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 of Group II (claims 20-27) in the reply filed on 06/18/2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-19 and 28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant’s election of the ABE8.8 fusion protein comprising an adenosine deaminase domain comprising an amino acid sequence with at least 85% identity to SEQ ID NO:4 and further comprising the amino acid alterations Y147R, Q154R, and Y123H, and an spCas9 nickase; and wherein the fusion protein comprises an amino acid sequence with at least 80% identity to SEQ ID NO: 442 as Species A; and gRNA 1772 comprising a spacer having the nucleotide sequence of SEQ ID NO: 478 (Table 2B and claim 24) as Species B in the reply filed on 06/18/2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 25-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 20-24 encompass the elected invention and elected species and are under examination.
Priority
This application is a CON of PCT/US2022/029278, filed 05/13/2022 which claims benefit of 63/189,060, filed 05/14/2021 as reflected by the filing receipt dated 11/28/2023.
Information Disclosure Statement
NPL Reference 27, Ousterout et al., on an IDS dated 10/17/2024 and NPL Reference 40, Hirano Seiichi et al., on an IDS dated 06/11/2026 were missing the date of the references. The Examiner added the dates of the references on each IDS respectively.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See page 318 reciting “https://”.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 23 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 23 recites “wherein the guide RNA(s) comprises a nucleotide sequence selected from one or more of those sequences listed in Table 1, Table 2A, or Table 2B”. See MPEP 2173.05(s). “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted)”. Therefore, claim 23 should be complete in itself, and list all of the nucleotide sequences that the claim intends to include.
In addition, the Markush grouping in claim 23 of “wherein the guide RNA(s) comprises a nucleotide sequence selected from one or more of those sequences listed in Table 1, Table 2A, or Table 2B; or any of the aforementioned sequences wherein 1,2,3,4, or 5 nucleotides is deleted from the 5’ and/or 3’ terminus of the nucleotide sequence” is improper because claim 23 recites “selected from one or more of those sequences listed in Table 1, Table 2A, or Table 2B; or any of the aforementioned sequences wherein 1,2,3,4, or 5 nucleotides is deleted from the 5’ and/or 3’ terminus of the nucleotide sequence”. The recitation of “or” between the options of the Markush grouping causes the claim to be written as an open list of alternatives and not a closed group of alternatives. See MPEP 2173.05(h). Alternatives may be set forth as "a material selected from the group consisting of A, B, and C"… A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members.
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.
Claims 20-24 are rejected under 35 U.S.C. 103 as being unpatentable over Bogorad et al. (WO 2018007871, Published 11 Jan 2018), cited on an IDS dated 07/08/2025, in view of Chadwick et al. (US 20230158174, EFD 09 April 2021).
As stated in the response to restriction/election above, Applicant elected ABE8.8 fusion protein comprising an adenosine deaminase domain comprising an amino acid sequence with at least 85% identity to SEQ ID NO:4 and further comprising the amino acid alterations Y147R, Q154R, and Y123H, and an spCas9 nickase; and wherein the fusion protein comprises an amino acid sequence with at least 80% identity to SEQ ID NO: 442 as Species A; and gRNA 1772 comprising a spacer having the nucleotide sequence of SEQ ID NO: 478 (Table 2B and claim 24) as Species B.
Regarding claims 20-24, Bogorad et al. teach components, kits, and compositions for performing cellular, ex vivo and in vivo methods for creating permanent changes to the genome by deleting, inserting, correcting, or modulating the expression of or function of one or more mutations within or near the Transthyretin (TTR) gene or other DNA sequences that encode regulatory elements of the TTR gene, which may be used to treat Familial Transthyretin Amyloidosis (FTA) (paragraph 0015). Bogorad et al. teach kits for carrying out the methods described herein. A kit can include one or more of a genome-targeting nucleic acid, a polynucleotide encoding a genome-targeting nucleic acid, a site-directed polypeptide, a polynucleotide encoding a site-directed polypeptide, and/or any nucleic acid or proteinaceous molecule necessary to carry out the aspects of the methods described herein, or any combination thereof (paragraph 00447).
Bogorad et al. teach nickase variants of RNA-guided endonucleases, for example Cas9, can be used to increase the specificity of CRISPR-mediated genome editing (paragraph 00218), and in some embodiments, the site-directed polypeptide comprises one or more non-native sequences (e.g., the site-directed polypeptide is a fusion protein) (paragraph 00221).
