DETAILED ACTION
Notice of 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 of Group II, claims 4, 9-10 and 38-39 in the reply filed on 02 December 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is deemed proper and therefore made Final.
Status of Application
Claims 1-5, 9-10, 12-17, 26-27, 33-34 and 38-40 are pending; Claims 1-3, 5, 12-17, 26-27, 33-34 and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Thus, claims 4, 9-10 and 38-39 are subject to examination on the merits.
Priority
The instant application is a CON of PCT/IL2021/050194 filed 18 February 2021 which claims benefit of US provisional application 62/978,895 filed 20 February 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 27 October 2024, 17 March 2024 and 11 February 2024 have been considered by the examiner. See initialed and signed PTO/SB/08’s.
Specification
The specification is objected to because it fails to meet the following sequence compliance requirement.
The sequence listing, filed in XML format on 20 June 2023, has been received and entered. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.831(b). However, this application fails to fully comply with the requirements of 37 C.F.R. § 1.831-1.839.
The peptide sequences on p. 87 (specification filed 06/24/2025), Tables 4-6, do not possess any sequence identifiers.
The peptides in Figure 24C each require a sequence identifier, either in the Figure itself or in the Brief Description of the Drawings.
* If the noted sequences are in the sequence listing as filed, Applicants must amend the specification to identify the sequences appropriately by SEQ ID NO:. If the noted sequences are not in the sequence listing as filed, Applicants must provide (1) an updated copy of the sequence listing containing the requisite sequences in XML form, (2) an amendment directing its entry into the specification, (3) a statement that no new matter has been added and (4) an amendment to the specification to identify the identified sequences by SEQ ID NO: and (5) an updated incorporation by reference statement with the new date of creation, sequence file name and size. – See also MPEP 2422.
Claim Objections
Claims 5, 9 and 38-39 are objected to because of the following informalities: periods in claims are not permitted except at the end of the claim and when used for abbreviations (See MPEP 608.01(m)). Thus, it is suggested to replace, for example, “a.” with “(a)” or “a)”, etc.
Appropriate corrections are required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph 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.
Claims 4-5, 9, 38-39 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
The claims in their broadest are drawn to a mutant aminoacyl-tRNA synthetase (aaRS) comprising an amino acid sequence of an aaRS as provided in SEQ ID NO: 1 and comprising at least one amino acid mutation selected from the group consisting of: tyrosine 32 mutated to leucine, tyrosine 32 mutated to glycine; leucine 65 mutated to valine; leucine 65 mutated to glycine; glutamic acid 107 mutated to serine; glutamic acid 107 mutated to asparagine; glutamic acid 107 mutated to aspartic acid; phenylalanine 108 mutated to valine; phenylalanine 108 mutated to arginine; glutamine 109 mutated to methionine; glutamine 109 mutated to serine; glutamine 109 mutated to leucine; and glutamine 109 mutated to cysteine; aspartic acid 158 mutated to glycine; isoleucine 159 mutated to tyrosine; leucine 162 mutated to serine; leucine 162 mutated to arginine; and alanine 167 mutated to phenylalanine. Thus, while the claim stipulates choosing at least one amino acid substitution from a closed Markush group, the claim is still open and comprising thus permitting an unlimited number of additional mutations. In paragraph 0080 of the instant specification (06/24/25), “mutation” is defined as: “any mutation such as can be introduced into an amino acid sequence or into a nucleic acid sequence by any known method in the art.” Thus, deletions, insertions, substitutions of one or more amino acids or nucleotides, which is further interpreted as insertions, substitutions of any natural or unnatural amino acids or nucleotides as well. Thus, the genus of amino acid sequences directed to a mutant aminoacyl-tRNA synthetase, having at least one specific amino acid mutations/substitution selected from the closed Markush group, and then also having an unlimited number of further “mutations” as defined in the specification in SEQ ID NO: 1 (which is from Methanocaldococcus jannaschii, formerly, Methanococcus jannaschii) is enormous and variable. While the sequence of and structure of M. jannaschii is well known and the structure well characterized (there being 37 protein crystal structures in the Protein Data Bank – See Result #1 in 20250808_112159_us-17-892-163d-1.rup file, and the noted PDB files), this does not detract from written description is also predicated upon that which Applicant’s have disclosed and have possession of as found in the specification, claims and drawings as filed. Here, the disclosure has limited amino acid substitutions: those that target residues in the uAA binding site/are evolved: L32, G34, L65, A67, E107, F108, Q109, Y151, G158, C159, R162 and A167 (Table 2, 3; Figures 1A, B); each mutant also possesses R257G and D286R substitutions (paragraph 0236). These substitutions, along with those as known in the art, do not represent the large and variable genus of aminoacyl-tRNA synthetases as claimed in terms of structure and function.
The MPEP in section 2163(I) states that the purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made/filed, of the specific subject matter claimed:
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonable conclude the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
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An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997)"
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed. Circ. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." Furthermore, the courts have also held that possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 4 and 38-39 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Schultz et al. (US 20130244245 – cited on IDS 02/11/2024).
