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 .
This action is in response to the amendment filed 01/21/2026, in which claims 116, 117, 120, 124, 125, 127, 129, 132, 138, 141, 142 and 145 were amended and claims 118, 119, 121, 122, 123, 126, 130, 131, 133-137, 139, 140, 143 and 144 are previously presented. Claims 116-118, 120-127 and 129-145 are currently pending.
Any rejection of record in the previous office actions not addressed herein is withdrawn. New grounds of rejection are presented herein that were not necessitated by applicant' s amendment of the claims since the office action mailed 10/21/2025. Therefore, this action is not final.
Election/Restriction
Applicant’s election without traverse of Group I, drawn to claims 116-133 and 141-144 in the reply filed on 09/22/2025 is acknowledged. Claims 138-140 are not patentably distinct from the claims of Group I. Claim 116 encompasses “a nucleic acid encoding the polypeptide, wherein the polypeptide comprises an amino acid sequence that is at least 85% identical to a sequence selected from SEQ ID NO: 1 and SEQ ID NO: 2”. Claim 138 encompasses the same nucleic acid. Therefore, the restriction between Group I and Group II have been withdrawn and claims 138-140 will also be examined.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
The restriction between Groups I/III and each of Groups II and IV is maintained.
Applicant’s election without traverse of a nucleic acid that encodes a nucleic acid encoding the polypeptide with 85% identity to SEQ ID NO: 1, a PAM sequence comprising SEQ ID NO: 3 and an engineered guide nucleic acid comprising a nucleotide sequence that is at least 85% identical to SEQ ID NO: 72 in the reply filed on 09/22/2025 is acknowledged.
Claims 119 and 128 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 was made without traverse in the reply filed on 09/22/2025.
Claims 134-137 and 145 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 was made without traverse in the reply filed on 09/22/2025.
Claims 116-118, 120-127, 129-133 and 138-144 are currently under examination.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statement filed on 01/21/2026 have been received and all references have been considered.
Response to Amendment - Specification
The previous objection of the specification has been withdrawn in view of Applicant’s amendments to the specification filed on 01/21/2026.
Claim Objections
Claim 138 is objected to because of the following informalities:
Claim 138 recites “An expression vector comprising a nucleic acid encoding: a) a polypeptide, or a nucleic acid encoding the polypeptide, wherein…”. The claim currently comprises the same limitation twice. It would be remedial to amend the claim to recite, “An expression vector comprising a nucleic acid encoding: a) a polypeptide, wherein …”.
Claim 138 recites “b) an engineered guide nucleic acid, or a nucleic acid encoding the engineered guide nucleic acid, wherein…”. The claim currently comprises the same limitation twice. It would be remedial to amend the claim to recite, “b) an engineered guide nucleic acid, wherein…”.
Appropriate correction is required.
Applicant is advised that should claim 116 be found allowable, claim 141 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Applicant is advised that should claim 127 be found allowable, claim 142 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Response to Amendments - Claim Objections
The previous objection to claim 125 has been withdrawn in view of Applicant’s amendments to the claim filed on 01/21/2026.
