By Kwame Mensah --
Last month's BIO International Conference kicked off on June 27th with a presentation entitled "IP Issues Affecting Biomarker-Based Diagnostics." The four panelists for the session were David Gass of Marshall, Gerstein & Borun, LLP; Dr. Thorlakur Jonsson, the Director of Intellectual Property at deCODE genetics ehf; Dr. Simon O'Brien of D. Young & Co. in the United Kingdom; and Dr. Jan Skouv, Director IPR at Exiqon A/S.
The session began with two talks related to recent developments in technology related to biomarkers. The first speaker was Dr. Jonsson, who focused on the use of the information provided by genome sequencing in personalized medicine. Dr. Jonsson began with a discussion of genetic variation in the human genome. He stated that the mere 1% genetic variation among humans can determine whether an individual may be at risk for a certain disease, may have certain drug metabolism, or may respond in a certain way to specific therapies. He referred to these as high risk Mendelian phenotypes, and touted the use of high throughput and microarray assays as providing faster analysis of genomic sequences. Dr. Jonsson concluded his presentation with a short summary of the work done by deCODE to investigate biomarkers for many diseases through correlation analyses of genealogy, genotype, phenotype, and genome databases.
The second speaker of the session was Dr. Skouv who discussed detection of microRNAs (miRNAs; RNA molecules of 22 nucleotides or less in length) in blood samples as biomarkers. These molecules have been found to be highly involved in the pathology of several types of cancer. Dr. Skouv stated that although the miRNA molecules were generally found to be stable when associated with blood serum and its components after EDTA treatment, introduction of locked nucleic acids (LNAs) to the miRNAs via PCR further increased stability of the miRNAs. LNAs are a class of nucleic acid analogues in which the ribose ring is "locked" by a methylene bridge connecting the 2'-O atom and the 4'-C atom of the ribose ring, which increases the molecule's affinity for other molecules. Dr. Skouv concluded his presentation by noting that Exiqon had successfully used LNA-associated miRNAs as biomarkers for the early detection of colorectal cancer, and that preliminary work had been done on the early detection of melanoma.
The next two speakers focused on patent-related issues. Generally speaking, two types of intellectual property protection exist for detection and use of biomarkers: (1) protection for the markers themselves (nucleic acid molecules, proteins, etc.) and (2) protection for use of the markers for diagnostics and therapeutics, including compositions, methods, systems, and kits. The first of the two speakers, David Gass provided a general discussion of the legal requirements for receiving a patent, and then discussed recent decisions in the federal courts within the last year relating to the patent eligibility of nucleic acid molecules and processes of analysis. He then moved to a discussion of two cases of particular relevance to biomarkers; Bilski v. Kappos and AMP v. USPTO (the "Myriad" case). Mr. Gass highlighted the fact that the Supreme Court in Bilski held that the "machine or transformation" test is not the exclusive test for determining whether a process or method of analysis is patent eligible. This is of particular relevance to the use of biomarkers because this holding indicates that determinative processes involved in the use of biomarkers do not necessarily have to be associated with a machine or be "transformative" to be patentable subject-matter.
Mr. Gass then moved to a discussion of the Myriad case, highlighting that the claims to isolated DNA molecules (gene products) were found invalid under 35 U.S.C. § 101, but that the claims related to vectors, host cells, probes. i.e., man-engineered DNA-type molecules were left intact. He specifically highlighted the amicus brief submitted during the appellate proceedings by the Department of Justice. The DOJ brief focused on the difference in the character of the nucleic acid molecules themselves, specifically asserting that "naturally occurring" nucleic acid molecules were not patentable subject-matter, whereas engineered nucleic acid molecules (e.g, vectors, host cells, cDNA) were patentable subject-matter. Mr. Gass then touched on the jurisdiction issues that were discussed during oral argument before the Federal Circuit. The panel also inquired about what it means to isolate a gene, i.e., that the breaking of covalent bonds, under traditional chemistry, creates a new molecule. Mr. Gass indicated that this line of inquiry suggests that the Federal Circuit could determine that isolated DNA is different from naturally-occurring DNA, therefore making it patentable subject-matter. This no doubt would be a big victory for the biotech industry. Mr. Gass concluded his discussion by focusing on diagnostic claims such as those in the Myriad patents. As discussed in this space previously, Myriad has argued that its diagnostic claims are not abstract and that each laboratory step is transformative.
The second patent law-related speaker of the afternoon was Dr. Simon O'Brien. He began his talk by stating that there has been a drastic decrease in the number of patent applications for gene patents since 2000. In contrast, applications for diagnostic methods have increased almost as dramatically, and the majority of these applications have been related to cancer diagnostics. Dr. O'Brien then gave a brief summary of the requirements for receiving a diagnostic method patent in Europe. The necessary steps in a claim are: examination, comparison, finding of a derivation, and attribution to a disease. Only one of these steps need be in vitro. He then pointed out that Myriad's BRCA-1 patents were found to be valid in opposition proceedings in Europe due to the fact that because isolated DNA molecules are patentable subject-matter, use of these molecules in diagnostic steps was also patentable.
Mr. Gass then returned to the microphone to discuss multi-party and multi-jurisdictional issues involved in enforcement. These are related to actions by multiple parties, in different jurisdictions or countries in performing a claimed diagnostic method. He focused on several cases that may provide some guidance as to what issues may arise regarding the enforcement of claims for biomarker-based diagnostic tests. One case discussed was BMC Resources, Inc. v. Paymentech, L.P. 478 F.3d 1373 (Fed. Cir. 2007), in which the Court stated that all steps of a method must be performed by one party in order for the claimed method to be infringed, unless a single mastermind is orchestrating performance of the method. Mr. Gass surmised that for a diagnostic method claim to be reasonably enforceable, one needs to draft a diagnostic method claim such that the method can only be performed by one party. Another case Mr. Gass discussed was Centillion Data Systems, LLC v. Qwest Communications International, Inc. (Fed. Cir. 2011), where the claim at issue was to a system with various components. The Court in Centillion stated that a party must put the system into service, control the system as a whole, and obtain a benefit from the system to infringe. Regarding territoriality issues, Mr. Gass again provided some insight into how this could affect biomarker/diagnostic claims stating that one or more steps of a method performed offshore would probably not be infringing, whereas one or more steps of a system performed offshore would be. Mr. Gass recommended using various types of diagnostic method claims within the same claim set to increase the likelihood of securing reasonably enforceable claims.
Dr. O'Brien concluded the session with a discussion of issues related to performing certain steps of a diagnostic method in another country as a means to circumvent infringement. He echoed Mr. Gass' suggestion that claims be drafted such that it is necessary for a method to be performed by the same person, such as by limiting the number of steps in the method. He stated that in Europe, one court determined that a patent holder may only receive protection for a method related to the DNA when the DNA is performing its native function. For example, using a cancer probe to diagnose a different disease would likely not be infringing.
Overall the session's discussion of use of biomarkers in diagnostic methods provided guidance for patent prosecutors in drafting good claims, and provided an excellent summary of the state of the industry related to biomarkers.
The POWERPOINT slides for this presentation can be obtained from Mr. Gass through the Marshall Gerstein & Borun website:
http://www.marshallip.com/professionals/34/david-a-gass
Posted by: Marshall Gerstein & Borun | July 14, 2011 at 10:36 PM