DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on May 7 2026 is acknowledged. Claims 1-25 are pending in the application. Claims 22-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 7 2026. Accordingly, claims 1-21 are being examined on the merits herein.
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 .
Priority
This application claims benefit of 63/423,951 (11/09/2022) as reflected in the filing receipt issued on October 27 2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 5 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to for the following reasons: 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."” In the current case, the view numbers for Figures 1-6 are preceded by the word "Figure" instead of the abbreviation "FIG.".
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Specifically, Figures 6A or 6B contain sequences with 4 or more specifically enumerated amino acids (glycine).
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. The hyperlinks are located in paragraph 51.
Claim Objections
Claim 1 is objected to because of the following informalities: The acronym “NAA” is not defined in the claims. When an acronym is used in a claim set, it should be defined the first time it appears in the claims. For the purposes of examination, the term “NAA” is interpreted to mean nucleobase amino acid. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 5-11 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 5-11 as currently written are vague and indefinite. The claims recites the polymer comprises greater than a particular number of nucleic acid monomers. These claims depend from claim 1 which recites a method for synthesizing a nucleic acid polymer. This nucleic acid polymer is made from nucleobase amino acids. The instant specification does not provide a limiting definition of nucleic acid polymer. Nucleic acids themselves are polymers. The instant specification in Fig. 6B depicts a NAA-poly-thymine sequence. This sequence itself does not include nucleotides specifically but includes nucleobase amino acids (thymine) as well as additional amino acids (glycine). Thus, none of the polymers themselves include what is typically known in the art as a nucleotide or even nucleic acid but includes a polymer made from nucleobase amino acids. Therefore, it isn’t clear if the number referred to in claims 5-11 is the total number of monomers (i.e. NAA and non-NAA) or if this is just the total number of nucleobase amino acids. While claim 1 refers to a nucleic acid polymer, paragraph 9, indicates it is a nucleobase amino acid polymer.
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 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-3, 5-13 and 15-21 are rejected under 35 U.S.C. 103 as being unpatentable over Ahadi (Thesis, 2010) in view of Kato et al. (USPGPUB No. 20180251759).
Applicant Claims
The instant application claims a method for synthesizing a nucleic acid polymer comprising: synthesizing a NAA polymer, wherein synthesizing a NAA polymer comprises providing a mRNA template, at least one ribosome, at least one NAA-tRNA, and at least one non-NAA- tRNA; and adding a polymerase and at least one primer to the NAA polymer.
The instant application claims a method for synthesizing a NAA polymer comprising: providing a mRNA template, at least one ribosome, at least one NAA-tRNA, and at least one non-NAA-tRNA.
The instant specification provides no limiting definition on nucleic acid polymer. Therefore, in light of the claimed method steps, this limitation is interpreted as being directed to any polymer which includes nucleobase amino acids incorporated.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Ahadi is directed to ribosomal synthesis of N-methylated peptides. An alternative method in making non-natural aminoacyl tRNAs is Flexizyme. Flexizyme can be used for the preparation of acyl tRNAs with nearly unlimited selection of amino acids and tRNAs (page 3). The combination of the Flexizyme system with PURE translation apparatus allow performing mRNA-dependent synthesis for preparation of peptides with multiple amino acids (page 4). Flexizyme is a ribozyme which catalyzes tRNA acylation (page 5). See also pages 8-10 for a discussion of tRNA and synthesis of tRNA. Taught is the preparation of a DNA template for tRNA, primers and polymerase, including a T7 polymerase, were utilized (page 24). For PURE translation, DNA templates of mRNA were made. Translation reaction was carried out in the presence of mRNA, methylated aminoacyl-tRNA and aminoacyl tRNA (which is required for translation except the ones which were reassigned for the N-methyl amino acids, i.e. non-NAA tRNA) (page 44).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Ahadi teaches the inclusion of non-natural amino acryl tRNAs, Ahadi does not expressly teach a nucleobase amino acid-tRNA. However, this deficiency is cured by Kato et al.
