Amgen Inc v. Bristol Myers Squibb Co

1. Case Identification

• Case #: IPR2025-00602
• Patent #: 10,174,113
• Filed: February 28, 2025
• Petitioner(s): Amgen Inc.
• Patent Owner(s): Bristol-Myers Squibb Company
• Challenged Claims: 1-20

2. Patent Overview

• Title: Methods for Treating Melanoma Using Nivolumab and Ipilimumab
• Brief Description: The ’113 patent relates to methods of treating melanoma using a combination of an anti-PD-1 antibody (nivolumab) and an anti-CTLA-4 antibody (ipilimumab), followed by monotherapy with a flat dose of the anti-PD-1 antibody.

3. Grounds for Unpatentability

Ground 1: Obviousness over NCT-505 and NCT-109 - Claims 1-4, 10-15, and 17-20 are obvious over NCT-505 in view of NCT-109

• Prior Art Relied Upon: NCT-505 (a clinical trial protocol posted May 1, 2013) and NCT-109 (a clinical trial protocol posted October 23, 2013).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that NCT-505 disclosed all elements of the claimed method except for the final monotherapy step using a flat dose of nivolumab. NCT-505 taught a two-stage treatment for advanced melanoma: (1) a combination phase of 1 mg/kg nivolumab and 3 mg/kg ipilimumab every three weeks for four doses, followed by (2) a monotherapy phase of weight-based 3 mg/kg nivolumab every two weeks. NCT-109 disclosed administering a flat dose of 240 mg of nivolumab every two weeks to treat solid tumors, including melanoma. The combination of these references allegedly rendered the claims obvious.
  • Motivation to Combine: A POSITA would combine these references to gain the well-known benefits of flat dosing (e.g., improved convenience, reduced error, better patient adherence) over the weight-based dosing taught in NCT-505 for the monotherapy phase. Petitioner asserted that for an antibody like nivolumab with a wide therapeutic window, flat dosing was known to be the "approach of choice." A POSITA would have simply substituted the known flat-dosing regimen from NCT-109 for the weight-based regimen in NCT-505.
  • Expectation of Success: A POSITA would have a reasonable expectation of success because nivolumab was known to have a wide therapeutic window and linear pharmacokinetics, making its effects dose-independent over a broad range. Furthermore, the 240 mg flat dose is a direct arithmetic conversion of the NCT-505 weight-based dose for a typical 80 kg patient (3 mg/kg × 80 kg = 240 mg). The 480 mg dose administered every four weeks is an obvious variation, achieved by doubling the dose and doubling the interval between treatments to improve patient convenience, a known optimization strategy.
  • Key Aspects: This ground asserted that the core inventive concept—switching to a flat dose—was a simple and predictable substitution of one known dosing regimen for another.

Ground 2: Obviousness over Postow and NCT-109 - Claims 1-6, 9-10, 13-15, and 19-20 are obvious over Postow in view of NCT-109

• Prior Art Relied Upon: Postow (a New England Journal of Medicine article published online April 20, 2015) and NCT-109.

• Core Argument for this Ground:

  • Prior Art Mapping: Petitioner contended that Postow, which published the successful clinical results of the NCT-505 trial protocol, disclosed successfully treating melanoma patients with the same two-stage regimen as NCT-505. This included combination nivolumab/ipilimumab followed by weight-based (3 mg/kg) nivolumab monotherapy. Postow confirmed the efficacy of this treatment, including in PD-L1-negative patients. As in Ground 1, NCT-109 supplied the missing element: a flat-dosing regimen of 240 mg nivolumab every two weeks for melanoma.
  • Motivation to Combine: The motivation was identical to that in Ground 1. A POSITA, aware of the successful regimen in Postow, would have been motivated to modify the monotherapy phase by substituting the known and more convenient flat-dosing regimen from NCT-109 for the weight-based dose used in the trial.
  • Expectation of Success: The expectation of success was the same as in Ground 1, further bolstered by Postow’s confirmation of the regimen's high efficacy and durable responses, which would encourage a POSITA to make predictable optimizations like switching to a more convenient flat-dosing scheme.

• Additional Grounds: Petitioner asserted additional obviousness challenges based on combinations including Cogswell (WO 2013/173223). These grounds argued that adding Cogswell to the primary combinations rendered dependent claims 5-9 and 16 obvious. Cogswell taught well-known methods for measuring PD-L1 expression (relevant to claims 5-9) and combining immunotherapy with other standard anti-cancer agents like chemotherapy (relevant to claim 16), which a POSITA would have been motivated to incorporate into the primary treatment regimens.

4. Key Technical Contentions (Beyond Claim Construction)

• Loss of Priority Date for Claims Reciting 480 mg Dose: A central contention was that claims 1-10, 12-16, and 18-20 are not entitled to the benefit of the ’973 Provisional’s April 28, 2015 filing date. Petitioner argued the provisional application failed the written description requirement under §112 because it never disclosed or suggested a 480 mg flat dose of an anti-PD-1 antibody. Because these claims recite "about 480 mg" as an alternative or requirement, the lack of support in the provisional pushed their effective filing date to the patent's actual filing date of April 28, 2016. This was critical because it made Postow (published April 20, 2015) indisputable §102 prior art against these claims.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be unwarranted. The primary prior art references central to the petition—NCT-505, NCT-109, and Postow—were never cited, discussed, or of record during prosecution. Furthermore, the Examiner never made any obviousness rejections, only an anticipation rejection based on a different reference (Wolchok) that the Patent Owner distinguished based on the specific dosing regimen. Petitioner contended this shows the Examiner did not consider art or arguments similar to those presented in the petition, and that the Office therefore erred in allowing the claims.

6. Relief Requested

• Petitioner requests institution of IPR and cancellation of claims 1-20 of the ’113 patent as unpatentable.