DETAILED ACTION
Claims 130-131, 148-159 and 167-172 are pending.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A preliminary amendment filed on 07/31/2024 adding a “Related Applications” and a “Reference to an Electronic Sequence Listing” section to the application is acknowledged.
A preliminary amendment filed on 11/06/2024 cancelling claims 1-129, 132-147 and 160-166, amending claims 130, 131, 148, 150, 151 and 154-159 and adding new claims 167-172 is acknowledged.
Priority
This application is a divisional of US application 17/057,398 filed on 11/20/2020 and claims domestic priority under 35 U.S. C. 119(e) to provisional application No. 62/675,726 filed on 05/23/2018.
Drawings
Figure 1A is objected to because it is illegible. The figure is small and makes it hard to make out all of the details needed to understand the figure. 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 Rejections - 35 USC § 112(b)
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 157 is 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.
Claim 157 is indefinite in the recitation of a broader range followed by a narrow range “at least 80%...99%” Correction is required.
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 130 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (GenBank Accession ELK10432, 2013).
Claim 130 is directed in part to a cytidine deaminase comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of any one of SEQ ID Nos: 6-9.
Zhang et al. (GenBank Accession ELK10432) is an 84.5% match to SEQ ID NO:6 (see sequence alignment below), which is a C->U-editing enzyme APOBEC-1 (a zinc-dependent cytidine deaminase) from Pteropus alecto (black flying fox).
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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, 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.
Claims 130, 148-159 and 167-169 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (GenBank Accession ELK10432, 2013), Maianti et al. (US 10,745,677 B2, filed on 12/22/2017), Liu et al.1(US 11,306,324 B2, filed on 10/13/2017) and in view of Liu et al.2 (US 11,268,082 B2, filed on 03/23/2018).
Zhang et al. teaches a cytidine deaminase that has 84.5% sequence identity to SEQ ID NO: 6 of the instant application.
Maianti et al. teaches a fusion protein comprising a Cas9 nickase-nucleic acid editing domain fused to a cytidine deaminase and a Gam protein, which is further fused to a UGI domain (see column 119, last paragraph). Maianti et al. teaches that the fusion proteins in some embodiments further comprise a nuclear localization sequence (NLS) (see column 121, second paragraph). Maianti et al. teaches that the Cas9 nickase cleaves the target strand that is base paired to a gRNA (see column 93, first paragraph). Maianti et al. teaches the Cas9 domain of SEQ ID NO: 3 of the instant application as SEQ ID NO: 704 (see alignment below). Maianti et al. teaches the UGI domain of SEQ ID NO: 108 as SEQ ID NO: 361 (see alignment below). Maianti et al. teaches a fusion protein comprising the structure: NH2- [cytosine deaminase domain]-[optional linker sequence]-[guide nucleic sequence programmable DNA-binding protein domain]-[optional linker sequence]-[UGI domain]-COOH (see claim 21).
Maianti et al. does not teach a cytidine deaminase with at least 80% sequence identity to SEQ ID NO: 6-9 as recited in claim 1. Maianti et al. does not teach the use of two UGI domains.
Liu et al.1 teaches a nuclear localization sequence that comprises the amino acid sequence of SEQ ID NO: 1 of the instant application as SEQ ID NO: 375 (see alignment below). Liu et al.1 teaches the use of bipartite nuclear localization sequences (see column 2, 5th paragraph).
Liu et al.2 teaches a nuclear localization sequence that comprises the amino acid sequence of SEQ ID NO: 2 of the instant application as SEQ ID NO: 740 (see alignment below). Liu et al.2 teaches a fusion protein that comprises a nucleic acid programmable binding protein (napDNAbp): a cytidine deaminase domain; and (iii) two uracil glycosylase inhibitor domains (see claim 1).
SEQ ID NO: 3 alignment with SEQ ID NO: 704 of Maianti et al.
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SEQ ID NO: 108 alignment with SEQ ID NO: 361 of Maianti et al.
