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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 17 December 2025 has been entered.
Application Status
This action is written in response to applicant’s correspondence received 17 December 2025. Claims 1-2, 55-56, 58, 64-69, 73, 80-81, 104, 109-110, 114-119, 121, 125-127, and 134-136 are currently pending. Claims 119, 121, and 125-127 are currently withdrawn. Accordingly, claims 1-2, 55-56, 58, 64-69, 73, 80-81, 104, 109-110, 114-118, and 134-136 are examined herein.
With regard to the previously pending rejections under 35 USC 103, Applicant’s amendments, filed 6 December 2024, have been fully considered and are deemed persuasive. Accordingly, the previously pending rejections under 35 USC 103 have been withdrawn.
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.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 18/984,585 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, copending claim 1 claims a method that utilizes a napDNAbp, an adenosine deaminase comprising 100% identity to the claimed SEQ ID NO: 3 (see SEQ ID NO: 1 on pg. 33 of attached sequence alignment), and two or more guide polynucleotides. Copending claim 2 claims that the adenosine deaminase comprises an I76Y mutation. Regarding the claimed functional limitations of “wherein the base editor has increased on-target editing frequency compared to an ABE7.10 base editor comprising the polynucleotide programmable DNA binding domain and an adenosine deaminase comprising SEQ ID NO: 3”, the functional limitations are inherent in the adenosine deaminase comprising the claimed mutations anticipated by the copending application.
Claims 55, 109-110, 114-118, and 134 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 18/984,585 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 55 and 134, the applicable teachings of claims 1 and 4 of the copending application are discussed above as applied to claim 1.
Copending claims 1 and 4 do not claim the use of a fusion protein (Claims 55 and 134). Copending claims 1 and 4 do not claim that the polynucleotide programmable DNA binding domain is a Cas9 or a Cas12 polypeptide (Claim 55).
However, one of ordinary skill in the art would have considered the teachings of Joung as both references are common fields of endeavor pertaining to the use of polynucleotide programmable DNA binding domains, adenosine deaminases, and guide RNAs.
Joung is drawn to an invention concerned with engineered adenine base editor variants with reduced RNA editing activity (Abstract). Joung teaches that adenine base editors are fusions of programmable DNA-binding domains, including a Cas9 polypeptide, fused to engineered adenosine deaminases that can induce programmable adenosine (A) to inosine (I) edits in single-stranded DNA that in turn result in A-to-G transitions after DNA repair or replication guided by the programmable DNA binding domain the ([005]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the copending claims such that the programmable DNA binding domain and adenosine deaminase were present within a fusion protein, as described by Joung. A person of ordinary skill in the art would have been motivated to do so in order to induce edits in target DNA that via a system that can be guided to a particular target region of interest within the target DNA. A person of ordinary skill in the art would have had a reasonable expectation of success because both the copending claims and Jong teach the use of programmable DNA binding domains and adenosine deaminases in order to edit a target nucleic acid of interest.
Regarding claims 109-110 and 114-118, the copending claims do not claim the use of a polynucleotide encoding the fusion protein (Claim 109), an expression vector comprising the polynucleotide (Claim 110), or a cell comprising the fusion protein (Claim 114), wherein the cell is a mammalian cell (Claim 115). The copending claims do not claim the use of guide RNAs that can complex with the fusion protein of claim 1 (Claim 116). The copending claims do not claim a pharmaceutical composition comprising the fusion protein of claim 1 and a pharmaceutically acceptable excipient (Claim 117). The copending claims do not claim the use of a kit comprising the fusion protein of claim 1 (Claim 118).
However, as described above, one of ordinary skill in the art would have considered the teachings of Joung as both references are common fields of endeavor pertaining to the use of polynucleotide programmable DNA binding domains, adenosine deaminases, and guide RNAs.
Joung teaches the use of an isolated nucleic acid encoding the TadA fusion protein ([0019]). Joung teaches the use of an expression vector comprising the isolated nucleic acid ([0020]). Joung teaches that nucleic acids encoding the TadA may be present and expressed within an in vitro isolated mammalian cell (i.e., an in vitro cell) via the use of the expression vectors ([0021]-[0022], [0124]). Joung teaches that at least one guide polynucleotide compatible with the base editor may be complexed with the fusion protein ([0018]). Joung teaches that the TadA may be delivered to a cell via lipid-mediated transfection (i.e., a method interpreted as utilizing a pharmaceutically acceptable excipient) ([0120]). Joung teaches the use of a kit comprising the fusion protein ([0121]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the copending claims such that a polynucleotide encoding the fusion protein and guide RNAs was present within a kit comprising an expression vector comprising the polynucleotide such that it could be expressed in a mammalian cell via the use of the expression vector or lipid-mediated transfection, as described by Joung. A person of ordinary skill in the art would have been motivated to do so in order to express the gene editing system in a target cell of interest. A person of ordinary skill in the art would have had a reasonable expectation of success because both the copending claims and Jong teach the use of programmable DNA binding domains and adenosine deaminases in order to edit a target nucleic acid of interest.
