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 .
Claim(s) 17-36 are pending.
Preliminary Amendments Filed
Applicant’s preliminary amendment filed on 05/18/2023 is acknowledged. Applicant amended to the specification to (1) change the title, (2) add “cross reference to related applications”, (3) add “incorporation by reference of sequence listing”, (4) substituted the sequence listing. Applicant replaced the drawings. Applicant cancelled claims 1-16 and added 17-36.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55 for application CN202110912085.0 filed on 08/10/2021.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 02/12/2026 is acknowledged. Group I is being considered to the extent that the claims are drawn to an isolated mutant polypeptide and not to the extent that they read on a nucleotide sequence encoding a polypeptide.
Claim(s) 20-28, 31-32, and 34-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected groups II-VII, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/12/2026.
Claim(s) 17-19, 29-30, and 33 are under consideration.
Information Disclosure Statement
Receipt of the information disclosure statement(s) on 05/18/2023 is acknowledged. The signed and initialed PTO-1449 form(s) has/have been mailed with this action.
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 – 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.
Figures with missing SEQ ID NOs:
Fig. 19
Fig. 22
Fig. 24
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 abstract of the disclosure is objected to because:
“N terminus” and “C terminus” in line 4 should recite “N-terminus” and “C-terminus”;
“It lowers off-target at the transcriptome level” in lines 8-9 should recite “It lowers off-target editing at the transcriptome level”
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 17 is objected to because of the following informalities: “A isolated mutant polypeptide…” should be “An isolated mutant polypeptide…”. Also, “…N terminus to the C terminus.”, should be “…N-terminus to the C-terminus.”
Claim(s) 29 and 30 are objected to because they contain subject matter to the non-elected invention.
Claim 29 recites:
A composition, characterized by comprising an effective amount of at least one of the mutant polypeptides according to claim 17, a fused protein comprising the mutant polypeptide according to claim 17, a polynucleotide encoding the mutant polypeptide according to claim 17, or a complementary sequence thereof, a vector comprising a polynucleotide which encodes the mutant polypeptide according to claim 17, or a complementary sequence thereof, or a host cell comprising the polynucleotide which encodes the mutant polypeptide according to claim 17, or a complementary sequence thereof,…
Claim 30 recites:
A base editing system, characterized by comprising the mutant polypeptide according to claim 17, or afused protein comprising the mutant polypeptide according to claim 17, or a polynucleotide encoding the mutant polypeptide according to claim 17, or a complementary sequence thereof , or a vector comprising a polynucleotide which encodes the mutant polypeptide according to claim 17, or a complementary sequence thereof, or the host cell comprising the polynucleotide which encodes the mutant polypeptide according to claim 17, or a complementary sequence thereof,…
A polynucleotide encoding the mutant polypeptide according to claim 17, A vector comprising a polynucleotide which encodes the mutant polypeptide according to claim 17, and A host cell comprising the polynucleotide which encodes the mutant polypeptide according to claim 17 is all subject matter that reads on the invention of Group II.
It would be remedial to remove the subject matter in the claim(s) that recite the non-elected invention of Group II.
Claim 30 is objected to because of the following informalities: “… characterized by comprising the mutant polypeptide according to claim 17, or afused protein…”, should have a space between a and fused.
Appropriate correction is required.
Claim Interpretation
Claim(s) 18, 19, 29, 30, and 33, recite “preferably” multiple times throughout each claim. For the purposes of compact prosecution, “preferably” will be interpreted as “optionally”.
Claim Rejections - 35 USC § 112(b) – indefiniteness
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.
Claim(s) 18, 19, 29, 30, and 33 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.
Regarding claim(s) 18, 19, 29, 30, and 33 the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention, i.e., required or an option limitation. See MPEP § 2173.05(d).
It would be remedial to either amend the word “preferably” to recite “optionally”.
Claim(s) 29 and 30 recite the limitation "…or a polynucleotide encoding the mutant polypeptide according to claim 17, … , or a vector comprising a polynucleotide which encodes the mutant polypeptide according to claim 17, …, or the host cell comprising the polynucleotide which encodes the mutant polypeptide according to claim 17,” in lines 3 through 6. There is insufficient antecedent basis for this limitation in the claim.
Claim 17 recites, “A isolated mutant polypeptide, characterized by comprising an N-terminal fragment of SpRY(D10A), a TadA8e fragment, and a C-terminal fragment of SpRy(D10A) polypeptide in sequence from the N terminus to the C terminus”. Regarding the phrase, “…or a polynucleotide encoding the mutant polypeptide according to claim 17”, the antecedent basis can be found in claim 20. Regarding the phrase, “… or a vector comprising a polynucleotide which encodes the mutant polypeptide according to claim 17,” the antecedent basis can be found in claim 22. Regarding the phrase, “… or the host cell comprising the polynucleotide which encodes the mutant polypeptide according to claim 17,” the antecedent basis can be found in claim 26.
It would be remedial to amend claim(s) 29 and 30 to have proper antecedent basis with the alternative embodiments.
Claim Rejections - 35 USC § 102
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.