Response to Amendments - Claim Rejections - 35 USC § 101
The previous rejection of claims 116, 123 and 129-131 under 35 U.S.C. 101 has been withdrawn in view of Applicant’s amendments to the claims filed on 01/21/2026.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 116-118, 120-127 and 129-133 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 116-118, 120-127 and 129-133 are drawn to a genus of polypeptides comprising “an amino acid sequence that is at least 400 amino acids and at least 95% identical to SEQ ID NO: 1.” Dependent claim 120 requires the polypeptide to be 400 to 500 amino acids. SEQ ID NO: 1 is 448 amino acids in length. Thus, the claims are reasonably interpreted to encompass sequences as short as 400 amino acids, where those sequences are at least 95% identical to a portion of SEQ ID NO: 1. The rejected claims thus comprise a genus of polypeptides comprising an amino acid sequence that is at least 400 amino acids and at least 95% identical to SEQ ID NO: 1 that function to bind a guide nucleic acid and have catalytic activity for a target region within a eukaryotic target sequence. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification teaches very specific functions of a specific Cas endonuclease protein, such as the CasM.265466, in order to be capable of Pcsk9 editing by indel formation [0519]. The specification envisions that the engineered polypeptide is CasM.265466 (instant SEQ ID NO: 1) with the most effective guide RNA sequences being listed within Tables 33, 34 and 35 that would be used for genome editing in eukaryotic cells (Pages 197-208; Examples 17-20). The specification teaches B2M editing in NK cells where the B2M guides targeting exon 2 of B2M were tested with CasM.265466 (SEQ ID NO: 1) for the ability to produce indels in primary NK Cells [0544]. The specification does not teach which domains, such as the REC domain, RuvC domain and/or HNH domain, is maintained in the 448 amino acid long sequence of the CasM.265466 protein or how the removal or modification of the catalytic domains would affect the function of the CasM.265466 protein. The specification does not describe any variants of the sequence of SEQ ID NO: 1 that are shorter than 448 amino acids, or that are less than 100% identical to the 448 amino acids of SEQ ID NO: 1 while guide RNA binding and nuclease activity.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of the editing efficiency and success of CasM.265466 protein of the sequence of SEQ ID NO: 1. The results are not necessarily predictive of the polypeptides that encompass an increase in catalytic activity relative to the nuclease activity of a polypeptide that is 100% identical to SEQ ID NO: 1 while maintaining 400 to 500 amino acids in length. Thus, it is impossible for one to extrapolate from the few examples described herein those Cas protein sequences with between 400 to 500 amino acids in length that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification. The
prior art discloses precise structural information about Cas9 will thus not only enhance our understanding of how this elegant RNA-guided, adaptive microbial immune system functions, but also facilitate further improvements in the Cas9 targeting specificity, the in vitro and in vivo delivery, and the engineering of Cas9 for novel functions and optimized features (Nishimasu et al, Cell. 2014 Feb 27; 156(5): Pages 1-25; Cited in Previous Office Action; Page 3, Paragraph 1). Nishimasu teaches the deletion of either the repeat-interacting region (Δ97–150) or the anti-repeat-interacting region (Δ312–409) of the REC1 domain abolished the DNA cleavage activity, indicating that the recognition of the repeat: antirepeat duplex by the REC1 domain is critical for the Cas9 function (Page 4, Paragraph 3). Nishimasu continues to teach that there are key structures that will create structural differences in the endonuclease domains, such as the key structural dissimilarities between the Cas9 RuvC domain and the RuvC nucleases, which explain their functional differences (Page 6, Paragraph 1). Thus, it would have been unpredictable to use any structure of a Cas protein, with a percentage instant SEQ ID NO: 1, to achieve the specific and desired functions of the genome editing of any gene.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 116-118, 120-127 and 129-133.
Claim 124 is drawn to a genus of polypeptides with increased catalytic and/or nuclease activity relative to the nuclease activity of a polypeptide that is 100% identical to SEQ ID NO: 1. The rejected claims thus comprise a genus of polypeptides that encompass an increase in catalytic activity relative to the nuclease activity of a polypeptide that is 100% identical to SEQ ID NO: 1 while maintaining 400 to 500 amino acids in length.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification teaches very specific functions of a specific Cas endonuclease protein, such as the CasM.265466, in order to be capable of Pcsk9 editing by indel formation [0519]. The specification envisions that the engineered polypeptide is CasM.265466 (instant SEQ ID NO: 1) with the most effective guide RNA sequences being listed within Tables 33, 34 and 35 that would be used for genome editing in eukaryotic cells (Pages 197-208; Examples 17-20). The specification teaches B2M editing in NK cells where the B2M guides targeting exon 2 of B2M were tested with CasM.265466 (SEQ ID NO: 1) for the ability to produce indels in primary NK Cells [0544]. The specification does not teach which domains, such as the REC domain, RuvC domain and/or HNH domain, is maintained in the 448 amino acid long sequence of the CasM.265466 protein or how the removal or addition of the catalytic domains would affect the function of the CasM.265466 protein.