As a typical experimental science, the predictability in the field of biotechnology is quite low. In patent examination, there are often some disputes over the predictability of technical effects. For example, the examiner may hold that the technical effects of the invention are unpredictable and the claims cannot be supported by the specification. Or, on the contrary, when there are only theoretical teachings or only general technical demand without specific technical questions, the examiner may believe that the prior art provides a motivation and the technical effect can be reasonably expected. However, this relatively subjective opinion cannot be successfully rebutted without solid evidence. The following are just a few examples to illustrate the above situation.
- The expectations of the technical effects of biological sequences are not supported by the specification
In one case, the claim is directed to a variant of parent Bacillus alpha-amylase, wherein the parent alpha-amylase is shown to have immunological cross-reactivity with the antibody produced against α-amylase having one of a sequence from SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, or SEQ ID NO.7, wherein the variant of alpha-amylase comprising sequences with R181+G182 deleted corresponding to SEQ ID NO:1, and compared to the parent α-amylase, the said variant α-amylase has increased thermal stability. The examiner held that the scope defined by the claims could comprise any additional mutations in addition to the double deletion of R181+G182 corresponding to SEQ ID NO:1. The biological activity of the protein depends on the spatial structure based on the amino acid sequence. Mutations of amino acid in certain sites may affect the biological activity of the protein. Therefore, if the variant contains other mutations other than RG double deletion, it may affect the thermal stability and even the biological activity of α-amylase. Therefore, it is impossible for those skilled in the art to determine in advance whether those α-amylase variants comprising additional mutations other than the double deletion of RG have improved thermal stability. Therefore, the examiner held that the claims could not be supported by the specification. However, the same family application of this patent was not rejected or invalidated because the open-ended claims cover sequences that are not in the examples.
- Does general technical demand provide motivation for improvement?
A reexamined case involved a method of introduction of double-strand breaks in the target nucleic acid sequence of human cells. The examiner pointed out in the rejection that the principle of the Streptococcus pyogenes CRISPR-Cas9 system to target DNA double-strand breaks was disclosed in the prior art, and the function of Cas9 nuclease is clear. Also, gene-editing technology can allow humans to edit target genes to achieve the purpose of modifying specific DNA fragments. It is generally pursued by those skilled in the art to apply gene editing technology from in vitro, prokaryotic cells to eukaryotic cells so that this technology can be more widely used. Those skilled in the art have the motivation to use this system to introduce site-specific double-strand breaks to the target nucleic acid sequence of eukaryotic cells for a wider range of applications. Also, nuclear DNA exists in the cell nucleus and the nuclear localization sequence allows Cas9 protein to enter the nucleus to cut nuclear DNA. Therefore, it is a common technique in the field to design nuclear localization sequences to localize the target protein in nucleus. Although the prokaryotic cells and eukaryotic cells are different, those skilled in the art still have motivations to apply CRISPR-Cas9 system in eukaryotic cells and have reasonable expectation of success. The technical effect is not unexpected. On the basis that the mechanism of use of CRISPR-Cas9 system to introduce double-strand break is already known, that it is generally pursued by those skilled in the art to apply gene editing technology from in vitro, prokaryotic cells to eukaryotic cells and that this process only requires conventional techniques, the examiner held that those skilled in the art have the motivation to apply the claimed gene-editing system from prokaryotic cells to eukaryotic cells, and have a reasonable expectation of success. Although the rejection of this application was withdrawn by the PRB, the reexamination panel did not overrule the comments stated above. In the reviewing process of another patent application also directed to the CRISPR-Cas9 system, the examiner held it is not inventive on the basis that the technical effects of using CRISPR-Cas9 in eukaryotes are expected based on the known technical effects of using it in prokaryotes in the prior art.
These examination comments represent a trend in patent examination in the field of biotechnology, i.e., a reasonable expectation of success exists when the prior art merely offers a possibility. Thus, this underestimates the technical contribution of an invention and in a way raises the criteria of inventive step in examination.