Kato et al. is directed to amino acid-modified nucleic acid and utilization thereof. Claimed is a method for synthesizing a protein into which an NBA (nucleobase amino acid) is introduced at a desired position wherein the method uses a tRNA acrylated with a nucleobase amino acid (claim 1; Figures). The tRNA with the NBA is prepared with flexizyme (claim 2-3). Peptide nucleic acids (PNAs) are unnatural nucleic acid analys that are artificially produced to have properties similar to DNA and RNA and have a peptide backbone. The PNA/DNA double strand or PNA.RNA double strand can be formed stably (paragraph 0004). The ribozymes may be generally used in aminoacylation reactions of tRNAs, and may be used, not only in the aminoacylation of tRNAs with NBAs, but also in the aminoacylation of tRNAs with any natural or unnatural amino acids (paragraph 0086).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ahadi and Kato et al. and either replace the methylated aminoacyl-tRNA of Ahadi with an NBA-tRNA or use an NBA-tRNA in addition to the methylated aminoacyl-tRNA. One skilled in the art would have been motivated to utilize an NBA-tRNA when desiring to incorporate nucleobase amino acids as taught by Kato et al. Since Ahadi teaches the incorporation of non-natural amino acids and both Ahadi and Kato et al. teach the use of flexizyme there is a reasonable expectation of success. Depending on the desired final sequence, one skilled in the art would have been motivated to utilize the NBA-tRNA to incorporate the nucleobase amino acid and the use of either methylated aminoacyl-tRNA and/or amino-acyl-tRNA to introduce non-nucleobase amino acids.
Regarding claim 1, Ahadi teaches the use of an mRNA template, ribosome (flexizyme) non-NAA-tRNA as well as the addition of a polymerase and a primer. The combination with Kato et al. would suggest the addition of an NAA-tRNA (aka NBA-tRNA).
Regarding claim 12, Ahadi et al. teaches the use of an mRNA template, ribosome (flexizyme), non-NAA tRNA and the combination with Kato et al. would suggest the use of a NAA (aka NBA)-tRNA.
Regarding claims 2 and 13, Kato et al. suggests incorporation of an NAA monomer at a desired location. Therefore, depending on the final desired sequence, one skilled in the art would alternate between NAA monomers and non-NAA monomers.
Regarding claim 3, as taught by Kato et al. peptide nucleic acids (PNAs) are unnatural nucleic acid analys that are artificially produced to have properties similar to DNA and RNA and have a peptide backbone. The PNA/DNA double strand or PNA.RNA double strand can be formed stably.
Regarding claims 5-11 and 15-21, these claims are directed to the total number of monomers present in the peptide sequence. Depending on the desired length and sequence, one skilled in the art would manipulate the type and concentration of tRNA and/or mRNA in order to achieve the desired peptide/protein length. Absent demonstration of the criticality in the length of the polymer, it is the examiners position one skilled in the art would utilize known techniques to achieve the desired length.
Claims 4 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Ahadi (Thesis, 2010) in view of Kato et al. (USPGPUB No. 20180251759) as applied to claims 1-3, 5-13 and 15-21 above and in further view of Jewett et al. (WO2022173627, cited on PTO Form 1449).
Applicant Claims
The instant application claims the step of providing at least one NAA- tRNA and at least one non-NAA-tRNA comprises flowing said NAA-tRNA and non-NAA- tRNAs in a sequential order to result in a NAA polymer of a desired sequence.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Ahadi and Kato et al. are set forth above.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While the use of two different types of tRNA are taught, Ahadi does not expressly teach flowing the tRNA in sequential or alternating order to achieve the desired sequence. However, this deficiency is cured by Jewett et al.
Jewett et al. is directed to ribosome-mediated polymerization of novel chemistries. Taught is the use of a flexizyme enzymes (paragraph 0005). Taught is consecutive incorporation of monomers in an alternating fashion (ABAB or ABABAB-type) (paragraph 0023; 0106)
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ahadi, Kato et al. and Jewett et al. and utilize consecutive incorporation of the tRNA in order to incorporate the monomers in an alternating fashion as taught by Jewett et al. Depending on the desired sequence, one skilled in the art would recognize that consecutive incorporation would allow for an alternating fashion of monomers as taught by Jewett et al. Thus, when desiring this type of sequence, this type of addition is obvious. One skilled in the art would have a reasonable expectation of success as Ahadi, Kato et al. and Jewett et al. all teach the use of flexizyme.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached on 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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