Bogorad et al. teach a genome-targeting nucleic acid that can direct the activities of an associated polypeptide (e.g., a site-directed polypeptide) to a specific target sequence within a target nucleic acid. The genome-targeting nucleic acid can be an RNA. A genome-targeting RNA is referred to as a "guide RNA" or "gRNA" herein. A guide RNA comprises at least a spacer sequence that hybridizes to a target nucleic acid sequence of interest, and a CRISPR repeat sequence (paragraph 00231). Bogorad et al. teach exemplary guide RNAs include the spacer sequences in SEQ ID NOs: 1-8,669 and SEQ ID NOs: 8,770-39,185, shown with the genome location of their target sequence and the associated Cas9 cut site, wherein the genome location is based on the GRCh38 human genome assembly. As is understood by the person of ordinary skill in the art, each guide RNA can be designed to include a spacer sequence complementary to its genomic target sequence (paragraph 00232). Bogorad et al. teach a composition comprising one or more guide ribonucleic acids (gRNAs) for editing a TTR gene in a cell, wherein the one or more gRNAs comprises a spacer sequence selected from the group consisting of nucleic acid sequences in SEQ ID NOs: 1-8,669 (paragraph 00571). Example 1 of Bogorad et al. teaches regions of the TTR gene were scanned for target sites. Each area was scanned for a protospacer adjacent motif (PAM) having the sequence NRG. gRNA 20 bp spacer sequences corresponding to the PAM were identified, as shown in SEQ ID NOs: 1-3,352 (paragraph 00590).
SEQ ID NO: 3035 of Bogorad et al. (Db) is 100% identical to all 20 nucleotides of instant SEQ ID NO: 478 (Qy):
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Table 5 on page 135 shows gRNA sequences and cutting efficiencies in HEK293T cells. The gRNA of SEQ ID NO: 3035 had an Indel % of 88.7%.
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While Bogorad et al. teach nickase variants of RNA-guided endonucleases, for example Cas9, can be used to increase the specificity of CRISPR-mediated genome editing and in some embodiments the site-directed polypeptide can be a fusion protein, Bogorad et al. do not teach a fusion protein that comprises an adenosine deaminase domain, or wherein the adenosine deaminase domain comprises an amino acid sequence with at least 85% identity to instant SEQ ID NO:4 and further comprising the amino acid alterations Y147R, Q154R, and Y123H, and wherein the fusion protein comprises an amino acid sequence with at least 80% identity to instant SEQ ID NO: 442.
Before the effective filing date, Chadwick et al. taught compositions for gene modification or editing (paragraph 0003) including base editor systems capable of nucleobase modifications. In some embodiments, the base editor system comprises (i) a guide polynucleotide or a nucleic acid encoding same, and (ii) a base editor fusion protein comprising a programmable DNA binding domain and a deaminase, or a nucleic acid encoding the same (paragraph 0121)…the base editor comprises a fusion protein comprising a programmable DNA binding protein fused to an adenosine deaminase. In some embodiments, the base editor comprises a fusion protein comprising a Cas9 protein and an adenosine deaminase. In some embodiments, the base editor is a Cas9 nickase (nCas9) fused to an adenosine deaminase (paragraph 0175). Chadwick et al. taught the Cas9 domain may be a SpCas9 nickase (paragraph 0266).
Chadwick et al. taught the sequence of the fusion protein comprises an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.7%, or at least 99.9% identical to any one of the amino acid sequences of SEQ ID NOs: 2137, 2149, 2154, 2158, 2188, 2140, 40, 2146, 2152, 2156, and 2160. In some embodiments, the fusion protein comprises any one of the amino acid sequences of SEQ ID NOs: 2137, 2149, 2154, 2158, 2188, 2140, 40, 2146, 2152, 2156, and 2160. In some embodiments, the sequence of the fusion protein is any one of the amino acid sequences of SEQ ID NOs: 2137, 2149, 2154, 2158, and 2188 (paragraph 0186).
SEQ ID NO: 2149 of Chadwick et al. (Db) has 99.9% identity to instant SEQ ID NO: 442 (Qy) and as shown in the alignment below, has the amino acid alterations Y147R, Q154R, and Y123H.