Patent application and protection strategies and suggestions based on examination and trial practice
As mentioned above, thanks to the rapid development of biotechnology, new technologies continue to emerge, and the grant rate in the field of biotechnology, especially in emerging hotspots, is generally higher than that in other fields. However, as a typical experimental subject, patents in the field of biotechnology are faced with a situation of underestimating the innovation level of the invention during the examination process, due to the poor predictability and the strong subjectivity of the examination. Meanwhile, some factors that affect patent examination in the field of biotechnology, such as social ethics, change rapidly with the rapid development of technology and the improvement of human cognition. Such rapid change also changes the patent examination policies and standards correspondingly and frequently. For example, in order to meet the needs of technological innovation and social development, in the latest version of the Guidelines for Patent Examination, the examination criteria for embryonic stem cells based on Article 5 of the Chinese Patent Law are changed. It is important to understand and grasp such dynamic changes of the examination, which would help the applicant (or patentee) to obtain and maintain the patent rights, and protect legitimate rights and interests. Due to space limitations, the examination and trial dynamics in this technical field would be analyzed from the three articles and perspectives of experimental data and sufficient disclosure of the description, support of biological sequences, and technical suggestion in inventiveness evaluation. Corresponding strategies and suggestions are provided on such bases.
- Experimental data and sufficient disclosure of the description
Due to the extreme complexity of life activities, it is less predictable whether or not the inventions in the field of biotechnology can be carried out successfully. They need to be confirmed by experimental data. Meanwhile, the design of an experimental scheme for obtaining the experimental data in the field of biotechnology is more complicated. It is more difficult to evaluate the experimental results (such as authenticity) only from the literal disclosures of the description. In examination practice, considering the administrative cost and operability, the examiner usually recognizes the authenticity and probative power of the experimental data based on the principle of trusting the applicant, unless the experimental data is found to have deficiencies in terms of the experiment design and/or results which are obvious enough to question the authenticity and the applicant cannot provide any reasonable explanations and clarifications. Even in patent invalidation proceedings, in order to protect the reliance interests, the burden of proof is allocated more to the invalidation petitioner who claims that the experimental data is defective. If the invalidation petitioner cannot provide sufficient evidence to deny the technical effect of the invention, and the reasons provided are not sufficient to make the collegiate panel have reasonable doubts, the collegiate panel still tends to believe in the probative power of the experimental data in the description, and to uphold the validity of the patent right. Even if there are some deficiencies in the experimental data disclosed in the description, the collegial panel would usually understand and explain in good faith, unless the deficiencies are already obvious to the extent that they cannot support each other.
However, after the former Patent Reexamination Board lost the trial of the Guipazide case, such situation is undergoing subtle changes. In this case, the court of first instance held that the experimental results on mortality and food intake provided in the description were unreasonable. Sihuan’s interpretations of the mortality and food intake were contrary to common sense under the premise that the original experimental report could not be provided. Accordingly, the authenticity and probative power of the experimental data disclosed in the description were not admitted, and the description was determined to be insufficiently disclosed. The original Invalidation Decision issued by the former Patent Reexamination Board was revoked. The court of second instance insisted on the Judgment of the first instance. The judgments of this case will prompt various departments of the Patent Office, including the Patent Reexamination and Invalidation Department, to further the comprehensive examination of the experimental data in the description from the formal and substantive aspects, in the subsequent substantive examination of invention patents and subsequent reexamination invalidation cases. During examination, interested parties including the invalidation petitioner will also pay attention to the experimental data disclosed in the patent documents with a critical eye, which makes it difficult for the patent applicant to sit back and relax even if it is granted. Therefore, for patent applications that have not yet been submitted, the correspondence between the items to be proved by the experimental data and the purpose of invention or the technical effect to be achieved by the invention, the logical rationality of the experimental design, and the rationality and credibility of the experimental results should be examined. Although it is not required that the description discloses the experimental examples comprehensively, the contents directly related to the inventive aspect or the technical contribution made by the invention should still be disclosed as clearly and completely as possible. Other contents not disclosed should belong to the common technical knowledge of those skilled in the art, or be facts that can be confirmed by solid evidence when being challenged. As for a patent application already submitted or granted, if it is challenged based on the experimental design being unreasonable or the experiment result unreliable, it is only possible to explain the non-necessity of the undisclosed content and the rationality of the experimental design and the results in the description by providing evidence or sufficient reasoning. If possible, the original experimental record should be submitted for consideration and support.
- Support for biological sequence inventions
The research and development in the biotechnology field requires a large investment, has great challenges, risks, and a long return cycle. After obtaining patent rights, there are still problems like difficulties with enforcement and easy circumvention. For example, if a patent claim only protects the nucleotides, proteins, antibodies, etc. of specific sequences, it is easy to circumvent it by restructuring, selecting highly homologous sequences, etc. However, due to the large number of variable sites in biological sequences and the difficulty in predicting the effects after site modifications, a set of strict criteria on the protection scope have long been adopted for patent examination in China. This elicits frequent criticisms from the innovative entities and the patent agency industry.