Claims 64-69, 73, 80, and 104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 18/984,585 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019), as applied to claims 55, 109-110, 114-118, and 134 above, further in view of further in view of Ribeiro (International journal of genomics 2018.1 (2018): 1652567).
Regarding claims 64-69, 73, 80, and 104, copending claims 1 and 4 in view of Joung render obvious claims 55, 109-110, 114-118, and 134 as described above.
Copending claims 1 and 4 in view of Joung does not teach or suggest that the adenosine deaminase variant domain is inserted within a flexible loop of the Cas9 polypeptide (Claims 64 and 80). Copending claims 1 and 4 in view of Joung does not teach or suggest that the flexible loop comprises a part of an alpha helix structure of the Cas9 polypeptide (Claim 65). Copending claims 1 and 4 in view of Joung does not teach or suggest that the adenosine deaminase variant domain is flanked by a N-terminal fragment and a C-terminal fragment of the Cas9 polypeptide (Claim 66). Copending claims 1 and 4 in view of Joung does not teach or suggest that the fusion protein comprises the structure: NH2-[N-terminal fragment of a Cas9]-[adenosine deaminase variant]-[C-terminal fragment of a Cas9]-COOH, wherein each instance of "]-[" is an optional linker (Claim 67). Copending claims 1 and 4 in view of Joung does not teach or suggest that the N-terminal fragment or the C-terminal fragment of the Cas9 or Cas12 polypeptide binds a target polynucleotide sequence (Claim 68). Copending claims 1 and 4 in view of Joung does not teach or suggest that a C-terminus of the N terminal fragment or an N-terminus of the C terminal fragment comprises a part of a flexible loop of the Cas9 or the Cas12 polypeptide (Claim 69). Copending claims 1 and 4 in view of Joung does not teach or suggest that neither the N-terminal fragment nor the C-terminal fragment comprises a RuvC domain (Claim 73). Copending claims 1 and 4 in view of Joung does not teach or suggest that the fusion protein comprises the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH (Claim 104).
However, one of ordinary skill in the art would have considered the teachings of Ribeiro as both references are analogous prior art pertaining to the study and use of Cas9 polypeptides.
Ribeiro is drawn towards a study concerned with protein engineering strategies to expand CRISPR-Cas9 applications (Abstract). Ribeiro teaches that active domains of proteins can be inserted around (i.e., within) flexible loops (i.e., alpha helix regions) of Cas9 RuvC domains via insertional fusion (pg. 7). Ribeiro teaches that deaminases can be inserted within an N-terminal and C-terminal of a Cas9 protein by domain insertion in which the deaminase is spliced into the functional Cas9 (i.e., the Cas9 of Ribeiro is able to still bind to target polynucleotides after having a deaminase inserted within it) (pg. 2, 4; see Figure 2b). Ribeiro teaches that a preferred insertional site is a Cas9 RuvC region (pg. 7) located at the C- or N-terminal of the Cas9 (pg. 3; see Figure 1A). Ribeiro teaches that the RuvC domain aids in binding the Cas9 to a target nucleic acid (pg. 3; Figure 1a). Ribeiro teaches that deaminases can be fused to either terminal of the Cas9 protein (pg. 4; see Figure 2a). Ribeiro teaches that domain insertions can create structural coupling among the combined domains, with the emergence of new functions of the proteins (pg. 2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the Cas9 fusion protein of copending claims 1 and 4 in view of Joung such that the TadA was inserted within flexible loops comprising alpha helix regions of the Cas9 via insertional fusion, the fusion protein comprised the structure NH2-[N-terminal fragment of a Cas9]-[adenosine deaminase variant]-[C-terminal fragment of a Cas9]-COOH, the fusion protein comprised the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH, wherein the N-terminal fragment or the C-terminal fragment of the Cas9 or Cas12 polypeptide binds a target polynucleotide sequence, the C-terminus of the N terminal fragment or an N-terminus of the C terminal fragment comprises a part of a flexible loop of the Cas9 polypeptide, the N-terminal fragment or the C-terminal fragment comprises a RuvC domain, as described by Ribeiro. A person of ordinary skill in the art would have been motivated to do so in order to create structural coupling among the combined Cas9 and TadA domains such that new, combined functions emerged from the fused proteins. A person of ordinary skill in the art would have had a reasonable expectation of success because copending claims 1 and 4 in view of Joung teaches the use of an adenosine deaminase while Ribeiro teaches that it was well known in the art that adenosine deaminases can be inserted within Cas9 domains and that the resulting fusion protein retained the ability to target and edit target nucleic acids. adenosine deaminases may be inserted into a Cas9 protein via insertional fusion.