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of the editing efficiency and success of CasM.265466 protein. The results are not necessarily predictive of the polypeptides that encompass an increase in catalytic activity relative to the nuclease activity of a polypeptide that is 100% identical to SEQ ID NO: 1 while maintaining 400 to 500 amino acids in length. Thus, it is impossible for one to extrapolate from the few examples described herein those Cas protein sequences with between 400 to 500 amino acids in length that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification. The prior art discloses precise structural information about Cas9 will thus not only enhance our understanding of how this elegant RNA-guided, adaptive microbial immune system functions, but also facilitate further improvements in the Cas9 targeting specificity, the in vitro and in vivo delivery, and the engineering of Cas9 for novel functions and optimized features (Nishimasu et al, Cell. 2014 Feb 27; 156(5): Pages 1-25; Cited in Previous Office Action; Page 3, Paragraph 1). Nishimasu teaches the deletion of either the repeat-interacting region (Δ97–150) or the anti-repeat-interacting region (Δ312–409) of the REC1 domain abolished the DNA cleavage activity, indicating that the recognition of the repeat: antirepeat duplex by the REC1 domain is critical for the Cas9 function (Page 4, Paragraph 3). Nishimasu continues to teach that there are key structures that will create structural differences in the endonuclease domains, such as the key structural dissimilarities between the Cas9 RuvC domain and the RuvC nucleases, which explain their functional differences (Page 6, Paragraph 1). Thus, it would have been unpredictable to use any structure of a Cas protein, with a percentage instant SEQ ID NO: 1, to achieve the specific and desired functions of the genome editing of any gene.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claim 124.
Claim 125 is drawn to a genus of PAM sequences. The rejected claims thus comprise a genus of a PAM sequence that encompass “a sequence of 5’-TNTR-3’, wherein N is selected from any nucleotide; and wherein R is selected from adenine and guanine”.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes the PAM sequences specifically used with claimed SEQ ID NO: 1 (Page 214, Table 41). No description is provided of how any PAM sequence would be capable of being used with SEQ ID NO: 1. The phrase “a sequence” refers to any two consecutive nucleotides rather than the entirety of the 5’-TNTR-3’ PAM sequence.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of the specific PAM sequence that would be capable of being used with SEQ ID NO: 1. The results are not necessarily predictive of any PAM sequence. Thus, it is impossible for one to extrapolate from the few examples described herein those PAM sequences that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification. The prior art discloses that despite the common role of the PAM in target recognition, its characteristics vary between the different types of CRISPR-Cas systems (Leenay et al. J Mol Biol. 2017 Jan 20;429(2):177-191; Page, 4, Paragraph 2). Leenay teaches one major difference is the location of the PAM, such as the PAM is located on the 5′ of the protospacer for Type I and V systems and on the 3′ end of the protospacer for Type II systems (J Mol Biol. 2017 Jan 20;429(2):177-191; Page, 4, Paragraph 2). Thus, it would have been unpredictable to use any PAM sequence, with SEQ ID NO: 1, to achieve the specific and desired functions of the genome editing of any gene.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claim 125.
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.
Claims 116-118, 120-127, 129-133 and 138-144 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 132 is indefinite for being incomplete in themselves. It is noted that “Table 8” recited in claim 132 is merely populated exclusively by sequences, and there is no reason, other than inconvenience, that the human genes cannot be recited in the claims.
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.” (emphasis added). Appropriate correction is required.
Claims 116, 138 and 141 are vague and indefinite in that the metes and bounds of the phrase “wherein the polypeptide binds the engineered guide nucleic acid…” are unclear. The phrase is unclear in that actions present within a product claim create confusion as to when direct infringement occurs. See MPEP 2173.05(p)(II). It would be remedial to replace the phrase “wherein the polypeptide binds the engineered guide nucleic acid…” with “wherein the polypeptide is capable of binding the engineered guide nucleic acid…”.
Response to Amendments - Claim Rejections - 35 USC § 112
The previous rejection of claims 116-118, 120-127, 129-133 and 138-144 under 35 U.S.C. 112(a) has been withdrawn in view of Applicant’s amendments to the claims filed on 01/21/2026.
Claim Rejections - 35 USC § 102
The previous rejection of claim 116, 120-126, 129, 132, 133, 138, 139, 141 and 144 under 35 U.S.C. 102(a)(2) as being anticipated by Thomas et al (WO 2023/039378 A1; Provisional priority date of 09/08/2021) has been withdrawn in view of Applicant’s amendments to the claims filed 01/21/2026.
