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 .
The TrackOne Request, filed October 31, 2025, was granted February 27, 2026. Therefore, this application is accorded special status.
Election/Restrictions
Applicant's election with traverse of Group I (claims 25-26, 29-42, 59-60, 62, 64-65, 70, 73, 75, and 85-86) in the reply filed on May 18, 2026 is acknowledged. The traversal is on the ground that there is not a serious burden in searching Groups I and II together. This is not found persuasive because, while the method requires the gene editing system, claims 83 and 84 also require additional searches relating to the treatment of a specific disease or condition. Thus, the searches are not deemed to be co-extensive and searching for the specific condition adds a significant search burden to the search for the gene editing system. It is noted that Applicants are correct in that claim 83 should have been part of Group II in the Requirement for Restriction of March 19, 2026.
Claims 83 and 84 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on May 18, 2026.
The requirement is still deemed proper and is therefore made FINAL.
Claims 25-26, 29-42, 59-60, 62, 64-65, 70, 73, 75, and 85-86 are under examination.
Regarding the election of species requirement, while Applicants elected the required species without traverse, upon further consideration, the election of species requirement is withdrawn. Therefore, claims 25-26, 29-42, 59-60, 62, 64-65, 70, 73, 75, and 85-86 will be examined in their entirety.
Information Disclosure Statement
The Information Disclosure Statement filed October 31, 2025 has been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers (Figures 2-14) in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at paragraphs [00119] and [00273]. 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.
The use of the terms GENSCRIPT at paragraph [00270]; NUCLEOFECTOR at paragraphs [00271] and [00272]; NUCLEOCUVETTE at paragraph [00272]; and SPECTRAMAX at paragraph [00275]; which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 59-60 are objected to because of the following informalities:
At claim 59, line 3, both occurrences of “deaminase” should be changed to “deaminases.”
At claim 60, line 2, “deaminase” should be changed to “deaminases.”
Appropriate correction is required.
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 26 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.
At claim 26, line 5, it is not clear what is required for an RNA aptamer to be a variant. How like the RNA aptamer must a variant be in order to function as required.
Claims 85-86 depend from claim 25, and are therefore included in this rejection.
At claim 35, line 3, it is not clear if the first spacer sequence is the same as the first spacer sequence of claim 25 or if it is a different first spacer sequence.
At claim 35, lines 3-4, it is not clear if the first linker sequence is the same as the first linker sequence of claim 25, or if it is a different first linker sequence.
At claim 35, line 6, it is not clear if the second spacer sequence is the same as the second spacer sequence of claim 25 or if it is a different second spacer sequence.
At claim 35, lines 6-7, it is not clear if the second linker sequence is the same as the second linker sequence of claim 25, or if it is a different second linker sequence.
Claims 36-42, 59-60, 62, 64-65, 67-68, 70, 73, depend from claim 35 and are therefore included in these rejections.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 75 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
At paragraph [00141] of the specification, a composition refers to any products, including cells. At paragraph [00253], the cells can be CAR-T cells, which can be administered to a subject. At paragraphs [00257]-[00258], the specification recites that the cell can be a composition, including a pharmaceutical composition. Thus, it is clear from the specification, that the cell comprising the gene editing system can be administered to a subject as a pharmaceutical composition.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 25-26, 31, 35-36, 38, 42, 59-60, 62, 65, 67-68, 70, 75, and 85 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Chen et al. (U.S. Patent Application Publication No. 2022/0064626, published March 3, 2022).
Regarding claims 25-26, Chen discloses a gene editing system comprising guide RNAs that include a crRNA and a tracrRNA, with the system comprising two guide RNAs, one a target guide RNA comprising a first spacer and a helper guide RNA comprising a second spacer (paragraphs [0016] and [0024]). Chen discloses guide RNA includes a linker (paragraph [0154]). Chen discloses that the guide RNAs bind to the Cas enzyme, which is interpreted as the guide RNAs including a protein-binding motif (paragraph [0117]).
Regarding claim 31, Chen discloses a gene editing system comprising guide RNAs that include a crRNA and a tracrRNA, with the system comprising two guide RNAs, each of which includes a tracrRNA, one a target guide RNA comprising a first spacer and a helper guide RNA comprising a second spacer (paragraphs [0016] and [0024]).
