Pfizer, Inc. v. Chugai Pharmaceutical Co. Ltd.

1. Case Identification

• Case #: IPR2017-01357
• Patent #: Patent 7,332,289
• Filed: May 19, 2017
• Petitioner(s): Pfizer, Inc.
• Patent Owner(s): Chugai Pharmaceutical Co., Ltd.
• Challenged Claims: 1-8 and 13

2. Patent Overview

• Title: Method of Purifying Protein
• Brief Description: The ’289 patent describes a four-step method for removing DNA contaminants from an antibody-containing sample. The method involves (1) applying the sample to Protein A or G affinity chromatography, (2) eluting the antibody using an acidic aqueous solution of low conductivity and low molarity, (3) neutralizing the eluate to form particles, and (4) removing the particles to yield a purified product.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-8 and 13 under 35 U.S.C. §102(b) over a single prior art reference.

• Prior Art Relied Upon: Shadle (International Publication No. WO 95/22389).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Example IA of Shadle expressly or inherently discloses every limitation of the challenged claims. Independent claim 1’s four-step process was allegedly met as follows:
    • Step 1 (Affinity Chromatography): Shadle explicitly taught applying a sample containing a humanized monoclonal antibody to a ProSep A affinity column, a form of Protein A chromatography.
    • Step 2 (Elution): Shadle disclosed eluting the antibody with a 25 mM citrate buffer at pH 3.5. Petitioner asserted this met the claim limitation of an "acidic aqueous solution of low conductivity having a molarity of 100 mM or less," as 25 mM is well below the 100 mM threshold.
    • Step 3 (Neutralization): Shadle described neutralizing the eluate to pH 5.5 by adding a 1M Tris base buffer. This pH is within the claimed 4-8 range. Petitioner contended that the resulting molarity of the neutralized eluate was inherently less than 100 mM, providing a calculation showing it to be approximately 47.2 mM. Petitioner further argued that the formation of particles is an inherent and necessary result of performing this neutralization step under these specific low-molarity conditions, a fact supported by the ’289 patent’s own specification.
    • Step 4 (Removing Particles): Shadle explicitly disclosed filtering the neutralized sample through 0.1 micron and 0.2 micron filters. Petitioner asserted this step would inherently remove the particles formed in the preceding step.
  • Key Aspects: Petitioner argued that Shadle also anticipated dependent claims 2-8 and 13 by teaching, for example, an elution molarity of 25 mM (anticipating claim 2’s <50 mM limit), the use of citric acid (anticipating claim 3), a pH of 3.5 (anticipating claim 4’s 1.5-3.9 range), and filtration (anticipating claim 13).

Ground 2: Obviousness of Claims 1-8 and 13 under 35 U.S.C. §103 over a single prior art reference.

• Prior Art Relied Upon: Shadle (International Publication No. WO 95/22389).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner presented this ground as an alternative to anticipation, arguing that even if Shadle did not inherently disclose every limitation, it rendered the claims obvious. The mapping of Shadle’s teachings to the claim elements was identical to that presented for Ground 1. Petitioner argued that Shadle disclosed an antibody purification process that was, at a minimum, so close to the claimed invention that it would have been obvious for a person of ordinary skill in the art (POSA) to arrive at the claimed method.
  • Motivation to Combine: As a single-reference obviousness challenge, the motivation was to apply known purification principles to the process disclosed in Shadle. A POSA would have been motivated to perform the filtration step taught by Shadle not only to follow the disclosed process but also for the well-known purpose of removing particulates to protect downstream equipment, a standard practice in bioprocessing.
  • Expectation of Success: A POSA would have had a reasonable expectation of success in achieving the claimed method because Shadle described a complete and functional antibody purification protocol. The specific parameters recited in the ’289 patent’s claims were either directly taught by Shadle or represented standard, predictable optimizations of a known process, such as adjusting pH and filtering to remove aggregates. The result—removal of DNA contaminants—was an expected outcome of the disclosed purification steps.

4. Key Claim Construction Positions

• Petitioner argued for the broadest reasonable construction of all claim terms. The central construction dispute concerned the term "molarity."
• Petitioner contended that "molarity" as used in the claims (e.g., "molarity of 100 mM or less") refers only to the concentration of the buffer components (e.g., citrate) in the eluting solution itself, without including any contribution from the antibody protein or contaminant DNA present in the sample.
• This construction was asserted to be consistent with the patent specification, which defines the acidic solution in terms of its own properties (pH, conductivity, buffer concentration) before it is used to elute the sample. This interpretation was critical to Petitioner's argument that Shadle's 25 mM citrate buffer directly met the claim limitations.

5. Key Technical Contentions (Beyond Claim Construction)

• A central technical contention was the principle of inherency. Petitioner argued that several key claim limitations were inherently disclosed in Shadle's Example IA, even if not explicitly stated.
• Specifically, Petitioner asserted that the molarity of the neutralized eluate (calculated to be 47.2 mM) and the subsequent formation of particles were the necessary and inevitable consequences of following Shadle's disclosed recipe of neutralization with a Tris buffer.
• This argument was supported by calculations based on Shadle's data and, critically, by citing the ’289 patent’s own specification and its European prosecution history, where the Patent Owner allegedly conceded that such low-molarity neutralization conditions inherently produce particles.

6. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-8 and 13 of the ’289 patent as unpatentable under 35 U.S.C. §102(b) and/or §103(a).