PTAB

IPR2013-00535

BioMarin Pharmaceutical Inc v. Duke University

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Method of Treating Glycogen Storage Disease Type II
  • Brief Description: The ’712 patent relates to methods of treating Pompe disease (glycogen storage disease type II) by administering human acid α-glucosidase (hGAA) that has been produced in Chinese hamster ovary (CHO) cell cultures.

3. Grounds for Unpatentability

Ground 1: Anticipation - Claims 1-4, 8, 9, 15 & 20 are anticipated by Synpac

  • Prior Art Relied Upon: Synpac (a June 1999 press release).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Synpac, a press release issued before the patent’s priority date, disclosed all limitations of the challenged claims. Synpac announced the start of clinical trials to treat human patients with Pompe disease by administering recombinant hGAA (rhGAA) produced in CHO cells. Petitioner asserted this taught treating the claimed disease (claim 1), the use of recombinant enzyme (claim 8), and the CHO cell production method. Synpac’s mention of infantile patients (claim 2) and plans to treat juveniles and adults (claims 3-4), along with the inherent need for life-long, periodic therapy, allegedly met further limitations.
    • Key Aspects: Petitioner contended that under Federal Circuit precedent (In re Montgomery), a detailed description of an initiated clinical trial protocol anticipates a method claim reciting that protocol, regardless of whether trial results are disclosed.

Ground 2: Anticipation/Obviousness - Claims 1-9, 15 & 20 are anticipated by, or alternatively obvious over, Reuser ’771

  • Prior Art Relied Upon: Reuser ’771 (WO 97/05771).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Reuser ’771, which primarily discloses producing hGAA in the milk of transgenic mammals for enzyme replacement therapy (ERT), also explicitly identifies expression in CHO cells as a known alternative. Reuser ’771 allegedly taught treating lysosomal storage disease (claim 1), using a recombinant precursor form of hGAA with the correct molecular weight (claims 8-9), and intravenous administration (claim 15). It also disclosed dosage ranges that anticipated or rendered obvious the dosages in claims 5-7. Petitioner argued that periodic administration was an inherent and well-understood requirement for any ERT.
    • Motivation to Combine (for §103 alternative): In the alternative obviousness argument, Petitioner asserted that because Reuser ’771 teaches that GAA from CHO cells and transgenic milk are functionally equivalent, it would have been obvious for a person of ordinary skill in the art (POSITA) to apply Reuser ’771’s detailed teachings on dosages and enzyme characteristics to the known CHO production method.

Ground 3: Obviousness over Synpac in view of Reuser ’771 and other art

  • Prior Art Relied Upon: Synpac, Reuser ’771, Kikuchi (a 1998 journal article), van der Ploeg (a 1988 article), Barton (a 1991 article), and Grabowski (a 1998 article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground asserted that even if not anticipated, the claims were obvious over combinations of the prior art. Synpac provided the foundational method of treating Pompe disease with CHO-produced rhGAA. Reuser ’771 provided extensive detail on the preferred precursor form of the enzyme, effective dosages, and administration protocols. For dependent claims, Petitioner argued that determining specific dosages (claims 5-7) was a routine optimization step, informed by animal studies like those in Kikuchi. Similarly, administration schedules like weekly or bimonthly infusions (claims 11-12) were standard practice for other ERTs, as shown in van der Ploeg and Barton. The use of immunosuppressants (claims 18-19) was a known technique to manage immune responses to therapeutic proteins, as taught by Grabowski.
    • Motivation to Combine: A POSITA would combine Synpac’s disclosure of a clinical trial with the detailed teachings of Reuser ’771 and other references to implement and optimize the therapy. The motivation stemmed from the clear, unmet need for a Pompe disease treatment and the well-established "roadmap" in the prior art for developing ERTs, where CHO cell production was the industry standard.
    • Expectation of Success: Petitioner argued there was a high expectation of success. The prior art, including statements from the inventor’s own research group, demonstrated that CHO-produced hGAA was effective in preclinical models and that the technology for its production was mature. The path to a successful therapy was predictable and involved only routine experimentation.
  • Additional Grounds: Petitioner asserted numerous additional obviousness challenges, primarily relying on Reuser ’771 as the base reference combined with Synpac, Fuller (a 1995 journal article), and/or Van Hove (a 1997 journal article) to reinforce the desirability and feasibility of using CHO cells as the production source.

4. Key Claim Construction Positions

  • “in conjunction with” (claim 18): Petitioner argued this term, as defined in the specification, means the immunosuppressant is administered at about the same time as the GAA.
  • “prior to any administration” (claim 19): Citing the specification’s teaching to begin the regimen prior to the first GAA administration to minimize antibody production, Petitioner proposed this phrase means “prior to the first administration.”

5. Key Technical Contentions (Beyond Claim Construction)

  • Product-by-Process Doctrine: A central contention was that the claim limitation “wherein the human acid α-glucosidase was produced in chinese hamster ovary cell cultures” is a product-by-process limitation. Petitioner argued this limitation does not confer patentability unless the resulting product is unobviously different from prior art products. Therefore, if hGAA produced in CHO cells is the same as or obvious from hGAA produced by other methods (e.g., in the milk of transgenic mammals, as in Reuser ’771), the claims are unpatentable regardless of the production method recited.

6. Relief Requested

  • Petitioner requested institution of an inter partes review and cancellation of claims 1-9, 11-12, 15, and 18-21 of the ’712 patent as unpatentable.