Regarding claim 35, Chen discloses that the hgRNA comprises a first CRISPR motif, the spacer, and a protein-binding motif, the hgRNA spacer, and a first protein-binding motif, or a DNA polynucleotide encoding the hgRNA; the mgRNA comprising a second CRISPR motif and the mgRNA spacer,or a DNA polynucleotide encoding the mgRNA; first CRISPR-associated protein (Cas protein), or a polynucleotide encoding the first Cas protein, wherein the first Cas protein binds to the first CRISPR motif; a second Cas protein, or a polynucleotide encoding the second Cas protein, wherein the second Cas protein binds to the second CRISPR motif; a first fusion protein comprising a nucleobase deaminase or a catalytic domain thereof and a first RNA binding domain, or a polynucleotide encoding the first fusion protein, wherein the nucleobase deaminase or the catalytic domain thereof and the first RNA binding domain are optionally connected by a linker, and wherein the first RNA binding domain binds to the first protein-binding motif, wherein the first Cas protein and second Cas protein are the same or different (paragraphs [0015], [0097], and [0121]).
Regarding claim 36, Chen discloses a protease, or a polynucleotide encoding the protease, and a nucleobase deaminase inhibitor domain, wherein the nucleobase deaminase inhibitor domain is connected to the nucleobase deaminase or the catalytic domain thereof in the first fusion protein optionally by a linker, and wherein there is a cleavage site for the protease between the nucleobase deaminase inhibitor domain and the nucleobase deaminase or the catalytic domain thereof paragraphs [0015], [0097], and [0121]).
Regarding claim 38, Chen discloses that the protease is split into a first protease fragment and a second protease fragment, wherein the first and/or second protease fragment alone is not able to cleave the cleavage site (paragraphs [0012]-[0014].
Regarding claim 42, Chen discloses that the protease can be a TEV protease (paragraphs [0014]-[0015]).
Regarding claim 59, Chen discloses that the fusion protein can include a nucleotide deaminase (paragraphs [0006]-[0015]).
Regarding claim 60, Chen discloses that the deaminase can be a cytidine deaminase or an adenosine deaminase or both (paragraphs [0006]-[0015]).
Regarding claim 62, Chen discloses that the fusion protein can include a uracil glycosylase inhibitor (UGI) and that the Cas protein can be a Cas9 can be an SpCas9, FnCas9, St1Cas9, St3Cas9, NmCas9, SaCas9, AsCpfl, LbCpfl, FnCpfl, VQR SpCas9, EQR SpCas9, VRER SpCas9, xSpCas9, SpCas9-NG, RHA FnCas9, KKH SaCas9, NmeCas9, StCas9, CjCas9, AsCpf1, FnCpf1, SsCpfl, PcCpf1, BpCpf1, CmtCpf1, LiCpf1, PmCpf1, Pb3310Cpf1, Pb4417Cpf1, BsCpfl, EeCpfl, BhCas12b, AkCas12b, EbCas12b, LsCas12b, RfCas13d, LwaCas13a, PspCas13b, PguCas13b, or RanCas13b (paragraphs [0011] and [0015]).
Regarding claims 65 and 85, Chen discloses that the binding domains can be MS2/MS2 coat protein (MCP), PP7/PP7 coat protein (PCP), and boxB/boxB coat protein (N22p) (paragraph [0014]).
Regarding claims 67 and 70, Chen discloses that the gene editing system can be encoded by a polynucleotide and included in a vector (paragraphs [0025]-[0031]).
Regarding claim 68, Chen discloses a kit comprising the polynucleotide encoding the gene editing system components (paragraph [0019]).
Regarding claim 75, Chen discloses a cell comprising the gene editing system (paragraphs [0016]-[0017] and [0028]).
Chen discloses each and every limitation of claims 25-26, 31, 35-36, 38, 42, 59-60, 62, 65, 67-68, 70, 75, and 85, and therefore Chen anticipates claims 25-26, 31, 35-36, 38, 42, 59-60, 62, 65, 67-68, 70, 75, and 85.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 37 and 39-41 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (U.S. Patent Application Publication No. 2022/0064626, published March 3, 2022).
Regarding claims 25-26, Chen discloses a gene editing system comprising guide RNAs that include a crRNA and a tracrRNA, with the system comprising two guide RNAs, one a target guide RNA comprising a first spacer and a helper guide RNA comprising a second spacer (paragraphs [0016] and [0024]). Chen discloses guide RNA includes a linker (paragraph [0154]). Chen discloses that the guide RNAs bind to the Cas enzyme, which is interpreted as the guide RNAs including a protein-binding motif (paragraph [0117]).
