PTAB

IPR2017-02131

Merck Sharp & Dohme Corp. v. Pfizer Inc.

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1. Case Identification

2. Patent Overview

  • Title: Immunogenic Compositions Comprising S. pneumoniae Glycoconjugates
  • Brief Description: The ’559 patent is directed to immunogenic compositions comprising a Streptococcus pneumoniae serotype 22F glycoconjugate. The patent distinguishes itself from the prior art by claiming specific ranges for the glycoconjugate's molecular weight (between 1,000 kDa and 12,500 kDa) and its polysaccharide-to-carrier protein ratio (between 0.4 and 2).

3. Grounds for Unpatentability

Ground 1: Obviousness of Core Vaccine Composition - Claims 1, 3-10, 16-19, 39, 41-42, and 45 are obvious over Merck 2011 in view of GSK 2008.

  • Prior Art Relied Upon: Merck 2011 (International Publication No. WO 2011/100151) and GSK 2008 (International Publication No. WO 09/000825).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of Merck 2011 and GSK 2008 teaches all limitations of independent claim 1. Merck 2011 was asserted to disclose an immunogenic composition with a serotype 22F glycoconjugate having a polysaccharide-to-protein ratio within the claimed range (0.4 to 2). While Merck 2011 did not specify the conjugate's molecular weight, Petitioner pointed to GSK 2008, which disclosed molecular weights for other pneumococcal conjugates in a multivalent vaccine that squarely overlap the claimed range (1,000 to 12,500 kDa). Petitioner contended the dependent claims merely add other well-known serotypes or features (e.g., CRM197 carrier protein, reductive amination chemistry) also taught by the prior art combination.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) developing a multivalent pneumococcal vaccine would combine the teachings of Merck 2011 and GSK 2008, as they represented state-of-the-art disclosures from leading vaccine competitors. GSK 2008 expressly taught adding a serotype 22F conjugate to a multivalent vaccine, providing a direct motivation to apply its teachings on conjugate characteristics like molecular weight to the 22F conjugate described in Merck 2011.
    • Expectation of Success: A POSITA would have a reasonable expectation of success because both references demonstrate that 22F conjugates are immunogenic. Furthermore, the routine conjugation chemistries disclosed in both references were known to produce conjugates with the desired and typical molecular weights and protein ratios, and achieving these parameters required only optimization of known variables.

Ground 2: Obviousness of Acetate Content - Claims 2, 40, and 43 are obvious over Merck 2011, GSK 2008, and PVP 2013.

  • Prior Art Relied Upon: Merck 2011 (WO 2011/100151), GSK 2008 (WO 09/000825), and PVP 2013 ("Pneumococcal Vaccine Polyvalent" revision from Japan's National Institute of Infectious Diseases).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground builds on the core combination of Merck 2011 and GSK 2008 by adding PVP 2013 to address claims related to acetate content. Petitioner argued that PVP 2013, which specifies requirements for a 23-valent pneumococcal polysaccharide vaccine, teaches a required O-acetate content for serotype 22F ("0.5 - 1.5" O-acetyl/polysaccharide unit molar ratio) that meets the limitation of "at least 0.1 mM acetate" in claim 2. Claims 40 and 43, which require preserving at least 60% of the native acetate content, were argued to be obvious for the same reason.
    • Motivation to Combine: A POSITA would have been motivated to consult PVP 2013 because it provided established quality standards for the very polysaccharides, including serotype 22F, being used in the conjugate vaccines of Merck 2011 and GSK 2008. Since O-acetylation was known to be important for the immunogenicity of the underlying polysaccharide, a POSITA would be motivated to preserve this feature in the final conjugate.
    • Expectation of Success: A POSITA would have expected to successfully preserve the claimed amount of acetate because the importance of O-acetyl groups was well-understood, and methods for preserving them during conjugation were known in the art.

Ground 3: Obviousness of Conjugate Characteristics - Claims 38 and 44 are obvious over Merck 2011, GSK 2008, and Hsieh 2000.

  • Prior Art Relied Upon: Merck 2011 (WO 2011/100151), GSK 2008 (WO 09/000825), and Hsieh 2000 ("Characterization of Saccharide-CRM197 Conjugate Vaccines," a 2000 article in Dev. Biol.).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground adds Hsieh 2000 to address claims directed to molecular size distribution (claim 38) and degree of conjugation (claim 44). Petitioner argued that Hsieh 2000, a paper authored by the Patent Owner, discloses that pneumococcal conjugates should have a high molecular weight fraction, teaching that a Kd value below 0.3 on a CL-4B column is desirable—rendering obvious the claim 38 limitation of "at least 30% of the glycoconjugates have a Kd below or equal to 0.3". For claim 44, Hsieh 2000 discloses a typical degree of conjugation for CRM197 conjugates in the range of 6-9, which falls entirely within the claimed range of 2-15.
    • Motivation to Combine: A POSITA would have considered Hsieh 2000 because it described standard, industry-accepted methods for characterizing the exact type of pneumococcal conjugate vaccines being developed. It provided a known framework and expected outcomes for key quality attributes.
    • Expectation of Success: Success would be expected because Hsieh 2000 establishes that the claimed values for molecular size distribution and degree of conjugation were standard and achievable results for routinely prepared pneumococcal conjugates.

4. Key Claim Construction Positions

  • "immunogenic": Petitioner argued that the term "immunogenic," recited in the preamble of claim 1, is a limiting feature of the claims and requires construction.
    • Proposed Construction: "elicits functional antibody against at least pneumococcus serotype 22F."
    • Rationale: Petitioner asserted that during prosecution of the ’559 patent, the Patent Owner overcame prior art rejections by repeatedly and explicitly arguing that its invention was distinguishable because it produced a serotype 22F conjugate that "elicited OPA titers," i.e., functional antibody. By relying on this specific feature to establish patentability, the Patent Owner imbued the term "immunogenic" with this narrower, limiting meaning for all claims.

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-10, 16-19, and 38-45 of the ’559 patent as unpatentable under 35 U.S.C. §103.