Claims 1, 55, 58, and 134-136 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7 and 11 of copending Application No. 18/031/547 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 1, 55, and 134 copending claim 7 claims the use of a fusion protein comprising a programmable DNA binding domain, and at least one adenosine deaminase variant that has 100% identity to the claimed SEQ ID NO: 3 (see SEQ ID NO: 1 on pg. 25 of attached sequence alignment). Copending claim 11 claims that the adenosine deaminase variant can comprise mutations at I76Y, Y147T, and Q154S. Regarding the claimed functional limitations of “wherein the base editor has increased on-target editing frequency compared to an ABE7.10 base editor comprising the polynucleotide programmable DNA binding domain and an adenosine deaminase comprising SEQ ID NO: 3”, the functional limitations are inherent in the adenosine deaminase comprising the claimed mutations anticipated by the copending application.
Regarding claims 58 and 135-136, copending claim 11 claims that the adenosine deaminase variant can comprise mutations at I76Y, Y147T, and Q154S.
Claims 109-110 and 114-118 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7 and 11 of copending Application No. 18/031/547 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 109-110 and 114-118, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 109-110 and 114-118 over copending Application No. 18/984,585 above.
Claims 64-69, 73, 80, and 104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7 and 11 of copending Application No. 18/031/547 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019), as applied to claims 1, 55, 58, and 134-136 above, further in view of further in view of Ribeiro (International journal of genomics 2018.1 (2018): 1652567).
Regarding claims 64-69, 73, and 80, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 64-69, 73, and 80 over copending Application No. 18/984,585 above.
Copending claims 7 and 11 in view of Joung does not teach or suggest that the fusion protein comprises the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH (Claim 104).
However, one of ordinary skill in the art would have considered the teachings of Ribeiro as both references are analogous prior art pertaining to the study and use of Cas9 polypeptides.
The missing limitation is taught by Ribeiro, whose teachings are discussed above as applied to claim 104 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the fusion protein such that the fusion protein comprised the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH, as described by Ribeiro. A person of ordinary skill in the art would have been motivated to do so in order to create structural coupling among the combined Cas9 and TadA domains such that new, combined functions emerged from the fused proteins. A person of ordinary skill in the art would have had a reasonable expectation of success because copending claim 22 in view of Joung teaches the use of an adenosine deaminase while Ribeiro teaches that it was well known in the art that adenosine deaminases can be inserted within Cas9 domains and that the resulting fusion protein retained the ability to target and edit target nucleic acids. adenosine deaminases may be inserted into a Cas9 protein via insertional fusion.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 22 of copending Application No. 18/418,751 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, copending claim 22 claims a composition comprising a gRNA, a Cas9 domain, and adenosine deaminase that comprises 100% identity to the claimed SEQ ID NO: 3 (see SEQ ID NO: 3 on pg. 27-28 of attached sequence alignment). Copending claim 22 claims that the adenosine deaminase comprises a I76Y mutation. Regarding the claimed functional limitations of “wherein the base editor has increased on-target editing frequency compared to an ABE7.10 base editor comprising the polynucleotide programmable DNA binding domain and an adenosine deaminase comprising SEQ ID NO: 3”, the functional limitations are inherent in the adenosine deaminase comprising the claimed mutations anticipated by the copending application.
Claims 55, 58, 109-110, 114-118, and 134-136 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 22 of copending Application No. 18/418,751 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 55 and 134, the applicable teachings of claim 22 of the copending application are discussed above as applied to claim 1.
Copending claim 22 does not claim the use of a fusion protein (Claims 55 and 134).
However, one of ordinary skill in the art would have considered the teachings of Joung as both references are common fields of endeavor pertaining to the use of polynucleotide programmable DNA binding domains, adenosine deaminases, and guide RNAs.
The missing limitation is taught by Joung, whose teachings are discussed above as applied to claims 55 and 134 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the copending claims such that the programmable DNA binding domain and adenosine deaminase were present within a fusion protein, as described by Joung. A person of ordinary skill in the art would have been motivated to do so in order to induce edits in target DNA that via a system that can be guided to a particular target region of interest within the target DNA. A person of ordinary skill in the art would have had a reasonable expectation of success because both the copending claims and Jong teach the use of programmable DNA binding domains and adenosine deaminases in order to edit a target nucleic acid of interest.
Regarding claims 55, 58, and 135-136, copending claim 22 claims that the adenosine deaminase variant comprises mutations at Y147T and Q154S.
