GlaxoSmithKline Biologicals SA v. Pfenex Inc

1. Case Identification

• Case #: IPR2020-00962
• Patent #: 8,530,171
• Filed: May 27, 2020
• Petitioner(s): GlaxoSmithKline Biologicals SA
• Patent Owner(s): Pfenex Inc.
• Challenged Claims: 1-36

2. Patent Overview

• Title: High Level Expression of Recombinant Toxin Proteins
• Brief Description: The ’171 patent claims methods for producing a recombinant toxin protein, specifically CRM197, in a Pseudomonad bacterial host cell. The core limitation of the independent claim is achieving a yield of soluble or active CRM197 protein between about 0.2 grams per liter (g/L) and 12 g/L.

3. Grounds for Unpatentability

Ground 1: Obviousness over Blais and Squires - Claims 1-3, 7, 9, 11, 12, 15, 17, 21-24, 27, 29, 32, and 33 are obvious over Blais in view of Squires.

• Prior Art Relied Upon: Blais (WO 2011/042516) and Squires (a 2004 scientific article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Blais taught all elements of claim 1 except for the use of a Pseudomonad host. Blais disclosed a method for achieving "unprecedented" high-yield (over 3 g/L) periplasmic expression of soluble and active CRM197 in an E. coli host cell. Blais also expressly identified Pseudomonas as another suitable host for its improved process. Squires taught that P. fluorescens (a species of Pseudomonas) was a superior expression platform to E. coli, describing it as a "compelling alternative" that was "unusually well suited for high-level expression" of various recombinant proteins, achieving yields of 1-5 g/L.
  • Motivation to Combine: A POSITA would have been motivated to combine the teachings by taking the successful high-yield CRM197 expression construct from Blais and using it in the superior P. fluorescens host system taught by Squires. The goal would be to improve upon Blais's already successful CRM197 production, leveraging a host system known for its advantages in producing soluble, active proteins at high yields.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success. Blais had already achieved yields of over 3 g/L in E. coli, which falls within the claimed range. Squires demonstrated that P. fluorescens was equivalent or superior to E. coli for expressing other complex proteins at similar high yields (1-5 g/L). Therefore, expressing Blais's construct in Squires's superior host would be reasonably expected to produce CRM197 at a yield within the claimed range of 0.2 to 12 g/L.

Ground 2: Obviousness over Blais, Squires, and Ramseier I - Claims 4, 5, 8, 10, 16, 18-20, 25, 28, and 34-36 are obvious over Blais in view of Squires and Ramseier I.

• Prior Art Relied Upon: Blais (WO 2011/042516), Squires (a 2004 scientific article), and Ramseier I (a U.S. Patent Application published on October 30, 2008).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground built upon the combination of Blais and Squires to argue that additional dependent claim limitations were also obvious. Ramseier I was introduced to teach modifying the superior P. fluorescens host system to further enhance protein yield. Specifically, Ramseier I taught using protease-deficient P. fluorescens host strains to reduce degradation of the protein of interest, methods for codon optimization to reflect the codon bias of P. fluorescens, and the use of tag sequences to facilitate protein purification.
  • Motivation to Combine: The motivation was to further optimize the already promising combination of Blais's construct and Squires's host system. Petitioner argued that using protease-deficient strains, optimizing codons, and adding purification tags were all well-known and routine strategies for improving the yield and recovery of recombinant proteins. Ramseier I provided explicit guidance for applying these techniques in P. fluorescens.
  • Expectation of Success: Given that Blais itself used a protease-deficient E. coli strain and Ramseier I demonstrated improved protein yield in protease-deficient P. fluorescens strains, a POSITA would reasonably expect similar success when applying these routine optimization techniques to the production of CRM197.

• Additional Grounds: Petitioner asserted additional obviousness challenges, including that claims 13, 14, 30, and 31 are obvious over Blais, Squires, and Choi (a 2000 scientific article) for teaching specific induction conditions at high cell density. Petitioner also argued claims 6 and 26 are obvious over Blais, Squires, Ramseier I, Ramseier II (Application # 2006/0110747), and Maunsell (a 2006 scientific article) for teaching the use of host cells deficient in specific, named proteases.

4. Key Technical Contentions (Beyond Claim Construction)

• Patent Not Entitled to Priority Date: Petitioner dedicated significant argument to establishing that the ’171 patent was not entitled to its claimed priority dates of 2010. The core contention was that the priority applications failed to meet the written description and enablement requirements of 35 U.S.C. §112 for the full scope of the claimed yield range (0.2-12 g/L). Petitioner argued the priority documents disclosed only a single actual data point of 1.263 g/L and a prophetic example speculating about higher yields. This speculation, Petitioner contended, was contrary to the common knowledge that scaling up protein production was unpredictable and often resulted in reduced, not increased, yields. This argument was central to establishing that Blais (a 2010 PCT application) qualifies as prior art.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) would be inappropriate because the primary prior art references relied upon in the petition (Blais, Squires, Choi, Ramseier I, Ramseier II, and Maunsell) were not cited or considered by the Examiner during the original prosecution. Petitioner also noted it had previously filed a petition (IPR2020-00890) against the same patent, and this second petition was filed to incorporate the new argument concerning the ’171 patent’s priority date to resolve any potential dispute over the prior art status of the Blais reference.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-36 of Patent 8,530,171 as unpatentable.