894 F.3d 1374
Fed. Cir.2018Background
- Endo owns Aveed®, a long-acting intramuscular testosterone undecanoate (TU) product; Bayer owns the listed patents: U.S. Patent Nos. 7,718,640 (’640) and 8,338,395 (’395). Custopharm filed an ANDA with a Paragraph IV certification and was sued for infringement; Custopharm stipulated infringement and litigated invalidity/obviousness of claim 2 of the ’640 and claim 18 of the ’395.
- The asserted claims recite (1) a 750 mg TU dose (250 mg/mL at 3 mL), (2) a vehicle of castor oil plus a co‑solvent with castor oil ≤42% by volume (benzyl benzoate in the ’640), and (3) for the ’395, a regimen of two initial injections 4 weeks apart followed by 10‑week maintenance intervals.
- Prior art relied on three clinical articles (Behre, Nieschlag, von Eckardstein) reporting 1000 mg TU injections at 250 mg/mL (4 mL) in castor oil; the articles did not disclose a co‑solvent or the 750 mg dose. Saad (2007) later revealed the articles actually used a 40% castor oil / 60% benzyl benzoate vehicle (Nebido®), but that disclosure post‑dates the patents’ 2003 priority date.
- Custopharm also cited Riffkin (teaching castor oil + benzyl benzoate among many vehicles) and Pushpalatha/Proluton (a commercial 40% castor oil/60% benzyl benzoate depot steroid product used weekly in pregnant women) to show motivation to use that vehicle.
- At bench trial the district court found Custopharm failed to prove obviousness: no disclosure or clear motivation to arrive at 750 mg from 1000 mg; the Articles did not inherently disclose benzyl benzoate or the specific 40/60 ratio; and the prior art did not render the claimed two‑phase 4‑week then 10‑week regimen obvious. The Federal Circuit affirmed.
Issues
| Issue | Custopharm (challenger) argument | Endo/Bayer (patent owners) argument | Held |
|---|---|---|---|
| Obviousness of 750 mg TU dose | Prior studies used 1000 mg; AACE guideline showed some patients supra‑normal → skilled artisan motivated to lower dose to 750 mg (3 mL) | FDA guidelines (prevailing) did not show systematic overdosing; no clear motivation to reduce dose; could instead alter interval | No obviousness: court found no clear and convincing motivation to lower dose from 1000 → 750 mg |
| Inherency of vehicle (40% castor oil/60% benzyl benzoate) | The Articles actually used that vehicle (later shown by Saad) and pharmacokinetic data implies that vehicle was necessarily present | Inherency requires that the missing limitation be necessarily present; pharmacokinetic profiles are consistent with multiple vehicles/co‑solvents; no proof only claimed vehicle yields those data | No inherency: court found Custopharm failed to show the vehicle formulation was necessarily present in the Articles |
| Motivation to combine Proluton vehicle with TU regimen/dose | Proluton (commercial product) used same 40/60 vehicle; Riffkin and others taught castor oil + benzyl benzoate → skilled artisan would combine with TU to make long‑acting product | Proluton is a weekly hydroxyprogesterone depot for pregnant women (not long‑acting TU); many alternative co‑solvents existed; not a clear teaching to use that vehicle for prolonged‑action TU | No motivation to combine: court found insufficient evidence that a skilled artisan would adopt Proluton’s vehicle for long‑acting TU |
| Obviousness of claimed injection schedule (2 doses 4 weeks apart then 10‑week maintenance) | Prior articles show accumulation and extended intervals (6–12 weeks) → routine clinician adjustments could produce claimed two‑phase regimen | Articles teach lengthening intervals, not an initial 4‑week loading phase followed by 10‑week maintenance; depot pharmacokinetics are unpredictable and require more than routine experimentation | No obviousness: court upheld that the specific regimen was not shown obvious by the prior art and motivation arguments |
Key Cases Cited
- Par Pharm., Inc. v. TWI Pharm., Inc., 773 F.3d 1186 (Fed. Cir.) (inherency requires limitation be necessarily present)
- Continental Can Co. USA v. Monsanto Co., 948 F.2d 1264 (Fed. Cir.) (inherency principles)
- In re Kao, 639 F.3d 1057 (Fed. Cir.) (inherent characteristics may be prior art if necessarily present)
- In re Omeprazole Patent Litig., 483 F.3d 1364 (Fed. Cir.) (inherency where characteristic results every time prior art process is followed)
- In re Crish, 393 F.3d 1253 (Fed. Cir.) (inherent anticipation where prior art necessarily contained claimed sequence)
- KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (U.S.) (motivation to combine and routine‑skill analysis in obviousness)
- Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir.) (burden on challenger to show by clear and convincing evidence motivation to combine)
- Motorola Mobility, LLC v. Int’l Trade Comm’n, 737 F.3d 1345 (Fed. Cir.) (burden of proof for inherency/anticipation)