906 F.3d 1031
Fed. Cir.2018Background
- Yeda owns three "Copaxone" patents claiming a 40 mg glatiramer acetate (GA) regimen administered as three subcutaneous injections over seven days (40mg GA 3x/week) to treat relapsing-remitting MS; earliest priority date Aug. 20, 2009.
- Prior art included FDA approval and clinical data for 20mg GA daily (COPAXONE® 20mg), studies of 20mg every-other-day (Flechter, Khan 2008/Caon) showing similar efficacy and better tolerability, and studies showing 40mg daily had comparable safety and possibly greater efficacy (Cohen, FORTE). Pinchasi (published 2007) disclosed 40mg every other day.
- Mylan and Amneal petitioned for inter partes review (IPR) challenging all claims as obvious over combinations including Pinchasi plus other references (e.g., FDA SBOA, Flechter). The Patent Trial and Appeal Board instituted and found the claims unpatentable as obvious; Yeda sought rehearing and appealed.
- Petitioners’ expert relied in a reply declaration on a 2009 pilot study (Khan 2009) that began before the priority date but was published after; the Board treated Khan 2009 as non-statutory but probative of motivation to investigate less-frequent dosing.
- The Board found (1) Pinchasi disclosed nearly all claim elements except the specific 3x/week schedule, (2) there was motivation to modify dosing frequency to improve compliance, and (3) a person of ordinary skill would have had a reasonable expectation of success combining the prior art to arrive at 40mg GA 3x/week. Objective indicia did not overcome obviousness.
Issues
| Issue | Yeda's Argument | Petitioners' Argument | Held |
|---|---|---|---|
| Use of Khan 2009 in IPR | Board violated due process and §311(b); Khan 2009 is not statutory prior art and Yeda lacked notice of Board reliance | Khan 2009 was disclosed in petitioners’ reply; Yeda had opportunity to respond; Khan 2009 is admissible non-prior-art evidence of motivation/knowledge | No due process violation; Board permissibly relied on Khan 2009 as non-prior-art evidence of motivation; any limited misuse was harmless error and decision stands |
| Obviousness of 40mg GA 3x/week | Unpredictability of GA (unknown PK/PD, mechanism) precludes reasonable expectation of success; Board engaged in hindsight and split dose/frequency improperly | Prior clinical studies (20mg daily, 20mg EOD, 40mg daily, Pinchasi) provided motivation and reasonable expectation; GA is a "forgiving drug"; only one dose difference from prior art | Affirmed: substantial evidence supports motivation to combine and reasonable expectation of success; Cyclobenzaprine does not control because here clinical data existed |
| Claims requiring improved tolerability / reduced reactions | Board failed to adequately analyze tolerability and conflicting references (Flechter, FORTE) | Prior studies showed less frequent dosing reduced injection reactions; FORTE and others did not teach away from 40mg | Affirmed: Board adequately considered tolerability evidence and substantial evidence supports obviousness of tolerability-related claims |
| Specific-day thrice-weekly schedules (’302 dependent claims) | Pinchasi does not disclose the enumerated day combinations | Choosing specific weekdays from a small set is routine, obvious, and driven by patient/physician choice | Affirmed: selecting particular days for injections is an obvious, predictable implementation once 3x/week regimen is obvious |
Key Cases Cited
- KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007) (establishes flexible obviousness analysis and reliance on common sense and predictable solutions)
- Graham v. John Deere Co. of Kan. City, 383 U.S. 1 (1966) (sets the Graham factual inquiries for obviousness)
- In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litig., 676 F.3d 1063 (Fed. Cir. 2012) (reasonableness of expectation of success requires evidence predicting therapeutic effect from prior art)
- Genzyme Therapeutic Prods. LP v. Biomarin Pharm. Inc., 825 F.3d 1360 (Fed. Cir. 2016) (new evidence in IPR is permissible if opposing party has notice and opportunity to respond)
- Novartis AG v. Torrent Pharm. Ltd., 853 F.3d 1316 (Fed. Cir. 2017) (APA substantial-evidence review of PTAB fact findings)
- Synopsys, Inc. v. Mentor Graphics Corp., 814 F.3d 1309 (Fed. Cir. 2016) (agency need not address every argument; decision upheld if its path is reasonably discernible)