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 without traverse of a Cas nuclease of SEQ ID NO:72 and a uracil DNA glycosylase inhibitor of SEQ ID NO:52 in the reply filed on 06/11/2026 is acknowledged. However, the species election requirement for uracil DNA glycosylase inhibitor species has been withdrawn.
As SEQ ID NO:72 is described as a Class 2 type II Cas endonuclease sequence, Class 2 type V Cas endonucleases are considered non-elected species. As such, claims 142-146 and 151-153 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to this nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/11/2026.
Claims Status
Claims 1-133 is/are cancelled. Claims 134-153 is/are currently pending with claims 142-146 and 151-153 withdrawn. Claims 134-141 and 147-150 is/are under examination.
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.
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.
Fig. 4 comprises a sequence of MG16-1; however, the specification does not provide a SEQ ID NO corresponding to MG16-1. Figs. 6, 8A, 8B, 8C, 10A, 10B, 13A, 13B, 14 show sequences with no corresponding SEQ ID NOs.
Drawings
The drawings are objected to because some figures have illegible attributes. Fig. 5 comprises labels which cannot be interpreted, and a higher-resolution version of Fig. 5 should be provided. 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.
Claim Interpretation
Claims 139 and 150 merely require that a Cas sequence comprise aspartate-to-alanine substitutions at specific residues determined by alignment to any one of SEQ ID NOs:70-76 or 597. This does not require that the Cas sequence have any amount of sequence identity to SEQ ID NOs:70-76 or 597. As such, claims 139 and 150 are interpreted to encompass any Class 2, type II Cas endonuclease sequence which comprises an aspartate-to-alanine mutation that, when the sequence is aligned to one of SEQ ID NOs:70-76 or 597, aligns to the corresponding residue indicated in claims 139 and 150.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claims 134-141, 147-150 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 134 and 147 recite an adenosine deaminase domain at least 60% identical to minimum 20 consecutive amino acids of SEQ ID NO:50. Claim 141 recites a uracil DNA glycosylase inhibitor (UGI) sequence at least 70% identical to SEQ ID NOs:52-56 and 67. Claims 139 and 150 recite Class 2 type II Cas endonucleases of any sequence, so long as when aligned to one of SEQ ID NOs:70-76 of 597, the sequence comprises an aspartate-to-alanine mutation at a residue aligned to residue 9 of SEQ ID NO:70, residue 13 of SEQ ID NOs:71, 72, or 74, residue 12 of SEQ ID NO:73, residue 17 of SEQ ID NO:75, residue 23 of SEQ ID NO:76, or residue 10 of SEQ ID NO:597.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, sequences 100% identical to SEQ ID NOs:50, 52-56, 67, 70-76, and 597 are the only species whose complete structures are disclosed. While the genera encompass large numbers of variants and molecules that have the same activity of an adenosine deaminase (SEQ ID NO:50), UGI (SEQ ID NOs:52-56, 67), or Class 2 type II Cas endonuclease (SEQ ID NOs:70-76, 597) and the genera encompass large numbers of variants and molecules that have different structures, the specification does not describe the complete structures of representative numbers of species of the large genera of adenosine deaminases at least 60% but less than 100% identical to SEQ ID NO:50 or UGIs at least 70% but less than 100% identical to SEQ ID NOs:52-56 and 67 or Class 2 type II Cas endonucleases of any sequence less than 100% identical to SEQ ID NOs:70-76 or 597 or functional equivalents thereof. Additionally, the specification does not describe the complete structures of representative numbers of species of the large genera of modified adenosine deaminases, Class 2 type II Cas endonucleases, or UGIs.
Next, then, it is determined whether representative numbers of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genera. In the instant case, the only other identifying characteristics are that sequences at least 60% identical to SEQ ID NO:50 function as base editors, that UGIs at least 70% identical to SEQ ID NOs:52-56 or 67 have uracil DNA glycosylase inhibitory function, and that Cas endonucleases have RNA-guided DNA binding function. Such a functional limitation cannot be an identifying characteristic for the claimed diverse genus of molecules since by Applicant’s definition of adenosine deaminases, Cas endonucleases, or UGIs or functional equivalents thereof, all members of the claimed genera will have those characteristics. Further, no identifying characteristics of the modified adenosine deaminases, Cas endonucleases, or UGIs are disclosed.
The inventions of claims 135-141 and 148-150 require the use of the inventions of claims 134 and 147 and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
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) 134-139, 147-150 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Joung (WO2020163396A1, of record).
Regarding claim 134, Joung teaches an adenine base editor comprising an adenosine deaminase and a DNA binding domain (claim 1), wherein the adenosine deaminase comprises SEQ ID NO:8 (SEQ ID NO:8 is 98.9% identical to the full length of instant SEQ ID NO:50, see alignment below) (Table B; page 13 lines 30-page 14 line 5).
