OTSUKA PHARMACEUTICAL CO., LTD. v. Sandoz, Inc.
678 F.3d 1280
| Fed. Cir. | 2012Background
- Otsuka owns the '528 patent on aripiprazole and its uses for schizophrenia, expiring in 2015.
- Defendants filed ANDAs seeking to market generic aripiprazole; Daubert-style district court bench trial on validity.
- The district court held claims 12, 17, and 23 nonobvious under 35 U.S.C. § 103 and not subject to nonstatutory double patenting, after lead-compound analysis.
- asserted lead compounds included unsubstituted butoxy, 2,3-dichloro propoxy, and OPC-4392, with clozapine/risperidone considered non-carbostyril leads at the time.
- Prior art includes Otsuka’s earlier '416 patent (unsubstituted butoxy) and Nakagawa declaration data; SE '945 and DE '105 references on 2,3-dichloro propoxy; OPC-4392 studies.
- The court concluded the prior art did not teach a motivation to select those leads or modify them to aripiprazole with reasonable expectation of success.
Issues
| Issue | Plaintiff's Argument | Defendant's Argument | Held |
|---|---|---|---|
| Whether aripiprazole would have been obvious under § 103 | Otsuka argues district court used proper lead-compound analysis and found no motivation to combine prior art. | Apotex/Teva contend obviousness by selecting lead compounds and modifying them would have produced aripiprazole with reasonable expectation of success. | No reversible error; district court correctly held not prima facie obvious. |
| Whether the district court properly used a lead-compound framework for chemical obviousness | Otsuka asserts two-step lead compound approach aligns with law and avoids hindsight. | Defendants claim rigid lead selection precludes proper obviousness analysis post-KSR. | Lead-compound analysis affirmed as proper under the flexible framework. |
| Whether unsubstituted butoxy is a proper lead or taught to yield aripiprazole | Otsuka argues '416 and Nakagawa data do not teach an antipsychotic lead; not a reasonable lead. | Defendants argue unsubstituted butoxy might lead to aripiprazole via modification. | Not a lead; no motivation to optimize to aripiprazole with reasonable expectation of success. |
| Whether 2,3-dichloro propoxy would have been obvious lead | Otsuka contends SE '945 lacks a meaningful antipsychotic suggestion and 2,3-dichloro propoxy not a lead. | Defendants assert generic disclosure plus Pfizer-style motivation would render it obvious. | Not obvious; no reason to pursue 2,3-dichloro propoxy as a lead for antipsychotic activity. |
| Whether OPC-4392 would have been a lead compound | Otsuka emphasizes OPC-4392 taught away due to weak antipsychotic action and adverse effects. | Defendants argue OPC-4392 as a potential lead given some activity at low doses. | Not a lead; teaching away and unpredictability negate obviousness. |
| Whether the asserted claims are invalid for nonstatutory obviousness-type double patenting over the unsubstituted butoxy of the '416 patent | Otsuka argues no reasonable motivation to modify unsubstituted butoxy to aripiprazole; not patentably distinct. | Defendants rely on 2,3-dichloro substitution to create a close variant. | Not invalid; no reason to modify unsubstituted butoxy to aripiprazole with reasonable expectation of success. |
Key Cases Cited
- Graham v. John Deere Co., 383 U.S. 1 (1966) (framework for obviousness analysis and factual underpinnings)
- KSR Int'l Co. v. Teleflex, Inc., 550 U.S. 398 (2007) (flexible obviousness standard; caution against hindsight)
- Daiichi Sankyo Co. v. Matrix Labs., Ltd., 619 F.3d 1346 (Fed. Cir. 2010) (lead compound analysis in chemical obviousness)
- Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir. 2007) (motivation to modify and reasonable expectation of success)
- Procter & Gamble Co. v. Teva Pharm. USA, Inc., 566 F.3d 989 (Fed. Cir. 2009) (antipatentability considerations in obviousness)
- In re Lonardo, 119 F.3d 960 (Fed. Cir. 1997) (nonstatutory double patenting doctrine framework)
- Geneva Pharm., Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373 (Fed. Cir. 2003) (distinction between obviousness and double patenting contexts)
- Ortho Pharmaceutical Corp. v. Smith, 959 F.2d 936 (Fed. Cir. 1992) (double patenting and comparison of claimed subject matter)