Against such background, the personnel from relevant departments of the former Patent Reexamination Board conducted in-depth research on this issue. Starting from the legislative purpose, different situations were distinguished and combined with some typical cases, and more operable examination suggestions were provided on the biological sequence inventions under Article 26.4 of the Chinese Patent Law from principles and practical aspects. That is, specific examination ideas and judgment rules are provided for several common drafting manners of claims involving the biological sequences. In addition, in order to unify the examination standards, the China National Intellectual Property Administration (“CNIPA”) has also issued some examination standards for specific technical fields such as inventions involving antibody sequences. In recent years, judicial trials have also provided guidance on how to determine the appropriate scope of protection for biological sequence inventions in the manner of leading cases.
The above-mentioned examination ideas and rules and judicial practice guidelines for biological sequence inventions from the perspective of patent examination undoubtedly provide a good perspective and means for the application and protection of such invention patents. For example, for structural genes or their encoded protein sequences, if you want to extend the scope of protection beyond the empirical scope, you should use theoretical explanations and/or pertinent examples in the description to clarify the relationship between sequence structure and efficacy, convincing the judges that the scope of the claim can be selected or verified by those skilled in the art through experiments according to the instructions in the description or the teachings based on the common technical knowledge in the art. If you want to limit the scope of protection of the claim by homology/identity, function, and source features, it is required that the description or the prior art has clearly disclosed the corresponding relationship between the structure and function of the sequence.
- Technical suggestion in inventiveness evaluation
At present, the CNIPA implements a comprehensive examination policy with “three properties (Novelty, inventiveness, and industrial applicability)” evaluation as the main line of reasoning, with the purpose of making timely and substantive responses as to whether a patent application should be granted and the scope of the right that should be granted. Under the guidance of this examination policy, inventiveness has become the most commonly used article in patent examinations. In evaluating the inventiveness, each step is carefully examined and discussed as if under a magnifying glass. For example, the relationship between the sufficient disclosure of the description and the inventiveness article, the selection of the closest prior art and its eligibility, the influence of changing the closest prior art on the inventiveness evaluation conclusion without changing the evidence combination, and the determination of the technical effect of the invention, the handling of the technical problem that the invention actually solves when it is not recognized or wrongly recognized, etc., have been studied and discussed on various occasions.
In response to a series of issues in the evaluation of inventiveness from procedure to substance, from fact finding to law application, there is a big difference in the focus and handling methods between reexamination procedure and litigation procedure. Therefore, different methods and ideas should be adopted according to the characteristics of different procedures. For example, as a relief measure after a patent application is rejected, the reexamination procedure is also a continuation of the patent administrative examination and approval procedure. Therefore, more attention is paid to the final substantive settlement of inventiveness disputes in the rejection decision. For some minor procedures or substantive deficiencies in the rejection decision, if they are not serious enough to incur an incorrect examination conclusion, the rejection decision will generally not be revoked just because of these minor procedural or physical deficiencies. Instead, the rejection decision will be upheld based on the compensation and improvement.
The litigation procedure is different. While paying attention to the substantive conclusion, the litigation procedure also pays attention to the procedural errors in the process of making the reexamination decision, and may revoke the reexamination decision on this ground. For example, many previous judgments revoked reexamination or invalidation decisions only on the grounds that the contents disclosed in the prior art, distinguishing features, and technical problems actually solved were wrongly determined, even though the final conclusion on inventiveness might be correct. Therefore, only for the consideration of the litigation strategies, it may be necessary to pay attention to the procedural or physical deficiencies in the examination process. However, it is worth noting that the Supreme People’s Court states in its recent judgment that: when it is difficult to extract and generalize a single technical problem that is actually solved, “it is necessary to return to the function and effect the technical feature play in the technical solution of the claim, and technical effect per se, instead of deliberately and subjectively extracting and generalizing a technical problem actually solved”. This means that judicial practice will also pay more attention to substantive results, rather than being too entangled in the process to avoid procedural shocks. Since the Supreme Court has given such guidelines in its judgment, and the generalization of the technical problems actually solved would be subjective. Disputes often arise due to different wordings. In the subsequent examination, the Patent Reexamination and Invalidation Department would pay more attention to the technical suggestion that directly affects the inventiveness conclusion, and further downplay the identification of the technical problem that is actually solved.