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SEQ ID NO: 1 alignment with SEQ ID NO: 375 of Liu et al.1
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SEQ ID NO: 2 alignment with SEQ ID NO: 740 of Liu et al.2
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Claim 130 is directed in part to a cytidine deaminase comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of any one of SEQ ID Nos: 6-9. Claim 148 is directed to a fusion protein comprising (i) a nucleic acid programmable DNA binding protein (napDNAbp; and (ii) the cytidine deaminase of claim 130. Claim 149 is directed to the fusion protein of claim 148, wherein the fusion protein further comprises (iii) one or more UGI domains. Claim 150 is directed to the fusion protein of claim 148, wherein the fusion protein further comprises (iv) one or more nuclear localization sequences. Claim 151 is directed to the fusion protein of claim 148, wherein the nucleic acid programmable DNA binding protein is a Cas9 domain. Claim 152 is directed to the fusion protein of claim 151, wherein the Cas9 domain is a Cas9 nickase domain. Claim 153 is directed to the fusion protein of claim 152, wherein the Cas9 nickase domain cuts a nucleic acid target strand of a nucleotide duplex, wherein the nucleotide target strand is the strand that binds a gRNA. Claim 154 is directed to the fusion protein of claim 151, wherein the Cas9 domain comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO:3. Claim 155 is directed to the fusion protein of claim 151, wherein the Cas9 domain comprises the amino acid sequence of SEQ ID NO: 3. Claim 156 is directed to the fusion protein of claim 149, wherein the fusion protein comprises two UGI domains. Claim 157 is directed to the fusion protein of claim 149, wherein the one or more UGI domains comprise an amino acid sequence that is at least 80%, 85%, 90%, 95%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 108. Claim 158 is directed to the fusion protein of claim 149, wherein the one or more UGI domains comprise the amino acid sequence of SEQ ID NO: 108. Claim 159 is directed to the fusion protein of claim 148, wherein the fusion protein comprises the structure: NH2-[cytidine deaminase of claim 130]-[Cas9 domain]- COOH;(ii) NH2-[cytidine deaminase of claim 130]-[Cas9 domain]-[UGI domain]-COOH:(iii) NH2-[cytidine deaminase of claim 130]-[Cas9 domain]-[first UGI domain]-[second UGI domain]-COOH:(iv) NH2-[cytidine deaminase of claim 130]-[Cas9 domain]-[nuclear localization sequence]-COOH:(v) NH2-[first nuclear localization sequence]-[cytidine deaminase of claim 130]-[Cas9 domain]-[second nuclear localization sequence]-COOH: or (vi) NH2-[first nuclear localization sequence]-[cytidine deaminase of claim 130]-[Cas9 domain]-[first UGI domain]-[second UGI domain]-[second nuclear localization sequence]-COOH:, and wherein each instance of "-" comprises an optional linker. Claim 167 is directed to the fusion protein of claim 150, wherein the one or more nuclear location sequences are bipartite nuclear localization sequences. Claim 168 is directed to the fusion protein of claim 150, wherein the one or more nuclear localization sequences comprises the amino acid sequence of SEQ ID NO:1 or SEQ ID NO: 2.
It would have been obvious to one of ordinary skill in the art before the effective filling date of the claimed invention to substitute the cytidine deaminase of Zhang et al. for the cytidine deaminase domains taught by Maianti et al., Liu et al.1 and Liu et al.2.
A person of ordinary skill in the art is motivated to substitute the cytidine deaminase of Zhang et al. because the protein was known in the prior art to catalyze the cytidine to uridine posttranslational editing of a variety of mRNAs.