Regarding claims 109-110 and 114-118, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 109-110 and 114-118 over copending Application No. 18/984,585 above.
Claims 64-69, 73, 80, and 104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 22 of copending Application No. 18/418,751 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019), as applied to claims 55, 109-110, 114-118, and 134 above, further in view of further in view of Ribeiro (International journal of genomics 2018.1 (2018): 1652567).
Regarding claims 64-69, 73, and 80, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 64-69, 73, and 80 over copending Application No. 18/984,585 above.
Copending claim 22 in view of Joung does not teach or suggest that the fusion protein comprises the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH (Claim 104).
However, one of ordinary skill in the art would have considered the teachings of Ribeiro as both references are analogous prior art pertaining to the study and use of Cas9 polypeptides.
The missing limitation is taught by Ribeiro, whose teachings are discussed above as applied to claim 104 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the fusion protein such that the fusion protein comprised the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH, as described by Ribeiro. A person of ordinary skill in the art would have been motivated to do so in order to create structural coupling among the combined Cas9 and TadA domains such that new, combined functions emerged from the fused proteins. A person of ordinary skill in the art would have had a reasonable expectation of success because copending claim 22 in view of Joung teaches the use of an adenosine deaminase while Ribeiro teaches that it was well known in the art that adenosine deaminases can be inserted within Cas9 domains and that the resulting fusion protein retained the ability to target and edit target nucleic acids.
Claims 1, 55, 58, and 134-136 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 17/214,643 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 1, 55, and 134 copending claim 1 claims the use of a fusion protein comprising a programmable DNA binding domain, and at least one adenosine deaminase variant that has 100% identity to the claimed SEQ ID NO: 3 (see SEQ ID NO: 2 on pg. 5-6 of attached sequence alignment). Copending claim 4 claims that the adenosine deaminase variant can comprise mutations at Y147T and Q154S. Regarding the claimed functional limitations of “wherein the base editor has increased on-target editing frequency compared to an ABE7.10 base editor comprising the polynucleotide programmable DNA binding domain and an adenosine deaminase comprising SEQ ID NO: 3”, the functional limitations are inherent in the adenosine deaminase comprising the claimed mutations anticipated by the copending application.
Regarding claims 58 and 135-136, copending claim 11 claims that the adenosine deaminase variant can comprise mutations at Y147T and Q154S.
Claims 109-110 and 114-118 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 17/214,643 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 109-110 and 114-118, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 109-110 and 114-118 over copending Application No. 18/984,585 above.
Claims 64-69, 73, 80, and 104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 17/214,643 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019), as applied to claims 1, 55, 58, and 134-136 above, further in view of further in view of Ribeiro (International journal of genomics 2018.1 (2018): 1652567).
Regarding claims 64-69, 73, and 80, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 64-69, 73, and 80 over copending Application No. 18/984,585 above.
Copending claims 1 and 4 in view of Joung does not teach or suggest that the fusion protein comprises the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH (Claim 104).
However, one of ordinary skill in the art would have considered the teachings of Ribeiro as both references are analogous prior art pertaining to the study and use of Cas9 polypeptides.
The missing limitation is taught by Ribeiro, whose teachings are discussed above as applied to claim 104 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the fusion protein such that the fusion protein comprised the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH, as described by Ribeiro. A person of ordinary skill in the art would have been motivated to do so in order to create structural coupling among the combined Cas9 and TadA domains such that new, combined functions emerged from the fused proteins. A person of ordinary skill in the art would have had a reasonable expectation of success because copending claim 22 in view of Joung teaches the use of an adenosine deaminase while Ribeiro teaches that it was well known in the art that adenosine deaminases can be inserted within Cas9 domains and that the resulting fusion protein retained the ability to target and edit target nucleic acids. adenosine deaminases may be inserted into a Cas9 protein via insertional fusion.
Claims 1, 55, 58, and 134-136 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 17/214,643 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 1, 55, and 134 copending claim 1 claims the use of a fusion protein comprising a programmable DNA binding domain, and at least one adenosine deaminase variant that has 100% identity to the claimed SEQ ID NO: 3 (see SEQ ID NO: 2 on pg. 5-6 of attached sequence alignment). Copending claim 4 claims that the adenosine deaminase variant can comprise mutations at Y147T and Q154S. Regarding the claimed functional limitations of “wherein the base editor has increased on-target editing frequency compared to an ABE7.10 base editor comprising the polynucleotide programmable DNA binding domain and an adenosine deaminase comprising SEQ ID NO: 3”, the functional limitations are inherent in the adenosine deaminase comprising the claimed mutations anticipated by the copending application.
Regarding claims 58 and 135-136, copending claim 11 claims that the adenosine deaminase variant can comprise mutations at Y147T and Q154S.
