Opinion ID: 799379
Heading Depth: 3
Heading Rank: 4

Heading: opc-4392

Text: The Defendants also assert that the district court erred by rejecting OPC-4392 as a lead compound. Again, we disagree. The Defendants rely selectively on the disclosure in Murasaki 1987 that OPC-4392 was an antipsychotic drug, J.A. 5907, and the fact that OPC-4392 proceeded to Phase II clinical trials. Taken as a whole, however, the prior art taught away from using OPC-4392 as a starting point for further antipsychotic research. For example, Murasaki 1987 teaches that the antipsychotic action [of OPC-4392] was not strong. Id. Based on that teaching, together with other prior art of record that focuses only on the effects of OPC-4392 on schizophrenia's negative symptoms, a skilled artisan would have concluded that OPC-4392 did not treat positive symptoms. Otsuka, 2010 WL 4596324, at -22, 2010 U.S. Dist. LEXIS 132595, at -69. The district court also credited the testimony of one of the Defendants' witnesses, who stated that clinical studies of OPC-4392 showed that it lacked [an] antipsychotic component. Id. at , 2010 U.S. Dist. LEXIS 132595 at . Furthermore, Murasaki 1987 taught that the strength of the activating action [of OPC-4392] stood out, J.A. 5907, a property that Dr. Roth testified would have been a red flag indicating that the drug was likely to cause patients to act out on their delusions and hallucinations. Otsuka, 2010 WL 4596324, at -22, 2010 U.S. Dist. LEXIS 132595, at . Another prior art reference, Murasaki 1988, taught that OPC-4392, even at a very low dose, id. at , 2010 U.S. Dist. LEXIS 132595 at , caused severe side effects, J.A. 10401. In light of the totality of the evidence before the district court, we perceive no clear error in the conclusion that OPC-4392 was considered a failure insofar as it did not treat the positive symptoms of schizophrenia and was not well-tolerated in modest doses. Otsuka, 2010 WL 4596324, at , 2010 U.S. Dist. LEXIS 132595, at . The court thus did not err in concluding that one of ordinary skill in the art would not have selected OPC-4392 as a lead compound for further antipsychotic research. Even assuming that one would have selected OPC-4392 as a lead compound, the district court found that the Defendants failed to prove that the prior art would have directed one to make the various modifications necessary to convert OPC-4392 into aripiprazole. Those modifications include: (1) converting OPC-4392's carbostyril core into a dihydrocarbostyril; (2) changing OPC-4392's propoxy linker to a butoxy; and (3) replacing OPC-4392's 2-methyl and 3-methyl groups with 2-chloro and 3-chloro substituents. On appeal, the Defendants rely in large part on the inventors' and Otsuka's own development efforts in an attempt to prove that aripiprazole would have been obvious. E.g., Br. Defs.-Appellants Apotex, at 46-47 (arguing that Otsuka's aripiprazole development involved a short timeline and only took a few months). Those arguments cannot trump the district court's careful fact finding, however. The inventor's own path itself never leads to a conclusion of obviousness; that is hindsight. What matters is the path that the person of ordinary skill in the art would have followed, as evidenced by the pertinent prior art. See 35 U.S.C. § 103(a) (Patentability shall not be negatived by the manner in which the invention was made.); Life Techs., Inc. v. Clontech Labs., Inc., 224 F.3d 1320, 1325 (Fed.Cir. 2000) ([T]he path that leads an inventor to the invention is expressly made irrelevant to patentability by statute.). We therefore agree with the district court that the Defendants failed to provide clear and convincing evidence that the skilled artisan would have known how to modify OPC-4392 to increase antipsychotic activity. Otsuka, 2010 WL 4596324, at , 2010 U.S. Dist. LEXIS 132595, at .