Claim Rejections - 35 USC § 103
The previous rejection of claims 130 and 131 under 35 U.S.C. 103 as being unpatentable over Thomas et al (WO 2023/039378 A1; Provisional priority date of 09/08/2021) in view of Kiani et al (Nat Methods 12, pgs. 1051–1054 with Supplemental information Pgs. 1/34 to 34/34; 2015) has been withdrawn in view of Applicant’s amendments to the claims filed 01/21/2026.
The previous rejection of claim 140 under 35 U.S.C. 103 as being unpatentable over Thomas et al (WO 2023/039378 A1; Provisional priority date of 09/08/2021) in view of Duque et al (Mol Ther. 2009 Jul;17(7):1187-96) has been withdrawn in view of Applicant’s amendments to the claims filed 01/21/2026.
The previous rejection of claims 143 and 144 under 35 U.S.C. 103 as being unpatentable over Thomas et al (WO 2023/039378 A1; Provisional priority date of 09/08/2021) in view of Chen et al (US 2022/0340898 A1; PCT filed 07/31/2019) has been withdrawn in view of Applicant’s amendments to the claims filed 01/21/2026.
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 116-118, 120 and 124 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 and 25-30 of U.S. Patent No. US 12,077,775 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-21 and 25-30 of U.S. Patent No. US 12,077,775 B2 teaches a composition comprising: a) an engineered polypeptide or a nucleic acid encoding the engineered polypeptide, wherein the engineered polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 1 (wherein SEQ ID NO: 1 is 100% identical to instant SEQ ID NO: 1), and wherein the engineered polypeptide comprises at least one amino acid substitution relative to SEQ ID NO: 1; and b) a guide nucleic acid comprising a first sequence and a second sequence, wherein the engineered polypeptide is capable of binding the first sequence, and wherein the first sequence and the second sequence are heterologous, and wherein the at least one amino acid substitution is selected from K58W, I80R, T84R, K105R, N193K, C202R, S209F, G210R, A218R, A218K, D220R, E225R, E225K, D237A, C246R, N286K, M298L, A306K, Y315M, E335A, E335Q, Q360R, D418A, and D418N; wherein the engineered polypeptide is fused to a fusion partner protein and wherein the fusion partner protein is selected from a polymerase, a deaminase, a reverse transcriptase, a transcriptional repressor, an integrase, a recombinase and a transcriptional activator; wherein the nucleic acid encoding the engineered polypeptide is a messenger RNA (mRNA); wherein the first sequence comprises at least one sequence that is at least 80% identical to any one of SEQ ID NO: 72 and SEQ ID NO: 22; wherein the second sequence is at least 90% complementary to a target sequence, wherein the target sequence is adjacent to a PAM of 5′-NNTN-3′; and a pharmaceutical composition comprising: a) the composition of claim 1; and b) a pharmaceutically acceptable excipient.
Claims 1-21 and 25-30 of U.S. Patent No. US 12,077,775 B2 anticipates claims 116-118, 120 and 124 of the instant application.
Claims 116-118, 120-122, 124-127, 131 and 141-142 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 73, 76, 78-82, 85-86 and 90 of copending Application No. 18/528,523 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 73, 76, 78-86 and 90 of copending Application No. 18/528,523 teaches a vector comprising: a) a first nucleotide sequence encoding a polypeptide comprising an amino acid sequence that is at least 90% similar to SEQ ID NO: 1 (where SEQ ID NO: 1 is 100% identical to instant SEQ ID NO: 1); and b) a second nucleotide sequence encoding a guide nucleic acid comprising: i) a handle region that is capable of being bound by the polypeptide, and ii) a spacer region that hybridizes to a target sequence of a target nucleic acid, wherein the polypeptide recognizes a protospacer adjacent motifs (PAM) comprising a nucleotide sequence of 5'-NNTN-3', wherein each N is independently any one of A, G, C, or T; wherein the target nucleic acid comprises a target strand and a non-target strand, wherein the spacer region hybridizes to the target sequence on the target strand, and wherein the PAM is located 5' of the target sequence on the non-target strand.