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809
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Per the alignment below, it is noted that nucleotides 1-167 of Instant SEQ ID NO: 4 (Db) align with nucleotides 1-167 of instant SEQ ID NO: 442 (Qy) other than instant SEQ ID NO: 4 contains Y at position 123, Y at position 147 and Q at position 154, and instant SEQ ID NO: 442 contains H at position 123, R at position 147 and R at position 154.
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Likewise, nucleotides 1-167 of Instant SEQ ID NO: 4 (Db) aligns with nucleotides 1-167 of SEQ ID NO: 2149 of Chadwick et al. (Qy) with the amino acid substitutions Y at position 123, Y at position 147 and Q at position 154, shown below:
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Therefore, SEQ ID NO: 2149 of Chadwick et al. teach the elected fusion protein comprising an adenosine deaminase domain comprising an amino acid sequence with at least 85% identity to SEQ ID NO:4 and further comprising the amino acid alterations Y147R, Q154R, and Y123H, and an spCas9 nickase; and wherein the fusion protein comprises an amino acid sequence with at least 80% identity to SEQ ID NO: 442.
Chadwick et al. also taught the nucleobase editor ABE8.8 comprises a fusion protein comprising the sequence as provided below: (SEQ ID NO: 3) (paragraphs 0188-0189). The nucleobase editor ABE8.8 of SEQ ID NO: 3 of Chadwick et al. has 100% identity to the elected sequence of SEQ ID NO: 442, also identified as ABE8.8 in instant claim 22. Chadwick et al. taught Adenine 8.8-m (hereafter referred to as ABE8.8) uses its core Streptococcus pyogenes nickase Cas9 (nSpCas9) protein with a guide RNA (gRNA) to engage a double-strand protospacer DNA sequence, flanked by an NGG protospacer-adjacent motif (PAM) sequence on its 3′ end. The protospacer sequence is specified via hybridization of the first 20 bases of the gRNA with a complementary sequence on the “target” DNA strand, leaving part of the other (“non-target”) strand in exposed single-strand form structure called the R-loop. The ABE base editor uses an evolved deoxyadenosine deaminase domain—fused to nSpCas9—to chemically modify an adenosine nucleoside, contained in the single-stranded DNA portion of the R-loop, into inosine and nicks the target DNA strand within the DNA:RNA heteroduplex of the R-loop. This nick biases DNA repair machinery to use the freshly deaminated strand as a template, enabling highly efficient transition mutation at the targeted site. The activity window of ABE8.8 typically ranges from positions 3 to 9 in the protospacer DNA sequence specified by the gRNA, 12 to 18 base pairs 5′ of the NGG PAM (positions 21 to 23), with peak editing observed at position 6 of the protospacer (paragraph 0652).
Chadwick et al. taught each of the gRNAs described in Table 8, with an equivalent amount of in vitro transcribed ABE8.8 mRNA MA002 (1:1 ratio by weight), were co-transfected into primary human hepatocytes and primary cynomolgus hepatocytes using various dilutions to assess for editing activity at different concentrations of test article. In both human and cynomolgus hepatocytes, as high as 60%-70% editing of the target splice site (PCSK9 intron 1 splice donor; ANGPTL3 intron 6 splice donor) were observed (Table 8) (paragraph 0668).
