PTAB

IPR2025-00604

Xencor Inc v. Merus NV

Log In
Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods and Means for the Production of Ig-Like Molecules
  • Brief Description: The ’286 patent discloses methods for producing heterodimeric antibodies, which are composed of two different heavy chains. The invention focuses on introducing specific amino acid substitutions in the CH3 domain of each heavy chain to promote the formation of the desired heterodimer over unwanted homodimers through electrostatic interactions.

3. Grounds for Unpatentability

Ground 1: Anticipation by Lazar - Claims 1, 7, 21-22, 24, 26, 28, and 30-32 are anticipated by Lazar.

  • Prior Art Relied Upon: Lazar (Application # US 2011/0054151).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Lazar expressly discloses every limitation of the challenged independent claims (1, 26, 30). The central inventive concept of the ’286 patent—substituting a neutral amino acid with a positively charged one on a first heavy chain and a neutral amino acid with a negatively charged one on a second heavy chain at the CH3 interface—was explicitly taught by Lazar. Petitioner asserted that Lazar’s tables of preferred “CH3 domain variants” provide multiple examples of these exact neutral-to-charged modification pairs at known interface locations. For dependent claim 7, Lazar teaches that its modifications increase heterodimer purity to "greater than 95%," which inherently discloses the claimed limitation of less than 5% contaminating homodimers.
    • Key Aspects: Petitioner emphasized that the Patent Owner overcame prior art during prosecution by arguing that the art did not disclose this specific neutral-to-charged substitution strategy. Lazar’s explicit disclosure directly contradicts this assertion and anticipates the claims.

Ground 2: Obviousness over Lazar in view of Arathoon - Claims 1-2, 7-24, 26-28, and 30-32 are obvious over Lazar in view of Arathoon.

  • Prior Art Relied Upon: Lazar (Application # US 2011/0054151) and Arathoon (WO 1998/050431).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner contended that Lazar provides the primary teachings for the independent claims, including the neutral-to-charged substitutions in the CH3 domain to promote heavy chain heterodimerization. Arathoon addresses the separate, well-known problem of light chain mispairing by teaching the use of a "common light chain" that can pair with both different heavy chains. This combination, Petitioner argued, renders dependent claims 2, 27, and 31 (which add the common light chain limitation) obvious. For the bispecific antibody claims (8-20, 23), Lazar teaches the application of its CH3 modifications to various bispecific antibody formats and targets, while Arathoon provides further detail on common bispecific antibody structures.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA), seeking to maximize the yield of pure, functional bispecific antibodies, would have been motivated to combine Lazar's method for solving heavy chain mispairing with Arathoon's known method for solving light chain mispairing. Both references are in the same technical field, address aspects of the same overall problem, and teach that their respective techniques are broadly applicable.
    • Expectation of Success: A POSA would have had a reasonable expectation of success because Arathoon itself teaches that its common light chain approach is complementary to and can be combined with other CH3 domain modifications (such as knob-in-hole) to further increase heterodimer yield. The combination was a straightforward application of known solutions to known problems.

Ground 3: Anticipation by Cabrera - Claims 1-2, 7, 21-22, 24, 26-28, and 30-32 are anticipated by Cabrera.

  • Prior Art Relied Upon: Cabrera (WO 2012/058768).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner presented Cabrera as an alternative reference that independently anticipates the challenged claims. Cabrera’s Example AZ34 explicitly describes a heterodimer with a specific neutral-to-positive substitution (N390R) on one heavy chain and a neutral-to-negative substitution (S400E) on the other, both at the CH3 interface. Cabrera reports that this method results in a heterodimer purity of ">95%," satisfying the limitation of claim 7. Furthermore, Cabrera teaches that its modified antibodies can be produced from a single host cell and can be constructed using a "common light chain," anticipating claim 2 and its related dependent claims.
  • Additional Grounds: Petitioner asserted an additional obviousness challenge based on the combination of Lazar, Arathoon, and Cabrera, arguing that the collective teachings of these references render all challenged claims obvious.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. §325(d) is inappropriate because the key prior art was not properly considered by the Examiner. Specifically, Cabrera was never cited, and while Lazar was of record, the Examiner’s reasons for allowance show a clear misunderstanding that the prior art lacked the claimed neutral-to-charged substitutions, a teaching central to both Lazar and Cabrera.
  • Petitioner also argued against discretionary denial under Fintiv. It contended that the parallel district court case is in its earliest stages with no trial date set, and a stay will be requested upon institution. Therefore, a Final Written Decision from the PTAB would likely issue well before any district court trial.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-2, 7-24, 26-28, and 30-32 of the ’286 patent as unpatentable.