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 .
Receipt is acknowledged of an amendment, filed 8/28/2023, in which claims 21-51 were canceled. Receipt is also acknowledged of an amendment, filed 1/30/2026, in which claims 3-6 and 12-14 were canceled, and claims 52-57 were added. Claims 1-2, 7-11, 15-20 and 52-57 are pending and under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/13/2023, 8/28/2023, 1/30/2026 have been considered by the examiner.
Specification
The use of the terms MISEQ, GENBANK, LIPOFECTAMINE, FUGENE, GLUTAMAX, CELLTITER-GLO, OPTI-MEM, HIBERNATE-E, TRIZOL, RNEASY, SMARTER PREPX, and QUBIT, which are trade names or marks used in commerce, has been noted in this application. Each 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.
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 § 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.
Claims 17, 19 and 20 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 17 recites the limitation "the cut DNA" in line 2. There is insufficient antecedent basis for this limitation in the claim because claim 1 does not recite this limitation.
Regarding claim 19, the recitation of “a nucleotide sequence selected from the group consisting of SEQ ID NO: 127, 165-176, 446, 453, and 767-769” renders the claim indefinite because the sequences are peptide sequences, not nucleotide sequences.
Regarding claim 20, the recitation of “selected from the stem loops described herein” renders the claim indefinite because it is unclear what are the stem loops being described.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claim(s) 1, 2, 7, 8, 10, 11, 18, 20, 52, 53, 55 and 56 is/are rejected under 35 U.S.C. 102(a1) and (a2) as being anticipated by Cotta-Ramusino et al (WO 2017/180711, IDS).
Claim 1 is drawn to a PEgRNA that comprises guide RNA (gRNA) and at least one nucleic acid extension arm comprising a DNA synthesis template and a primer binding site.
Cotta-Ramusino teaches a gRNA fusion molecule that is a gRNA molecule covalently or non-covalently linked to a template nucleic acid (extension arm of the instant claim) (e.g., page 16, lines 19-23; page 24, lines 1-26; page 46, lines 23-31). Cotta-Ramusino teaches the gRNA fusion molecule where the template nucleic acid comprises one primer binding site from the endogenous gene sequence targeted by the template nucleic acid, which is capable of hybridizing to a second strand of the double stranded DNA (page 207-208, bridging paragraph). Therefore, the claimed invention of claim 1 is anticipated by the teaching from Cotta-Ramusino.
Regarding claim 2, Cotta-Ramusino teaches the template nucleic acid sequence is positioned 3’ to the gRNA (page 3, lines 27-30).
Regarding claims 7 and 8, Cotta-Ramusino teaches the template nucleic acid linked to the gRNA is about 100-200 nucleotides in length (page 27, lines 10-19), which meets the limitation of at least 5…50 or at least 3…15 nucleotides as claimed.
Regarding claim 10 and 18, Cotta-Ramusino teaches the gRNA fusion further comprises hairpin loops (page 24, last paragraph, and claim 5). Regarding claim 20, the recitation of “stem loops described herein” renders the claim unclear what structure it is being described, as such, the hairpin loop taught by Cotta-Ramusino meets this limitation.
Regarding claim 11, Cotta-Ramusino teaches single stranded donor DNA (template nucleic acid) was ligated to the 3’ end of TracrRNA and other gRNA constructs, where the fusion gRNA is targeting HBB locus (page 209-210, bridging paragraph, line 13-14).
Regarding claim 52, Cotta-Ramusino teaches the linked single stranded donor (template nucleic acid) is DNA (page 209-210, bridging paragraph).
Regarding claim 53, Cotta-Ramusino teaches the fusion of gRNA and the template nucleic acid, forming a single molecule (examples 12).
Regarding claims 55-57, Cotta-Ramusino teaches the gRNA fusion further comprises an MS2 binding site sequence (claim 6 and Figure 3, page 211, line 34).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim(s) 9, 16 and 54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cotta-Ramusino.
Regarding claim 9, the teaching from Cotta-Ramusino does not specifically teach the length of the primer binding site.
Cotta-Ramusino teaches PCR and/or sequencing primers being used following HDR gene editing (page 207-208, bridging paragraph).
It would have been obvious to an ordinary skilled in the art to recognize the primer binding site is at least 3…15 nucleotide in length because the length of the primer are known in prior art and varying the length would have been optimization for a particular reaction, rather than a method of innovation.