It is also noted that additional sequences of fusion proteins of Chadwick et al. read on the elected species, including SEQ ID NO: 2137,2154,2158 and which are taught in paragraph 0186.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified the TTR gene editing composition of Bogorad et al. comprising the gRNA comprising a spacer sequence of SEQ ID NO: 3035 and substitute the Cas9 nickase of Bogorad et al. with the nucleobase editor fusion protein of SEQ ID NO: 2149 or SEQ ID NO: 3 of Chadwick et al. to arrive at the instant claims with a reasonable expectation of success. There would be a reasonable expectation of success as this amounts to simple substitution of one known element for another to obtain predictable results, and because both Bogorad et. al and Chadwick et al. pertain to gene editing using gRNAs and Cas9 and Bogorad et al. suggested that the site-directed polypeptide can be a fusion protein (paragraph 00221). One of ordinary skill in the art would have been motivated to modify the TTR gene editing composition of Bogorad et al. comprising the gRNA comprising a spacer sequence of SEQ ID NO: 3035 and substitute the Cas9 nickase protein of Bogorad et al. with the nucleobase editor fusion protein of SEQ ID NO: 2149 or SEQ ID NO: 3 of Chadwick et al. because Chadwick et al. taught Adenine 8.8-m (hereafter referred to as ABE8.8) uses its core Streptococcus pyogenes nickase Cas9 (nSpCas9) protein with a guide RNA (gRNA) to engage a double-strand protospacer DNA sequence, flanked by an NGG protospacer-adjacent motif (PAM) sequence on its 3′ end. The protospacer sequence is specified via hybridization of the first 20 bases of the gRNA with a complementary sequence on the “target” DNA strand, leaving part of the other (“non-target”) strand in exposed single-strand form structure called the R-loop. The ABE base editor uses an evolved deoxyadenosine deaminase domain—fused to nSpCas9—to chemically modify an adenosine nucleoside, contained in the single-stranded DNA portion of the R-loop, into inosine and nicks the target DNA strand within the DNA:RNA heteroduplex of the R-loop. This nick biases DNA repair machinery to use the freshly deaminated strand as a template, enabling highly efficient transition mutation at the targeted site and because the activity window of ABE8.8 typically ranges from positions 3 to 9 in the protospacer DNA sequence specified by the gRNA, 12 to 18 base pairs 5′ of the NGG PAM (positions 21 to 23), with peak editing observed at position 6 of the protospacer (paragraph 0652). An ordinary artisan would have been motivated by the teachings of Chadwick et al. regarding gRNAs described in Table 8, with an equivalent amount of in vitro transcribed ABE8.8 mRNA MA002 (1:1 ratio by weight), were co-transfected into primary human hepatocytes and primary cynomolgus hepatocytes and resulted in as high as 60%-70% editing of the target splice site (paragraph 0668), and would therefore be motivated to use the ABE8.8 base editor (SEQ ID NO: 3) with gRNA for editing other target genes, including TTR.
Accordingly, the limitations of claims 20-24 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
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 20-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/515,118 (‘118) (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-5 and 11-15 of ‘118 recite an isolated polynucleotide or a nucleic acid encoding same, the polynucleotide comprising a 5'- spacer sequence
comprising about 17 to about 23 nucleotides that is homologous to a targeted protospacer sequence within a gene encoding Transthyretin (TTR) adjacent to a NGG protospacer-adjacent motif (PAM) sequence within the genome; the isolated polynucleotide serving as a guide polynucleotide to direct a base editor system to effect a nucleobase alteration in the TTR gene, with claim 4 reciting specific spacer sequences of SEQ ID NOs: 1-5.
Instant claims 20-24 recite “A composition comprising one or more polynucleotides encoding a fusion protein and a guide RNA, wherein the guide RNA comprises a nucleic acid sequence that is complementary to a transthyretin (TTR) polynucleotide, and wherein the fusion protein comprises a polynucleotide programmable DNA binding domain and an adenosine or cytidine deaminase domain, with claim 21 reciting the adenosine deaminase domain has at least 85% identity to SEQ ID NO: 4, claim 22 reciting the fusion protein is at least 80% identical to ABE8.8 (SEQ ID NO: 442), and claims 23-24 reciting the guide RNA comprises a nucleotide sequence 5'-GCCAUCCUGCCAAGAAUGAG-3' (SEQ ID NO: 478; gRNA1772) (the elected sequence).
SEQ ID NO: 1 (5'-GCCAUCCUGCCAAGAAUGAG-3' (SEQ ID NO: 1) (GA457)) of ‘118 is the same sequence as the spacer sequence of the gRNA of instant SEQ ID NO: 478 (5'-GCCAUCCUGCCAAGAAUGAG-3' (SEQ ID NO: 478; gRNA1772)) being examined in instant claim 24.
