Sanofi Aventis US LLC v. Immunex Corp

1. Case Identification

• Case #: IPR2017-01884
• Patent #: 8,679,487
• Filed: July 31, 2017
• Petitioner(s): Sanofi-Aventis U.S. LLC, Genzyme Corp., and Regeneron Pharmaceuticals, Inc.
• Patent Owner(s): Immunex Corporation
• Challenged Claims: 1-17

2. Patent Overview

• Title: Human Antibodies that Bind Human IL-4R
• Brief Description: The ’487 patent is directed to isolated human antibodies that bind to the human interleukin-4 receptor (hIL-4R) and block the activity of both interleukin-4 (IL-4) and interleukin-13 (IL-13). The claims define the antibodies functionally, by their ability to compete for binding to hIL-4R with a specified reference antibody.

3. Grounds for Unpatentability

Ground 1: Claims 1-17 are obvious over Hart in view of Schering-Plough.

• Prior Art Relied Upon: Hart (a 1999 journal article) and Schering-Plough (European Patent Application No. EP 0604693).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Hart disclosed a murine (mouse) antibody, MAb230, which blocks the human IL-4 receptor (hIL-4R) and neutralizes both IL-4 and IL-13 signaling. Petitioner provided expert testimony and experimental data to show that Hart's MAb230 inherently possesses the central functional limitation of claim 1: it "competes" with the ’487 patent’s reference antibody (mAb 12B5) for binding to hIL-4R. Thus, Hart's MAb230 was alleged to meet every limitation of the independent claim except for being "human." Dependent claims reciting inhibition of IL-4/IL-13 signaling and high binding affinity were also alleged to be taught by Hart's disclosure of MAb230's properties.
  • Motivation to Combine: Petitioner contended that a person of ordinary skill in the art (POSITA) would combine Hart with Schering-Plough. Schering-Plough taught that murine antibodies cause an undesirable immune response in humans (HAMA reaction) and disclosed specific techniques, such as CDR grafting, to "humanize" murine anti-hIL-4R antibodies for therapeutic use. A POSITA would combine Schering-Plough's established humanization methods with Hart's potent MAb230 to create a viable therapeutic for allergic disorders.
  • Expectation of Success: Petitioner asserted that humanization techniques were routine and well-understood by the patent's 2001 priority date. The art demonstrated that such techniques could successfully preserve the critical binding characteristics of a parent murine antibody, including its specificity and affinity, in the resulting humanized antibody. Therefore, a POSITA would have reasonably expected to create a humanized version of MAb230 that retained its ability to compete with the reference antibody and block IL-4/IL-13 signaling.

Ground 2: Claims 1-17 are obvious over Hart in view of Schering-Plough and Hoogenboom.

• Prior Art Relied Upon: Hart (a 1999 journal article), Schering-Plough (European Patent Application No. EP 0604693), and Hoogenboom (Patent 5,565,322).
• Core Argument for this Ground: This ground was presented as an alternative in case the term "human" was narrowly construed to mean "fully human" rather than "partially human" (e.g., humanized).
  • Prior Art Mapping: Petitioner argued that Hoogenboom taught a technique known as epitope imprinted selection (EIS) for converting a murine antibody into a fully human antibody while preserving the binding specificity and affinity of the original murine antibody. Combining Hart's MAb230 with the method of Hoogenboom would result in a fully human antibody that competes with the reference antibody and meets all other functional limitations of the challenged claims.
  • Motivation to Combine: A POSITA would combine Hoogenboom with Hart and Schering-Plough to create a superior therapeutic. Hoogenboom taught that fully human antibodies generated via EIS are advantageous over partially human antibodies from CDR grafting because they are less likely to provoke an immune response. This provided a clear motivation to use the EIS technique on a promising candidate like MAb230 to develop an even safer and more effective drug for allergic diseases.
  • Expectation of Success: Hoogenboom provided detailed examples of successfully transforming a murine anti-TNF antibody into a fully human one (which later became the blockbuster drug HUMIRA). This success demonstrated that the EIS method was a viable and predictable technique for creating fully human antibodies that retain the essential binding characteristics of their murine precursors.

4. Key Claim Construction Positions

• "human" (claim 1): Petitioner argued that the broadest reasonable interpretation (BRI) of "human" is "partially or fully human." This position was based on the patent's own specification, which explicitly stated that "[a]ntibodies of the invention include... partially human (preferably fully human) monoclonal antibodies" and that embodiments include "chimeric antibodies, e.g., humanized versions of murine monoclonal antibodies."
• "antibody" (claim 1): Petitioner argued the term should be given its broad BRI consistent with the specification, which defined it as encompassing "whole antibodies and antigen binding fragments thereof." This construction was supported by dependent claims directed to various antibody fragments, fusion proteins, and isotypes.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that the petition should not be denied discretionarily because the grounds presented were not cumulative with other pending IPRs against the same patent (IPR2017-01129 and IPR2017-01879), which were based on different anticipation theories and prior art. Furthermore, the petition relied on experimental cross-competition data and prior art references (Hart and Hoogenboom) that were not considered by the USPTO during the original prosecution of the ’487 patent.

6. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-17 of Patent 8,679,487 as unpatentable.