DETAILED CORRESPONDENCE
Application Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Support for the amendments are within the instant application specification.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/24/2026 has been entered.
Applicant’s amendment to the claims filed on 2/24/2026 in response to the Final Rejection mailed on 11/28/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 1-19, 24, 26, 28, 31, 36-80, 90, 92, 94, 96 are canceled.
Claims 20-23, 25, 27, 29-30, 32-35, 81-89, 91, 93, 95 are pending.
Applicant’s remarks filed on 2/24/2026 in response to the Final Rejection mailed on 11/28/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
The terminal disclaimers filed on 2/24/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent Application No. 17541398 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Withdrawn Rejections
The rejection of claims 34, 81-85, 93 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in view of Applicant’s amendment of claims 34 and 81 to remove the recitation ‘wherein the portion of the donor polynucleotide is about 50% or more complementary to the target DNA.’
The rejection of claims 34, 81-85, 93 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of Applicant’s amendment of claims 34 and 81 to remove the recitation ‘about.’
The rejection of claims 20-23, 25, 27, 29-30, 32-35, 91 under 35 U.S.C. 102 (a)(2) as being anticipated by Zhang et al (WO2021055874 A1, Date Filed: 18 September 2020, cited on IDS dated 10/14/2025) {herein Zhang ‘20} is withdrawn in view of Applicant amendment of claims 20, 91 to recite ‘with the proviso that the at least two HEPN sequences are not both selected from SEQ ID NOs: 94, 95, and 111.’
The provisional rejection of claims 20-23, 81, 86 on the grounds of nonstatutory double patenting as being unpatentable and obvious over claims 1, 4, 6, 81-83 of copending US Application 17/541,405 is withdrawn as said Application is drawn to product claims, whereas the instant application is drawn to method claims.
New 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.
Claims 20-23, 25, 27, 29-30, 32-35, 91 are newly rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (WO2021055874 A1, Date Filed: 18 September 2020, cited on IDS dated 10/14/2025) {herein Zhang ‘20} in view of DE VASCONCELOS et at (WO2004/056960, Filing Date: 16 December 2003, Examiner cited() {herein DE VASCONCELOS}. The new rejection is necessitated by Applicant’s amendment to claim 20 to recite ‘with the proviso that the at least two HEPN sequences are not both selected from SEQ ID NOs: 94, 95, and 111.’
As amended, claims 20-23, 25, 27, 29-30, 32-35, 91 are drawn to a method of modifying a target DNA or RNA, the method comprising contacting the target DNA with (a} a Class 2 CRISPR-Cas endonuclease or a nucleic acid encoding the endonuclease, wherein the Class 2 CRISPR-Cas endonuclease is: (i) a Class 2 Type II CRISPR-Cas endonuclease comprising at least one RuvC motif sequence selected from the entire amino acid sequence of SEQ ID NOs: 116, 117, 118, 121, 122, 123, 126, 127, 128, 131, or 132; (ii) a Class 2 Type V CRISPR-Cas endonuclease comprising at least two RuvC motif sequence selected from the entire amino acid sequence of SEQ ID NOs:62, 63, 64, 67, 68, 69, 71, 72, 73, 75, 76, 77, 80, 81, 82, 85, 86, 87, 89, 90, 91, 135, 136, or 137; or (iii) a Class 2 Type VI CRISPR-Cas endonuclease comprising at least two HEPN motif sequences selected from the entire amino acid sequence of SEQ ID NOs: 94, 95, 97, 99, 102, 104, 105, 107, 108, 110, 111, or 113, and with the proviso that the at least two HEPN sequences are not both selected from SEQ ID NOs: 94, 95, and 111; (b) a guide RNA (gRNA} or a nucleic acid encoding the gRNA, wherein the gRNA and the Class 2 CRISPR-Cas endonuclease do not naturally occur together, wherein the gRNA is capable of hybridizing to a target sequence in a target DNA or RNA, and the gRNA is capable of forming a complex with the Class 2 CRISPR-Cas endonuclease, wherein the gRNA hybridizes with the target sequence whereby modification of the target DNA or RNA occurs.
