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 without traverse of Group I in the reply filed on 16 December 2025 is acknowledged. Claims 18-19, 21, 30, 35, 46-48, 52-54, 58, 68, and 72-73 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 2-4, 6, 10-17, 20, 22-29, 31-34, 36-45, 49-51, 55-57, 59-67, and 69-71 were previously cancelled.
While still withdrawn from further consideration, the restriction between Groups IV, V, VI and VII are withdrawn as they are overlapping in scope. Therefore, these claims are grouped into the invention of Invention IV.
Claims 1, 5, and 7-9 are being examined on the merits.
Priority
This application claims priority to application 63/363,259 filed 04/20/2022.
Information Disclosure Statement
The information disclosure statements filed 11/27/2023 and 12/03/2024 have been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in 00168. 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 term Illumina, Lucigen, QuickExtract, NEB, MiSeq, American Type Culture Collection (ATCC), Thermo Fisher Scientific, Lipofectamine 3000, and GlutaMAX, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. A cursory review of the specification has revealed these trade names or marks. It would be remedial to identify and amend all trade names or marks in the specification upon amendment.
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 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 1, 5, and 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng (US20230295615A1, filed 8/6/2021) in view of Maresca (WO2021204877 A2).
Regarding claim 1 and 7-8, Cheng teaches prime editing using CRISPR nucleases and reverse transcriptase (RT) to insert Bxb1 integrase attachment sites into genome of cells [0054, 0062]. Cheng teaches a fusion protein (i.e., components linked by a linker) comprising a type II CRISPR-Cas effector enzyme (i.e., a DNA-binding protein), a reverse transcriptase, and an integrase [0072, 0222]. Cheng teaches the integrase can be Bxb1 [0152]. Cheng teaches in the fusion protein the functional domains (i.e., the RT and the integrase) are linked to the effector enzyme (i.e., the CRISPR Cas effector DNA-binding domain) "by a linker sequence of appropriate length to provide beneficial orientation and flexibility between the effector enzyme and the functional domains" [0216]. Chen also teaches different integrases [0016]. Chen teaches that the effector enzyme is a Cas9 nickase that lacks HNH endonuclease activity due to a point mutation (H840A) at the endonuclease catalytic site of the HNH endonuclease [0045-0046].
Regarding claim 9, Chen teaches that the reverse transcriptase is the M-MLV RT from the Moloney murine leukemia virus [0298].
While Cheng provides for the complex to comprise a recruitment sequence capable of being bound by a protein domain such as MCP or PP7 [0073-0074], Cheng does not specifically teach a recruitment sequence on the fusion protein comprising a CRISPR-Cas effector enzyme, a reverse transcriptase, and an integrase.
Maresca teaches prime editing using a fusion protein comprising a Cas nuclease and a reverse transcriptase (RT), a DNA polymerase, a DNA ligase, or a combination thereof [abstract]. Maresca teaches fusing MCP domains, which binds to MS2 aptamers, to the Cas9-RT protein [00212]. Maresca teaches that the template for reverse transcription was fused to MS2 aptamers [00212]. Maresca teaches that a DNA sequence was successfully copied and inserted specifically from MS2-RT template by PRINS editing [00213; Fig. 18].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to additionally fuse MCP domains, via an additional linker, to the fusion protein of Cheng. One of ordinary skill would be motivated to make the modification for the advantage of copying and inserting DNA from a MS2-RT template into a target genome sequence. One f ordinary skill would have a reasonable expectation of success since Cheng and Maresca both teach prime editing using Cas9-RT fusion proteins.
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 1, 5, and 7-9 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 18 of copending Application No. 19/016260 (reference application) in view of Cheng (US20230295615A1, filed 8/6/2021) in view of Maresca (WO2021204877 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claim teaches all the limitation of the instant application except wherein the composition comprises an aptamer binding protein. The teachings of Cheng and Maresca are discussed above.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to additionally fuse MCP domains, via an additional linker, to the fusion protein composition of the copending application. One of ordinary skill would be motivated to make the modification for the advantage of copying and inserting DNA from a MS2-RT template into a target genome sequence. One of ordinary skill would have a reasonable expectation of success since the copending application, Cheng, and Maresca teach prime editing using Cas9-RT fusion proteins.
For additional limitations of the instant claims, see the additional teachings of the copending application. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Cheng and Maresca are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 5, and 7-9 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 87-88, 99-103, 106, 110-111 of copending Application No. 18/067214 (reference application) in view of Cheng (US20230295615A1, filed 8/6/2021) in view of Maresca (WO2021204877 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claim claims a complex for genome editing comprising: (i) an RNA-guided nuclease; (ii) a fusion protein comprising a reverse transcriptase domain linked to a nucleic acid binding protein such as MCP or PP7; and (iii) at least one guide RNA (gRNA) comprising a 5′ end and a 3′ end and comprising at least one protein-recruiting stem-loop nucleic acid sequence, wherein the protein-recruiting stem-loop nucleic acid sequence binds to the nucleic acid binding protein [claims 87, 88, 101]. The copending application claims that 0ne or both of the RNA-guided nuclease and fusion protein are linked to an integration enzyme or fragment thereof [110]. The copending application teaches fusion via a linker [106]
The copending application claims that the reverse transcriptase domain is selected from the group consisting of Moloney Murine Leukemia Virus (M-MLV) reverse transcriptase domain [claim 103].
The copending application claims that the CRISPR nuclease is selected from Cas9-D10A, Cas9-H840A, and Cas12a/b nickase [claim 102].
The copending application claims that the integration enzyme is selected from the group consisting of Cre, Dre, Vika, Bxb1, BceINT φC31, RDF, FLP, φBT1, R1, R2, R3, R4, R5, TP901-1, A118, φFC1, φC1, MR11, TG1, φ370.1, Wβ, BL3, SPBc, K38, Peaches, Veracruz, Rebeuca, Theia, Benedict, KSSJEB, PattyP, Doom, Scowl, Lockley, Switzer, Bob3, Troube, Abrogate, Anglerfish, Sarfire, SkiPole, ConceptII, Museum, Severus, Airmid, Benedict, Hinder, ICleared, Sheen, Mundrea, BxZ2, φRV, retrotransposases encoded by R2, L1, Tol2 Tc1, Tc3, Mariner Himar 1, Mariner mos 1, and Minos, and any mutants thereof.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 5, and 7-9 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19-21, 34, and 118 of copending Application No. 18/048,238 (reference application) in view of Cheng (US20230295615A1, filed 8/6/2021) in view of Maresca (WO2021204877 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claim teaches all the limitation of the instant application except wherein the composition comprises an aptamer binding protein. The teachings of Cheng and Maresca are discussed above.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to additionally fuse MCP domains, via an additional linker, to the fusion protein composition of the copending application. One of ordinary skill would be motivated to make the modification for the advantage of copying and inserting DNA from a MS2-RT template into a target genome sequence. One of ordinary skill would have a reasonable expectation of success since the copending application, Cheng, and Maresca teach prime editing using Cas9-RT fusion proteins.
For additional limitations of the instant claims, see the additional teachings of the copending application. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Cheng and Maresca are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637