Dependent claims 78-86 teach that the polypeptide comprises a sequence that is at least 98% similar to SEQ ID NO: 1 with a length between 300 contiguous nucleotides and 500 nucleotides; wherein there is not more than 20 amino acid substitutions of SEQ ID NO: 1; wherein the polypeptide has reduced nuclease activity relative to the nuclease activity of SEQ ID NO: 1 and comprises a fusion partner.
Claims 73, 76, 78-86 and 90 of copending Application No. 18/528,523 anticipates 116-118, 120-122, 124-127, 131 and 141-142 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 116-118, 120-122, 124-127, 131 and 141-142 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 60, 63, 66, 67 and 69 of copending Application No. 18/653,793 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 60, 63, 66, 67 and 69 of copending Application No. 18/653,793 teaches A system for modifying a target nucleic acid of a hematopoietic stem cell (HSC), the system comprising: (i) a polypeptide, or a nucleic acid encoding the polypeptide, wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to any one of the amino acid sequences set forth in TABLE 1, such as SEQ ID NO: 1 (which is 100% identical to instant SEQ ID NO: 1); and (ii) an engineered guide nucleic acid, or a nucleic acid encoding the engineered guide nucleic acid, wherein: a) the engineered guide nucleic acid comprises a first region and a second region, b) the polypeptide at least partially binds to the first region to form an RNP complex, c) the second region comprises a nucleotide sequence that is at least 80% complementary or at least 80% reverse complementary to a target sequence of the target nucleic acid, d) the RNP complex, upon hybridization of the second region to the target nucleic, modifies the target nucleic acid of the HSC, e) the first region and the second region are heterologous to each other, and f) the HSC following modification by the RNP complex retains at least one of cell viability, cell proliferation, and multi-lineage development potential relative to an unmodified HSC; wherein the polypeptide comprises an effector protein, an effector partner, a fusion protein or a combination thereof; wherein the polypeptide recognizes a protospacer adjacent motif (PAM) as set forth in TABLE 4, such as NNTN wherein N is any nucleic acid (which comprises the first four nucleotides of the instant 5’NNTNTR3’; wherein the engineered guide nucleic acid comprises a nucleotide sequence that is at least 85% identical to any one of the nucleotide sequences set forth in TABLE 9, such as SEQ ID NO: 251 (which is 100% identical to instant SEQ ID NO: 72); and a pharmaceutical composition comprising the system of claim 60, and a pharmaceutically acceptable carrier.
Claims 60, 63, 66, 67 and 69 of copending Application No. 18/653,793 anticipates 116-118, 120-122, 124-127, 131 and 141-142 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 116, 117, 120, 143 and 144 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, 24 and 27 of copending Application No. 19/044,826 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 11, 24 and 27 of copending Application No. 19/044,826 teaches a system comprising: a) an effector protein or a nucleic acid encoding the effector protein, wherein the effector protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 346 (SEQ ID NO: 346 is 100% identical to instant SEQ ID NO: 1); b) an RNA polymerase (RDDP) or a nucleic acid encoding the RDDP;c) a guide RNA or nucleic acid encoding the guide RNA, wherein the guide RNA comprises i) a first region comprising a protein binding sequence, andii) a second region comprising a spacer sequence that hybridizes to a target sequence of a first strand of a double stranded DNA (dsDNA) target nucleic acid,(a) wherein the first region is located 5' of the second region; and d) a template RNA (rettRNA) or nucleic acid encoding the rettRNA, wherein the rettRNA comprises i) a primer binding sequence (PBS), and ii) a template sequence that hybridizes to the target sequence of a second strand of the dsDNA target nucleic acid; Wherein the length of the effector protein is less than 500 linked amino acids; and a pharmaceutical composition comprising the effector protein, the RDDP, the guide RNA, and the retRNA of claim 1, or one or more nucleic acids encoding the same; and a pharmaceutically acceptable excipient.
