Nov. 12, 2002
| Twenty-two years after the U.S. Supreme Court's seminal decision in Diamond v. Chakrabarty opened the door to the patentability of "anything under the sun that is made by man," and two years after both Celera Genomics Group and the government-led Human Genome Project announced they had completed draft sequences of the human genome, the desks of biotech patent attorneys are piled higher than ever with patent applications for gene-related inventions.
The U.S. Patent and Trademark Office (PTO) has already granted approximately 20,000 patents involving genes, the polypeptides they encode, or fragments of either. In addition, there are more than 20,000 patent applications for such inventions currently undergoing "prosecution" (an examination and negotiation process between patent attorneys and PTO technical experts called examiners). Large numbers of gene-related patents have also been granted or applied for in Europe, Japan, Canada, Australia, and elsewhere.
What's "Under the Sun"?
Much more remains for the patenting. If one accepts an estimate of 35,000 human genes, then many, if not most, of these remain unpatented. Within each gene there may be significant amounts of sequence variability. In addition, biologists have scratched no more than the surface of the myriad interactions that can occur among these genes. Beyond humans, an estimated 17.5 million other living species occupy the earth, and all but a handful those genomes remain unexplored. Add a potential infinity of artificially designed sequences, and there's clearly no end in sight of patentable gene-related inventions.
Patent law affords protection to, among other things, "compositions of matter" and "processes." Compositions of matter can include nucleic acids, polypeptides, vectors, cell lines, and even genetically modified organisms, while processes can involve uses of nucleic acids or other compositions of matter in industrial processes, or to predict, detect, or treat diseases. Patents are also available for inventions based on new uses for previously known inventions (e.g., use of a previously patented gene to detect a disease).
Another class of gene-related inventions involves methods for generating research tools or lead compounds that can themselves be used to improve the discovery rate of new drugs or therapies. Controversy has arisen because owners of such patents often seek "reach-through" royalties on sales of commercial products developed using their patented methods.
These end products are not themselves covered by the pat-ents, so patent owners often attempt to incorporate reach-through royalties into the terms of patent licenses. It's likely that many disputes between patent owners and licensees will end up in court, where judges will decide whether licenses conditioned on such royalties constitute illegal patent misuse.
See You in Court
Indeed, this past year has seen a flurry of court cases with important implications for gene-related patents. The Supreme Court decided cases about patentable subject matter and the "doctrine of equivalents." The Court of Appeals for the Federal Circuit (CAFC), a special federal appeals court established to improve predictability in patent law, twice decided a case about deposits of genes. And a small biotech company announced its intention to sue a large pharmaceutical company for infringing its patent involving a biologically fundamental signaling pathway.
In Pioneer Hi-Bred v. J.E.M., the Supreme Court reaffirmed its "anything under the sun" patentability standard. The Court decided that genetically improved breeds of corn did indeed qualify for standard "utility" patent protection, rather than only the weaker forms of protection available for plant inventions.
Then, in Festo v. Shoketsu, the Supreme Court considered the applicability of the doctrine of equivalents, which extends patent protection to include not only the "literal scope" of a claimed invention, but also a penumbra of obvious variants. Such protection is vitally important in gene-related patents because potential infringers could often avoid literal infringement merely by making trivial alterations to a claimed nucleotide or amino acid sequence without affecting its function.
The CAFC had earlier established a clear but harsh standard under which most claim amendments made during prosecution would preclude later availability of the doctrine of equivalents to defend against non-literal infringement. In a rare unanimous decision, the Supreme Court rejected much of this new standard, and sent the case back to the CAFC with instructions to craft a standard that will likely be more generous towards patent owners.
The two-headed Enzo v. Gen-Probe case offered the unsettling spectacle of a panel of CAFC judges deciding an important case one way, and then decisively reversing itself. It involved a patent claiming DNA probes useful for detecting eubacteria that cause gonorrhea. The inventors had deposited copies of the probes in a public depository to satisfy the patent law's "written description" requirement that an inventor demonstrate possession of a claimed invention. First, the court decided that the patent's claims were invalid because public deposits were inadequate to satisfy the written description requirement. Then, the same judges reheard the case, reversed themselves, and held that the deposited probes could indeed satisfy the written description requirement.
Although far from resolution, a final case is notable for its potentially far-reaching implications for biotech companies and many gene-related patents. On June 25, 2002, the PTO granted Patent No. 6,410,516 on "Nuclear Factors Associated with Transcriptional Regulation" to a group of scientists that included Nobel laureate David Baltimore. The patent claims are very broad in scope, covering methods of modulating the biologically fundamental NF-kB pathway, and are based on research done back in the 1980s.
The NF-kB pathway is implicated in many diseases, thousands of papers have been published about it, and numerous existing drugs may infringe the claimed invention. Furthermore, the patent will remain in force until June 25, 2019.
ARIAD Pharmaceutical Inc., based in Cambridge, Mass., owns an exclusive license on the patent. On the same day the NF-kB patent was granted, ARIAD sued Eli Lilly and Co., alleging that sales of Lilly's drugs for osteoporosis (Evista) and septic shock (Xigris) infringe its new patent. Corporations as well as nonprofit institutions now fear coming into ARIAD's crosshairs, and intently await the results of the first case involving this broad patent. They might also worry about the implications of other "superpatents" that may be working their way through the PTO.
The numbers and importance of gene-related patents seem certain to increase. However, challenges also loom. The PTO perennially faces underfunding and critical shortages of biotechnology examiners, leading to prolonged and needlessly expensive prosecution. Internationally, this past year has witnessed countries threatening to "break" existing patents on drugs (e.g., HIV and anthrax) allegedly to promote the public good. And efforts to harmonize and internationalize patent law to spur biotech innovation worldwide are routinely condemned as "biological imperialism" by those opposed to globalization.
One thing is certain: Patent attorneys are unlikely to see the surfaces of their desks again anytime soon.
Andrew W. Torrance is a biotech patent attorney at Fish & Richardson P.C. and a lecturer at Harvard University, where he received his doctorate in biology and his J.D. in law. Information was contributed to this column by colleagues at Fish & Richardson P.C. and USPTO Director John Doll. Torrance may be reached at email@example.com.