Schultz et al. teach:
Regarding claim 4, an aminoacyl-tRNA synthetase from Methanococcus jannashii (now called Methanocaldococcus jannaschii) comprising SEQ ID NO: 3 and further having specific substitutions. Specific mutations/substitutions are: Y32L, E107S, D158P, I159L, H160N, L162E – See Example 2, paragraph 0296. Said SEQ ID NO: 3 and instant SEQ ID NO: 1 have 100% sequence identity to one another (See Supplemental Content, 20250808_112200_us-17-892-163d-1.rapbm file, Duplicates for Result #1).
In Example 9, substitutions for various mutants were as follows: Y32G, L65G, F108A, Q109R, D158E, L162Y.
In Example 12, the substitutions are as follows: Y32D, L65E, F108R, D158G, L162N (See paragraph 0378).
In Example 13, the substitutions are as follows: Y32A, L65F, F108W, Q109S, D158S, L162H.
In Example 14, the substitutions are as follows: Y32G, L65V, F108T, D158G, L162S.
Bold = exact substitution in claim 4; Underline = substitution at same amino acid position/number, different amino acid substituted.
Regarding claims 38 and 39, the mutant aminoacyl-tRNA synthetases (aaRS) are comprised an orthogonal translation systems comprising orthogonal tRNA’s recognized by the mutant aaRS’s and which further incorporate unnatural amino acids recognized by said aaRS and which also has a TAG stop codon (See Example 1; paragraphs 0303, 0308 0313, 0318, 0323, 0357, 0362, 0368, 0376).
Claim(s) 4 and 38-39 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Fasan (US 20160355552 – cited herein).
Fasan teach:
A mutant aminoacyl-tRNA synthetase from Methanococcus jannashii (now called Methanocaldococcus jannaschii) comprising SEQ ID NO: 77 and further having specific substitutions:
the engineered variant of Methanococcus jannaschii tyrosyl-tRNA synthetase (SEQ ID NO: 77) comprises at least one of the features selected from the group consisting of: X32 is Tyr, Leu, Ala, Gly, Thr, His, Glu, Val, or Gin; X65 is Leu, His, Tyr, Val, Ser, Thr, Gly, or Glu; X67 is Ala or Gly; X70 is His, Ala, Cys, or Ser; X107 is Glu, Pro, Asn, or Thr; X108 is Phe, Trp, Ala, Ser, Arg, Gly, Tyr, His, Trp, or Glu; X109 is Gln, Met, Asp, Lys, Glu, Pro, His, Gly, Met, or Leu; X155 is Gin, Glu, or Gly; X158 is Asp, Gly, Glu, Ala, Pro, Thr, Ser, or Val; X159 is Ile, Cys, Pro, Leu, Ser, Trp, His, or Ala; X160 is His or Gin; X161 is Tyr or Gly; X162 is Leu, Arg, Ala, Gln, Gly, Lys, Ser, Glu, Tyr, or His; X163 is Gly or Asp; X164 is Val or Ala; X167 is Ala or Val; X286 is Asp or Arg.
Not taught are E107S/D; F108V; Q109S/C; I159Y; and A167F, although each of these amino acid positions are substituted, just not by these exact amino acids.
Regarding claims 38 and 39, the mutant aminoacyl-tRNA synthetases (aaRS) are comprised an orthogonal translation systems comprising orthogonal tRNA’s recognized by the mutant aaRS’s and which further incorporate unnatural amino acids recognized by said aaRS and which also has an amber stop codon, which is TAG (See claim 10 and paragraph 0217).
Said SEQ ID NO: 77 and instant SEQ ID NO: 1 have 100% sequence identity to one another (See Supplemental Content, 20250808_112200_us-17-892-163d-1.rapbm file, Duplicates for Result #1).
Claim(s) 4 and 38-39 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Schultz et al. (US 20080241903 – cited herein).
Schultz et al. teach:
A mutant aminoacyl-tRNA synthetase from Methanococcus jannashii (now called Methanocaldococcus jannaschii) comprising SEQ ID NO: 5 and further having one or more specific substitutions: Tyr32Phe, Tyr32Gln, Tyr32Ala, Tyr32Leu, Ala67Pro, Ala67Ser, Ala67Thr, His70Pro, His70Lys, Leu98Ile, Glu107Pro, Val149Ile, Gln155Ser, Asp158Val, Asp158Cys, Ile159Tyr, Leu162Arg, Gly163Cys, and Ala167Val.
Original screening/directed evolution resulted in specific clones being selected with enhanced activity, wherein the positions were each randomly mutagenized as a group: Tyr32, Glu107, Asp158, Ile159 and Leu162 – See paragraph 0299-0304, including Table 2, producing 2.6x109 clones. Specific multiple substitutions resulted in E107P, D158C, I159Y, L162R (SI-90) – See Table 2 and paragraph 0316.
Regarding claims 38 and 39, the mutant aminoacyl-tRNA synthetases (aaRS) are comprised an orthogonal translation systems comprising orthogonal tRNA’s recognized by the mutant aaRS’s and which further incorporate unnatural amino acids recognized by said aaRS and which also has an amber TAG stop codon (See paragraph 00317)
Said SEQ ID NO: 5 and instant SEQ ID NO: 1 have 100% sequence identity to one another (See Supplemental Content, 20250808_112200_us-17-892-163d-1.rapbm file, Duplicates for Result #1).
Conclusion
No claim is allowed. Claim 10 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached M-F (7-4).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 30 January 2026