Pfizer Inc v. Genentech Inc

1. Case Identification

• Case #: To Be Assigned
• Patent #: 9,249,218
• Filed: August 29, 2017
• Petitioner(s): Pfizer, Inc.
• Patent Owner(s): Genentech, Inc.
• Challenged Claims: 1, 5-7

2. Patent Overview

• Title: Protein Purification
• Brief Description: The ’218 patent claims therapeutic compositions comprising the anti-HER2 antibody humMAb4D5-8 (trastuzumab) and a specified low amount of acidic variants. The claims are directed to a composition with less than about 25% acidic variants, which are predominantly deamidated variants of the antibody.

3. Grounds for Unpatentability

Ground 1: Claims 1, 5-7 are invalid under 35 U.S.C. §102(b) as anticipated by, or alternatively under §103 as obvious over, Andya.

• Prior Art Relied Upon: Andya (International Publication No. WO 97/04801).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Andya, a publication by the Patent Owner, explicitly discloses all limitations of the challenged claims. Andya describes stable, lyophilized formulations of the specific anti-HER2 antibody humMAb4D5-8 for therapeutic use. It teaches that the antibody degrades via deamidation at asparagine residue 30 (Asn30) of the light chain, which forms acidic variants. Critically, Petitioner asserted that figures in Andya show compositions with 78-82% native protein, meaning the total amount of degraded variants (including acidic variants) is necessarily 18-22%, which is below the claimed threshold of "less than about 25%." Andya further discloses that the compositions are provided in lyophilized and reconstituted aqueous forms (claims 6-7) and inherently possess the specific amino acid sequences of humMAb4D5-8 (claim 5).
  • Motivation to Combine (for §103 grounds): For the alternative obviousness ground, Petitioner contended that a person of ordinary skill in the art (POSITA) reading Andya would be motivated to produce the claimed composition. The motivation arises from the well-established goal of creating a stable, pure, and effective therapeutic antibody product with minimal degradation, a goal explicitly addressed by Andya itself.
  • Expectation of Success (for §103 grounds): A POSITA would have had a high expectation of success, as Andya provides detailed descriptions of the antibody, its degradation pathways, and formulation strategies, rendering the achievement of the claimed purity level a matter of routine optimization.

Ground 2: Claims 1, 5-7 are obvious over Waterside.

• Prior Art Relied Upon: Waterside (slides from a 1996 conference presentation by a Genentech scientist).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Waterside renders the claims obvious because it discloses compositions of rhuMAb HER2 (understood by a POSITA to be humMAb4D5-8) purified using cation-exchange chromatography. The presentation includes chromatograms that separate the native antibody from its acidic variants. Based on analysis by its expert, Petitioner argued the chromatograms inherently show the acidic variants comprise less than 25% of the total composition (calculated as 14-24%). Waterside further confirms that the primary acidic variant (peak 1) is deamidated at Asn30 and converted to aspartate. Thus, Waterside taught a composition containing the specific antibody, a mixture of acidic variants below the 25% threshold, and the specific deamidation that characterizes those variants.
  • Motivation to Combine: This is a single-reference ground. Petitioner argued a POSITA would be motivated to arrive at the claimed composition based on Waterside's disclosure that the antibody was in Phase III clinical trials and produced at a 12,000 L scale. This context indicates the antibody was intended for therapeutic use, providing a clear motivation to formulate it with acceptable carriers and ensure high purity by limiting acidic variants, which were known contaminants.
  • Expectation of Success: A POSITA would have had a high expectation of success because Waterside details the exact chromatographic techniques used to separate and characterize the acidic variants, demonstrating that achieving the claimed purity was a known and predictable outcome.

Ground 3: Claims 1, 5-7 are obvious over Harris.

• Prior Art Relied Upon: Harris (a 1995 journal article by a Genentech scientist).
• Core Argument for this Ground:
  • Prior Art Mapping: The argument against Harris closely mirrors the one against Waterside. Petitioner contended Harris, which describes purifying proteins from mammalian cell culture, discloses running "three lots of rhuMAb HER2" through cation-exchange chromatography. The publication includes chromatograms nearly identical to those in Waterside, from which Petitioner’s expert calculated the acidic variants made up 13-24% of the total protein, well under the 25% claimed limit. Harris explicitly identifies the acidic peaks as being "deamidated at Asn30 in one light chain." A POSITA would have understood the rhuMAb HER2 in Harris was humMAb4D5-8, as it was the only such variant in clinical trials at the time.
  • Motivation to Combine: A POSITA reviewing Harris, an article focused on protein purification and analysis of variants, would be motivated to prepare a final therapeutic product with a low, controlled level of such variants. The motivation is inherent to the field of biopharmaceutical development: to maximize purity and stability for safety and efficacy.
  • Expectation of Success: The expectation of success was high because Harris, like Waterside, provided a clear road map, showing that known chromatographic methods successfully separated and quantified the very acidic variants recited in the claims to a level within the claimed range.

4. Key Claim Construction Positions

• "A therapeutic composition" (Preamble): Petitioner argued this preamble term is not limiting because the claim body describes a structurally complete invention. Alternatively, if the term were found to be limiting, Petitioner proposed its broadest reasonable interpretation is simply an anti-HER2 antibody with the claimed degree of purity, not a composition requiring a specific manufacturing scale or unstated therapeutic property. This construction is intended to prevent the Patent Owner from importing limitations from the specification that are not in the claims.
• "pharmaceutically acceptable carrier": Petitioner proposed the standard definition: a non-toxic carrier, excipient, or stabilizer suitable for administration. This construction opposes any attempt to narrow the term to only those carriers used in full-scale manufacturing, which is not required by the claim language.

5. Key Technical Contentions (Beyond Claim Construction)

• Petitioner’s central technical argument across all grounds was that the claimed features were inherent properties of the prior art compositions. It was contended that any preparation of humMAb4D5-8 using the standard methods disclosed by Andya, Waterside, and Harris would necessarily and inevitably result in a composition with less than 25% acidic variants deamidated at Asn30. To support this, Petitioner relied on expert analysis that used software (Data Thief and MATLAB™) to mathematically prove from the published chromatograms that the acidic variant levels were inherently below the claimed 25% threshold.

6. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1 and 5-7 of Patent 9,249,218 as unpatentable.