Conjupro Biotherapeutics Inc v. Ascletis Pharma China Co Ltd

1. Case Identification

• Case #: PGR2025-00057
• Patent #: 12,234,236
• Filed: June 20, 2025
• Petitioner(s): Conjupro Biotherapeutics, Inc.
• Patent Owner(s): Ascletis Pharma China Co Ltd
• Challenged Claims: 1-9, 12-17, and 21-25

2. Patent Overview

• Title: GLP-1R agonist and therapeutic method thereof
• Brief Description: The ’236 patent is directed to a class of non-peptidic small-molecule compounds that function as modulators of the glucagon-like peptide-1 (GLP-1) receptor, and methods of using them. The challenged claims are directed to specific Markush structures, individual compounds, and pharmaceutical compositions thereof.

3. Grounds for Unpatentability

Ground 1: Obviousness over Su, Yoshino, and Kawai in view of Talele - Claims 1-4, 6, 12-14, 24, and 25 are obvious over [Su](https://ai-lab.exparte.com/case/ptab/PGR2025-00057/doc/1005), [Yoshino](https://ai-lab.exparte.com/case/ptab/PGR2025-00057/doc/1008), and [Kawai](https://ai-lab.exparte.com/case/ptab/PGR2025-00057/doc/1004) in view of [Talele](https://ai-lab.exparte.com/case/ptab/PGR2025-00057/doc/1009).

• Prior Art Relied Upon: Su (WO 2025/026270), Yoshino (Patent 10,858,356), Kawai (a 2020 journal article), and Talele (a 2016 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued this combination renders obvious at least Compound 19. Su, through its selective deuteration of only a few compounds out of over 200 examples, identified a small subset of promising lead candidates. These leads included Compound 175 (which replaces the methyl group of the known drug orforglipron with a cyclopropyl group) and Compound 44 (which removes the dimethyl groups from the tetrahydropyran ring of orforglipron). Yoshino taught that removing these same dimethyl groups from similar scaffolds maintains or improves biological activity, resulting in an achiral ring.
  • Motivation to Combine: A POSITA would have been motivated to pursue lead compound optimization based on Su’s identification of promising structures. A POSITA would combine the two distinct, favorable modifications taught by Su’s lead compounds—replacing the methyl with a cyclopropyl (from Compound 175) and removing the dimethyls on the tetrahydropyran ring (from Compound 44)—to arrive at the structure of Compound 19.
  • Expectation of Success: The teachings in Su and Yoshino that these individual modifications were favorable and preserved the core scaffold’s activity would have provided a POSITA with a reasonable expectation of success in combining them.

Ground 2: Obviousness over Yoshino and Kawai in view of Talele - Claims 1-9, 12-17, 24, and 25 are obvious over Yoshino and Kawai in view of Talele.

• Prior Art Relied Upon: Yoshino (Patent 10,858,356), Kawai (a 2020 journal article), and Talele (a 2016 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued this combination renders obvious at least Compound 1. Yoshino disclosed orforglipron (Compound 67) as a lead compound for GLP-1R agonists. Kawai provided a high-resolution 3D structure of orforglipron bound to the GLP-1 receptor, revealing that the methyl group on the indazole moiety sits in a spacious, flexible, and hydrophobic pocket. Talele is a review article teaching that replacing a methyl group with a cyclopropyl ring is a well-established medicinal chemistry strategy to increase metabolic stability and improve other drug-like properties.
  • Motivation to Combine: A POSITA would combine these references to improve the known lead compound, orforglipron. Guided by Kawai's structural data showing the pocket could accommodate a bulkier substituent, a POSITA would have been motivated to apply the well-known methyl-to-cyclopropyl substitution taught by Talele to enhance metabolic stability. This single, predictable modification of orforglipron results directly in the structure of Compound 1.
  • Expectation of Success: The structural data from Kawai, combined with Yoshino's data showing other ring substitutions at that position preserved activity, and Talele's teachings on the widespread success of this specific modification, would give a POSITA a strong expectation of success.

Ground 3: Obviousness over multiple references including Meng, Patel, and Ren - Claims 1-4 and 21-25 are obvious over Su, Yoshino, Kawai, Talele, and [Meng](https://ai-lab.exparte.com/case/ptab/PGR2025-00057/doc/1028) in view of [Patel](https://ai-lab.exparte.com/case/ptab/PGR2025-00057/doc/1026) and [Ren](https://ai-lab.exparte.com/case/ptab/PGR2025-00057/doc/1030).

• Prior Art Relied Upon: Su (WO 2025/026270), Yoshino (Patent 10,858,356), Kawai (a 2020 journal article), Talele (a 2016 journal article), Meng (Chinese Patent Publication No. CN117069743A), Patel (a 2022 journal article), and Ren (Patent 12,037,339).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued this combination renders obvious at least Compound 65. This ground builds upon the argument that Compound 19 was obvious. The key difference between Compound 19 and Compound 65 is the incorporation of a nitrogen atom into a core aromatic ring. Meng taught that adding a nitrogen atom at this specific position in the orforglipron scaffold (creating Compound II) resulted in a 1.6-fold improvement in potency. Ren provided further evidence, showing that an analogous nitrogen-for-carbon substitution in a similar scaffold (Compound 90 vs. Compound 76) nearly doubled oral bioavailability. Patel provided general support, describing such "N-scans" as a routine drug discovery strategy.
  • Motivation to Combine: A POSITA, starting with the obvious structure of Compound 19, would have been motivated by the express teachings of Meng and Ren to incorporate a nitrogen atom at the corresponding position to further optimize the compound and predictably enhance its potency and bioavailability.
  • Expectation of Success: The clear, positive experimental data in both Meng and Ren showing improved properties from this exact type of modification would have provided a POSITA with a very high expectation of success.
• Additional Grounds: Petitioner asserted an additional obviousness challenge against claims 4 and 9 over Su and Bethel based on Bethel's disclosure of successful clinical trials using a specific calcium salt of orforglipron, motivating a POSITA to prepare the same salt form of Su's analogous compound.

4. Key Technical Contentions (Beyond Claim Construction)

• Effective Filing Date: A central contention of the petition was that the challenged claims were not entitled to their earliest claimed priority date of September 14, 2023. Petitioner argued that the early priority documents failed to provide adequate written description for specific compounds (e.g., Compounds 19, 65), disclosing only a vast Markush genus with millions or billions of possible permutations. Petitioner asserted the specific structures were not disclosed until later-filed applications, making key references like Su and Meng intervening prior art under §102(a)(2).

5. Arguments Regarding Discretionary Denial

• Petitioner argued against discretionary denial under §325(d). The core reasons were that the Examiner committed material errors by: (1) failing to substantively consider the asserted prior art combinations, instead relying on a third-party search report and citing only a single, non-analogous compound from Yoshino; and (2) failing to conduct any analysis of the claims' entitlement to priority, which prevented the consideration of material, intervening prior art references that are central to the petition's grounds.

6. Relief Requested

• Petitioner requested institution of Post Grant Review and cancellation of claims 1-9, 12-17, and 21-25 of the ’236 patent as unpatentable.