DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
1. Applicant's election with traverse of Group I (Invention I) in the reply filed on 07/08/2025 is acknowledged. The arguments filed have been considered but are not persuasive. Restriction for examination purposes as previously stated is proper because Inventions I-V are independent or distinct for the reasons of record and there would be a serious search and examination burden if restriction were not required because one or more of the following reasons apply: (a) the inventions have acquired a separate status in the art in view of their different classification; (b) the inventions have acquired a separate status in the art due to their recognized divergent subject matter; and (c) the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries). Claims 3-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention. The requirement is still deemed proper and is therefore made FINAL.
2. Claims 1 and 2 are under consideration in this Office Action.
Claim Objection
3. Claim 1 is objected for reciting the phrase “SEQ ID No.2”, which should be recited as “SEQ ID NO: 2”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ) 2nd Paragraph
4. The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claims 1 and 2 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 1 encompasses any polyphosphate kinase mutant obtained by mutations of the amino acid at position 79, 106, 108, 111 and 285 of the amino acid sequence shown in SEQ ID No. 2. However, the claim is vague and indefinite since it is unclear if the claimed polyphosphate kinase mutant comprises the amino acid sequence of SEQ ID NO: 2, and the specific mutations to the amino acids are not known and not recited in the claim. Dependent claim 2 is also rejected because the claim does not correct the defect. For examination purposes, the claims will not be limited to any amino acid sequence and any specific SEQ ID NO.
Claim Rejections - 35 USC § 112
6. The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
7. Claims 1 and 2 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a polyphosphate kinase mutant comprising the amino acid sequence of SEQ ID NO: 2 and amino acid substations of A79G, S106C, I108F, and L285P; does not reasonably provide enablement for any other embodiment as recited in the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
According to MPEP 2164.01(a), factors considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue” include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. MPEP§ 2164.04 states that while the analysis and conclusion of a lack of enablement are based on the factors discussed in MPEP § 2164.01(a) and the evidence as a whole, it is not necessary to discuss each factor in the written enablement rejection. The language should focus on those factors, reasons, and evidence that lead the examiner to conclude that the specification fails to teach how to make and use the claimed invention without undue experimentation, or that the scope of any enablement provided to one skilled in the art is not commensurate with the scope of protection sought by the claims. Accordingly, the factors most relevant to the instant rejection are addressed in detail below.
The nature and breadth of the claims encompass any polyphosphate kinase mutant of any amino acid sequence and structure obtained by any single- or multi-site mutations of the amino acid at position 79, 106, 108, 111 and 285 of the amino acid sequence shown in SEQ ID NO: 2.
The reference of Chica et al. (Curr Opin Biotechnol. 2005 Aug;16(4):378-84; IDS filed 01/13/2025) teaches that the complexity of the structure/function relationship in enzymes has proven to be the factor limiting the general application of rational enzyme modification and design, where rational enzyme modification and design requires in-depth understanding of structure/function relationships. The reference of Singh et al. (Curr Protein Pept Sci. 2017, 18, 1-11; IDS filed 01/13/2025) reviews protein engineering methods including directed evolution, rational design, semi-rational design, and de-novo design; and states that despite the availability of a growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see entire publication especially Figs.1 and 3, and page 7, left column, lines 8-17). Such protein engineering methods, however, only provide guidance for searching and screening for the claimed polyphosphate kinase mutant.
The specification only provides guidance, prediction, and working examples for a polyphosphate kinase mutant comprising the amino acid sequence of SEQ ID NO: 2 and amino acid substations of A79G, S106C, I108F, and L285P.
Thus, one skilled in the art must perform an undue amount of trial and error experimentation which includes searching and screening for the recited polyphosphate kinase mutant from any biological source and determining whether the polyphosphate kinase mutant has any improved properties compared to wild-type polyphosphate kinase. In the alternative, undue amount of trial and error experimentation which includes making any amino acid mutations including amino acid mutations, substitutions, additions, deletions, and combinations thereof at position 79, 106, 108, 111 and 285 of the amino acid sequence shown in SEQ ID NO: 2; and searching and screening for a polyphosphate kinase having any improved properties compared to wild-type polyphosphate kinase. Therefore, in view of the overly broad scope of the claims, the specification’s lack of specific guidance and prediction, the specification’s lack of additional working examples, and the amount of experimentation required; it would require undue experimentation for one skilled in the art to make and/or use the invention commensurate in scope with these claims. Dependent claim 2 is also rejected because they do not correct the defect.
Claim Rejections - 35 USC § 103
8. 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 of this title, 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.
9. Claims 1 and 2 are rejected under 35 U.S.C. 103 as being unpatentable over Accession A0A6N4SMB5 (07-OCT-2020; PTO 892) in view of Nocek et al. (ACS Catalysis 2018, 8 (11), 10746-10760; PTO 892), Bornscheuer et al. (Curr Protoc Protein Sci. 2011 Nov;Chapter 26:Unit26.7; PTO 892), Yoshikuni et al. (Curr Opin Chem Biol. 2007 Apr;11(2):233-9; PTO 892).