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Regarding claims 135-138, Joung teaches that the DNA binding domain is a Class 2 type II Cas endonuclease (Cas9) that is a nickase or is catalytically inactive (claims 10-12). In order for the Cas endonuclease to be catalytically inactive, both the RuvC domain and HNH domain must lack nuclease activity (required by claim 136) (see Table C).
Regarding claim 139, Joung teaches that the Cas9 may be SpCas9 comprising the mutation D10A (Table C; page 20). SEQ ID NO:21 of Joung, a base editor comprising an SpCas9 D10A domain, when aligned optimally to instant SEQ ID NO:72, comprises a aspartate-to-alanine mutation at residue 13 relative to SEQ ID NO:72 (see alignment below) (page 66).
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Regarding claim 147, Joung teaches an adenine base editor comprising an adenosine deaminase and a DNA binding domain (claim 1), wherein the adenosine deaminase comprises SEQ ID NO:8 (SEQ ID NO:8 is 98.9% identical to the full length of instant SEQ ID NO:50, see alignment above) (Table B; page 13 lines 30-page 14 line 5). Joung teaches that the DNA binding domain is a Class 2 type II Cas endonuclease (Cas9) that is a nickase or is catalytically inactive (claims 10-12). In order for the Cas endonuclease to be catalytically inactive, both the RuvC domain and HNH domain must lack nuclease activity (see Table C). Joung teaches an engineered gRNA comprising a crRNA and tracrRNA segment (page 22).
Regarding claims 148-149, Joung teaches that the DNA binding domain is a Class 2 type II Cas endonuclease (Cas9) that is a nickase or is catalytically inactive (claims 10-12).
Regarding claim 150, Joung teaches that the Cas9 may be SpCas9 comprising the mutation D10A (Table C; page 20). SEQ ID NO:21 of Joung, a base editor comprising an SpCas9 D10A domain, when aligned optimally to instant SEQ ID NO:72, comprises a aspartate-to-alanine mutation at residue 13 relative to SEQ ID NO:72 (see alignment above) (page 66).
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 134-141 is/are rejected under 35 U.S.C. 103 as being unpatentable over Joung (WO2020163396A1, of record), in view of Liu (WO2018027078A1, of record).
Regarding claim 134, Joung teaches an adenine base editor comprising an adenosine deaminase and a DNA binding domain (claim 1), wherein the adenosine deaminase comprises SEQ ID NO:8 (SEQ ID NO:8 is 98.9% identical to the full length of instant SEQ ID NO:50, see alignment below) (Table B; page 13 lines 30-page 14 line 5).
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Regarding claims 135-138, Joung teaches that the DNA binding domain is a Class 2 type II Cas endonuclease (Cas9) that is a nickase or is catalytically inactive (claims 10-12). In order for the Cas endonuclease to be catalytically inactive, both the RuvC domain and HNH domain must lack nuclease activity (required by claim 136) (see Table C).
Regarding claim 139, Joung teaches that the Cas9 may be SpCas9 comprising the mutation D10A (Table C; page 20). SEQ ID NO:21 of Joung, a base editor comprising an SpCas9 D10A domain, when aligned optimally to instant SEQ ID NO:72, comprises a aspartate-to-alanine mutation at residue 13 relative to SEQ ID NO:72 (see alignment below) (page 66).
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However, Joung does not teach that the adenosine deaminase or Cas9 is fused to a UGI domain.
Liu teaches adenosine deaminase-Cas9-UGI fusion proteins.
Regarding claims 140-141, Liu teaches a fusion protein comprising an adenosine deaminase, a Cas9, and a UGI of SEQ ID NO:3 (SEQ ID NO:3 comprises a sequence 100% identical to instant SEQ ID NO:54, see alignment below) (paragraphs [0009], [0099]-[00101], [00202], [00205]-[00207], [00319]-[00321]; claims 114-123).
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Liu teaches that a UGI domain improves nucleobase editing efficiency in cells by blocking the cellular mechanisms for inosine base excision repair (paragraph [00319]; Fig. 90). It would have been obvious to an artisan at the time of filing that the base editing efficiency of an adenosine deaminase-Cas9 fusion protein, such as that of Joung, could be improved by the addition of a UGI domain, such as in Liu. As such, it would have been obvious to an artisan at the time of filing to modify the base editor of Joung to further comprise a UGI domain of Liu, such as that of SEQ ID NO:3, in order to improve editing efficiency.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFRICA M MCLEOD whose telephone number is (703)756-1907. The examiner can normally be reached Mon-Fri 9:00AM-6:00PM EST.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636
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