Amgen Inc v. Bristol Myers Squibb Co

1. Case Identification

• Case #: IPR2025-00601
• Patent #: 9,856,320
• Filed: February 28, 2025
• Petitioner(s): Amgen Inc.
• Patent Owner(s): Bristol-Myers Squibb Company
• Challenged Claims: 1-22

2. Patent Overview

• Title: Cancer Treatment with Checkpoint Inhibitors
• Brief Description: The ’320 patent discloses methods for treating cancer by administering anti-Programmed Death-1 (PD-1) and anti-Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) antibodies using a multi-phase induction and maintenance dosing structure.

3. Grounds for Unpatentability

Ground 1: Claims 1-4, 6-12, and 14-17 are obvious over NCT-231 in view of Korman and Wolchok.

• Prior Art Relied Upon: NCT-231 (a January 2010 clinical trial protocol), Korman (WO 2006/121168), and Wolchok (a 2010 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the NCT-231 clinical trial protocol disclosed the exact multi-phase dosing structure recited in independent claim 1. Specifically, NCT-231 taught an induction phase where both anti-PD-1 and anti-CTLA-4 antibodies are administered together (every three weeks for four doses), followed by a phase of administering anti-PD-1 alone (every three weeks for four doses), and concluding with a maintenance phase of both antibodies (every 12 weeks for 8 doses). Petitioner contended this protocol falls squarely within the options of claim 1. While the patent’s lengthy list of specific dose concentrations (options a-m) was not entirely present in NCT-231, Petitioner asserted that Korman and Wolchok disclosed these exact concentrations or ranges encompassing them. For example, Korman disclosed 3 mg/kg as the known dose for anti-CTLA-4, and Wolchok confirmed this dose in its Phase II trial. Korman also disclosed preferred anti-PD-1 dosages of 1 mg/kg and 3 mg/kg, and ranges covering other claimed options.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine the known and effective dose concentrations from Korman and Wolchok with the established dosing framework of NCT-231. The petition argued this was not invention, but a routine optimization strategy. A POSA seeking to develop a combination therapy would logically start with a known protocol (NCT-231) and integrate known effective and/or FDA-approved dosages (such as the 3 mg/kg dose of ipilimumab from Wolchok). The motivation was to maximize efficacy and minimize toxicity by using well-documented concentrations within a known, structured clinical trial format.
  • Expectation of Success: Petitioner argued a POSA would have a reasonable expectation of success. This was based on the known clinical success of each antibody administered alone at similar concentrations, demonstrated positive results for the combination in animal models (disclosed in Korman), and the inherent reliability of the iterative, dose-escalation approach central to immuno-oncology trials, as evidenced by the very title of the NCT-231 protocol ("Dose-escalation Study").

Ground 2: Claims 5, 13, and 18-22 are obvious over Korman in view of Wolchok and Sznol.

• Prior Art Relied Upon: Korman (WO 2006/121168), Wolchok (a 2010 journal article), and Sznol (a 2010 journal abstract).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that the prior art collectively taught every element of independent claim 5, which recites a method of administering 1 mg/kg anti-PD-1 and 3 mg/kg anti-CTLA-4 together every 3 weeks for 4 doses, followed by administering anti-PD-1 alone every 2 weeks. Korman was cited for disclosing the concurrent administration of these two antibodies at these exact concentrations (1 mg/kg anti-PD-1 and 3 mg/kg anti-CTLA-4). Wolchok was cited for establishing the safety and efficacy of an "every 3 weeks for 4 cycles" schedule for anti-CTLA-4, which became the FDA-approved regimen. Finally, Sznol was cited for demonstrating that bi-weekly (every 2 weeks) monotherapy with anti-PD-1 at 1, 3, or 10 mg/kg was safe and effective.
  • Motivation to Combine: The primary motivation argued by Petitioner was safety and toxicity management. By 2012, a POSA understood that anti-CTLA-4 antibodies were associated with significant immune-related adverse events, whereas anti-PD-1 antibodies had a milder toxicity profile. A POSA would therefore combine Korman's dosages with Wolchok's proven 4-dose schedule to limit exposure to the more toxic anti-CTLA-4 agent. To extend the therapeutic benefit while minimizing risk, the POSA would then be motivated to continue treatment with the safer anti-PD-1 antibody alone, logically adopting the bi-weekly schedule shown to be safe and effective by Sznol.
  • Expectation of Success: A POSA would reasonably expect success because the proposed combination merely assembles known, effective, and clinically validated components. The safety and efficacy of the 1 mg/kg anti-PD-1 dose and the 3 mg/kg anti-CTLA-4 dose were known, as were the respective schedules. Combining these elements in a manner designed to optimize the known risk/benefit profile of each drug would have been a predictable path for a skilled artisan.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) is unwarranted because the petition advances new art and arguments not previously considered by the USPTO. It was asserted that while two key references, Korman and Wolchok, were cited in an Information Disclosure Statement during prosecution, they were never substantively analyzed, discussed, or applied by the Examiner against the claims. A third reference, Sznol, was presented as entirely new art.
• Furthermore, Petitioner argued the Examiner’s analysis was materially different from the petition’s grounds. The Examiner’s rejection was based solely on anticipation using a later version of the NCT-231 protocol. The Examiner never considered an obviousness combination involving different prior art references to supply the claimed dosage concentrations, which is the core of the petition's arguments. Petitioner contended the Examiner committed a material error by allowing the claims after an amendment without considering these obviousness combinations.
• Petitioner also stated that there is no co-pending litigation involving the ’320 patent, making discretionary denial under the Fintiv factors inapplicable.

5. Relief Requested

• Petitioner requests that the Board institute an inter partes review (IPR) and find claims 1-22 of Patent 9,856,320 unpatentable.