CSPC MegaLith BioPharmaceuTical Co Ltd v. Shanghai Miracogen Inc

1. Case Identification

• Case #: IPR2025-00685
• Patent #: 10,792,370
• Filed: March 3, 2025
• Petitioner(s): CSPC Megalith Biopharmaceutical Co., Ltd.
• Patent Owner(s): Shanghai Miracogen Inc.
• Challenged Claims: 1-23

2. Patent Overview

• Title: Antibody-Drug Conjugate
• Brief Description: The ’370 patent relates to an antibody-drug conjugate (ADC) comprising an anti-epidermal growth factor receptor (EGFR) antibody covalently linked to a cytotoxic agent via a cleavable linker. The claims specify the antibody by the amino acid sequences of its heavy and light chain complementarity-determining regions (CDRs).

3. Grounds for Unpatentability

Ground 1: Obviousness over Wei and Liu - Claims 1-23 are obvious over Wei and Liu.

• Prior Art Relied Upon: Wei (Application # US 2015/071923) and Liu (Chinese Application # CN103772504).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Wei disclosed the core framework of the claimed invention: an anti-EGFR ADC using a modified cetuximab antibody, a well-known anti-EGFR antibody, conjugated to the cytotoxic agent Monomethyl auristatin E (MMAE) via a cleavable valine-citrulline (vc) linker. Petitioner asserted that Liu disclosed the exact humanized anti-EGFR antibody (named BA03) recited in the challenged claims, including all specified CDR and framework sequences. Liu described BA03 as a humanized, superior version of cetuximab with higher binding affinity and lower immunogenicity.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine Wei and Liu because it represented a predictable path to improving upon the ADC taught in Wei. Since Wei taught making ADCs with a modified version of the chimeric cetuximab antibody, a POSA would have been motivated to substitute it with the superior, humanized BA03 antibody from Liu. This substitution followed the well-known progression in antibody engineering to use humanized antibodies over chimeric ones to reduce immunogenicity and improve efficacy.
  • Expectation of Success: A POSA would have had a reasonable expectation of success in making this combination. Both the linker-payload system (vc-MMAE) from Wei and the humanized antibody from Liu were known to be functional and effective. Combining these known, compatible elements to create an improved ADC would have been a straightforward application of established principles.

Ground 2: Obviousness over Leanna, Liu, and Wei - Claims 1-23 are obvious over Leanna and Liu in view of Wei.

• Prior Art Relied Upon: Leanna (WO 2014/152199), Liu (Chinese Application # CN103772504), and Wei (Application # US 2015/071923).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Leanna provided a general blueprint for the claimed invention, disclosing ADCs comprising a humanized anti-EGFR antibody linked to a cytotoxic agent (MMAE) via a cleavable vc-linker. As in Ground 1, Liu disclosed the specific, superior BA03 antibody recited in the claims. Wei provided additional context by teaching the use of cetuximab variants in ADCs, reinforcing the suitability of using the humanized BA03 variant from Liu.
  • Motivation to Combine: A POSA would combine these references to optimize the ADC taught by Leanna. Leanna taught a general anti-EGFR ADC, and a POSA would have sought to incorporate the best available anti-EGFR antibody into that framework. Liu expressly taught that its BA03 antibody was a superior version of cetuximab with numerous benefits. Therefore, a POSA would have been motivated to replace the general humanized antibody in Leanna with the specific, improved BA03 antibody from Liu, resulting in the claimed invention. Wei’s disclosure further supported the rationale of using cetuximab-family antibodies for creating ADCs.
  • Expectation of Success: Success would be expected, as this ground also involves combining known and compatible components. Substituting a specific, high-performance humanized antibody into a known ADC construct is a standard and predictable method for developing improved biotherapeutics.

4. Key Technical Contentions

• Ineffective Priority Claim: Petitioner argued that the ’370 patent is not entitled to its claimed priority date of February 17, 2015, from a Chinese patent application. Petitioner contended the priority application's disclosure of only four specific cleavable linkers fails to provide adequate written description support for the broad genus of "cleavable linker" recited in the claims. Therefore, the effective filing date is the actual U.S. filing date of February 16, 2016, making all asserted prior art references available under §102.

5. Arguments Regarding Discretionary Denial

• New Art and Arguments: Petitioner argued that discretionary denial under 35 U.S.C. §325(d) is inappropriate because the grounds rely on prior art (Wei and Leanna) that was never presented to or considered by the Examiner during prosecution.
• Flawed Prosecution History: Petitioner contended that the Patent Owner overcame prosecution rejections by arguing that the primary reference then under consideration, Tikhomirov, "taught away" from using cleavable linkers due to toxicity concerns. Petitioner argued its new references, Wei and Leanna, directly contradict this by teaching the successful use of anti-EGFR ADCs with cleavable linkers without raising such concerns. Thus, the Examiner was materially misled by the Patent Owner's flawed "teaching away" and "unexpected results" arguments, which do not apply to the new art presented in the petition.

6. Relief Requested

• Petitioner requests institution of an inter partes review (IPR) and cancellation of claims 1-23 of Patent 10,792,370 as unpatentable.