Furthermore, as mentioned above, despite the relatively high granting rate in the field of biotechnology, judging from the current examination practice, the examination on the relevant technical suggestion in a small number of cases still has a certain bias, i.e., the abstract technical requirements are considered as the technical teaching with specific directions, thereby underestimating the technical contribution of the invention. In the field of biotechnology, after finding some important biological mechanisms, researchers usually predict their possible applications and prospects in medical or other scenarios, and immediately publicize and report them. However, the life activities are extremely complicated and unpredictable. There is still a lot of work to be done in the actual clinical application of this finding. For example, if only the concepts and principles of gene editing and cell therapy are considered, such technology would appear in the 1980s and 1990s. However, the CAR-T cell therapy technology has only recently been approved for clinical application. The gene editing has not yet been applied to the clinic. At present and in the foreseeable future, for the technologies including CAR-T technology and gene editing, we will still be committed to overcoming the deficiencies or shortcomings of its clinical application, such as finding a variety of more effective gene editing tools, overcoming off-target effects, and solving the continuous proliferation or side effects of CAR–T cells in the body. All these efforts are inventive work that pushes a concept or idea to practical application, and their technical contributions should be recognized.
Judicial practice also maintains that when confronted with the objective technical problems to be solved, the suggestion that those skilled in the art learn from the prior art should in principle be a concrete and clear technical means, rather than the abstract ideas or general research directions. Therefore, for the tendency to underestimate the technological contribution of inventions in the hearing of cases, we should try to make the judges understand and appreciate the particularity of the field through active evidence production and sufficient reasoning, and truly take in the stance of those skilled in the art.
The field of biotechnology is a rapidly developing technical field. Generally speaking, the number of patent applications in this technical field have experienced rapid and continuous growth in the past two decades. Some specific technical fields, such as CAR-T technology and CRISPR-based gene editing technology, were developed in recent years and have become a technological and social hotspot. Accordingly, the number of patent applications has increased significantly in recent years, and the number of applications in some subdivisions increases and decreases following social emergencies such as epidemics. Due to the rapid development of technology in the biological field, there are relatively few existing technologies that can affect its novelty or inventiveness. This is reflected in the higher granting rate of the patent applications than in other technical fields. Further, patent applications involving technological breakthroughs such as the CAR-T technology and CRISPR-based gene editing technology involved in this article have significantly higher granting rate than that in the biological field.
Due to complex considerations such as social ethics, as well as faster technological development and lower predictability, the field of biotechnology is more special than the field of traditional chemistry. This specialty in patent examination is mainly reflected in the more frequent changes in examination policies and examination standards. Therefore, it is necessary to have a timely and accurate understanding and grasp of the examination dynamics in this technical field. This article introduces and analyzes the current patent examination and trial dynamics from three articles or perspectives: experimental data and the sufficient disclosures of the description, support of the biological sequences by the description, and technical suggestion in inventiveness evaluation. It also provides corresponding strategies and suggestions of handling. That is, with regard to experimental data, it is recommended that for patent applications that have not yet been submitted, the drafting of the application documents should be improved from the aspects of the completeness and rationality of the experimental design and experimental results. For patents that have been submitted or granted, when they are challenged by the examiner or the public, the non-necessity of the undisclosed content and the rationality of the experimental design and results should be elaborated by evidence and sufficient reasoning. If possible, the original experimental record should be submitted for compensation and support. As to the patent protection scope involving the biological sequences, the CNIPA’s current examination thinking and rules and the guidance of judicial practice should be accurately understood and grasped. As to inventiveness, appropriate differentiated response ideas and strategies should be adopted. In addition, for cases that appear in the trial in which there is a tendency to underestimate the technological contribution of inventions, we should try to make the judges understand and appreciate the specialty of the field through active evidence production and sufficient reasoning, and truly take in the stance of those skilled in the art.
- Guidelines for Patent Examination, effective on February 1, 2020, CNIPA
- (2017) J. 73 X. Ch. No. 5365 Administrative Judgment issued by Beijing Intellectual Property Court, (2018) J. X. Zh. No. 2962 Administrative Judgment issued by Beijing Higher People’s Court.
- (2016) Z. G. F. X. Z. No. 85 Administrative Judgment issued by Supreme People’s Court (leading case of protection of intellectual property right of 2016 collected by the Supreme People’s Court).
- ZHENG Huifen, Strengthen the policy guidance of patent examination and help improve the quality and efficiency, People’s Daily Online, Intellectual Property Channel, 2019.12.18.
- (2018) Z. G. F. X. Z. No. 33 Administrative Judgment issued by Supreme People’s Court
- Z. G. Zh. X. Zh. Zi No. 127 issued by Supreme People’s Court