Claims 1, 11, 24 and 27 of copending Application No. 19/044,826 anticipates 116, 117, 120, 143 and 144 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 116-118, 120-122, 124-127, 131 and 141-142 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 9-11, 16 and 17 of copending Application No. 18/919,415 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 2, 9-11, 16 and 17 of copending Application No. 18/919,415 teaches a composition that comprises:(a)an effector protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 1, or a nucleic acid encoding the same, and (b) a guide nucleic acid that comprises a spacer sequence that hybridizes to a target sequence of a human dystrophin (DMD) locus, or a nucleic acid encoding the same; wherein the guide nucleic acid comprises a nucleotide sequence that is at least 90% identical to SEQ ID NO: 441 or a nucleotide sequence that is at least 90% identical to SEQ ID NO: 443 (where SEQ ID NO: 443 is 100% identical to instant SEQ ID NO: 72); wherein the guide nucleic acid comprises a nucleotide sequence that is at least 90% identical to any one of SEQ ID NOs: 223-440 (where SEQ ID NO: 440 comprises the sequence of instant SEQ ID NO: 72 with 100% identity); Wherein the PAM sequence is NNTN (which is comprised within the instant PAM sequence of NNTNTR); wherein the partner protein is fused or linked to the effector protein.
Claims 1, 2, 9-11, 16 and 17 of copending Application No. 18/919,415 anticipates claims 116-118, 120-122, 124-127, 131 and 141-142 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 116-118, 120-122, 124-127, 131 and 141-142 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 272, 273, 276, 277, 279, 281-283 and 286 of copending Application No. 18/732,352 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 272, 273, 276, 277, 279, 281-283 and 286 of copending Application No. 18/732,352 teaches An engineered T cell comprising a gene that is modified by contacting a T cell with:(a) an effector protein comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2435 (SEQ ID NO: 2435 is 100% identical to SEQ ID NO: 1 of the instant application); and (b) a guide nucleic acid, wherein the guide nucleic acid comprises a nucleotide sequence that is at least 90% identical to 5'-AAGGAUGCCAAAC-3' (nucleotides 57 to 69 of SEQ ID NO: 2522) (the sequence listed in the claims is 100% identical to SEQ ID NO: 72 from the instant application), and a spacer sequence that is complementary to a target sequence of the gene; wherein the effector protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 2435 and wherein the effector protein and guide nucleic acid recognize a protospacer adjacent motif (PAM) selected from 5'-NNTN-3' and 5'- TNTR-3'; wherein wherein the effector protein is fused to a fusion partner protein and wherein the effector protein comprises an amino acid substitution relative to SEQ ID NO: 2435 selected from I80R, T84R, K105R, G210R, C202R, A218R, E225R, C246R, and Q360R.
Claims 272, 273, 276, 277, 279, 281-283 and 286 of copending Application No. 18/732,352 anticipates claims 116-118, 120-122, 124-127, 131 and 141-142 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 116-118, 120, 122-131, 141, 142 and 144 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6-9 and 23 of copending Application No. 19/230,223 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 2, 6-9 and 23 of copending Application No. 19/230,223 teaches a composition comprising a guide ribonucleic acid (RNA) or a polynucleotide encoding the same, wherein the guide RNA comprises: a) a first region comprising a protein binding sequence, and b) a second region comprising a targeting sequence that is complementary to a target sequence that is within a DUX4 gene, wherein the target sequence is adjacent to a protospacer adjacent motif (PAM) selected from 5'-NTTN-3' and 5'-NNTN-3' wherein the targeting sequence comprises a nucleotide sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or 100% identical to any one of SEQ ID NOs: 1-114, 275-349, 456-460, and 476-596 (SEQ ID NO: 275 comprising SEQ ID NO: 350 where SEQ ID NO: 350 is 100% identical to SEQ ID NO: 72 of the instant application); wherein the PAM is 5'- NNTN-3', and wherein a. the targeting sequence comprises a nucleotide sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or 100% identical to any one of SEQ ID NOs: 275-349, 457-460, and 476-480, and b. the protein binding sequence comprises a nucleotide sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or 100% identical to SEQ ID NO: 350 (SEQ ID NO: 275 comprising SEQ ID NO: 350 where SEQ ID NO: 350 is 100% identical to SEQ ID NO: 72 of the instant application); wherein the composition or system comprises an effector protein or a nucleic acid encoding the same, wherein the effector protein comprises an amino acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 428 (SEQ ID NO: 428 is 100% identical to SEQ ID NO: 1 of the instant application) and wherein a pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable excipient.