Regarding claim 16, Cotta-Ramusino teaches the donor template has high homology with the target sequence, comprising all or part of a target sequence (page 174, 15-18). Cotta-Ramusino teaches the donor template may be a repair template for gene correction, including point mutation, and comprises 5’ and/or 3’ homology arm (page 81, line 20-25). Although Cotta-Ramusino does not teach percent homology specifically, Cotta-Ramusino teaches the replacement sequence may be homologous, but not identical to the target nucleic acid. It would have been obvious to an ordinary skilled in the art that a nucleic acid having 80%-99% homology with the target as claimed, is homologous but not identical as taught by Cotta-Ramusino.
Regarding claim 54, Cotta-Ramusino teaches the template has the general orientation of “homology arm-replacement sequence-homology arm,” page 79, lines 32-34). Cotta-Ramusino teaches PCR amplicons can either span the entire donor region, only part of the donor region (page 208, 1st paragraph). It would have been obvious to an ordinary skilled in the art to place the primer binding site in 5’ to 3’ orientation or 3’ to 5’ orientation based on the position of the region to be amplified. It would have been routine experimentation rather than method of innovation.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cotta-Ramusino, in view of the sequence having accession number BFB11213 (WO2018027078).
The teaching from Cotta-Ramusino has been discussed above. Cotta-Ramusino further teaches that the gRNA may be linked to the template nucleic acid directly, or through an adapter molecules that is a protein (i.e., a peptide linker) (page 46, 2nd paragraph).
However, Cotta-Ramusino does not specifically teaches a linker having sequence such as SEQ ID NO: 127.
The nucleic acid having accession number BFB11213 disclosed in WO2018027078 is a peptide linker having 100% sequence homology with SEQ ID NO: 127 (see alignment attached).
It would have obvious to an ordinary skilled in the art to use prior art known peptide linker as adapter to create fusion of the gRNA and nucleic acid template. Since SEQ ID NO: 127 is a known linker in prior art, using it for its intended purpose would have yield predictable result, and thus would have been obvious at the time the application was filed.
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, 2, 7-11, 16-20, 52-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-60 of U.S. Patent No. 11643652. Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA of claims 1-60 of ‘652 patent anticipates all the presently claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57.
Claims 1, 2, 7-11, 16-20, 52-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11912985. Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA in the system claimed in claims 1-29 ‘985 patent anticipates all the presently claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57.
Claims 1, 2, 7-11, 16-20, 52-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11795452. Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA as part of the prime editing system claimed in claims 1-30 of‘452 patent anticipates all the presently claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57.
Claims 1, 2, 7-11, 16-20, 52-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,447,770. Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA used in the method of site specific modification as claimed in claims 1-30 of ‘652 patent anticipates all the presently claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57.
Claims 1, 2, 7-11, 16-20, 52-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of U.S. Patent No. 12031126. Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA used in the method of site specific modification as claimed in claims 1-41 of ‘126 patent anticipates all the presently claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57.
Claims 1, 2, 7-11, 16-20, 52-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,281,303. Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA of claims 1-30 of ‘303 patent anticipates all the presently claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57.
Claims 1, 2, 7-11, 16-20, 52-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 12509680. Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA that is part of the multiplex prime editing system claimed in claims 1-32 of ‘680 patent anticipates all the presently claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57.
Claims 1, 2, 7-11, 16-20, 52-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 12,570,972. Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA as part of the prime editing system claimed in claims 1-31 ‘972 patent anticipates all the presently claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57.
Claims 1, 2, 7-11, 16-20, 52-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12624353. Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA of claims 1-30 of ‘353 patent anticipates all the presently claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57.
Claims 1, 2, 7-11, 16-20, 52-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 12624354. Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA as part of the prime editing system claimed in claims 1-31 of ‘354 patent anticipates all the presently claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57.
Claim 1 and 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25 and 50 of copending Application No. 18/712922 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA claimed in claims 25 and 50 of ‘922 application anticipates claims 1 and 2 of present application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 7-11, 16-20, 52-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/028,183 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the PegRNA of ‘183 application anticipates the claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57 of present application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 7-11, 16-20, 52-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-8,10, 13-17, 34-42 of copending Application No. 18/431,323 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the PegRNA of ‘323 application anticipates the claimed PEgRNA of claims 1, 2, 7-11, 16-20, 52-57 of present application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 and 2 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 140 of copending Application No. 18/903,447 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA claimed in clam 140 of ‘447 application anticipates the PEgRNA of presently claimed in claims 1 and 2.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 7-11, 16-20, 52-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 233-252 of copending Application No. 18961,081 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the PEgRNA as part of the prime editing system claimed in claims 233-252 of ‘081 application anticipates claims 1, 2, 7-11, 16-20 and 52-57 of present application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claim 15 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/Primary Examiner, Art Unit 1637
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