In Mylan Pharm v. Research Corp Tech, the Fed. Cir. affirmed the PTAB’s conclusion of not unpatentable, finding the Board’s rejection of Petitioner’s argument of motivation based on bioisosterism to be supported by substantial evidence.  Offering compound 31 as a lead compound, Petitioner argued that the methoxyimino group was recognized as 1) uncommon; 2) difficult to synthesize and 3) unstable and one of ordinary skill would have been motivated to replace the amine of methoxyimino with a methylene to yield the compound of claim 8, with an expectation that the compound would have a more stable, synthetically accessible, pharmaceutically common and acceptable moiety.  Petitioner’s expert also testified that the proposed modification, yielding a racemic compound would be expected to be less potent but more stable.  The Fed. Cir. found the Board’s finding of an expectation of a reduced potency and an unpredictable change in critical conformation based on expert testimony which they found to be more credible, to be within the Board’s discretion.  The Board was entitled to reject bioisosterism as motivation because the record did not indicate why one would use bioisosterism and the lead compound was already highly potent and of low toxicity.  When arguing against structural obviousness, motivation should be based on the entire record.