Molecular Biotechnology: Principles and Applications - Glick B., Pasternak J. 2002

Regulation of Research in Molecular Biotechnology and the Patenting of Biotechnological Inventions
Patenting of Biotechnological Inventions
Patenting of DNA Sequences

Since 1980, patent offices worldwide have received over 5,000 Applications for full-length genes, with approximately 1,500 resulting in granted patents. The most significant patent issued for a human Gene-based product is arguably the one for recombinant Erythropoietin, which generated over $1 billion in revenue for the applicant in 1996 alone. Erythropoietin stimulates red Blood Cell production and is used to prevent anemia in dialysis patients with renal failure. Numerous other patented nucleotide sequences serve as diagnostic probes (biomarkers).

Following the launch of the Human Genome Project, including the partial sequencing of human cDNA from various Tissues and Organs, the patenting of partial-length genes sparked considerable debate and controversy. In 1991, the U.S. National Institutes of Health (NIH) filed a patent application for 315 partially sequenced human cDNA fragments (ESTs). Two subsequent applications increased the total number of ESTs under patent review to 6,869. In 1994, the PTO notified the NIH of its intent to reject the applications on the grounds that the Functions of these sequences were unknown. In other words, the partial sequences alone failed to meet the "industrial applicability" patentability requirement. The NIH chose not to appeal, leaving the patentability of ESTs an open question to this day.

Meanwhile, by 1997, over 350 patent applications covering more than 500,000 partial-length genes had been filed, primarily by private companies. A single application alone sought patent protection for approximately 18,500 ESTs. The U.S. PTO has yet to issue a ruling on any such applications. However, to streamline the examination process and encourage applicants to submit a more reasonable number of claimed inventions in the future, it has been proposed to cap the number of sequences per application at 10.

Opponents of patenting DNA fragments with unknown functions argue that, despite the undeniable value of such sequences, seeking patent protection for them is premature. Furthermore, There is a risk that granting such patents would not only grant overly broad rights to patent holders but also hinder The Development of various diagnostic and therapeutic tools. Consequently, thousands of ESTs are currently viewed as intermediate research tools rather than final products. Conversely, proponents of EST patenting maintain that these sequences are novel because they are complementary to mRNA from various tissues and organs, and that they possess industrial applicability since each set of ESTs can be used diagnostically to determine how a disease correlates with altered mRNA expression in different organs. Moreover, proponents argue that historical precedent shows patent protection does not stifle product development; rather, it stimulates it. Thus, the issue of EST patenting remains unresolved. It may take some time before it is definitively settled, especially if applicants whose claims were rejected by the PTO decide to litigate. Furthermore, ongoing research will eventually decode the full sequences of many partially sequenced cDNAs, leading to new patent filings. This could create a conflict between the patentability of partial versus full-length cDNAs.

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Until recently, securing patents for newly identified genes in the U.S. was challenging, even when such inventions were proven useful. The PTO typically ruled that such inventions lacked an "inventive step," deeming them obvious and therefore unpatentable. In short, PTO examiners concluded that obtaining a gene or cDNA using synthetic probes based on published partial or complete Amino acid sequences was a routine Procedure for anyone skilled in the art and flowed directly from prior art, rendering the methodology unpatentable. On two occasions, the U.S. Court of Appeals for the Federal Circuit ruled that knowing an Amino Acid Sequence does not uniquely determine The nucleotide sequence of the corresponding cDNA or gene due to the degeneracy of METABOLISM/28.html">The Genetic Code—meaning that given a specific amino acid sequence, neither the cDNA nor the gene sequence is obvious. In other words, as stated in one regulatory document, "what is not predetermined cannot be considered obvious." Nevertheless, the U.S. PTO maintains its current approach to gene patenting and recently rejected at least one application on the grounds that the Methods used to determine the gene's nucleotide sequence were routine and obvious. Patent attorneys, conversely, argue that an invention's patentability should not depend on how it was made, but rather on whether it meets the statutory criteria for patentability. The question of whether utilizing a conventional method to obtain a gene precludes establishing its non-obviousness must be resolved through the courts. Since the PTO relies on precedent when evaluating biotechnology applications, there is likely no absolute standard for assessing such inventions, and the courts will likely play an integrative role in determining gene patentability.