Accession A0A6N4SMB5 teaches the Cytophaga hutchinsonii polyphosphate kinase having 97% identity to SEQ ID NO: 2 (see attached record). The teachings of the reference differ from the claims in that the reference does not teach the claimed polyphosphate kinase having the recited single- or multi-site mutations.
Nocek et al. teach biochemical and structural studies on polyphosphate (polyp) kinases from bacteria including CHU0107 from Cytophaga hutchinsonii, which is a member of the PPK2 class III family and can be used for polyphosphate-dependent ATP regeneration. Nocek et al. teach that structure-based site-directed mutagenesis of CHU0107 from Cytophaga hutchinsonii demonstrated the critical role of several conserved residues from the PPK2 core and lid domains, which are involved in the coordination of both substrates and two Mg2+ ions. Nocek et al. teach a two-times higher activity is observed following deletion of the C-terminal in the CHU0107 mutant protein L285Stop. Nocek et al. teach that the polyphosphate kinase CHU0107 has the Walker A loop which is involved in the binding of polyphosphate (polyP) kinase and the Mg2+ ion, and the Walker B loop which coordinates the nucleotide phosphate groups, where the loops are located at residues 75-81 and 131-136, respectively. Nocek et al. teach the conservative substitutions of the Walker-A Gly to Ala (Ala75 in CHU0107) and Walker-B Asp to Asn (Asn132 in CHU0107) in phylogenetic analysis of the PPK2 family of polyP kinases (see Fig. 1). Nocek et al. teach structure of the CHU0107-ADP complex demonstrated binding of the adenine base and ribose, with the two phosphates of ADP forming ionic interactions with the side chains of Lys103, Arg133, Lys81, and Asp82. Nocek et al. teach polyP and ADP are bound in the active site in close proximity to each other with two Mg2+ ions coordinated by conserved aspartates Asp77 and Asp222 in CHU0107 (see Fig. 7). Nocek et al. teach the Lys81, Arg133, Arg208, Lys214 and Lys217 in CHU0107 are involved in phosphate binding, orientation, transfer and charge compensation; and the Asp77 and Asp222 are involved in the coordination of Mg2+. Nocek et al. teach the mutation analysis provides information for engineering highly-activity polyphosphate kinases for use in biocatalytic applications. See entire publication and abstract especially MATERIALS AND METHODS section, RESULTS AND DISCUSSION section, Figs. 1-7, and pages 10748-10757.
Bornscheuer et al. teach protein engineering strategies to improve or change the properties of proteins, teach concepts for protein engineering using rational design including substitution and/or deletion of amino acids, directed evolution, and combinations of them where different strategies are presented for identifying the best mutagenesis method, how to identify desired variants by screening or selection, and examples for successful applications are shown which enable researchers to choose the most promising tools to solve their protein engineering challenges (see entire publication especially pages 26.7.1- 26.7.10 and Tables 26.7.1, 26.7.2, and 26.7.3).
Yoshikuni et al. (Curr Opin Chem Biol. 2007 Apr;11(2):233-9; PTO 892) teach protein engineering methodology to redesign enzyme function which was developed on the basis of the theories of divergent molecular evolution: (i) enzymes with more active and specialized functions have evolved from ones with promiscuous functions; (ii) this process is driven by small numbers of amino acid substitutions (plasticity); and (iii) the effects of double or multiple mutations are often additive (quasi-additive assumption). Yoshikuni et al. teach the impact of multiple mutations can be calculated by first determining the effects of a mutation at a single position and subsequently summing these effects using the quasi-additive assumption where the shape of the fitness landscape of a particular enzyme function can be estimated, and the combinations of mutations predicted to yield global optima for desired functions can then be selected and introduced into the enzymes. Yoshikuni et al. teach that the methodology has been demonstrated to be very powerful to redesign enzyme function. See entire publication and abstract especially pages 234-7 and Fig. 2.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by using the protein engineering strategies and protein engineering methodology of taught by Bornscheuer et al. and Yoshikuni et al. on the the Cytophaga hutchinsonii polyphosphate kinase of Accession A0A6N4SMB5 to make the claimed polyphosphate kinase mutant having the recited amino acid substitutions at position 79, 106, 108, 111, and/or 285. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a polyphosphate kinase mutant having improved properties compared to the wild-type polyphosphate kinase mutant where Nocek et al. teach the mutation analysis provides information for engineering highly-activity polyphosphate kinases for use in biocatalytic applications. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because using protein engineering strategies and protein engineering methodology to improve or change the properties of enzymes are known in the art as shown by the above reference teachings including the teachings of Nocek et al. Hence, the claimed invention as a whole is prima facie obvious.
Conclusion
10. No claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christian L Fronda whose telephone number is (571)272 0929. The examiner can normally be reached Monday-Thursday and alternate Fridays between 9:00AM-5:00PM.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652
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