Introduction

Biopharma patentability search demands an exceptionally high level of specialized expertise — one must not only be proficient in general patent search methodologies but also master specialized capabilities such as sequence alignment, target analysis, and biological activity evaluation. If a patentability search misses a highly homologous sequence or a paper that foreshadows a core biological effect, the entire patent prosecution strategy may collapse at any moment.

This article focuses on the practical aspects of biopharma patentability search, covering the most critical sub-domains from sequence searches to target novelty searches, from antibodies to CAR-T.

1. Sequence Searching: The Cornerstone of Biopharma Patentability Search

Why Sequence Searching Differs from Conventional Keyword Searching

In the biomedical field, the core of a technical solution is often a nucleotide or amino acid sequence. This sequence simply cannot be found using ordinary text keywords — because its only “language” is that string of A, T, G, C (or single-letter amino acid codes).

For example: an siRNA sequence, “5′-UGCAUGCUAGC-3′,” would return thousands upon thousands of hits if searched solely with the keyword “siRNA” — what you need is the precise sequence, which serves as its true “identity card.”

Sequence Search Tools and Workflow

Core Tools:

Standard Sequence Search Workflow:

Step 1: Run Multi-Mode BLAST

For a set of sequences to be protected, perform the following searches separately:

• BLASTn: sequence vs. nucleotide database
• BLASTp: amino acid sequence vs. protein database
• tBLASTn: translate the amino acid sequence and align against the nucleotide database (useful for discovering prior art where “the same protein is encoded but the nucleotide sequence has been optimized”)
• BLASTx: translate the nucleotide sequence and align against the protein database

Step 2: Homology Threshold Analysis

Step 3: Functional Comparison

Even when sequence homology falls below the threshold, if the high-homology region happens to coincide with a “functionally critical domain” (e.g., the active center of an enzyme, the binding domain of a receptor), and the prior art has already demonstrated that the function of that region is similar to the present invention — inventive step may still be problematic.

Case Study: Biopharma Patentability Search for a Novel Antibody-Drug Conjugate (ADC)

Client’s Invention: An ADC drug comprising:

• A monoclonal antibody targeting Her2 (sequence publicly disclosed — Trastuzumab)
• A novel linker
• An approved chemotherapeutic agent as the payload

Decomposition of the Sequence Patentability Search:

1. Antibody component: The sequence of Trastuzumab has been fully disclosed → the antibody itself lacks novelty. However, the ADC as a whole (the combination of antibody + linker + payload) can be independently assessed for novelty
2. Linker: A chemical structure search for the linker is required (switching to chemistry-domain methodologies). No prior art document disclosing an identical structure was found
3. Payload: An approved drug with a fully disclosed structure
4. The combination as a whole: The combination of a known antibody + a novel linker + a known payload. The key patentability search question: has any prior art disclosed this specific combination?

Patentability Search Findings:

• Multiple patent documents exist disclosing ADCs of “Trastuzumab + other types of linkers + the same payload”
• However, the combination of “Trastuzumab + the specific linker of the present invention + said payload” has not been disclosed
• The novel linker of the present invention delivers a critical effect: significantly improved stability in plasma (3-fold extension of half-life), resulting in a markedly reduced rate of “premature release” of the payload before reaching the tumor

Patentability Search Conclusion:

• Novelty: Established (a completely new combination of a specific linker + specific antibody + specific payload)
• Inventive Step: Favorable. The “3-fold half-life extension” achieved by the novel linker is not merely a quantitative change — it addresses a critical pain point in the ADC field (systemic toxicity caused by premature payload release)

2. Target Patentability Search

The Core Logic of Target Patentability Search

In biopharmaceutical innovation, the discovery of a new target is often the greatest source of value. The core question that must be answered in a patentability search is:

Is the association between this target and the disease novel?

Search Workflow:

Step 1: Construct the Target-Disease Association Query

(disease name OR 疾病名称) AND (target name OR 靶点名称) AND (expression OR 表达 OR overexpression OR 过表达 OR knockout OR 敲除 OR inhibition OR 抑制)

Step 2: Trace the Target Discovery Timeline

• When was this target first discovered to be associated with the disease?
• What distinguishes it from the “new discovery” of the present invention? (It may be a specific modification state of the target, a specific downstream signaling pathway, etc.)
• If the target-disease relationship is already known, it is necessary to identify where the technical innovation of the present invention lies — is it a new molecular entity targeting that target? Or a new therapeutic strategy (e.g., agonist vs. antagonist)?

Case Study: A Novel Tumor Immunology Target

Client’s Invention: “First discovery that Protein X is highly upregulated in the tumor microenvironment, and that inhibition of Protein X can activate the anti-tumor activity of CD8+ T cells.”

Patentability Search Findings:

Keyword search revealed:

• 2017 Nature paper: reported the role of Protein X in autoimmune diseases
• 2019 Cancer Research paper: elevated expression of Protein X in tumor tissues (but without exploring its function)
• 2020 bioRxiv preprint: discovered the role of Protein X’s ligand Y in tumor immune evasion

No document was found that explicitly discloses that “inhibition of Protein X can activate T cell anti-tumor activity.”

Patentability Search Conclusion:

• Novelty of target-function relationship: Established. The specific function of Protein X in tumor immunity (modulating T cell activity) has not been disclosed in the prior art
• Inventive Step: Favorable. From the role of Protein X in autoimmunity, one cannot “obviously” deduce its functional mechanism in tumor immunity
• Recommendation: File the application promptly, as competition in this field is intense and relevant papers may be published at any time

3. Biopharma Patentability Search Considerations for Biosimilars

The patentability search for biosimilars differs from that for innovative drugs — the “reference product” (originator) you are studying already has a substantial body of publicly available patents. The focus of the search at this stage is:

1. The Patent Cliff timeline of the originator: Track the expiration dates of the originator’s core patents and identify patents that may be challenged
2. “Surrounding patents” on manufacturing processes: The originator’s core molecule patents may have expired, but there remain numerous valid patents at the level of cell lines, culture medium formulations, purification processes, and formulation — these are the true focus of patentability searches in biosimilar development
3. Indication patents: Even if you are able to manufacture a biosimilar, if the originator holds valid patents on expanded indications, the associated risks must be assessed

Key Takeaways: Biopharma patentability search should combine sequence, target, and formulation evidence. The core of biopharmaceutical patentability search consists of sequence searching (multi-mode BLAST, with attention to homology thresholds and differences in functional domains) and target-disease association analysis. For combination drugs such as ADCs and CAR-T, each component should be searched separately before assessing the novelty and inventive step of the overall combination. The patentability search for biosimilars should focus on the originator’s process patents and indication patents rather than the core molecular sequence. Competition in this field is intense, and the patentability search cycle should be shortened as much as possible.

For teams handling repeated biopharma patentability search projects, PatSnap Analytics can support patent family review, assignee monitoring, and technical landscape checks around targets, sequences, and formulations.