Regarding claim 31, Chen discloses a gene editing system comprising guide RNAs that include a crRNA and a tracrRNA, with the system comprising two guide RNAs, each of which includes a tracrRNA, one a target guide RNA comprising a first spacer and a helper guide RNA comprising a second spacer (paragraphs [0016] and [0024]).
Regarding claim 35, Chen discloses that the hgRNA comprises a first CRISPR motif, the spacer, and a protein-binding motif, the hgRNA spacer, and a first protein-binding motif, or a DNA polynucleotide encoding the hgRNA; the mgRNA comprising a second CRISPR motif and the mgRNA spacer,or a DNA polynucleotide encoding the mgRNA; first CRISPR-associated protein (Cas protein), or a polynucleotide encoding the first Cas protein, wherein the first Cas protein binds to the first CRISPR motif; a second Cas protein, or a polynucleotide encoding the second Cas protein, wherein the second Cas protein binds to the second CRISPR motif; a first fusion protein comprising a nucleobase deaminase or a catalytic domain thereof and a first RNA binding domain, or a polynucleotide encoding the first fusion protein, wherein the nucleobase deaminase or the catalytic domain thereof and the first RNA binding domain are optionally connected by a linker, and wherein the first RNA binding domain binds to the first protein-binding motif, wherein the first Cas protein and second Cas protein are the same or different (paragraphs [0015], [0097], and [0121]).
Regarding claim 36, Chen discloses a protease, or a polynucleotide encoding the protease, and a nucleobase deaminase inhibitor domain, wherein the nucleobase deaminase inhibitor domain is connected to the nucleobase deaminase or the catalytic domain thereof in the first fusion protein optionally by a linker, and wherein there is a cleavage site for the protease between the nucleobase deaminase inhibitor domain and the nucleobase deaminase or the catalytic domain thereof paragraphs [0015], [0097], and [0121]).
Regarding claim 38, Chen discloses that the protease is split into a first protease fragment and a second protease fragment, wherein the first and/or second protease fragment alone is not able to cleave the cleavage site (paragraphs [0012]-[0014].
Regarding claim 42, Chen discloses that the protease can be a TEV protease (paragraphs [0014]-[0015]).
Regarding claim 59, Chen discloses that the fusion protein can include a nucleotide deaminase (paragraphs [0006]-[0015]).
Regarding claim 60, Chen discloses that the deaminase can be a cytidine deaminase or an adenosine deaminase or both (paragraphs [0006]-[0015]).
Regarding claim 62, Chen discloses that the fusion protein can include a uracil glycosylase inhibitor (UGI) and that the Cas protein can be a Cas9 can be an SpCas9, FnCas9, St1Cas9, St3Cas9, NmCas9, SaCas9, AsCpfl, LbCpfl, FnCpfl, VQR SpCas9, EQR SpCas9, VRER SpCas9, xSpCas9, SpCas9-NG, RHA FnCas9, KKH SaCas9, NmeCas9, StCas9, CjCas9, AsCpf1, FnCpf1, SsCpfl, PcCpf1, BpCpf1, CmtCpf1, LiCpf1, PmCpf1, Pb3310Cpf1, Pb4417Cpf1, BsCpfl, EeCpfl, BhCas12b, AkCas12b, EbCas12b, LsCas12b, RfCas13d, LwaCas13a, PspCas13b, PguCas13b, or RanCas13b (paragraphs [0011] and [0015]).
Regarding claims 65 and 85, Chen discloses that the binding domains can be MS2/MS2 coat protein (MCP), PP7/PP7 coat protein (PCP), and boxB/boxB coat protein (N22p) (paragraph [0014]).
Regarding claims 67 and 70, Chen discloses that the gene editing system can be encoded by a polynucleotide and included in a vector (paragraphs [0025]-[0031]).
Regarding claim 68, Chen discloses a kit comprising the polynucleotide encoding the gene editing system components (paragraph [0019]).
Regarding claim 75, Chen discloses a cell comprising the gene editing system (paragraphs [0016]-[0017] and [0028]).
However, Chen does not explicitly disclose or suggest multiple fusion proteins comprising additional binding domains.
However, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to include multiple additional guideRNAs, fusion proteins, which include Cas proteins and deaminases, and associated binding domains, linkers, and spacers because that provides for multiplex gene editing. One of ordinary skill in the art would have been motivated to increase the number of guideRNAs, Cas proteins and deaminase proteins in order to effect editing of genomic sequences at multiple sites in a single round of editing.