With respect to claims 20, 21, 35, 91, Zhang ’20 teaches a method of modifying a target sequence via Class 2 Type VI Cas proteins that contain one or more-higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domains (para 0114, claim 4). Said HEPN domains are 100% identical to the instant application SEQ ID Nos: 94, 95, 111 (appendix A, B, C, respectively). Specifically, the instant application SEQ ID NO: 94 has 100% homology to Zhang ’20 SEQ ID NO: 4424; the instant application SEQ ID NO: 95 has 100% homology to Zhang ’20 SEQ ID NO: 4627; the instant application SEQ ID NO: 111 has 100% homology to Zhang ’20 SEQ ID NO: 4569 (Zhang ’20 claim 4, appendix A, B, C, respectively). Regarding the recitation ‘with the proviso (provision) that the at least two HEPN sequences are not both selected from SEQ ID NOs: 94, 95, and 111’ in claim 20 of the instant application, it is the Examiner’s position that one of the HEPN sequences (SEQ ID NO: 94, 95, 99 or 111) taught by Zhang ’20 meet said claim limitation. Zhang ’20 further teaches the method comprises contacting a target RNA or DNA (para 0024) with one or more non-naturally occurring or engineered compositions comprising a mutated Cas13 effector protein and a crRNA, wherein the crRNA comprises a guide sequence that hybridizes to a target RNA or DNA (para0024) sequence in a cell (para 0191). The Cas13 effector protein forms a complex with the crRNA (para 0161), of which comprises DNA (para 0191), along with the guide sequence and directs sequence-specific binding to the target RNA sequence in a cell, whereby forming a CRISPR complex comprising the Cas13 effector protein complexed with the guide sequence that is hybridized to the target sequence, modifying the expression of the target locus of interest (apar 0161). Zhang ’20 further teaches a donor RNA can be mRNA (para 0123). As such, absent evidence otherwise, it is the Examiner’s position that the mRNA taught by Zhang ’20 is a donor polynucleotide of which DNA binds. In addition, Zhang ’20 teaches the exogenous RNA template (mRNA) comprises a sequence to be integrated into the target sequence (para 0123). The exogenous RNA template (mRNA) has about 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the targeted RNA sequence (para 0123), of which Examiner is interpreting said teaching to be the same as ‘about 50% or more complimentary to the target DNA’ as recited in instant application claims 20 and 81. The modification of target sequence may comprise a deletion of nucleotides (para 0097). The complex can be formed in vitro or ex vivo and introduced into a cell or contacted with RNA; or can be formed in vivo (para 0124, 0161).
With respect to claim 22, Zhang ’20 teaches a method comprising a non-naturally occurring or
engineered composition consisting of an mRNA encoding the Cas protein, and a guide
sequence capable of forming a complex with the Cas protein and directing the complex to
bind to a target sequence (para 0009).
With respect to claim 23, Zhang ’20 teaches the target nucleic acid is a DNA molecule and the
method further comprises contacting the target DNA molecule with a primer comprising an
RNA polymerase site and RNA polymerase (para 0024).
With respect to claim 25, Zhang ’20 teaches a method wherein the CRISPR-Cas system is utilized for the targeting of the genome of eukaryotic organisms (para 0109). It is known by those of ordinary skill in the art that all Eukaryotes have chromosomal DNA, as such Examiner is interpreting said teaching by Zhang ‘20 to be the CRISPR-Cas system targeting DNA that is part of the chromosome since all Eukaryotes have chromosomes.
With respect to claims 27, 29, Zhang ’20 teaches the method of modifying a target RNA can be in a eukaryotic cell, which may be in vivo, ex vivo or in vitro (para 0124), such as a plant cell (para 0019).
With respect to claim 30, Zhang ’20 teaches a method of providing a Cas13 transgenic cell in which one or more nucleic acids encoding one or more guide RNAs are provided or introduced operably connected in the cell with a regulatory element comprising a promoter of one or more genes of interest (para 0130).
With respect to claim 32, Zhang ’20 teaches a method wherein a strand break may be a double-strand break (para 0110, 0209) of target DNA (para 0109).
With respect to claim 33, Zhang ’20 teaches a method of Cas9-mediated genome editing via non-homologous end joining (NHEJ) (page 31, para 2).
With respect to claim 34, Zhang ’20 teaches a method comprising contacting one or more target sequences with the CRISPR-Cas system (para 0161).
However, Zhang ’20 does not teach (iii) a Class 2 Type VI CRISPR-Cas endonuclease comprising at least two HEPN motif sequences selected from the entire amino acid sequence of SEQ ID NOs: 94, 95, 97, 99, 102, 104, 105, 107, 108, 110, 111, or 113, and with the proviso that the at least two HEPN sequences are not both selected from SEQ ID NOs: 94, 95, and 111 (claim 20).
With respect to claim 20, DE VASCONCELOS teaches a method wherein the integration of an HEPN motif sequence, SEQ ID NO: 12, confers resistance to nematodes in plant cells as a long-lasting way for controlling pests (page 12, lines 9-13 and page 26, lines 5, appendix D).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to apply the teachings of Zhang ‘20 et al. of a method of modifying a target sequence via Class 2 Type VI Cas proteins that contain one or more-higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domains (para 0114, claim 4) or combine the teachings of DE VASCONCELOS of a method wherein the integration of an HEPN motif sequence, SEQ ID NO: 12, confers resistance to nematodes in plant cells as a long-lasting way for controlling pests (page 12, lines 9-13 and page 26, lines 5, appendix D).
