PTAB

IPR2018-01219

Pfizer Inc v. Hoffman La Roche Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Heavy Chain Mutant Leading to Improved Immunoglobulin Production
  • Brief Description: The ’225 patent relates to specific nucleic acid sequences encoding the C-terminal glycine-lysine dipeptide of an immunoglobulin heavy chain. The patent also claims methods for improving immunoglobulin expression by using these modified sequences, purportedly to address issues like unwanted splicing that can lead to aberrant by-products.

3. Grounds for Unpatentability

Petitioner asserted that the challenged claims are unpatentable as anticipated under 35 U.S.C. §102 and, in the alternative, obvious under 35 U.S.C. §103. The core of the petition is that the claimed nucleic acid sequences are merely the few possible alternatives to the wild-type sequence and were widely disclosed in prior art related to routine codon optimization for improving antibody expression.

Ground 1: Anticipation and/or Obviousness over Denney

  • Prior Art Relied Upon: Denney (Application # 2002/0160006).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Denney expressly disclosed every limitation of the challenged claims. Denney described nucleic acid and amino acid sequences for IgG3 and IgG4 immunoglobulins derived from B-cell lymphoma cells. Specifically, Denney’s SEQ ID NOs: 44 and 46 disclosed nucleic acids encoding the C-terminal part of an IgG heavy chain and used the sequence "ggcaag" to encode the glycine-lysine dipeptide, which is one of the specific sequences recited in claim 1 of the ’225 patent. Petitioner asserted that Denney’s corresponding amino acid sequences (SEQ ID NOs: 45 and 47) were identical to SEQ ID NOs: 7 and 8 of the ’225 patent, thereby anticipating claim 2. Denney also explicitly disclosed the use of plasmids (claim 10), transfection into isolated mammalian cells (claim 11), including the use of CHO cells (claim 12), and a standard method for expression and recovery (claim 20).
    • Motivation to Combine (for §103 grounds): As an alternative to anticipation, Petitioner argued the claims were obvious. Denney’s stated goal was to use codon optimization to achieve "improved methods for the amplification and expression of recombinant genes in cells." This express teaching provided a clear motivation for a person of ordinary skill in the art (POSA) to apply its methods.
    • Expectation of Success (for §103 grounds): A POSA would have had a reasonable expectation of success because Denney reported successful high-level expression using codon-optimized sequences in mammalian cells and cited other successful examples of the technique.

Ground 2: Anticipation and/or Obviousness over Loetscher

  • Prior Art Relied Upon: Loetscher (WO 2007/068429).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner contended Loetscher anticipated the challenged claims by describing an anti-amyloid beta human IgG1 antibody ("Antibody A") with sequences optimized for recombinant production. Loetscher’s SEQ ID NO:23, a nucleic acid encoding the heavy chain of Antibody A, disclosed the sequence "ggcaaa" to encode the C-terminal glycine-lysine dipeptide, another sequence explicitly claimed in claim 1. The corresponding amino acid sequence in Loetscher (SEQ ID NO:6) was shown to be identical to SEQ ID NO:5 of the ’225 patent, anticipating claim 2. Loetscher further disclosed the use of plasmids to transfect mammalian CHO cells and detailed methods for cultivation and recovery, anticipating claims 10-12 and 20.
    • Motivation to Combine (for §103 grounds): For the alternative obviousness ground, Petitioner argued that Loetscher’s explicit statement that its nucleic acid sequence was "optimized for recombinant production" would have motivated a POSA to use its disclosed sequences and methods to improve protein expression.
    • Expectation of Success (for §103 grounds): A POSA would reasonably expect success, as Loetscher provided a complete, optimized sequence and detailed protocols for expressing and purifying the resulting antibody, demonstrating a proven method.

Ground 3: Anticipation and/or Obviousness over Rosenthal

  • Prior Art Relied Upon: Rosenthal (Application # 2006/0292152).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued Rosenthal anticipated the claims by disclosing a human IgG2 monoclonal antibody ("6G") against amyloid beta. Rosenthal’s nucleic acid SEQ ID NO:13, encoding the 6G heavy chain, used the codon pair "ggaaag" to encode the C-terminal glycine-lysine dipeptide, a sequence recited in claim 1. The corresponding amino acid sequence (SEQ ID NO:11) was identical to SEQ ID NO:6 of the ’225 patent, anticipating claim 2. Rosenthal also disclosed cloning the heavy chain into mammalian expression vectors (claim 10), transfecting them into isolated HEK 293 cells (claim 11), noting that CHO cells were also suitable hosts (claim 12), and using standard methods for protein expression and purification (claim 20).
    • Motivation to Combine (for §103 grounds): For the alternative obviousness argument, Petitioner pointed to Rosenthal’s teaching of using codon optimization and selecting host cells "capable of over-expressing" the protein of interest as a clear motivation for a POSA seeking to improve immunoglobulin expression.
    • Expectation of Success (for §103 grounds): The detailed examples in Rosenthal, which described the successful expression and purification of the 6G antibody from transfected mammalian cells, would have provided a POSA with a strong expectation of success.

4. Key Claim Construction Positions

  • Petitioner argued that the preamble of independent method claim 20, "A method for improving the expression of an immunoglobulin in a mammalian cell," is not a claim limitation under the broadest reasonable interpretation standard. Petitioner contended the preamble merely stated the intended purpose of the method, while the body of the claim described a structurally complete invention (transfecting, cultivating, and recovering).
  • In the alternative, if the Board were to determine the preamble is limiting, Petitioner proposed it should be construed to require "codon modification." This was based on the argument that codon modification is the only technique for "improving expression" that is actually described and enabled by the ’225 patent’s specification.

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-5, 10-12, and 20 of the ’225 patent as unpatentable.