Duke University v. Biomarin Pharmaceutical Inc.
685 F. App'x 967
Fed. Cir.2017Background
- Duke owns U.S. Patent No. 7,056,712, claiming methods of treating Pompe disease (GSD‑II) by periodic administration of human acid α‑glucosidase (hGAA) produced in CHO cell cultures; claims 1 and 20 are independent; claim 9 recites that the hGAA "is a precursor"; claim 19 requires an immunosuppressant "administered prior to any administration" of hGAA.
- BioMarin petitioned for IPR; the PTAB found claims 1–9, 11, 12, 15, and 18–21 unpatentable as anticipated by van Bree and/or obvious over Reuser in view of Van Hove (and sometimes Brady).
- van Bree and Reuser disclose use of rhGAA (including 110/100 kD precursor and mature forms) to treat Pompe disease and mention CHO cells as an alternative production source; Van Hove discloses purification of 110 kD precursor from CHO cell culture; Brady reports using immunosuppression to manage antibody responses in Gaucher disease.
- The PTAB construed "precursor" broadly to encompass administering precursor and non‑precursor forms together; it construed claim 19 to mean immunosuppressant given before the first hGAA dose. The PTAB found anticipation/obviousness for most challenged claims.
- The Federal Circuit (panel opinion by Lourie) reviewed anticipation and obviousness: it affirmed most PTAB holdings but reversed anticipation for claim 9 (because claim 9 requires exclusively precursor form) and reversed the obviousness finding for claim 19 (insufficient evidence that prophylactic immunosuppression was taught or predictable).
Issues
| Issue | Plaintiff's Argument (Duke) | Defendant's Argument (BioMarin / PTAB) | Held |
|---|---|---|---|
| Whether van Bree anticipates claims 1 and 20 (administration of CHO‑derived hGAA) | van Bree focuses on transgenic‑animal sources; it does not disclose administering CHO‑produced hGAA in therapeutically effective periodic amounts | van Bree teaches CHO as an alternative and equates post‑translational processing between sources, providing dosages/intervals applicable to CHO‑derived hGAA | Affirmed: substantial evidence supports anticipation of claims 1 and 20 under PTAB reading of van Bree |
| Proper construction of "precursor" in claim 9 and whether van Bree anticipates claim 9 | "Precursor" should be construed to require that the claimed hGAA is exclusively the precursor form produced in CHO cells; van Bree discloses mixtures, not exclusive precursor administration | PTAB construed precursor broadly (allows precursor + non‑precursor together) and found anticipation | Reversed: court holds correct construction is exclusive precursor form; van Bree does not disclose that, so claim 9 not anticipated |
| Obviousness of claim 9 (Reuser + Van Hove) under the correct construction | Under exclusive‑precursor construction, Reuser/Van Hove do not clearly teach administering exclusively precursor CHO‑produced hGAA; motivation/expectation and objective indicia must be considered | BioMarin points to disclosures/purification teaching and expert testimony that precursor would be used and thus combination renders claim obvious | Vacated and remanded: Board must apply the correct claim construction and reassess obviousness, motivation to combine, expectation of success, and objective indicia |
| Obviousness of claim 19 (prophylactic immunosuppressant) | Brady and other art do not teach giving immunosuppressant prophylactically prior to any hGAA admin; expert testimony was conclusory and lacked record support about incidence of antibody responses | PTAB/majority relied on expert testimony and common‑sense predictability (prophylaxis is a predictable variation to prevent immune response) | Reversed: insufficient substantial evidence to support obviousness of claim 19; expert testimony was conclusory and record lacked evidence of conditions (high incidence of neutralizing antibodies) making prophylaxis predictable |
Key Cases Cited
- KSR Int’l Co. v. Teleflex, 550 U.S. 398 (2007) (framework for obviousness and predictable variations)
- Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131 (2016) (IPR uses the broadest reasonable construction standard)
- Teva Pharm. USA, Inc. v. Sandoz, Inc., 135 S. Ct. 831 (2015) (subsidiary factual findings in claim construction reviewed for substantial evidence)
- In re Gleave, 560 F.3d 1331 (Fed. Cir. 2009) (enablement and anticipation: no actual reduction to practice required)
- In re Magnum Oil Tools Int’l, Ltd., 829 F.3d 1364 (Fed. Cir. 2016) (petitioner must provide reasoned, evidentiary support for obviousness)