Holding: Argument or analysis of a reasonable expectation of success is not required to show obviousness when the only disputed limitation of a claim is an inherent property of a claimed composition that has already been determined to be obvious.
Cytiva owns several patents related to chromatography matrices and processes for isolating targeted biomolecules using those matrices. JSR challenged 83 claims from these patents in a total of six IPRs. The PTAB found 79 claims to be unpatentable and 4 of the claims to be not unpatentable. The Cytiva patents are directed to a process called affinity chromatography which uses a ligand that easily binds to the target biomolecule as a part of a chromatography matrix. The matrices are packed into a column and a fluid including the target biomolecule is introduced into the column. The ligands bind to the target biomolecule in the mixture, and a washing step is used to remove impurities from the column leaving the target biomolecule bound to the ligands of the chromatography matrix. In a process known as elution, another solution is poured into the column to break the bond between the ligand the target biomolecule, to isolate the target biomolecule.
When the isolation process is finished, an alkaline solution is run over the column to remove contaminants in the column. This alkaline solution can degrade proteins, so ligands that are made from proteins that have greater stability in alkaline environments are desirable. Each of the Cytiva patents uses a ligand from a Protein A which is well known in the field of chromatography because of its ability to bind to immunoglobulins. Protein A has five natural domains known as Domain A, B, C, D, and E. Scientists have also designed a synthetic domain for Protein A, known as Domain Z, which is derived from a genetically altered Domain B. The claims of the Cytiva proteins make a similar genetic modification to Domain C to improve the stability of Protein A in alkaline solutions.
In addition to the genetic mutation of Domain C, some of the Cytiva claims also recite that the ligand of the chromatography matrix binding to the Fab region of an antibody. Antibodies are comprised of different regions, such as the Fc region and the Fab region. When the Fab region is separated from the antibody, it is known as a Fab fragment.
In holding most of the Cytiva claims unpatentable, the district court found that it would be obvious to make the genetic modification to Domain C to improve stability in alkaline solutions based on the prior art. However, for the claims that were directed to binding to the Fab region of the antibody, the PTAB came to different decisions for the composition claims and the process claims. The PTAB determined that the composition claims were unpatentable since Fab binding is an inherent property of the genetically modified Domain C. In contrast, for the process claims, the PTAB used a different claim construction for the term “Fab part of an antibody” which limited this term to only Fab fragments, and found these claims to not be obvious.
Cytiva argued that the PTAB erred by failing to conduct lead compound analysis in determining that its genetically modified Domain C was obvious in view of the prior art. Lead compound analysis is a two-part inquiry. First, the court determines whether a chemist of ordinary skill would have selected the prior art compounds as starting points for further development. Second, the court determines whether the prior art would have given a person of ordinary skill in the art a reason to modify the lead compound to make the claimed compound with a reasonable expectation of success. However, the Federal Circuit holds that lead compound analysis is not always required to show obviousness, particularly where the prior art references expressly suggest the claimed modification. As stated in KSR, an obviousness analysis is flexible and does not have rigid and formalistic rules. In some instances, it is appropriate to use an obvious-to-try rationale rather than the lead compound test to determine obviousness.
With regard to the claims that are directed to binding to the Fab region of the antibody, the Federal Circuit found that there was no material difference between Cytiva’s composition claims and process claims, so the claim construction for each should be the same. In particular, the PTAB improperly limited the term “Fab part of an antibody” to only the Fab fragments in the process claims, when this term should also apply to both the Fab fragments and the Fab part of an entire antibody.
Obviousness analysis typically requires evidence that a person of ordinary skill would have selected and combined the cited references in the manner of the claimed invention with a reasonable expectation of success. In this case, JSR did not present a reference that describes the capability of binding to the Fab part of an antibody, but instead argued that this capability is an inherent result of making the claimed genetic modification to Domain C. The Federal Circuit held that JSR was not required to further show that the prior art would have led a person of ordinary skill in the art to make the claimed compound with a reasonable expectation of success. When a claim recites an inherent property of an otherwise obvious composition or process, there is no need to show a reasonable expectation of success to prove obviousness. In contrast, when a claim requires prior knowledge of the inherent property for a motivation to combine, then a reasonable expectation of success is required to prove obviousness. In this case, the Federal Circuit found the binding to the Fab part of the antibody feature of the genetically modified Domain C to be an inherent property of an already obvious composition. Therefore, JSR was not required to show a reasonable expectation of success to prove obviousness.
Federal Circuit Precedential 
Leave a comment