One of ordinary skill in the art would be motivated to either use the teachings of Zhang ‘20 et al. by itself or combine the teachings of DE VASCONCELOS because DE VASCONCELOS provides Zhang ’20 the motivation to modify a target DNA or RNA with a Class 2 Type VI CRISPR-Cas endonuclease comprising SEQ ID NO: 12 (instant application SEQ ID NO: 97) (appendix D) in addition to one of the HPEN taught by Zhang ’20 as DE VASCONCELOS teaches plant cells with SEQ ID NO: 12 (instant application SEQ ID NO: 97) confers resistant to nematodes. One of ordinary skill in the art knowing the benefit of Class 2 Type VI CRISPR-Cas endonuclease comprising a HEPN that confers resistance to pests based on the teachings of Zhang ’20 and DE VASCONCELOS would have a reasonable expectation of success that substituting one of the HPEN taught by Zhang ’20 (SEQ ID NO: 94, 95 or 111) with the HPEN taught by DE VASCONCELOS would provide additional targeted pest control as there would be a greater likelihood that the cells are genetically modified to confer resistance to nematodes, thereby reducing the need to utilize external pesticides such as spray which could negatively impact surrounding plant material. MPEP 2143.I.B. states “The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.” In addition, utilizing said construct would be cost effective as there would be a greater probability that the resistance to nematodes would be passed down to the offspring of the plants, thereby reducing the need to apply topical pesticides and retaining plants that would of ordinarily been destroyed by nematodes and topical pesticides.
One of skill in the art would have a reasonable expectation of success to make and use the claimed HPEN (SEQ ID NO: 94, 95 or 111) taught by Zhang ’20 and the HPEN taught by DE VASCONCELOS (SEQ ID NO: 97) because Zhang ’20 provides the basic Class 2 Type VI CRISPR-Cas endonuclease comprising one HEPN (SEQ ID NO: 94, 95 or 111) and its uses and methods of making it. Reference of DE VASCONCELOS provides the teachings of a method wherein the integration of an HEPN motif sequence, SEQ ID NO: 12, confers resistance to nematodes in plant cells as a long-lasting way for controlling pests (page 12, lines 9-13 and page 26, lines 5, appendix D). Therefore there would be a reasonable expectation of success to arrive at the above invention. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Allowable Subject Matter
Claims 81-89, 93, 95 are allowed as there is no prior art that teaches ‘(a) a Class 2 CRISPR-Cas endonuclease, wherein the Class 2 CRISPR-Cas endonuclease is: (i) a Class 2 Type II CRISPR-Cas endonuclease comprising at least one RuvC motif sequence selected from the entire amino acid sequence of SEQ ID NOs: 116, 117, 118, 121, 122, 123, 126, 127, 128, 131, or 132; or (ii) a Class 2 Type V CRISPR-Cas endonuclease comprising at least two RuvC motif sequence selected from the entire amino acid sequence of SEQ ID NOs: 62, 63, 64,67, 68, 69, 71, 72, 73, 75, 76, 77, 80, 81, 82, 85, 86, 87, 89, 90, 91, 135, 136, or 137; and (b) a gRNA encoding the gRNA’ (claims 81 and 95) .
Conclusion
Status of claims
Claims 20-23, 25, 27, 29-30, 32-35, 81-89, 91, 93, 95 are pending.
Claims 1-19, 24, 26, 28, 31, 36-80, 90, 92, 94, 96 are cancelled.
Claims 20-23, 25, 27, 29-30, 32-35, 91 are rejected.
Claims 81-89, 93, 95 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Appendix A
Zhang ’20 et al SEQ ID NO: 4424 vs Instant Application SEQ ID NO: 94
Query Match 100.0%; Score 38; Length 323;
Best Local Similarity 100.0%;
Matches 6; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RNYYTH 6
||||||
Db 111 RNYYTH 116
Appendix B
Zhang ’20 et al SEQ ID NO: 4627 (claim 4) vs Instant Application SEQ ID NO: 95
Query Match 100.0%; Score 34; Length 386;
Best Local Similarity 100.0%;
Matches 6; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RNKFSH 6
||||||
Db 337 RNKFSH 342
Appendix C
Zhang ’20 et al SEQ ID NO: 4569 vs Instant Application SEQ ID NO: 111
Query Match 100.0%; Score 34; Length 308;
Best Local Similarity 100.0%;
Matches 6; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RNKAFH 6
||||||
Db 220 RNKAFH 225
Appendix D
Kovalic et al SEQ ID NO: 12 vs Instant Application SEQ ID NO: 97
Query Match 100.0%; Score 35; Length 323;
Best Local Similarity 100.0%;
Matches 6; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RNNFSH 6
||||||
Db 105 RNNFSH 110