In the practice of patent validity determination in the biochemical field, Article 26, Paragraph 4 of the Chinese Patent Law (Claims shall be supported by the specification) is often one of the most frequent and difficult grounds for rejection in office action notifications.
Unlike fields with relatively strong “predictability” such as machinery and electrical engineering, the biochemical field is a typical “experimental science”. Due to the high complexity and unpredictability of life systems and chemical reactions, examiners usually hold a more prudent and even stringent attitude towards the scope of generalization of claims.
1. Core Logic of Examiners: Lack of “Reasonable Prediction”
Regarding the “support issue” in the biochemical field, the examiner’s examination logic is usually based on the following standard: “Based on the limited experimental data provided in the application documents, it is difficult for a person skilled in the art to reasonably predict that other technical solutions generalized within the scope of the claims, besides the specific technical solutions verified by the examples, can also solve the same technical problem and achieve the expected technical effect”.
In other words, if the scope of protection of a claim covers a large number of solutions that have not been verified by experiments, and a person skilled in the art cannot confirm that these solutions are all effective, the claim may be found to be “lacking support from the specification”.
2. Response Strategies: Constructing an Evidence Chain of “Common General Knowledge + Experimental Data”
Faced with such office actions, argument alone is often ineffective. Patent agents need to formulate response strategies on the basis of accurately grasping the inventive concept and clarifying the technical contribution.
The core response logic should focus on the following two points:
1) Generality of Technical Principles: Combining common general knowledge and technical principles in the field to demonstrate that the solutions within the scope of the claims are consistent in mechanism;
2) Representativeness of Experimental Data: Proving that the examples in the specification are sufficiently representative to support a person skilled in the art to make reasonable inferences about a broader scope.
3. Practical Case Analysis: Limitation of Antibody Sequence Variants
Taking antibody patents as an example, applicants often hope to obtain a wider scope of protection through homology limitation, such as drafting the following claim:
“A kind of antibody, comprising a heavy chain variable region having at least 95% (or 99%) homology with SEQ ID NO: 1...”.
However, if the specification only records the specific sequence of SEQ ID NO: 1 or only a small number of variants, such claims are extremely vulnerable to rejection.
1) Examiner’s Points of Query: Examiners usually hold that the complementarity-determining regions (CDRs) of antibodies are extremely sensitive to sequence changes. CDRs determine the specificity of antigen binding. Even 99% homology (meaning 1-3 amino acid differences may exist), if the mutation occurs in the CDRs, it will most likely lead to antibody inactivation or a sharp drop in affinity. Therefore, a general limitation of “more than 90% homology of the entire variable region” is usually regarded as including invalid solutions with “CDR mutations”, thus lacking support.
2) Breakthrough Point in Framework Regions (FRs): In contrast, examiners are relatively more tolerant of homology limitations on framework regions (FRs). It is generally recognized by examiners that as long as the sequences of the 6 CDRs are correctly arranged and the FRs can maintain the required spatial conformation, the antibody function is usually retained.
3) Specific Response Strategy: In a specific case, the examiner pointed out that the claimed antibody must clearly define the sequences of the 6 CDRs and the sequences of the FRs; otherwise, the antigen-binding function cannot be guaranteed.
In response to this, we adopted a modification strategy of “locking the core and moderately opening up”:
Locking CDRs: Specifically defining the amino acid sequences of the 6 CDRs to ensure no mutations occur in the core binding regions;
Opening up FRs: For the FRs, instead of directly defining them as specific full-length sequences, based on the example data in the specification and combined with the common general knowledge of “conservative amino acid substitution”, limiting specific amino acid sites in the FRs to “2 or 3 alternative amino acid residues”.
4) Result: Through the above limitations, combined with legal arguments on “conservative substitution does not change protein function”, the examiner finally recognized that the amended technical solutions can be supported by the specification.
4. Conclusion
In summary, when dealing with the “support issue” in the biochemical field involving antibodies and the like, it is recommended to follow the following principles:
1) Prioritize ensuring the certainty of CDR sequences, which are the cornerstone of antibody function;
2) Explore the generalization space of FRs, and use example data to limit a limited number of sites with “conservative substitution” instead of generally pursuing the homology percentage of the entire sequence.
This strategy not only avoids unduly narrowing the claims to specific single examples and protects the inventive work of the applicant, but also excludes those obviously unachievable “overgeneralization” solutions, reflecting the principle of interest balance of “disclosure in exchange for protection” in the Patent Law.
