.S. 7 22 (2002 ). patents. More recently, in Enzo Biochem, Inc. v. Gen-ProbeInc.,6 the Federal Circuit re-affirmed its precedent on the application of the written description doctrine to gene patents, but applied that precedent in a manner that renders uncertain when a person who discovers a gene may obtain claims to analog sequences. In this article, we propose an analytical framework for determining whether variant nucleotide or amino acid sequences infringe patents covering their natural analogs. In Part II, we review briefly the background principles of protein engineering and patent law. In Part III, we analyze the existing case law. The most significant precedent is (...truncated)


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Antony L. Ryan, Roger G. Brooks. Innovation vs. Evasion: Clarifying Patent Rights in Second-Generation Genes and Proteins, Berkeley Technology Law Journal, 2014, Volume 17, Issue 4,