Claims 109-110 and 114-118 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 17/214,643 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 109-110 and 114-118, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 109-110 and 114-118 over copending Application No. 18/984,585 above.
Claims 64-69, 73, 80, and 104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 17/214,643 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019), as applied to claims 1, 55, 58, and 134-136 above, further in view of further in view of Ribeiro (International journal of genomics 2018.1 (2018): 1652567).
Regarding claims 64-69, 73, and 80, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 64-69, 73, and 80 over copending Application No. 18/984,585 above.
Copending claims 1 and 4 in view of Joung does not teach or suggest that the fusion protein comprises the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH (Claim 104).
However, one of ordinary skill in the art would have considered the teachings of Ribeiro as both references are analogous prior art pertaining to the study and use of Cas9 polypeptides.
The missing limitation is taught by Ribeiro, whose teachings are discussed above as applied to claim 104 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the fusion protein such that the fusion protein comprised the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH, as described by Ribeiro. A person of ordinary skill in the art would have been motivated to do so in order to create structural coupling among the combined Cas9 and TadA domains such that new, combined functions emerged from the fused proteins. A person of ordinary skill in the art would have had a reasonable expectation of success because copending claim 22 in view of Joung teaches the use of an adenosine deaminase while Ribeiro teaches that it was well known in the art that adenosine deaminases can be inserted within Cas9 domains and that the resulting fusion protein retained the ability to target and edit target nucleic acids. adenosine deaminases may be inserted into a Cas9 protein via insertional fusion.
Claims 1, 55, 58, and 134-136 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16 and 21 of copending Application No. 17/641,343 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 1, 55, and 134 copending claim 16 claims the use of a fusion protein comprising a programmable DNA binding domain, and at least one adenosine deaminase variant that has 100% identity to the claimed SEQ ID NO: 3 (see SEQ ID NO: 1 on pg. 18 of attached sequence alignment). Copending claim 21 claims that the adenosine deaminase variant can comprise mutations at Y147T and Q154S. Regarding the claimed functional limitations of “wherein the base editor has increased on-target editing frequency compared to an ABE7.10 base editor comprising the polynucleotide programmable DNA binding domain and an adenosine deaminase comprising SEQ ID NO: 3”, the functional limitations are inherent in the adenosine deaminase comprising the claimed mutations anticipated by the copending application.
Regarding claims 58 and 135-136, copending claim 16 claims that the adenosine deaminase variant can comprise mutations at Y147T and Q154S.
Claims 109-110 and 114-118 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16 and 21 of copending Application No. 17/641,343 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 109-110 and 114-118, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 109-110 and 114-118 over copending Application No. 18/984,585 above.
Claims 64-69, 73, 80, and 104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16 and 21 of copending Application No. 17/641,343 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019), as applied to claims 1, 55, 58, and 134-136 above, further in view of further in view of Ribeiro (International journal of genomics 2018.1 (2018): 1652567).
Regarding claims 64-69, 73, and 80, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 64-69, 73, and 80 over copending Application No. 18/984,585 above.
Copending claims 16 and 21 in view of Joung does not teach or suggest that the fusion protein comprises the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH (Claim 104).
However, one of ordinary skill in the art would have considered the teachings of Ribeiro as both references are analogous prior art pertaining to the study and use of Cas9 polypeptides.
The missing limitation is taught by Ribeiro, whose teachings are discussed above as applied to claim 104 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the fusion protein such that the fusion protein comprised the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH, as described by Ribeiro. A person of ordinary skill in the art would have been motivated to do so in order to create structural coupling among the combined Cas9 and TadA domains such that new, combined functions emerged from the fused proteins. A person of ordinary skill in the art would have had a reasonable expectation of success because copending claim 22 in view of Joung teaches the use of an adenosine deaminase while Ribeiro teaches that it was well known in the art that adenosine deaminases can be inserted within Cas9 domains and that the resulting fusion protein retained the ability to target and edit target nucleic acids. adenosine deaminases may be inserted into a Cas9 protein via insertional fusion.
Claims 1-2, 55-56, 58, and 134-136 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/430,274 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 1, 55, and 134 copending claim 1 claims the use of a base editor in a complex with one or more guide RNAs, wherein the base editor comprises a napDNAbp and an adenosine deaminase that has 100% identity to the claimed SEQ ID NO: 3 (see SEQ ID NO:3 on pg. 8 of attached sequence alignment). Copending claim 1 claims that the adenosine deaminase comprises at least one mutation selected from I76Y, V82S, Y147T, Y147R, Q154S, and T166R.
Regarding claims 2, 56, 58, and 135-136 copending claim 1 claims that the adenosine deaminase comprises at least one mutation selected from I76Y, V82S, Y147T, Y147R, Q154S, and T166R.