Claims 6-10 of ‘118 recite a composition comprising the isolated polynucleotide or nucleic acid encoding the same of claim 1, and claim 7 adds a nucleic acid encoding a base editor fusion protein comprising a programmable DNA binding
domain and a deaminase, with claim 8 reciting the deaminase comprises a cytosine deaminase or adenine deaminase, claim 9 reciting the programmable DNA binding domain comprises a catalytically impaired Cas9 protein, and claim 10 reciting the deaminase comprises ABE8.8. ABE8.8 is the same fusion protein recited in instant claim 22 that is being examined and is recited as instant SEQ ID NO: 442. Claims 16-20 of ‘118 recite a composition for editing a TTR gene comprising (a) a mRNA encoding a base editor protein having an editing window and (b) a guide RNA comprising a tracr sequence that serves as a binding scaffold for the base editor protein and a spacer sequence that serves to guide the base editor protein to a protospacer sequence on the TTR gene, with claim 17 reciting the base editor protein comprises a cytidine deaminase or adenosine deaminase and claim 18 reciting the base editor fusion protein is ABE8.8 which is recited in instant claim 22. Claims 19-20 of ‘118 again recite specific gRNA spacer sequences including SEQ ID NOs: 6-10, and SEQ ID NO: 6 of ‘118 has the same sequence as instant SEQ ID NO: 478 under examination. Therefore, the claims are not patently distinct from each other as they recite the same gRNA sequences and same fusion protein (ABE8.8) for editing the same gene (TTR) and are of the same scope or overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 20-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 19/204,091 (‘091) (reference application), and claims 1-19 of copending Application No. 19/209,589 (‘589) (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-19 of ‘091 recite a base editor system for modifying a target Transthyretin (TTR) gene comprising a guide RNA, comprising a sequence defined by mG*mC*mC*AUCCUGCCAAGAAUGAGmGUUUUAGmAmGmCmUmAGmA mAmAmUmAmGmCmAmAGUUmAAmAAmUAmAmGmGmCmUmAGUmC mCGUUAmUmCAAmCmUmUGmAmAmAmAmAmGmUmGGmCmAmCmC mGmAmGmUmCmGmGmUmGmCmU*mU*mU*mU (GA521, SEQ ID NO:11)…the guide RNA directing the base editor system to effect a nucleobase alteration in the TTR gene, and claim 2 of ‘091 recites an engineered, non-naturally occurring base editing system for modifying a target Transthyretin (TTR) gene, comprising (a) a guide RNA molecule having a sequence defined by mG*mC*mC*AUCCUGCCAAGAAUGAGmGUUUUAGmAmGmCmUmAGmA mAmAmUmAmGmCmAmAGUUmAAmAAmUAmAmGmGmCmUmAGUmC mCGUUAmUmCAAmCmUmUGmAmAmAmAmAmGmUmGGmCmAmCmC mGmAmGmUmCmGmGmUmGmCmU*mU*mU*mU (SEQ ID NO: 11), and (b) a codon-optimized nucleic acid encoding a Cas9 protein fused to a deaminase, wherein the Cas9 protein fusion is capable of binding to the guide RNA and of editing the target TTR sequence complementary to the guide RNA. Claim 3 recites the deaminase comprises a cytosine deaminase or adenine deaminase, claim 5 recites nickase Cas9, claim 7 recites the Cas9 is fused to ABE8.8.
Claims 1-12 and 15-19 of ‘589 recite a lipid nanoparticle comprising a guide polynucleotide comprising a sequence selected from those recited in claim 1 (and are disclosed for editing the TTR gene), and claims 13-14 add a polynucleotide encoding a base editor comprising a nucleic acid programmable DNA binding protein and a deaminase domain.
Instant claims 20-22 recite “A composition comprising one or more polynucleotides encoding a fusion protein and a guide RNA, wherein the guide RNA comprises a nucleic acid sequence that is complementary to a transthyretin (TTR) polynucleotide, and wherein the fusion protein comprises a polynucleotide programmable DNA binding domain and an adenosine or cytidine deaminase domain, with claim 21 reciting the adenosine deaminase domain has at least 85% identity to SEQ ID NO: 4, and claim 22 reciting the fusion protein is at least 80% identical to ABE8.8 (SEQ ID NO: 442).
Therefore, ‘091 claims the same fusion protein as instantly claimed (ABE8.8), and the species of the gRNA recited in ‘091 falls within the scope of the gRNA of instant claims 20-22.
The claims of ‘589 fall within the scope of instant claims 20-22 as the recited gRNAs of ‘589 are species that fall within the scope of the genus of those in instant claims 20-22, and ‘589 also recite a nucleic acid programmable DNA binding protein and a deaminase domain as in instant claims 20-22.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 20-24 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHANIE L SULLIVAN whose telephone number is (703)756-4671. The examiner can normally be reached Monday-Friday, 7:30-3:30 EST.
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/STEPHANIE L SULLIVAN/Examiner, Art Unit 1635
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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