Sanofi Pasteur Inc v. Pfizer Inc

1. Case Identification

• Case #: IPR2018-00187
• Patent #: 9,492,559
• Filed: November 20, 2017
• Petitioner(s): Sanofi Pasteur Inc. and SK Chemicals Co., Ltd.
• Patent Owner(s): Pfizer, Inc.
• Challenged Claims: 1-45

2. Patent Overview

• Title: Immunogenic Compositions Comprising S. Pneumoniae Serotype 22F Glycoconjugates
• Brief Description: The ’559 patent relates to immunogenic compositions containing a glycoconjugate of Streptococcus pneumoniae serotype 22F polysaccharide and a carrier protein. The invention claims specific ranges for the glycoconjugate's molecular weight and the ratio of polysaccharide to carrier protein, intended to provide protection against emerging pneumococcal serotypes not covered by previous vaccines like Prevnar®13.

3. Grounds for Unpatentability

Ground I: Obviousness over GSK-711 and Merck-086 (Claims 1, 3-19, 23-37, 41-42, 45)

• Prior Art Relied Upon: GSK-711 (WO 2007/071711), Merck-086 (Application # 2011/0195086), and general knowledge in the art.
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that independent claim 1, which requires a serotype 22F glycoconjugate, a polysaccharide-to-protein ratio of 0.4-2, and a molecular weight (MW) of 1,000-12,500 kDa, was obvious. GSK-711 explicitly disclosed making 22F glycoconjugates and provided a working example with a ratio of 0.46, falling within the claimed range. While GSK-711 did not explicitly state the MW for its 22F conjugate, it disclosed ten other pneumococcal glycoconjugates made with the same CDAP chemistry that all had MWs within the 1,000-12,500 kDa range (specifically, 1,303-9,572 kDa). Merck-086 also taught making immunogenic 22F-CRM197 conjugates.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would have been motivated to produce 22F conjugates within the claimed MW range for practical reasons. A MW above 1,000 kDa was desirable to effectively separate the conjugate from smaller, unconjugated free polysaccharides, which are less immunogenic. A MW below 12,500 kDa was desirable to avoid purification difficulties (e.g., gelling, precipitation) and to remain within the analytical capabilities of the purification columns disclosed in GSK-711 (which had exclusion limits below 10,000 kDa).
  • Expectation of Success: A POSA would have had a high expectation of success. Standard conjugation chemistry (CDAP) was known to produce large, cross-linked lattice structures naturally falling in the multi-million Dalton range. Given that ten other serotypes in GSK-711 yielded conjugates in the claimed MW range using the same methods, it was highly predictable that the 22F conjugate would as well. A POSA could have used routine monitoring to quench the reaction to achieve the target size.

Ground II: Obviousness over GSK-711, Merck-086, Lees-2008, PVP-2013, and Pfizer-605 (Claims 2, 40, 43)

• Prior Art Relied Upon: GSK-711 (WO 2007/071711), Merck-086 (Application # 2011/0195086), Lees-2008 (a book chapter on conjugation chemistry), PVP-2013 (a Japanese regulatory document), and Pfizer-605 (Patent 7,955,605).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground focused on claims requiring a minimum O-acetylation level on the 22F conjugate (claim 2) and a minimum ratio of O-acetylation preservation compared to the starting polysaccharide (claims 40, 43). Lees-2008 taught that preserving O-acetyl groups was important for immunogenicity. PVP-2013, a Japanese regulatory standard, set a permitted O-acetylation level for 22F polysaccharides of 0.5-1.5 mM acetate, well above the claimed threshold of 0.1 mM.
  • Motivation to Combine: A POSA was motivated to preserve O-acetylation to maintain or enhance the vaccine's protective immunogenicity, a known desirable characteristic.
  • Expectation of Success: A POSA would have had a reasonable expectation of achieving the claimed O-acetylation levels. It was known that protic solvents (like water) used in the GSK-711 process could remove O-acetyl groups. Pfizer-605 taught an alternative method: using an aprotic solvent (DMSO) during reductive amination specifically to preserve O-acetyl groups. A POSA would have been motivated to apply the established process from Pfizer-605 to the 22F conjugate taught in GSK-711 with a high likelihood of successfully preserving the desired O-acetyl groups.

Ground IV: Obviousness over GSK-711, Merck-086, and Pfizer-605 (Claims 38, 39)

• Prior Art Relied Upon: GSK-711 (WO 2007/071711), Merck-086 (Application # 2011/0195086), and Pfizer-605 (Patent 7,955,605).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground addressed claim 38, requiring at least 30% of glycoconjugates to have a distribution coefficient (Kd) of ≤ 0.3 on a CL-4B column, and claim 39, requiring less than 50% free polysaccharide. Pfizer-605 explicitly described using a CL-4B column for characterization and taught a preferred value of about 70% of conjugates having a Kd ≤ 0.3, far exceeding the claimed 30% threshold. Pfizer-605 also taught a preferred free polysaccharide level below 20-25%. Furthermore, examples in GSK-711 disclosed free polysaccharide levels below 12%.
  • Motivation to Combine: These parameters (high percentage of large conjugates and low free polysaccharide) were standard quality control metrics for ensuring vaccine efficacy and consistency. A POSA would have been motivated to optimize the conjugation process to meet these well-established targets for any pneumococcal conjugate, including 22F.
  • Expectation of Success: A POSA would have had a reasonable expectation of success, as Pfizer-605 demonstrated that these parameters were achievable through routine optimization of conjugation and purification protocols.

• Additional Grounds: Petitioner asserted additional obviousness challenges, including that claims 20-22 (combination vaccines) are obvious over GSK-711, Merck-086, and GSK-531, and that claim 44 (degree of conjugation) is obvious over GSK-711, Merck-086, and Hsieh-2000, based on established practices of creating higher-valent vaccines and routine characterization of conjugates.

4. Key Claim Construction Positions

• "immunogenic": Petitioner argued that the term "immunogenic," appearing in the preamble of claim 1, should not be treated as a claim limitation under the broadest reasonable construction standard, as it only states an intended use or inherent property of a structurally complete invention.
• If the Board finds the term limiting, Petitioner proposed construing it as "capable of producing an immune response as determined by an immunogenic assay known in the art by a POSA including an OPA assay," based on assays used in the ’559 patent and standard dictionary definitions.

5. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-45 of the ’559 patent as unpatentable.