Formulation fight: Amgen case tests patentability of biopharmaceuticals in India

Summary: In a high-stakes case, the Madras High Court examines whether Amgen’s specific formulation is non-obvious and patentable, and whether the prior art guides a skilled person to the invention. It also tests whether its broad claims on a genus of antibodies meet India’s strict sufficiency of disclosure rules, despite having data for only one example.

Modern medicine has been transformed by biopharmaceuticals, i.e., pharmaceutical substances or drugs derived from biological sources, which offer innovative treatments for a wide range of diseases. Recently, the High Court of Madras, in Amgen Inc. v. Assistant Controller of Patents & Intas Pharmaceuticals (decision dated 22.8.2025 in CMA (PT) No.28 of 2023), dealt with the patentability for inventions concerning biopharmaceuticals, specifically lyophilized (freeze-dried) peptide-antibody fusion proteins, or “peptibodies”. The judgment is an insight into how Indian patent law approaches statutory exclusions from patentability, inventive step analysis, and the sufficiency of disclosure requirements in this space.

Patent Application and Refusal

Amgen sought to patent a specific lyophilized peptibody formulation (Indian Patent Application No. 5857/CHENP/2008). This formulation combined a peptibody (engineered for therapeutic activity) with the following excipients in precise concentrations:

• 10 mM histidine (buffer, pH 5.0)
• 4% w/v mannitol (bulking agent)
• 2% w/v sucrose (stabilizer/lyoprotectant)
• 0.004% w/v polysorbate-20 (surfactant)

The composition was claimed both as a product and as a method for its preparation through lyophilization. However, the application was refused under the following provisions of the Patents Act, 1970 (“the Act”):

1. Section 3(d): Bars the patenting of mere new forms of known substances/processes unless they enhance efficacy.
2. Section 3(e): Excludes mere admixtures unless they exhibit a synergistic effect.
3. Section 2(1)(ja): Concerns inventive step (non-obviousness).
4. Section 10: Requires sufficient and clear disclosure of the invention so a person skilled in the art (PSITA) can carry it out.

A pre-grant opposition filed against this application also alleged obviousness in view of prior art documents describing related formulations and excipients.

Court’s findings

After briefly describing the science behind biopharmaceuticals, and peptibodies in particular, the  Madras High Court proceeded to examine the patentability of the invention in question against the grounds of refusal and objection.

• Section 3(d)
  Section 3(d) was invoked on the ground that the method claimed was mere use of a known process, i.e., lyophilization. The Court, however, differentiated the specific use case in the present matter and the specific combination of excipients used, from generic lyophilization. It held that where a process leads to a new composition and specifically claimed concentrations tailored to the peptibody, it is not precluded under Section 3(d).
• Section 3(e)
  Section 3(e) excludes mere admixtures that do not provide a synergistic effect beyond the sum of individual ingredient properties. The Patent Office argued that Amgen failed to provide pre-lyophilization vs. post-lyophilization data, alleging lack of synergy. However, the Court ruled that demonstrating interaction between ingredients, i.e., showing that the composition is more than the sum of its parts, is sufficient to establish synergy. The Court deemed the pre-lyophilization and post-lyophilization data requirement irrelevant for Section 3(e) purposes, rejecting the objection.
• Inventive Step
  The key argument against inventive step in this case was that lyophilization is a well-known technique used to stabilize proteins and improve their shelf life, and that the use of common excipients such as buffers, bulking agents, stabilizing agents, and surfactants in the lyophilization process is well disclosed in the prior art.

  The Court held:

  • While lyophilization and the use of excipients like mannitol, sucrose, or polysorbate are common, their specific selection and concentration are context-dependent, influenced by the protein in question, and specific stability requirements.
  • The formulation of peptibodies (as opposed to generic proteins) presents unique challenges, and the process to select precise excipient concentrations was empirically intensive. In other words, this was a non-obvious, unpredictable process.
  • Without explicit “teaching, suggestion or motivation” in the prior art connecting specific excipients, their concentrations, and the exact peptibody structure, a person skilled in the art (who, in such a scenario, would be a formulation scientist) would not be led directly to the claimed invention.
  • The Court emphasised that, while the settled law for testing for obviousness allows a mosaic of prior arts to be made, such a mosaic cannot be made by resorting to hindsight analysis. Instead, the prior art must specifically guide the skilled person to the claimed invention.

  Thus, although certain elements (lyophilization, types of excipients, and the peptibody structure) were individually disclosed in different references, the Court held that prior art did not provide guidance or motivation to arrive at the specific combination or concentrations, especially given the difference between proteins and peptibodies, formulation challenges, and the concentration and selection of excipients required for stability and performance.

• Sufficiency of Disclosure
  The Patent Office alleged insufficient disclosure because experimental data supported only one sequence out of 52 peptibody variants covered by the broad claim. The Court held that, given the complexity and variability of amino acid sequences, sufficiency was only satisfied for those embodiments where adequate data existed. As a result, it narrowed the patent grant to those variants actually demonstrated to a sufficient extent.

Implications

The Amgen decision highlights the technical and legal requirements that govern the grant of biopharmaceutical patents in India. For innovators, it highlights the importance of presenting comprehensive experimental data that clearly demonstrates synergy, while ensuring that claims are fully supported by the specification. For the examiners, the Court specifies, among other things, that while mosaicing is a recognised test for obviousness, it cannot be resorted to using hindsight. In order for obviousness to be established, the prior art must teach, suggest or motivate a skilled person to be guided to the claimed invention.