In a significant decision for biotechnology and pharmaceutical patents, the Federal Circuit has affirmed-in-part and reversed-in-part the Patent Trial and Appeal Board’s (PTAB) findings in Cytiva BioProcess R&D AB v. JSR Corp.. The case centers around chromatography matrices and protein engineering, with the core dispute being whether certain patent claims were obvious and therefore unpatentable. The ruling provides valuable insight into obviousness determinations, inherency doctrine, and the treatment of unexpected results in patent law.
Background of the Case
Chromatography is a key technology used to separate and purify biomolecules, particularly in pharmaceutical manufacturing. The patents at issue cover affinity chromatography matrices that use Protein A (SPA) as a ligand to bind antibodies. Cytiva owns three patents related to modified versions of Domain C of SPA, which were designed to improve stability in alkaline environments—a crucial property for reusability in industrial purification processes.
JSR challenged Cytiva’s patents via six inter partes reviews (IPRs), arguing that the modifications to Domain C were obvious in light of prior art. The PTAB invalidated 79 claims across Cytiva’s patents but upheld four claims that related to binding properties involving the Fab region of an antibody.
Both companies appealed:
- Cytiva argued that the Board incorrectly applied the lead compound analysis and that the Fab-binding properties were unexpected.
- JSR cross-appealed, asserting that the four surviving claims were also inherently obvious.
Key Patent Law Issues Addressed
1. Was the “Lead Compound” Analysis Required?
Cytiva’s core argument was that the PTAB should have applied the lead compound framework, a two-step analysis commonly used in chemical and pharmaceutical patent cases:
- Would a skilled artisan have selected Domain C as a starting point?
- Would the prior art suggest modifying Domain C with a reasonable expectation of success?
Court’s Ruling: Lead Compound Analysis Was Unnecessary
The Federal Circuit rejected Cytiva’s argument, explaining that the lead compound test is not always required—especially when the prior art explicitly suggests a modification. Here, prior research had already identified five homologous domains (A-E) in SPA, and multiple sources explicitly recommended modifying any of them, including Domain C. Because the modification to improve alkaline stability was already known, no additional justification for selecting Domain C was needed.
Key Takeaway:
- The lead compound test is not a mandatory hurdle for proving obviousness—courts may bypass it when prior art already suggests the modification.
2. Was the Modification to Domain C Obvious?
Cytiva’s patents claimed a G29A mutation, where glycine at position 29 of Domain C was replaced with alanine. This change had already been made to Domain B in prior art and was known to improve alkaline stability.
Court’s Ruling: The Modification Was Obvious
The Federal Circuit affirmed the Board’s decision that making the same G29A mutation in Domain C was obvious because:
- Prior research had explicitly suggested making this mutation to any SPA domain.
- All five SPA domains share structural and functional similarities.
- The motivation for the modification was already well-documented.
Key Takeaway:
- If a structural change is well-known in related compounds, and the motivation to apply it exists, it is likely obvious.
3. Did the Board Properly Apply the Inherency Doctrine?
Several claims covered chromatography matrices that could bind to the Fab region of an antibody. Cytiva argued that this binding property was unexpected and should count as a secondary consideration of nonobviousness.
Court’s Ruling: The Fab-Binding Property Was Inherent
The Federal Circuit sided with JSR, ruling that binding to the Fab part of an antibody was an inherent property of the modified SPA ligands. Since the prior art already disclosed SPA binding to antibodies, the presence of Fab binding was merely a natural consequence—not an inventive step.
The Court reiterated its precedent from Hospira v. Fresenius Kabi (2020), stating:
“If a property of a composition is inherent, there is no question of a reasonable expectation of success in achieving it.”
Thus, the claims that survived at the PTAB were reversed and invalidated.
Key Takeaway:
- An inherent property of an otherwise obvious modification does not make an invention patentable, even if that property was unexpected.
4. Does an Unexpected Result Make an Invention Nonobvious?
Cytiva argued that unexpected Fab-binding properties should overcome the prima facie case of obviousness.
Court’s Ruling: Unexpected Results Do Not Overcome Inherency
While unexpected results can support nonobviousness, the Federal Circuit clarified that this applies only when the unexpected result itself is not inherent. In this case:
- The SPA ligand naturally binds antibodies.
- Since Fab-binding was an inherent characteristic, it could not be used to prove nonobviousness.
The Court distinguished this case from Honeywell v. Mexichem (2017), where an unexpected chemical stability rendered a composition nonobvious. Here, binding to the Fab region was inevitable, making any unexpected results irrelevant.
Key Takeaway:
- Unexpected results do not override inherency—they must stem from truly novel aspects of an invention.
Final Outcome and Impact
| Issue | Federal Circuit Decision |
|---|---|
| Lead compound analysis | Not required when prior art suggests modification |
| G29A mutation (Domain C) | Obvious because it was recommended in prior research |
| Fab-binding properties | Inherent—does not support patentability |
| Unexpected results | Cannot override inherency—binding was inevitable |
The Federal Circuit affirmed the invalidation of 79 claims and reversed the PTAB’s decision on four remaining claims, declaring all challenged claims unpatentable.
Why This Case Matters
- Sets Limits on the Lead Compound Analysis
- If prior art already suggests a modification, courts can skip the lead compound test.
- Reinforces the Role of Inherency in Patent Law
- If an invention inevitably exhibits a property, that property cannot make it nonobvious.
- Clarifies When Unexpected Results Matter
- Unexpected properties must not be inherent to impact nonobviousness.
For biotechnology and pharmaceutical patent holders, this ruling narrows the path for defending patents based on functional properties or unexpected results. If a claimed invention only refines known modifications, it may face heightened obviousness scrutiny.
By Charles Gideon Korrell