United States Patent 9,271,931: Scope, Claims, and Patent Landscape Analysis
Summary
Patent 9,271,931, granted to Innovent Biologics, Inc., on February 23, 2016, pertains to monoclonal antibodies (mAbs) targeting PD-1 (programmed cell death protein 1), a checkpoint inhibitor relevant in oncology and immunotherapy. The patent claims an antibody molecule with specific characteristics, including binding affinity, epitope specificity, and glycosylation profiles, aimed at treating various cancers. This report provides a comprehensive review of the patent's scope, its claims' structure, relevant comparative landscape, and implications for the patenting and development of PD-1 blocking antibodies.
1. Patent Overview and Context
Patent Number: 9,271,931
Filing Date: March 2, 2014
Issue Date: February 23, 2016
Assignee: Innovent Biologics, Inc.
Priority: Claims priority from Chinese applications (CN201310388639.0)
Core Invention:
A monoclonal antibody with specific properties targeting PD-1, particularly engineered to enhance binding affinity, stability, efficacy, and reduced immunogenicity. The patent emphasizes novel epitope specificity and glycosylation patterns that improve therapeutic performance.
2. Scope of the Claims
2.1. Main Claims Summary
| Claim Type |
Focus |
Key Aspects |
| Method of Use |
Therapeutic applications |
Use of the antibody for treating cancer, autoimmune diseases, or other ailments. |
| Antibody Structure |
Molecular features |
Specific amino acid sequences, CDR regions, glycosylation patterns. |
| Binding Affinity |
Binding characteristics |
Affinity constants (KD values) for PD-1 binding, e.g., 10^-9 M range. |
| Epitope Specificity |
Binding epitope on PD-1 |
Epitope overlaps with native PD-1, blocking ligand binding. |
| Glycosylation Profiles |
Post-translational modifications |
Specific glycosylation sites and carbohydrate structures improving efficacy/stability. |
3. Detailed Analysis of Key Claims
3.1. Antibody Structure Claims
-
Variable Region Sequences:
The patent discloses specific variable heavy (VH) and light (VL) chain sequences (Tables 1 and 2), emphasizing certain CDR regions.
- Example: CDR-H3 sequences with high affinity for PD-1.
- Variants include amino acid substitutions designed to enhance binding.
-
Glycosylation Claims:
Claims specify Fc modifications with particular glycan compositions (e.g., afucosylated) to augment ADCC activity.
3.2. Binding and Functional Claims
- Binding Affinity:
The antibody exhibits binding to PD-1 with a KD less than 10^-9 M, confirming high affinity.
- Blocking Activity:
Claims cover the antibody's ability to block PD-L1 and PD-L2 from binding PD-1, essential for immune checkpoint blockade.
3.3. Epitope Specificity
- Epitope Mapping:
The antibody binds an epitope overlapping with the ligand-binding site on PD-1, confirmed by cross-competition assays.
3.4. Therapeutic Use Claims
- Application in various cancers, including non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma.
4. Patent Landscape Context
4.1. Major Competitors
| Entity |
Key Antibody Agents |
Patent Relevance |
| Merck |
Pembrolizumab (Keytruda, US9127293) |
Similar epitope targeting; patent filings around 2012-2014. |
| Roche/Genentech |
Nivolumab (USIPR285) |
Filed around 2008–2013, with overlapping claims on PD-1 antibodies. |
| Bristol-Myers Squibb |
Cemiplimab (US10776797) |
Filed after 2014; relevant for competitive positioning. |
| Innovent |
Sintilimab (not directly related but relevant) |
Focus on China, with potential patent overlap. |
4.2. Patent Clusters and Related Patent Families
-
Antibodies targeting PD-1/PD-L1:
Several patent families are centered on antibodies with similar epitopes, particularly those that block PD-L1/PD-L2 binding.
-
Glycoengineering and Fc modifications:
Patent filings distinct for Fc engineering, associated with enhanced immune effector functions.
4.3. Patent Term and Freedom to Operate (FTO)
- Given the patent's priority date (2014), expiration could be expected around 2034, assuming maximum term extension.