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 25, 31, and 59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,840,685.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘685 patent claims a dual guide RNA system and the instant application claims a gene editing system comprising a dual guide RNA system.
Regarding claims 25, 31, and 59, the ‘685 patent claims a double guide RNA system comprising a target (main) single guide RNA comprising a first spacer and a helper single guide RNA comprising a second spacer. The ‘685 patent claims a CRISPR-Cas protein and a nucleobase deaminase. Because the ‘685 patent claims single guide RNAs, each of these guide RNAs will inherently include a tracr sequence.
While the ‘658 patent does not explicitly claim a linker sequence comprising a protein-binding motif, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the guide RNAs comprise a linker that includes a protein-binding motif because, in order for the guides to function for gene editing as required, each guide must have a sequence (i.e., a linker) that will bind to a protein (i.e., the CRISPR-Cas/deaminase proteins).
Claims 25, 31, 35-40, and 59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1of copending Application No. 19/124,014 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘014 application claims a dual guide RNA system and the instant application claims a gene editing system comprising a dual guide RNA system.
Regarding claims 25, 31, and 59, the ‘014 application claims a guide RNA system comprising a target (main) single guide RNA comprising a first spacer and a helper single guide RNA comprising a second spacer. The ‘014 application claims a CRISPR-Cas protein and a nucleobase deaminase. Because the ‘014 application claims single guide RNAs, each of these guide RNAs will inherently include a tracr sequence.
Regarding claim 35, the ‘014 application claims that the hgRNA comprises a first CRISPR motif, the spacer, and a protein-binding motif, the hgRNA spacer, and a first protein-binding motif, or a DNA polynucleotide encoding the hgRNA; the mgRNA comprising a second CRISPR motif and the mgRNA spacer,or a DNA polynucleotide encoding the mgRNA; first CRISPR-associated protein (Cas protein), or a polynucleotide encoding the first Cas protein, wherein the first Cas protein binds to the first CRISPR motif; a second Cas protein, or a polynucleotide encoding the second Cas protein, wherein the second Cas protein binds to the second CRISPR motif; a first fusion protein comprising a nucleobase deaminase or a catalytic domain thereof and a first RNA binding domain, or a polynucleotide encoding the first fusion protein, wherein the nucleobase deaminase or the catalytic domain thereof and the first RNA binding domain are optionally connected by a linker, and wherein the first RNA binding domain binds to the first protein-binding motif, wherein the first Cas protein and second Cas protein are the same or different.
Regarding claim 36, the ‘014 application claims a protease, or a polynucleotide encoding the protease, and a nucleobase deaminase inhibitor domain, wherein the nucleobase deaminase inhibitor domain is connected to the nucleobase deaminase or the catalytic domain thereof in the first fusion protein optionally by a linker, and wherein there is a cleavage site for the protease between the nucleobase deaminase inhibitor domain and the nucleobase deaminase or the catalytic domain thereof.
Regarding claim 37, the ‘014 application claims a second fusion protein comprising the protease and a second RNA binding domain, or a polynucleotide encoding the second fusion protein, wherein the protease and the second RNA binding domain are optionally connected by a linker, wherein the mgRNA further comprises a second protein-binding motif, and wherein the second RNA binding domain binds to the second protein-binding motif.
Regarding claim 38, the ‘014 application claims that the protease is split into a first protease fragment and a second protease fragment, wherein the first and/or second protease fragment alone is not able to cleave the cleavage site.
Regarding claim 39, the ‘014 application a second fusion protein comprising the first protease fragment and a second RNA binding domain, or a polynucleotide encoding the second fusion protein, wherein the first protease fragment and the second RNA binding domain are optionally connected by a linker, and b. a third fusion protein comprising the second protease fragment and a third RNA binding domain, or a polynucleotide encoding the third fusion protein, wherein the second protease fragment and the third RNA binding domain are optionally connected by a linker, wherein the mgRNA further comprises a second protein-binding motif and a third protein-binding motif, wherein the second RNA binding domain binds to the second protein-binding motif, and wherein the third RNA binding domain binds to the third protein-binding motif.
Regarding claim 40, the ‘014 application claims that the second and third RNA binding domains are the same or different, and the second and third protein-binding motifs are the same or different.
While the ‘014 application claims specific sequences not expressly claimed by the instant application, the claims of the ‘014 application encompass the generic claims of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 29-30, 32-34, and 86 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, NEIL HAMMELL can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
Prosecution Insights