Claims 109-110 and 114-118 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/430,274 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 109-110 and 114-118, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 109-110 and 114-118 over copending Application No. 18/984,585 above.
Claims 64-69, 73, 80, and 104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/430,274 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019), as applied to claims 1-2, 55-56, 58, and 134-136 above, further in view of further in view of Ribeiro (International journal of genomics 2018.1 (2018): 1652567).
Regarding claims 64-69, 73, and 80, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 64-69, 73, and 80 over copending Application No. 18/984,585 above.
Copending claim 1 in view of Joung does not teach or suggest that the fusion protein comprises the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH (Claim 104).
However, one of ordinary skill in the art would have considered the teachings of Ribeiro as both references are analogous prior art pertaining to the study and use of Cas9 polypeptides.
The missing limitation is taught by Ribeiro, whose teachings are discussed above as applied to claim 104 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the fusion protein such that the fusion protein comprised the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH, as described by Ribeiro. A person of ordinary skill in the art would have been motivated to do so in order to create structural coupling among the combined Cas9 and TadA domains such that new, combined functions emerged from the fused proteins. A person of ordinary skill in the art would have had a reasonable expectation of success because copending claim 22 in view of Joung teaches the use of an adenosine deaminase while Ribeiro teaches that it was well known in the art that adenosine deaminases can be inserted within Cas9 domains and that the resulting fusion protein retained the ability to target and edit target nucleic acids. adenosine deaminases may be inserted into a Cas9 protein via insertional fusion.
Claims 1-2 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of copending Application No. 17/430,665 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, copending claim 1 claims a method that utilizes one or more guide RNAs alongside a programmable DNA binding domain and an adenosine deaminase that comprises 100% identity to the claimed SEQ ID NO: 3 (see SEQ ID NO: 3 on pg. 11 of attached sequence alignment). Copending claim 5 claims that the adenosine deaminase can comprise the mutations V82S and T166R alongside one or more mutations selected from I76Y and Q154S. Regarding the claimed functional limitations of “wherein the base editor has increased on-target editing frequency compared to an ABE7.10 base editor comprising the polynucleotide programmable DNA binding domain and an adenosine deaminase comprising SEQ ID NO: 3”, the functional limitations are inherent in the adenosine deaminase comprising the claimed mutations anticipated by the copending application.
Regarding claim 2, copending claim 5 claims that the adenosine deaminase can comprise the mutations V82S and T166R.
Claims 55-56, 58, 109-110, 114-118, and 134-136 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of copending Application No. 17/430,665 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 55 and 134, the applicable teachings of claims 1 and 5 of the copending application are discussed above as applied to claim 1.
Copending claim 22 does not claim the use of a fusion protein (Claims 55 and 134).
However, one of ordinary skill in the art would have considered the teachings of Joung as both references are common fields of endeavor pertaining to the use of polynucleotide programmable DNA binding domains, adenosine deaminases, and guide RNAs.
The missing limitation is taught by Joung, whose teachings are discussed above as applied to claims 55 and 134 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the copending claims such that the programmable DNA binding domain and adenosine deaminase were present within a fusion protein, as described by Joung. A person of ordinary skill in the art would have been motivated to do so in order to induce edits in target DNA that via a system that can be guided to a particular target region of interest within the target DNA. A person of ordinary skill in the art would have had a reasonable expectation of success because both the copending claims and Jong teach the use of programmable DNA binding domains and adenosine deaminases in order to edit a target nucleic acid of interest.
Regarding claims 55, 58, and 135-136, copending claim 5 claims that the adenosine deaminase variant comprises mutations at V82S and Q154S.
Regarding claims 109-110 and 114-118, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 109-110 and 114-118 over copending Application No. 18/984,585 above.
Claims 64-69, 73, 80, and 104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of copending Application No. 17/430,665 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019), as applied to claims 55-56, 58, 109-110, 114-118, and 134-136 above, further in view of further in view of Ribeiro (International journal of genomics 2018.1 (2018): 1652567).
Regarding claims 64-69, 73, and 80, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 64-69, 73, and 80 over copending Application No. 18/984,585 above.
Copending claims 1 and 5 in view of Joung does not teach or suggest that the fusion protein comprises the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH (Claim 104).
However, one of ordinary skill in the art would have considered the teachings of Ribeiro as both references are analogous prior art pertaining to the study and use of Cas9 polypeptides.
