PTAB

IPR2018-01229

Merck Sharp & Dohme Corp v. GlaxoSmithKline Biologicals SA

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Process for Conjugating Bacterial Saccharides
  • Brief Description: The ’645 patent discloses a process for creating vaccine components by conjugating a specific bacterial saccharide (S. pneumoniae capsular saccharide 23F) to a carrier protein. The process involves using a low concentration of periodate for saccharide activation to purportedly reduce degradation, referred to as the "sizing effect."

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-11 by WO'376

  • Prior Art Relied Upon: WO'376 (PCT Application # WO 2004/043376A2).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that WO'376 anticipates every limitation of claims 1-11. Specifically, Example 4 of WO'376 was asserted to disclose the complete claimed process for the same saccharide (23F), including: (a) reacting the saccharide with 0.31 molar equivalents (MEq) of periodate, which falls within the claimed range of 0.001-0.7 MEq; (b) performing the reaction in a 100 mM phosphate buffer, meeting the claimed 1-100 mM concentration range; (c) mixing the activated saccharide with a carrier protein (pneumolysin); and (d) reacting the mixture with a reducing agent (sodium cyanoborohydride) to form the conjugate. Petitioner contended that the preamble phrase "reducing the sizing effect" is an inherent result of using the low periodate concentration disclosed in WO'376 and is therefore also anticipated.
    • Key Aspects: The core of the anticipation argument rested on a direct mapping of Example 4 in WO'376 to the steps of independent claim 1 and the specific limitations of dependent claims 2-11.

Ground 2: Obviousness of Claims 1-11 over WO'376 in view of Frasch and Lees

  • Prior Art Relied Upon: WO'376, Frasch (a 2009 article in Vaccine), and Lees (a 2008 chapter in Pneumococcal Vaccines).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner argued that even if not anticipated, the claims are obvious. WO'376 provided the foundational process. Frasch and Lees, representing the common knowledge of a person of ordinary skill in the art (POSITA), taught that periodate activation was a standard but potentially harsh method that could cleave chemical bonds and reduce saccharide size (the "sizing effect"). Both references explained that this degradation could be controlled or minimized by using milder reaction conditions, including lower concentrations of periodate, to preserve the saccharide's structure and immunogenicity.
    • Motivation to Combine: A POSITA implementing the conjugation process disclosed in WO'376 would be motivated to consult general knowledge references like Frasch and Lees to understand and optimize the reaction. These references would explicitly teach the known trade-off between saccharide activation and degradation and would direct a POSITA to use lower periodate concentrations—such as the 0.31 MEq level already disclosed in WO'376—to achieve the desired goal of reducing the sizing effect. The motivation was to preserve important epitopes for immunogenicity, a known concern addressed by Frasch and Lees.
    • Expectation of Success: The combination of references would have yielded a reasonable expectation of success. The underlying chemical principles were well-understood: less periodate results in less oxidation and bond cleavage. Therefore, a POSITA would have fully expected that applying the process in WO'376 would result in less saccharide degradation compared to using higher periodate concentrations, thereby achieving the claimed "reducing the sizing effect."

  • Additional Grounds: Petitioner asserted further obviousness challenges against dependent claims 4, 5, 6, and 10, adding GSK 2009 PCT and Prevnar to the primary combination to teach specific molecular weights and carrier proteins.

4. Key Claim Construction Positions

  • "reducing the sizing effect": Petitioner argued this term, located in the preamble of claim 1, is a non-limiting statement of intended purpose. The argument was that the body of the claim fully recites the process steps, and this phrase merely describes the outcome without imposing any additional limitations on how the steps are performed. Alternatively, if the term were found to be limiting, Petitioner proposed its plain and ordinary meaning: "decreasing the reduction in the size of the bacterial saccharide."
  • "molar equivalents": Petitioner proposed this term be construed as "the ratio of moles of periodate to the moles of saccharide repeating unit." This construction was argued to be critical for the mathematical calculations used to demonstrate that the 0.31 MEq of periodate disclosed in WO'376 falls squarely within the claimed range.

5. Relief Requested

  • Petitioner requested institution of an inter partes review (IPR) and cancellation of claims 1-11 of the ’645 patent as unpatentable.