PTAB

IPR2017-01489

Pfizer Inc v. Genentech Inc

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Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Method for making humanized antibodies
  • Brief Description: The ’213 patent describes methods for making humanized antibodies by grafting non-human complementarity-determining regions (CDRs) onto human antibody frameworks. The invention claims to maintain or improve antigen-binding affinity by making specific amino acid substitutions in the human framework regions (FRs), reverting them back to the corresponding non-human residue at specified locations.

3. Grounds for Unpatentability

Ground 1: Obviousness over Queen and the PDB Database - Claims 1-2, 4, 12, 25, 29, 62-67, 69, 71-81 are obvious over Queen 1989 or Queen 1990 in view of the PDB Database.

  • Prior Art Relied Upon: Queen 1989 (a 1989 scientific publication), Queen 1990 (WO 1990/07861), and the Protein Data Bank (PDB Database).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the Queen references provided a detailed "roadmap" for humanizing antibodies to reduce immunogenicity while preserving binding affinity. This roadmap involved replacing mouse FRs with human FRs and then selectively "back-mutating" certain human FR residues to the original mouse residue if they were likely to affect CDR conformation. Queen explicitly taught using computer modeling of known antibody crystal structures to identify these critical FR residues. Petitioner asserted that by applying the Queen methodology to the antibody structures publicly available in the PDB Database prior to 1991, a person of ordinary skill in the art (POSITA) would have readily identified many of the specific FR positions recited in the challenged claims as candidates for back-mutation because of their proximity to the CDRs.
    • Motivation to Combine: The motivation was inherent, as Queen explicitly instructed a POSITA to consult known antibody structures, such as those in the PDB Database, to implement its humanization method.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success because Queen's own teachings asserted that the method would produce humanized antibodies that retain high binding affinity and are substantially non-immunogenic.

Ground 2: Obviousness over Queen, PDB Database, and Tramontano - Claims 65, 75-77, and 79 are obvious over Queen 1989 or Queen 1990 and the PDB Database, further in view of Tramontano.

  • Prior Art Relied Upon: Queen 1989, Queen 1990, the PDB Database, and Tramontano (a 1990 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground focused on claims requiring substitution at heavy chain position 71H (and others). Petitioner contended that while the Queen/PDB combination would have identified residue 71H as a likely candidate for back-mutation due to its proximity to the CDRs, Tramontano provided a distinct and compelling reason for its selection. Tramontano specifically taught that the residue at position 71H is a major determinant of the conformation of the second heavy chain CDR (H2), directly impacting antigen binding.
    • Motivation to Combine: A POSITA following Queen’s general instructions to preserve CDR structure would have been motivated to consult specific literature like Tramontano, which analyzed the structural importance of individual FR residues. Tramontano's focused teaching confirmed and strengthened the rationale for substituting at position 71H.
    • Expectation of Success: The combined teachings provided an even greater expectation of success in preserving antibody function, as Tramontano explained the precise structural role of residue 71H, making its substitution a predictable, rather than experimental, step.

Ground 3: Obviousness over Queen, PDB Database, and Hudziak - Claims 30-31, 33, 42, and 60 are obvious over Queen 1989 or Queen 1990, the PDB Database, and Hudziak.

  • Prior Art Relied Upon: Queen 1989, Queen 1990, the PDB Database, and Hudziak (a 1989 journal article).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground addressed claims directed to humanized antibodies that bind the p185HER2 antigen, a known cancer target. Petitioner argued that Hudziak identified p185HER2 as a critical therapeutic target and disclosed a specific murine monoclonal antibody, 4D5, that was highly effective against HER2-expressing tumor cells. With 4D5 established as a promising therapeutic candidate, the logical and necessary next step for a POSITA was to humanize it for clinical use. The Queen references provided the well-established, state-of-the-art method for performing such humanization.
    • Motivation to Combine: The motivation was clear and powerful: to apply the known general method for creating safer, more effective antibodies (Queen) to a specific, highly promising anti-cancer antibody (4D5 from Hudziak) to develop a viable human therapy.
    • Expectation of Success: A POSITA would have reasonably expected that applying the established Queen roadmap to the proven 4D5 antibody would yield a humanized antibody retaining the therapeutic binding properties identified by Hudziak.

  • Additional Grounds: Petitioner asserted an additional obviousness challenge (Ground 5) based on Queen 1989, the PDB Database, and Kabat 1987. This ground argued that Kabat provided the consensus sequences that a POSITA, following Queen's motivation to make an antibody "more human," would have used as the human acceptor framework.

4. Key Claim Construction Positions

  • "a humanized antibody...": Petitioner argued for a broad construction, asserting the claims are not limited to any single, specific antibody but cover any antibody fragment that has been humanized. Even claim 30, which recites binding to p185HER2, was argued not to be limited to a particular antibody.
  • Markush Group of FR sites: Petitioner contended that the recited lists of amino acid residues for substitution in the independent claims should be treated as functional equivalents. Under the broadest reasonable interpretation, any of the recited residues could be substituted in any given antibody to fall within the claim scope.
  • "numbering system set forth in Kabat": Petitioner argued this phrase encompasses the amino acid residue positions and boundary designations for FR and CDR structures as defined in both the Kabat 1987 and Kabat 1991 reference databases.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-2, 4, 12, 25, 29-31, 33, 42, 60, 62-67, 69, and 71-81 of Patent 6,407,213 as unpatentable under 35 U.S.C. §103.