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)