PTAB

IPR2017-01512

CSL Behring GmbH v. Shire ViroPharma Inc

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Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Method for Treating Hereditary Angioedema
  • Brief Description: The ’111 patent discloses methods for treating hereditary angioedema (HAE) by subcutaneously administering a composition comprising a C1 esterase inhibitor (C1-INH). The claimed method requires administering the C1-INH at a concentration of at least 400U/mL and a dose of at least 1000U to achieve and maintain a therapeutic blood level of at least 0.4U/mL.

3. Grounds for Unpatentability

Ground 1: Claims 1-18 are obvious over Schranz in view of Gatlin, Pharming, and Levi.

  • Prior Art Relied Upon: Schranz (a 2012 poster presentation), Gatlin (a 1999 textbook chapter on parenteral formulations), Pharming (WO 2007/073186), Levi (a 2006 journal article), the Cinryze® Label, and Bock (a 1986 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Schranz, the closest prior art, disclosed every limitation of independent claim 1 except for the specific C1-INH concentration. Schranz taught the successful subcutaneous (sc) administration of a 2000U dose of C1-INH (Cinryze®) at a 333U/mL concentration. This administration regimen was shown to achieve the claimed therapeutic plasma level of over 0.4U/mL in HAE patients. The Cinryze® Label and Bock were cited to establish the claimed buffer, pH, and amino acid sequence identity.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine Schranz with the teachings of Gatlin. Gatlin taught that sc injections should target low volumes (e.g., 0.5 to 2.0 mL) to reduce injection pain, minimize tissue damage, and improve patient compliance. Schranz's 333U/mL formulation required a large total injection volume of 6mL (administered as four separate 1.5mL injections). A POSA would thus be motivated to increase the concentration from 333U/mL to the claimed ≥400U/mL to reduce the total injection volume and number of injections, enhancing patient convenience.
    • Expectation of Success: A POSA would have a reasonable expectation of success. The required ~17% increase in concentration represented a routine optimization, not a significant technical hurdle. Petitioner argued that the known physical and chemical characteristics of C1-INH (e.g., viscosity, stability) were not barriers to creating a more concentrated formula. This expectation would be reinforced by Pharming, which taught intramuscular C1-INH formulations with a median concentration of ~455U/mL, reassuring a POSA that such concentrations were achievable and stable.

Ground 2: Claims 1-18 are obvious over Jiang in view of Gatlin, Pharming, Zuraw, and Levi.

  • Prior Art Relied Upon: Jiang (a 2010 journal article), Gatlin (a 1999 textbook chapter), Pharming (WO 2007/073186), Zuraw (a 2010 journal article), and Levi (a 2006 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that Jiang established the fundamental viability and safety of sc C1-INH administration. Jiang demonstrated that sc infusion of C1-INH at a 100U/mL concentration in an animal model (pigs) achieved plasma levels comparable to those from effective intravenous (IV) administration. As the Office's primary reference during prosecution, Jiang taught all elements of the claims except the high concentration.
    • Motivation to Combine: The motivation to increase the concentration of Jiang's formulation was driven by the same principles articulated in Gatlin. The study in Jiang used large injection volumes (8-11.5mL) to deliver therapeutic doses. A POSA, guided by Gatlin's preference for smaller sc injection volumes (~2mL), would combine these teachings to increase the concentration of Jiang's 100U/mL formulation to ≥400U/mL. This modification would allow the same effective dose to be administered in a significantly smaller, more patient-friendly volume.
    • Expectation of Success: A POSA would have a reasonable expectation of success in concentrating the formulation and achieving the claimed therapeutic effect. Concentrating protein formulations was a well-known technique in the art. The successful sc administration in Jiang, combined with data from Levi showing that IV administration routinely achieves the target plasma levels (>0.4U/mL), provided a strong scientific basis to expect that a more concentrated sc formulation would also be safe and effective.

4. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-18 of the ’111 patent as unpatentable under 35 U.S.C. §103.