One of ordinary skill in the art has a reasonable expectation of success at substituting the cytidine deaminase of Zhang et al. for the cytidine deaminase domains taught by Maianti et al., Liu et al.1 and Liu et al.2 to arrive at the claimed invention because it was well known in the art to have the same activity as the cytidine deaminase of claim 130. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 130, 148-149, 151-155 and 159 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 21 of U.S. Patent No. 10,745,677 (‘677) in view of Zhang et al. Claim 130 of the instant application requires a cytidine deaminase that is at least 80% of any of the amino acid sequences of SEQ ID NO: 6-9. U. S Patent No. 10,745,677 does not disclose this limitation in the claims but does recite in claims 9 and 22 that the cytosine deaminase comprises an apolipoprotein B mRNA-editing complex (APOBEC) family deaminase. Zhang et al. teaches an APOBEC-1 protein that has 84.5% sequence identity to SEQ ID NO: 6 of the instant application and therefore, it would be obvious to substitute the cytosine deaminase of claim 1 of U.S Patent 10, 745, 677 with the APOBEC-1 protein of Zhang et al. to arrive at claims 130 of the instant application. Claim 1 of ‘677 comprises the limitations of claims 148-149 of the instant application in view of Zhang et al. Claim 3 of ‘677 comprises the limitations of claims 151-153 of the instant application in view of Zhang et al. Claim 4 of ‘677 comprises the limitations of claim 155 of the instant application as SEQ ID NO: 1 of ‘677 is at least 80% identical to the amino acid sequence of SEQ ID NO:3 of the instant application in view of Zhang et al. Claim 21 of ‘677 teaches the limitation of NH2-[cytidine deaminase of claim 130]-Cas9 domain]-[UGI]-COOH in view of Zhang et al.
Claims 130, 148-149, 151, 156 and 159 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6, 10 and 11 of U.S. Patent No. 11,319,532 (‘532) in view of Zhang et al. Claim 130 of the instant application requires a cytidine deaminase that is at least 80% of any of the amino acid sequences of SEQ ID NO: 6-9. U. S Patent No. 10,745,677 does not disclose this limitation in the claims. However, claim 1 of ‘532 teaches a cytidine deaminase domain. Zhang et al. teaches an APOBEC-1 protein that has 84.5% sequence identity to SEQ ID NO: 6 of the instant application and therefore, it would be obvious to substitute the cytidine deaminase of claim 1 of U.S Patent 11,319, 532 with the APOBEC-1 protein of Zhang et al. Claim 1 of ‘532 teaches the limitations of claim 148 of the instant application in view of Zhang et al. Claim 2 of ‘532 further limits with a UGI domain which is recited in claim 149 of the instant application in view of Zhang et al. Claim 3 of ‘532 further limits the napDNAbp domain to a Cas9 domain which is recited in claim 151 of the instant application in view of Zhang et al. Claim 6 recites that the fusion protein has a second UGI domain and claim 156 of the instant application requires two UGI domains in view of Zhang et al. Claim 159 of the instant application recites a fusion protein comprising the same limitations as claims 10 and 11 of ‘532.
Claims 130, 148-149, 151, 156 and 159 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-8 ,12 and 13 of U.S. Patent No. 11,932,884 (‘884) in view of Zhang et al. Claim 130 of the instant application requires a cytidine deaminase that is at least 80% of any of the amino acid sequences of SEQ ID NO: 6-9. U. S Patent No. 11,932,884 does not disclose this limitation in the claims. However, claim 1 of ‘884 teaches a cytidine deaminase domain. Zhang et al. teaches an APOBEC-1 protein that has 84.5% sequence identity to SEQ ID NO: 6 of the instant application and therefore, it would be obvious to substitute the cytidine deaminase of claim 1 of U.S Patent 11,932,884 with the APOBEC-1 protein of Zhang et al. Claim 1 of ‘884 teaches the limitations of claim 148 of the instant application in view of Zhang et al. Claim 2 of ‘884 further limits with a UGI domain which is recited in claim 149 of the instant application in view of Zhang et al. Claim 3 of ‘884 further limits the napDNAbp domain to a Cas9 domain which is recited in claim 151 of the instant application in view of Zhang et al. Claim 7 of ‘884 teaches a second UGI domain which is recited in claim 156 of the instant application. Claim 159 of the instant application recites a fusion protein comprising the same limitations as claims 10 and 11 of ‘884.
Allowable Subject Matter
Claims 131 and 170-172 are 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. SEQ ID Nos: 6-9 are free of prior art. SEQ ID Nos: 12-14 are free of prior art.
Conclusion
No claim is in condition for allowance.
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/DALTON EDWARD KIEFER/Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
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