The missing limitation is taught by Ribeiro, whose teachings are discussed above as applied to claim 104 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the fusion protein such that the fusion protein comprised the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH, as described by Ribeiro. A person of ordinary skill in the art would have been motivated to do so in order to create structural coupling among the combined Cas9 and TadA domains such that new, combined functions emerged from the fused proteins. A person of ordinary skill in the art would have had a reasonable expectation of success because copending claim 22 in view of Joung teaches the use of an adenosine deaminase while Ribeiro teaches that it was well known in the art that adenosine deaminases can be inserted within Cas9 domains and that the resulting fusion protein retained the ability to target and edit target nucleic acids.
Claims 1-2 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 6 of copending Application No. 17/430,676 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, copending claim 1 claims a method that utilizes one or more guide RNAs alongside a programmable DNA binding domain and an adenosine deaminase that comprises 100% identity to the claimed SEQ ID NO: 3 (see SEQ ID NO: 3 on pg. 14 of attached sequence alignment). Copending claim 3 claims that the adenosine deaminase can comprise the mutations V82S and T166R. Copending claim 6 claims that the adenosine deaminase can further comprise one or more mutations selected from Q154S. Regarding the claimed functional limitations of “wherein the base editor has increased on-target editing frequency compared to an ABE7.10 base editor comprising the polynucleotide programmable DNA binding domain and an adenosine deaminase comprising SEQ ID NO: 3”, the functional limitations are inherent in the adenosine deaminase comprising the claimed mutations anticipated by the copending application.
Regarding claim 2, copending claim 3 claims that the adenosine deaminase can comprise the mutations V82S and T166R.
Claims 55-56, 58, 109-110, 114-118, and 134-136 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 6 of copending Application No. 17/430,676 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 55 and 134, the applicable teachings of claims 1, 3, and 6 of the copending application are discussed above as applied to claim 1.
Copending claim 22 does not claim the use of a fusion protein (Claims 55 and 134).
However, one of ordinary skill in the art would have considered the teachings of Joung as both references are common fields of endeavor pertaining to the use of polynucleotide programmable DNA binding domains, adenosine deaminases, and guide RNAs.
The missing limitation is taught by Joung, whose teachings are discussed above as applied to claims 55 and 134 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the copending claims such that the programmable DNA binding domain and adenosine deaminase were present within a fusion protein, as described by Joung. A person of ordinary skill in the art would have been motivated to do so in order to induce edits in target DNA that via a system that can be guided to a particular target region of interest within the target DNA. A person of ordinary skill in the art would have had a reasonable expectation of success because both the copending claims and Jong teach the use of programmable DNA binding domains and adenosine deaminases in order to edit a target nucleic acid of interest.
Regarding claims 55, 58, and 135-136, copending claims 2 and 6 claims that the adenosine deaminase variant comprises mutations at V82S and Q154S.
Regarding claims 109-110 and 114-118, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 109-110 and 114-118 over copending Application No. 18/984,585 above.
Claims 64-69, 73, 80, and 104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 6 of copending Application No. 17/430,676 in view of Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019), as applied to claims 55-56, 58, 109-110, 114-118, and 134-136 above, further in view of further in view of Ribeiro (International journal of genomics 2018.1 (2018): 1652567).
Regarding claims 64-69, 73, and 80, each dependent claim is rendered obvious by the combination of the copending claims and Joung and for the same reasons as discussed above in the NSDP rejections of claims 64-69, 73, and 80 over copending Application No. 18/984,585 above.
Copending claims 1, 3, and 6 in view of Joung does not teach or suggest that the fusion protein comprises the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH (Claim 104).
However, one of ordinary skill in the art would have considered the teachings of Ribeiro as both references are analogous prior art pertaining to the study and use of Cas9 polypeptides.
The missing limitation is taught by Ribeiro, whose teachings are discussed above as applied to claim 104 over copending Application No. 18/984,585 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the fusion protein such that the fusion protein comprised the structure NH2-[TadA*8]-[Cas9 with an adenosine deaminase variant fused within the Cas9]-COOH, as described by Ribeiro. A person of ordinary skill in the art would have been motivated to do so in order to create structural coupling among the combined Cas9 and TadA domains such that new, combined functions emerged from the fused proteins. A person of ordinary skill in the art would have had a reasonable expectation of success because copending claim 22 in view of Joung teaches the use of an adenosine deaminase while Ribeiro teaches that it was well known in the art that adenosine deaminases can be inserted within Cas9 domains and that the resulting fusion protein retained the ability to target and edit target nucleic acids.
Closest Prior Art
Regarding claims 1, 55, 104, and 134, the claims require a fusion protein comprising an adenosine deaminase variant that has at least 85% identity to the claimed SEQ ID NO: 3, comprises an amino acid alteration selected from I76Y, V82S, Y147T, Y147R, Q154S, and T166R, and has increased on-target editing frequency compared to an ABE7.10 fusion protein comprising the polynucleotide programmable DNA binding domain and an adenosine deaminase comprising SEQ ID NO: 3. The unexpected results demonstrated by Applicant are not taught or suggested in the closest prior art.
