PTAB

IPR2022-00036

JSR Corp v. Cytiva BioProcess R&D Ab

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1. Case Identification

2. Patent Overview

  • Title: Chromatography matrix for antibody separation
  • Brief Description: The ’765 patent discloses an affinity chromatography matrix for purifying antibodies. The matrix comprises a solid support coupled to a ligand based on the C domain of Staphylococcal protein A (SPA), where the protein sequence has been engineered with a specific G29A mutation (glycine at position 29 is replaced with alanine) to improve stability.

3. Grounds for Unpatentability

Ground 1: Claims 1-4, 12, 14-17, and 25 are obvious over Linhult in view of Abrahmsén.

  • Prior Art Relied Upon: Linhult (a 2004 journal article on improving Protein A tolerance) and Abrahmsén (Patent 5,143,844).
  • Core Argument:
    • Prior Art Mapping: Petitioner argued that Linhult taught all elements of a basic SPA-based chromatography matrix, including the solid support and ligand. Linhult identified the asparagine-glycine (Asn28-Gly29) sequence as the most sensitive to alkaline conditions used in cleaning procedures and acknowledged that a G29A mutation was a known method to "avoid" this instability. While Linhult described the choice to use the C domain as "obvious," it did not explicitly disclose a C-domain with a G29A mutation. Abrahmsén was argued to supply this missing element by expressly disclosing a recombinant DNA sequence coding for "any of the E D A B C domains of [SPA]" where the Asn28-Gly29 sequence is replaced by a G29A mutation.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine these references to solve a known problem. Linhult established the desirability of improving the alkali-stability of SPA C-domain ligands, and Abrahmsén provided the explicit, known solution of a G29A mutation for the C domain.
    • Expectation of Success: A POSA would have a high expectation of success because Abrahmsén confirmed the G29A mutation would not interfere with the protein's folding or its ability to bind to antibodies, ensuring the resulting matrix would function as intended.

Ground 2: Claims 1-7, 10-20, and 23-26 are obvious over Linhult in view of Hober.

  • Prior Art Relied Upon: Linhult (a 2004 journal article) and Hober (WO 03/080655).
  • Core Argument:
    • Prior Art Mapping: This argument paralleled Ground 1 but substituted Hober for Abrahmsén. Hober was asserted to teach that the G29A mutation is "advantageous for structural stability reasons" and can be performed on any of the five SPA domains, including the C domain. Hober further taught conventional features relevant to dependent claims, such as using linkers to connect monomer units, thioether bonds for coupling, and porous, spherical solid supports. Hober also provided data showing that ligands with C-domain-specific features retained over 95% of their binding capacity after alkaline treatment.
    • Motivation to Combine: A POSA would combine Linhult's teaching of an alkali-stable C-domain matrix with Hober's explicit disclosure of using a G29A mutation on the C domain to achieve that stability. Hober also provided the necessary teachings for conventional, performance-enhancing features like porous supports and linker segments.
    • Expectation of Success: A POSA would reasonably expect success, as Hober provided experimental data confirming that ligands with the key mutations retained high binding capacity after prolonged exposure to alkaline conditions, demonstrating the viability of the combination.

Ground 3: Claims 1-7, 10-20, and 23-26 are obvious over Abrahmsén in view of Hober.

  • Prior Art Relied Upon: Abrahmsén (Patent 5,143,844) and Hober (WO 03/080655).

  • Core Argument:

    • Prior Art Mapping: Petitioner asserted that while Abrahmsén taught the key C-domain G29A mutation, its disclosure was in the context of a fusion-protein strategy. Hober provided the necessary context of using SPA-based ligands in affinity chromatography, describing it as the "most widely-used affinity medium for isolation of monoclonal antibodies." Hober also taught the use of multimeric ligands, solid supports (e.g., agarose beads), and coupling chemistries.
    • Motivation to Combine: A POSA would be motivated to apply Abrahmsén's specific, stability-enhancing mutation to the general affinity chromatography matrix platform described by Hober. Petitioner argued that the teachings of Abrahmsén were widely acknowledged and applied in the affinity chromatography field, making this combination a matter of applying a known improvement to a standard system.
    • Expectation of Success: Success would be expected because the combination involved implementing a known, stability-conferring mutation (from Abrahmsén) into a well-understood and conventional product format (from Hober) to achieve a predictable improvement in performance.

  • Additional Grounds: Petitioner asserted an additional obviousness challenge against claims 1-7, 10-20, and 23-26 based on the combination of Linhult in view of Abrahmsén and Hober, arguing the references collectively rendered the claims obvious.

4. Key Claim Construction Positions

  • Petitioner contended that no terms required explicit construction but proceeded with its challenge based on an implicit construction of the term "the ligand comprising at least two polypeptides."
  • Based on the Patent Owner's infringement contentions in a related district court case, Petitioner argued this term should be understood to mean a multimeric ligand (e.g., a dimer or tetramer) composed of multiple individual polypeptide monomers. This construction was foundational to arguments that the prior art's teaching of multimerization rendered the claims obvious.

5. Key Technical Contentions (Beyond Claim Construction)

  • A central technical contention was that several claim limitations were inherent properties of the proposed prior art combination.
  • Petitioner argued that retaining at least 95% of original binding capacity after 5 hours in 0.5M NaOH (claims 3 and 16) was an inherent result of creating a chromatography matrix with a C(G29A)-based SPA ligand. This was supported by data in the ’765 patent itself, which allegedly showed the wild-type C domain already possessed this property.
  • Similarly, the capability of binding to the Fab part of an antibody (claims 4 and 17) was argued to be an inherent property of a C(G29A)-based ligand, or, alternatively, was explicitly taught by Linhult.

6. Arguments Regarding Discretionary Denial

  • Petitioner argued against discretionary denial under both §314(a) (Fintiv factors) and §325(d).
  • Under §314(a): Petitioner asserted that the Fintiv factors favored institution because a stay in the co-pending district court litigation was likely, the trial date was over two years away, and significant investment in the litigation had not yet occurred.
  • Under §325(d): Petitioner argued that the same or substantially the same art and arguments were not previously presented to the Office. It was noted that neither Linhult nor Abrahmsén were considered during prosecution, and while Hober was cited in an Information Disclosure Statement (IDS), it was never substantively relied upon in any rejection. Petitioner contended the examiner erred by not considering the clear teachings in these references regarding the well-known G29A mutation.

7. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-7, 10-20, and 23-26 of the ’765 patent as unpatentable.