Claims 1, 2, 6-9 and 23 of copending Application No. 19/230,223 anticipates claims 116-118, 120, 122-131, 141, 142 and 144 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments - Double Patenting
The previous rejection of claims 116-118, 120 and 124 rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 1-21 and 25-30 of U.S. Patent No. 12,077,775 B2 (hereinafter '775) has been maintained. Applicant’s arguments have been fully considered but are not persuasive.
Applicant argues that because claim 116 has been recited to include the following: the engineered guide nucleic acid comprises at least 15 contiguous nucleotides that are complementary to a target sequence in a target nucleic acid, the length of the polypeptide is at least 400 amino acids, the target sequence is a eukaryotic target sequence, and the polypeptide binds the engineered guide nucleic acid to form a ribonucleoprotein complex having a catalytic activity for a target region within the eukaryotic target sequence, the claims are patentably distinct from U.S. Patent No. 12,077,775 B2.
However, as stated above, claims 1-21 and 25-30 of U.S. Patent No. US 12,077,775 B2 teaches a composition comprising: a) an engineered polypeptide or a nucleic acid encoding the engineered polypeptide, wherein the engineered polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 1 (wherein SEQ ID NO: 1 is 100% identical to instant SEQ ID NO: 1), and wherein the engineered polypeptide comprises at least one amino acid substitution relative to SEQ ID NO: 1; and b) a guide nucleic acid comprising a first sequence and a second sequence, wherein the engineered polypeptide is capable of binding the first sequence, and wherein the first sequence and the second sequence are heterologous, and wherein the at least one amino acid substitution is selected from K58W, I80R, T84R, K105R, N193K, C202R, S209F, G210R, A218R, A218K, D220R, E225R, E225K, D237A, C246R, N286K, M298L, A306K, Y315M, E335A, E335Q, Q360R, D418A, and D418N; wherein the engineered polypeptide is fused to a fusion partner protein and wherein the fusion partner protein is selected from a polymerase, a deaminase, a reverse transcriptase, a transcriptional repressor, an integrase, a recombinase and a transcriptional activator; wherein the nucleic acid encoding the engineered polypeptide is a messenger RNA (mRNA); wherein the first sequence comprises at least one sequence that is at least 80% identical to any one of SEQ ID NO: 72 and SEQ ID NO: 22; wherein the second sequence is at least 90% complementary to a target sequence, wherein the target sequence is adjacent to a PAM of 5′-NNTN-3′; and a pharmaceutical composition comprising: a) the composition of claim 1; and b) a pharmaceutically acceptable excipient.
The previous rejection of claims 116-118, 120-122, 124-127, 131 and 141-142 are provisionally rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 73, 76, 78- 82, 85-86 and 90 of copending Application No. 18/528,523 (hereinafter '523) has been maintained. Applicant’s arguments have been fully considered but are not persuasive.
The previous rejection of claims 116-118, 120-122, 124-127, 131 and 141-142 are provisionally rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 60, 63, 66, 67 and 69 of copending Application No. 18/653,793 (hereinafter '793) has been maintained. Applicant’s arguments have been fully considered but are not persuasive.
The previous rejection of claims 116, 117, 120, 143 and 144 are provisionally rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 1, 11, 24 and 27 of copending Application No. 19/044,826 (hereinafter '826) has been maintained. Applicant’s arguments have been fully considered but are not persuasive.
The previous rejection of claims 116-118, 120-122, 124-127, 131 and 141-142 are provisionally rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 1, 2, 9-11, 16 and 17 of copending Application No. 18/919,415 (hereinafter '415) has been maintained. Applicant’s arguments have been fully considered but are not persuasive.
The previous rejection of claims 116-118, 120-122, 124-127, 131 and 141-142 are provisionally rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 272, 273, 276, 277, 279, 281-283 and 286 of copending Application No. 18/732,352 (hereinafter '352) has been maintained. Applicant’s arguments have been fully considered but are not persuasive.
The previous rejection of claims 116-118, 120, 122-131, 141, 142 and 144 are provisionally rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 1, 2, 6-9 and 23 of copending Application No. 19/230,223 (hereinafter '223) has been maintained. Applicant’s arguments have been fully considered but are not persuasive.
Applicant argues that if a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, then the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent.
However, the instant application does not have any allowable claims as well as pending rejections. Therefore, the provisional nonstatutory double patenting rejections have been maintained.
Conclusion
No claims are allowed.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637