Claim(s) 17-19, 29-30, and 33 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gaudelli et al (US 2021/0130805 A1, published May 6th, 2021, Filed December 18th, 2020; listed under US Patent Documents on the 892 form from 12/29/2025).
Gaudelli et al teaches, “...compositions comprising novel adenosine base editors (e.g., ABE8) that have increased efficiency and methods of using these adenosine deaminase variants for editing a target sequence.”, (abstract).
The breadth of claim 17 includes embodiments wherein the amino acid sequence of the N-terminal fragment of SpRY (D10A) protein has at least 90% sequence identity with an amino acid sequence show as SEQ ID NO: 1; wherein the amino acid sequence of TadA8e fragment has at least 90% sequence identity with an amino acid sequence shown as SEQ ID NO: 3; and embodiments wherein the amino acid sequence of the C-Terminal fragment of SpRY (D10A) protein has at least 90% sequence identity with an amino acid sequence show as SEQ ID NO: 5, (see page 3, first paragraph of the instant specification)
Regarding claim 17-19, Gaudelli et al teaches a fusion protein wherein the adenosine deaminase (with at least one alteration in the amino acid sequence) is flanked by N- and C- terminal fragments, in that order.
More specifically, Gaudelli et al teaches, “In various embodiments of the above aspects, the polynucleotide programmable DNA binding domain is a nuclease inactive or nickase variant. In various embodiments of the above aspects, the nickase variant comprises an amino acid substitution D10A or a corresponding amino acid substitution thereof… In various embodiments, the adenosine deaminase variant is a TadA deaminase. In various embodiments of the above aspects, the TadA deaminase is TadA*7.10. In various embodiments, the TadA deaminase is a TadA*8 variant. adenosine deaminase variant is capable of deaminating adenine in deoxyribonucleic acid (DNA)…”, (see paragraphs [0011] and [0012]).
Gaudelli et al further teaches, “A fusion protein comprising: an adenosine deaminase variant domain, wherein the adenosine deaminase variant domain comprises the amino acid sequence of: MSEVEFSHEYWMRHALTLAKRARDEREVPVGAVLVLNNRVIGEGWNRAIGLHDPT AHAEIMALRQGGLVMQNYRLIDATLYVTFEPCVMCAGAMIHSRIGRVVFGVRNAKT GAAGSLMDVLHYPGMNHRVEITEGILADECAALLCYFFERMPRQVFNAQKKAQSST, wherein the amino acid sequence comprises at least one alteration, and a Cas9 or a Cas12 polypeptide, wherein the adenosine deaminase variant domain is inserted within the Cas9 or the Cas12 polypeptide... In some embodiments, the adenosine deaminase variant domain is flanked by a N-terminal fragment and a C-terminal fragment of the Cas9 polypeptide. In some embodiments, the fusion protein comprises the structure: NH.sub.2—[N-terminal fragment of a Cas9]-[adenosine deaminase variant]-[C-terminal fragment of a Cas9]-COOH, wherein each instance of “]-[” is an optional linker. In some embodiments, the N-terminal fragment or the C-terminal fragment of the Cas9 or Cas12 polypeptide binds a target polynucleotide sequence.”, (see paragraphs [0015] to [0017]).
Wherein, SEQ ID NO: 3 of the instant application is 93.9% similar to the adenosine deaminase variant taught by Gaudelli et al, see overlay below.
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332
658
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Moreover, “In some embodiments, dCas9 corresponds to, or comprises in part or in whole, a Cas9 amino acid sequence having one or more mutations that inactivate the Cas9 nuclease activity. For example, in some embodiments, a dCas9 domain comprises D10A and an H840A mutation or corresponding mutations in another Cas9. In some embodiments, the dCas9 comprises the amino acid sequence of dCas9 (D10A and H840A):..”, (see paragraph [0098]), which goes on to teach the dCas9 sequence, which has 99.7% sequence similarity to instant SEQ ID NO: 1, and 95.6% sequence similarity to instant SEQ ID NO: 5, see below.
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370
618
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372
642
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Regarding claim 29, Gaudelli et al teaches composition comprising an effect amount of the mutant polypeptides (see paragraphs [0804] and [0808]).
Regarding claim 30, Gaudelli et al teaches, a base editing system, “In one aspect, the invention provides a base editor comprising any of the fusion polypeptides provided herein in a complex with one or more guide polynucleotides.”, (see paragraph [0031]).
Regarding claim 33, Gaudelli et al teaches a gene editing method characterized in the gene editing is performed with the base editing system discloses, “ In one aspect, the invention provides a method of treating a genetic defect in a subject, the method comprising administering to the subject a base editor comprising or consisting essentially of any of the fusion proteins provided herein, or a polynucleotide encoding said base editor and one or more guide polynucleotides that direct the base editor to deaminate a target nucleobase in a target nucleotide sequence of the subject, thereby treating the genetic defect.”, (see paragraph [0035]).
Accordingly, claim(s) 17-19, 29, 30, and 33 are anticipated by Gaudelli et al.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEXUS M TATGE whose telephone number is (571)272-0061. The examiner can normally be reached Monday-Friday: 8:30am to 5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.M.T./Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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