Regarding the closest prior art, Joung (PG Pub No. US 2020/0308571 A1, earliest effective filing date of 4 Feb 2019) is drawn to an invention concerned with engineered adenine base editor variants with reduced RNA editing activity (Abstract). Joung teaches that adenine base editors are fusions of programmable DNA-binding domains, including a Cas9 polypeptide, fused to engineered adenosine deaminases that can induce programmable adenosine (A) to inosine (I) edits in single-stranded DNA that in turn result in A-to-G transitions after DNA repair or replication ([005]). Joung teaches the use of an engineered TadA-heterodimer ABE 7.10 (i.e., an engineered adenine base editor) having 99.4% sequence identity to the claimed SEQ ID NO: 3 ([0035]; see SEQ ID NO: 21 in previously attached sequence alignment). Joung teaches that the TadA can comprise residue changes in either or both TadA domains of the TadA-heterodimer (i.e., present in ABE7.10) at positions I76, V82, and Q154 with any substitution other than the WT amino acid in order to generate a TadA with an RRE phenotype ([0067]).
Although Joung does teach that the TadA can comprise residue changes in either or both TadA domains of the TadA-heterodimer at positions I76, V82, and Q154 with any substitution other than the WT amino acid in order to generate a TadA with an RRE phenotype ([0067]), Joung teaches that the TadA with an RRE phenotype is directed towards a TadA that “induced DNA editing comparable to [emphasis added] that observed with miniABEmax and ABEmax” (i.e., non-mutated TadA variants) ([0172]) and “reasonably maintained [emphasis added] DNA on-target editing capabilities ([0175]). Joung teaches that mutating the ABEmax with a V82G substitution did not result in a mutated ABEmax that had increased editing frequency nor demonstrated the surprising result demonstrated by Applicant; rather, Joung teaches that the ABEmax V82G mutant had either maintained or reduced editing frequency when compared to an unmutated ABEmax and that the mutant did not show an increased editing frequency at all genomic sites tested of about 1.94 fold when compared to the unmutated ABEmax ([0039]; see FIGs. 7A-7B).
Thus, Joung does not teach or suggest the surprising result demonstrated by Applicant wherein the mutations at the claimed amino acid positions present within the claimed SEQ ID NO: 3 resulted in an adenosine deaminase that outperformed ABE7.10 at all genomic sites tested (Instant specification; page 421, lines 31-32) wherein the median increase in editing frequency across all positions tested, and in all sites tested, was about 1.94-fold (Instant specification; page 421, lines 23-24). Accordingly, the prior art does not teach or suggest the surprising result demonstrated by Applicant.
Therefore, if all outstanding double patenting rejections are overcome, the application would be placed in condition for allowance.
Regarding claim 81, the closest prior art is Jayaram (PG Pub No. US 2018/0135109 A1). Jayaram is drawn towards an invention concerned with the design of Cas9/gRNA molecule complexes (Abstract). Jayaram teaches the use of an S. pyogenes Cas9 amino acid sequence that comprises 100% sequence identity to the claimed SEQ ID NO: 1 ([0045]; see SEQ ID NO: 2 in attached sequence alignment). Jayaram teaches that the RuvC domains (i.e., flexible loops) of the S. pyogenes Cas9 amino acid sequence are located at positions 10-21, 759-766, and 982-989 of the amino acid sequence (pg. 55-59).
However, Jayaram does not teach or suggest that the S. pyogenes Cas9 amino acid sequence comprises flexible loops in a region selected from the group consisting of amino acid residues at positions 530-537, 569-579, 686-691, 768-793, 943-947, 1002-1040, 1052-1077, 1232-1248, and 1298-1300 as numbered in the claimed SEQ ID NO: 1 (see Claim 81), nor that an adenosine deaminase can be inserted in the claimed regions of the claimed SEQ ID NO: 1.
Applicant has demonstrated that Cas9 sequence comprising the claimed SEQ ID NO: 1, and a Cas12b protein that has corresponding amino acid positions thereof, that comprises flexible loops that an adenosine deaminase can be inserted into at the claimed positions (Instant specification; pg. 333-334, 378, 409-410; see Tables 10A-10B). Accordingly, Applicant has provide adequate written description support for the claimed insertion of an adenosine deaminase at the claimed positions as numbered in SEQ ID NO: 1, or corresponding amino positions thereof.
Accordingly, claim 81 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.
Response to Arguments
With regard to the previously pending rejections under 35 USC 103, Applicant’s amendments, filed 6 December 2024, have been fully considered and are deemed persuasive. Accordingly, the previously pending rejections under 35 USC 103 have been withdrawn.
Conclusion
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636