DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of claims 3 and 13-14 in the reply filed on 6/24/2026 is acknowledged. The traversal is on the ground(s) that the examiner did not show lack of unity, because the restriction requirement does not identify the unique special technical feature of each group and does not address the narrower technical relationship recited by the claims as amended and the claims have been amended to require the polynucleotide sequence of SEQ ID NO: 14. This is not found persuasive because at the time of the restriction requirement, the common shared feature among all of the groups of claims was a recombinant type I allergen protein according to claim 1, which is taught by Yong et al., CN108265065. Further, the groups of claims as amended do not all require SEQ ID NO: 14 (claims 1-2 do not require a specific nucleotide sequence). Additionally, SEQ ID NO: 14 is obvious in view of Yong et al. and Singh et al. as set forth in the rejection under 35 U.S.C. § 103 below.
Additionally, Applicant argues that the examiner has failed to establish that search of the application would be an undue burden as required by MPEP § 803. This is not found persuasive because the instant application is a national stage application submitted under 35 U.S.C. 371 and therefore requires unity of invention analysis rather than the independent and distinct analysis required for applications filed under 35 U.S.C. 111(a). Applicant is directed to MPEP § 823. The unity of invention analysis does not require establishment of undue burden.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-2 and 4-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 6/24/2026.
Priority
This application is a 371 of PCT/CN2022/144026 (12/30/2022) which claims priority to CN202111654407.2 (12/30/2021).
The certified copy of the foreign priority document is not in English. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 8/13/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 3 and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Yong et al., CN108265065A in view of Singh et al., Inflammation & Allergy-Drug Targets-Inflammation & Allergy). 2006 Jan 1;5(1):53-9; as evidenced by Xu et al., Microbial cell factories. 2021 Apr 26;20(1):91 and NCBI “Art an 1.0102 allergen precursor [Artemisia annua]”, GenBank ANC85006.1.
Regarding claim 3, Yong teaches a gene encoding a recombinant Artemisia annua class 1 allergen protein, rArt a1 (Yong p. 2 para. 2; p. 6 para. 9). Yong teaches that the gene encoding rArt a1 has a sequence according to SEQ ID NO: 1 (Yong pp. 49-51). This sequence is 81.1% identical to instant SEQ ID NO: 14 (see sequence alignment in OA appendix).
Yong does not teach a gene comprising the sequence according to instant SEQ ID NO: 14. However, Yong teaches that the DNA sequence encoding the rArt a1 gene is codon-optimized for recombinant expression in a host cell, the mammalian CHO cell line (Yong p. 7 para. 10). As evidenced by Xu, it is known in the art that the genetic code is redundant, with 64 codons encoding 20 amino acids, and different organisms prefer different codons, which regulates the rate of protein synthesis (see Xu “Introduction”). Codon-optimization provides the preferred codons used by the host organism in order to optimize expression of the recombinant gene in the host (Yong p. 29 para. 56). Instant SEQ ID NO: 14 is codon-optimized for the Pichia pastoris expression system (see instant specification p. 5 para. 1).
Regarding claim 3, Singh teaches that recombinant allergen proteins can be expressed in yeast systems, with Pichia pastoris being one of the most commonly used yeast strains for expression of recombinant allergens (Singh p. 53 para. 1; p. 55 “Yeast Based Expression”). Singh further teaches that systems for recombinant expression of allergen proteins are critical for clinical applications, and that adjusting the codon frequency of the allergen to match the heterologous expression system is often a prerequisite to obtain enhanced expression levels. Singh additionally teaches that codon optimization can be readily achieved by constructing synthetic genes based on conversion of amino acid sequences into a DNA sequence with codon usage similar to the host organism (Singh p. 53 para. 1). The codon preferences of Pichia pastoris are known in the art, and codon optimization for Pichia pastoris is an established technique (see Xu “Introduction”).
It would have been obvious for a skilled artisan, based on the teachings of Yong and Singh, to arrive at a nucleotide sequence encoding a recombinant type I allergen protein of Artemisia annua pollen (Art a 1), with a sequence according to instant SEQ ID NO: 14. Yong teaches a gene sequence encoding recombinant Art a1 protein, with a sequence that is 81.1% identical to SEQ ID NO: 14. Yong additionally teaches codon-optimizing the sequence according to the host cell codon preferences, as discussed above. As the gene sequence according to SEQ ID NO: 14 is codon-optimized for use in Pichia pastoris, and Singh teaches that Pichia pastoris is commonly used for recombinant expression of allergens, it would have been obvious to codon-optimize the Art a1 gene sequence as taught by Yong for Pichia pastoris, arriving at a sequence according to instant SEQ ID NO: 14.
A person of ordinary skill in the art would have been motivated to codon optimize the sequence for Pichia pastoris because yeast is an attractive host for the production of recombinant allergens, as yeast cells are eukaryotes and can therefore carry out post-translational modifications required for active allergen proteins, and have advantages of unicellular microorganisms such as ease of genetic manipulation and high density growth (Singh p. 55 “Yeast Based Expression”). As Pichia pastoris is a commonly used strain for such purposes and is easy to genetically transform and produce recombinant proteins in high amounts, a skilled artisan would have been motivated to select Pichia pastoris as the host for recombinant production of the rArt a1 protein, and prepare a nucleotide sequence that is optimized for such a purpose (Singh p. 55 “Yeast Based Expression”).
A skilled artisan would have had a reasonable expectation of success in identifying and producing a nucleotide sequence according to SEQ ID NO: 14, which is optimized for Pichia pastoris. As Singh teaches that the gene sequences encoding allergen proteins should be codon optimized for expression in a host cell, and Yong teaches codon-optimization of the sequence encoding rArt a1, a skilled artisan could expect success in obtaining a codon-optimized version of the rArt a1 sequence for expression in a commonly used system, Pichia pastoris. As the codon preferences of Pichia pastoris are established and the redundancy of the genetic code is known (see Xu “Introduction”), there would be a reasonable expectation of success in obtaining a sequence optimized for Pichia pastoris as set forth in SEQ ID NO: 14.
Regarding claim 13, as discussed above, arriving at a nucleotide sequence according to SEQ ID NO: 14 via codon optimization of a gene sequence encoding the known protein Art a1 for expression in Pichia pastoris is considered obvious. The redundancy of the genetic code and the amino acids encoded by each codon of SEQ ID NO: 14 are known in the art (see Xu, sequence alignment in OA appendix showing translation of SEQ ID NO: 14). Therefore, a nucleotide sequence according to SEQ ID NO: 14 must encode the amino acid sequence of SEQ ID NO: 4. Further, a sequence according to SEQ ID NO: 4, encoding an Artemisia annua allergen, is known in the art (see NCBI GenBank ANC85006.1). Thus, given the degeneracy of the genetic code and the known codon preferences of Pichia pastoris, it would have been obvious for a skilled artisan to obtain a sequence according to SEQ ID NO: 14 which encodes the amino acid of SEQ ID NO: 4.
Regarding claim 14, as discussed above, codon optimization of a gene sequence encoding the known protein Art a1 for expression in Pichia pastoris is considered obvious. Given the known degeneracy of the genetic code, a skilled artisan would have been able to readily identify and produce a polynucleotide consisting of the base sequence set forth in SEQ ID NO: 14 based on the codon use preferences of Pichia pastoris (see Xu “Introduction”).
Conclusion
Claims 3 and 13-14 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
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/EMILY F EIX/Examiner, Art Unit 1653
/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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