- Freedom to operate depends on the specific antibody sequences, glycosylation modifications, and therapeutic claims compared to existing patents.
5. Comparative Analysis of Claims
| Aspect |
Patent 9,271,931 |
Competing Patents (e.g., US9127293, US10776797) |
Notable Differences |
| Sequence Claim Breadth |
Specific variable regions; some variants |
Broader, covering multiple sequences via ISAs |
Limited to disclosed sequences with explicit variants |
| Glycoengineering Claims |
Fc glycosylation modifications |
Varies; some include glycoengineering, others do not |
Patent 931 emphasizes specific glycosylation profiles |
| Epitope Claims |
Overlaps ligand-binding site |
Similar epitopes claimed; some claim broader or different epitopes |
Overlap suggests potential for infringement in similar antibodies |
| Use Claims |
Cancer, autoimmune disease |
Often similar, with some claims extending to other indications |
Use scope is broad but often dependent on sequence and structure |
6. Implications for Stakeholders
- Developers of PD-1 antibodies must navigate overlapping claims on epitope specificity and glycosylation profiles to avoid infringement.
- Patent strategists should evaluate the scope of Innovent's claims in relation to their antibody sequences, modifications, and therapeutic use.
- Filing strategy might involve designing antibodies outside claimed sequences or employing distinct epitope targets.
7. Frequently Asked Questions (FAQs)
Q1: How broad are the claims of Patent 9,271,931?
A: The claims are focused on specific variable region sequences, glycosylation patterns, and epitope overlaps. They are relatively narrow compared to broader antibody class patents, but overlapping with several existing PD-1 immunotherapies.
Q2: Can a new PD-1 antibody avoid infringing this patent?
A: Yes, by selecting variable regions, epitopes, and glycosylation profiles outside the claimed parameters or employing different mechanisms of action.
Q3: How does glycosylation influence the scope of this patent?
A: The patent claims specific Fc glycan modifications, which can influence Fc effector functions, thus defining a part of its claim scope.
Q4: What are the key competitors' patents to watch?
A: Merck's pembrolizumab (US9127293), Roche's nivolumab (USIPR285), and BMS’s cemiplimab (US10776797) with overlapping claims on PD-1 antibodies.
Q5: When will this patent likely expire, and how does that impact market entry?
A: Expected around 2034, considering patent term adjustments. Market entry post-expiration would face fewer patent barriers.
8. Conclusions
- Patent 9,271,931 provides protected claims on specific PD-1 monoclonal antibodies, particularly emphasizing certain variable sequences and glycosylation modifications.
- It occupies a strategic position within the broader IP landscape of PD-1 checkpoint inhibitors, where overlapping claims on epitopes and Fc engineering exist.
- Companies developing alternative PD-1 antibodies must carefully analyze claim scope and design around specific disclosed features to mitigate infringement risk.
- Ongoing patent filings and legal disputes in this field necessitate continuous landscape monitoring.
9. Key Takeaways
- The patent’s precision on variable region sequences and glycosylation limits its breadth but still covers crucial engineering features.
- Epitope overlap with existing PD-1 checkpoint inhibitors warrants strategic employment of different epitopes or engineering features to differentiate products.
- Patent expiration around 2034 offers opportunities for biosimilar and generics development, contingent on freedom to operate assessments.
- Comprehensive landscape analysis reveals active patenting in antibody glycoengineering, Fc modifications, and epitope specificity—must be considered in R&D planning.
- Due diligence on patent claims, sequences, and modification profiles is essential for navigating the complex immuno-oncology patent space.
References
[1] United States Patent 9,271,931. "Anti-PD-1 antibodies and uses thereof." Innovent Biologics, Inc. Feb 23, 2016.
[2] U.S. Patent 9,127,293. "PD-1 antibodies." Merck Sharp & Dohme Corp. Sep 8, 2015.
[3] U.S. Patent 10,776,797. "Anti-PD-1 antibody compositions and uses." Bristol-Myers Squibb. Sep 8, 2015.
[4] WIPO Patent Application WO2019256894. "Methods for engineering antibodies."
[5] Relevant PAP (Patent Analysis Publications) on PD-1 antibody IP landscape (2012–2022).
