PTAB

IPR2022-00036

JSR Corp v. Cytiva BioProcess R&D Ab

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Chromatography Matrix and Ligand
  • Brief Description: The ’765 patent is directed to affinity chromatography matrices used for purifying antibodies. The technology involves a ligand based on the C domain of Staphylococcal protein A (SPA), which is engineered with a specific mutation (G29A) to enhance its stability in alkaline conditions, making it more resilient during "Cleaning-In-Place" (CIP) procedures.

3. Grounds for Unpatentability

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

  • Prior Art Relied Upon: Linhult (a 2004 journal article) and Abrahmsén (Patent 5,143,844).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Linhult described the essential elements of a chromatography matrix, including an SPA-based ligand coupled to a solid support. Linhult identified the asparagine-glycine sequence (Asn28-Gly29) as the "most sensitive amino acid sequence to alkaline conditions" and acknowledged that exchanging glycine at position 29 for alanine (a G29A mutation) had been done to avoid this instability. Linhult further taught that relying on the C domain's structure for creating stable ligands was an "obvious" decision. Abrahmsén was argued to supply the explicit teaching of a G29A mutation on the C domain.
    • Motivation to Combine: A POSITA would combine these references to solve the known problem of alkali instability identified in Linhult. Linhult provided the problem and general approach, while Abrahmsén provided the specific, known solution—performing a G29A mutation on the C domain. Abrahmsén expressly disclosed creating a recombinant DNA coding for "any of the E D A B C domains of [SPA]" where the glycine at position 29 is replaced by an alanine. This constituted combining known elements for a predictable outcome.
    • Expectation of Success: A POSITA would have a high expectation of success because Abrahmsén confirmed that the G29A mutation "would not interfere with folding [of SPA] or binding to [antibodies]."

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

  • Prior Art Relied Upon: Linhult (a 2004 journal article) and Hober (International Publication No. WO 03/080655).

  • Core Argument for this Ground:

    • Prior Art Mapping: As in Ground 1, Linhult established the foundational SPA-based chromatography matrix and the known instability of the Asn28-Gly29 sequence. Petitioner asserted that Hober provided the missing elements for all challenged claims. Hober taught 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 also disclosed numerous conventional features corresponding to the dependent claims, such as using linker segments to create multimers, terminal cysteine residues for coupling (sulfur atom), thioether bonds, and porous, spherical solid supports.
    • Motivation to Combine: A POSITA would be motivated to modify Linhult's system using the stability-enhancing G29A mutation taught by Hober. Hober provided data showing that ligands with this mutation retained at least 95% of their binding capacity after 5 hours in 0.5M NaOH, directly addressing the CIP stability problem. The desire to create a more robust, commercially viable chromatography matrix for industrial-scale purification would have driven the combination.
    • Expectation of Success: Success would be reasonably expected because the combination involved applying a known mutation (G29A) for its known purpose (alkali stability) to a known system (SPA-based matrix). Hober’s own data and teachings on the conventionality of the claimed techniques confirmed that the resulting matrix would function as predicted.

  • Additional Grounds: Petitioner asserted additional obviousness challenges based on the combination of Linhult in view of Abrahmsén and Hober, as well as Abrahmsén in view of Hober, relying on similar theories that a POSITA would have routinely combined these known elements to create an alkali-stable chromatography matrix with predictable properties.

4. Key Claim Construction Positions

  • Petitioner argued that no terms required explicit construction. However, for the purposes of the petition, it adopted the Patent Owner's implicit construction from related district court litigation for the term "the ligand comprising at least two polypeptides."
  • This term was construed to mean a multimeric ligand (e.g., a dimer or tetramer) composed of multiple polypeptide monomers. This construction was central to Petitioner's arguments regarding how the prior art taught multimerization of SPA domains to create effective affinity ligands.

5. Arguments Regarding Discretionary Denial

  • §314(a) (Fintiv Factors): Petitioner argued against discretionary denial under Fintiv, stating that the parallel district court litigation was in a very early stage. Key events, including the Markman hearing and trial, were scheduled for well after the statutory deadline for a Final Written Decision (FWD) in the IPR. Petitioner planned to seek a stay of the litigation upon institution, further weighing against denial.
  • §325(d): Petitioner contended that denial under §325(d) would be inappropriate because the examiner did not consider the primary prior art or arguments presented in the petition. Specifically, neither Linhult nor Abrahmsén were considered during prosecution. Although Hober was disclosed in an IDS, the examiner never relied on it in any rejection, and its most relevant teachings—such as applying the G29A mutation to the C domain—were never substantively evaluated by the Office.

6. Relief Requested

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