Application of KSR in Biotechnology- IN RE MAREK Z. KUBIN and RAYMOND G. GOODWIN( April 03 , 2009)

This case presents a claim to a classic biotechnology invention – the isolation and sequencing of a human gene that encodes a particular domain of a protein. Specifically, appellants claim DNA molecules (“polynucleotides”) encoding a protein (“polypeptide”) known as the Natural Killer Cell Activation Inducing Ligand (“NAIL”).
Natural Killer (“NK”) cells, thought to originate in the bone marrow, are a class of cytotoxic lymphocytes that play a major role in fighting tumors and viruses. NK cells express a number of surface molecules which, when stimulated, can activate cytotoxic mechanisms. NAIL is a specific receptor protein on the cell surface that plays a role in activating the NK cells.
The specification of the claimed invention recites an amino acid sequence of a NAIL polypeptide. The invention further isolates and sequences a polynucleotide that encodes a NAIL polypeptide. Moreover, the inventors trumpet their alleged discovery of a binding relationship between NAIL and a protein known as CD48. The NAIL-CD48 interaction has important biological consequences for NK cells, including an increase in cell cytotoxicity and in production of interferon.
Appellants claim a genus of isolated polynucleotides encoding a protein that binds CD48 and is at least 80% identical to amino acids 22-221 of SEQ ID NO:2 – the disclosed amino acid sequence for the CD48-binding region of NAIL. Apart from disclosing two polynucleotides falling within the scope of the claimed genus, specification also contemplates variants of NAIL that retain the same binding properties( however the specification does not indicate any example variants of NAIL that make conservative amino acid substitutions). Based on this the board raised a 112 rejection.
Under 103, the Board rejected appellants’ claims over the combined teachings of U.S. Patent No. 5,688,690 (“Valiante”) , 2 Joseph Sambrook et al., Molecular Cloning: A Laboratory Manual 43-84 (2d ed. 1989) (“Sambrook”) & Mathew et al., Cloning and Characterization of the 2B4 Gene Encoding a Molecule Associated with Non-MHC-Restricted Killing Mediated by Activated Natural Killer Cells and T Cells, 151 J. Immunology 5328-37 (1993) (“Mathew”).. Valiante discloses a receptor protein called “p38” that is found on the surface of human NK cells. Valiante also discloses and claims a monoclonal antibody specific for p38 called “mAB C1.7.” The Board found (and appellants do not dispute) that Valiante’s p38 protein is the same protein as NAIL. Sambrook, incorporated by reference in Valiante, describes methods for molecular cloning. Sambrook does not discuss how to clone any particular gene, but provides detailed instructions on cloning materials and techniques. The Board found that Mathew’s signaling molecule 2B4 is the murine (mouse) version of Valiante’s p38 and hence is cumulative to the teaching in Valiante and Sambrook.
Because of NAIL’s important role in the human immune response, the Board further found that “one of ordinary skill in the art would have recognized the value of isolating NAIL cDNA, and would have been motivated to apply conventional methodologies, such as those disclosed in Sambrook and utilized in Valiante, to do so.
Invoking the Supreme Court’s decision in KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Board concluded that appellants’ claim was “‘the product not of innovation but of ordinary skill and common sense,’ leading us to conclude NAIL cDNA is not patentable as it would have been obvious to isolate it.” Board Decision at 9 (citing KSR, 550 U.S. at 421).
Court stated that the record shows that the prior art teaches a protein of interest, a motivation to isolate the gene coding for that protein, and illustrative instructions to use a monoclonal antibody specific to the protein for cloning this gene. Therefore, the claimed invention is "the product not of innovation but of ordinary skill and common sense." Or stated in the familiar terms of this court’s longstanding case law, the record shows that a skilled artisan would have had a resoundingly "reasonable expectation of success" in deriving the claimed invention in light of the teachings of the prior art.
The present patent at issue may represents some minor advance in the art. But "[g]ranting patent protection to advances that would occur in the ordinary course without real innovation retards progress.” KSR, 550 U.S. at 419. “Were it otherwise patents might stifle, rather than promote, the progress of useful arts." Id. at 427. In light of the concrete, specific teachings of Sambrook and Valiante, artisans in this field, as found by the Board in its expertise, had every motivation to seek and every reasonable expectation of success in achieving the sequence of the claimed invention. In that sense, the claimed invention was reasonably expected in light of the prior art and "obvious to try."