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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 response filed 7/13/2026 has been received and entered into the application file. All arguments have been fully considered. Claims 1, 3-4, 6, 9, 11, 15-17, 20-23, 27, 33, 48 and 50-54 are currently pending. Claims 2, 5, 7-8, 10, 12-14, 18-19, 24-26, 28-32, 34-47 and 49 are cancelled. Claims 9, 11, 15-17, 20-23, 27 and 48 are withdrawn. Claims 1, 4 and 50-51 are currently amended. Claim 54 is new.
REJECTIONS WITHDRAWN
Claim Rejections - 35 USC § 103
RE: Rejection of Claim(s) 1, 3-4, 6, 33 and 50-52, under 35 U.S.C. 103 as being unpatentable over Dellinger:
The previous rejection of record is withdrawn in view of Applicant’s amendment submitted 7/13/2026. Applicant’s amendment removed the CAVA nucleotide 5-nitrodiole, which was taught by Dellinger. It is noted however that Applicant’s amendment has necessitated new grounds of rejection as set forth below.
RE: Rejection of Claim 53 under 35 U.S.C. 103 as being unpatentable over Dellinger, as applied to claims 1, 3-4, 6, 33 and 50-52 above, and further in view of May et al., (WO 2016/123230; PTO-892) (“May”).
For the reasons discussed above, the rejection of claims 1, 3-4, 6, 33 and 50-52 is withdrawn, and thus the rejection of claim 53 that is based on the same basis is likewise withdrawn. However, the amendment submitted has necessitated new grounds of rejection, as set forth below.
NEW GROUND(S) OF REJECTION, NECESSITATED BY AMENDMENT
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, 3-4, 6, 33, 50 and 52 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Hummel et al., (WO 2018/202800; see PTO-892) (“Hummel”).
Hummel is directed to compositions for genome engineering using CRISPR/CasX system (page 2, third para). Hummel teaches the CRISPR/CasX system can be delivered into plant cells (page 3, second and third para).
Regarding claim 1, Hummel teaches introducing into the plant cells:
a CRISPR RNA (crRNA) and a trans-activating crRNA (tracrRNA), or introducing a chimeric cr/tracrRNA hybrid (sgRNA); and
a CRISPR/CasX endonuclease molecule (page 4, lines 26-29 to page 5, lines 1-5).
Hummel further teaches the crRNA comprises a repeat sequence of about 23 nucleotides and a spacer sequence of about 20 nucleotides, wherein the crRNA comprises modified nucleotides including 5-Methyl dC bases, 5-hydroxybutynl-2'-deoxyuridine bases, and deoxyinosine bases (page 5, lines 10-15), as recited in claim 1.
Thus, Hummel anticipates claim 1.
Regarding claims 3 and 4, Hummel teaches the crRNA or the sgRNA is targeted to a sequence within the gene or within an RNA molecule encoded by the gene to be edited and the CRISPR/CasX endonuclease (i.e., nucleoprotein complex with a CRISPR-associated (Cas) protein, claim 3) introduces a double strand break or a single strand break at or near the sequence to which the crRNA or sgRNA is targeted, i.e. the guide is capable of forming a nucleoprotein complex with CRISPR-associated (Cas) protein (claim 4).
Regarding claims 6, 33 and 52, Hummel teaches the CRISPR polynucleotide comprising crRNA or sgRNA (ribonucleotide bases) having modified nucleotides including 5-hydroxybutynl-2'-deoxyuridine bases (i.e., deoxyribonucleotide bases), deoxyinosine (i.e., deoxyribonucleotide base) and 5-Methyl dC bases (i.e., deoxyribonucleotide bases), thus anticipating claims 6, 33 and 52.
Regarding claim 50, Hummel teaches the modified nucleotides of the spacer sequence include 5-nitroindole bases (page 5, lines 13-15), thus anticipating claim 50.
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.
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.
Claim(s) 51 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Hummel, as applied to claims 1, 3-4, 6, 33, 50 and 52, and further in view of Dellinger et al., (previously cited).
The teaching of Hummel is set forth above.
Regarding claims 51 and 54, Dellinger is directed to CRISPR technology and specifically teaches CRISPR polynucleotides comprising guide RNAs with chemical modifications that provide enhanced specificity for target sequence, thus minimizing off-target effects of the gRNA:Cas nuclease complex, and the modifications encompass consecutive modifications, such as 1-24 consecutive specificity enhancing modifications (Abstract; [0005] and [0046]).
Dellinger, at paragraphs [0078]—[0094] and [0111]-[0136], teaches of numerous modifications to the guide RNA that are specificity-enhancing modifications (e.g., stability-altering to resist degradation by nucleases, reduces off-target effects, optimizes melting temperature), and the modifications take place within the guide sequence or crRNA segment of the guide RNA ([0091]).
Dellinger’s paragraph [0079] teaches the chemically modified guide RNA comprises any nucleotide other than the four canonical ribonucleotides (A, C, G, and U). Dellinger at paragraph [0080] teaches the modifications include deoxyribose nucleotides and paragraph [0082] teaches the modifications encompass abasic nucleotide modifications, which reads on apurinic and apyrimidinic deoxyribose nucleotides.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include modifications to the guide RNA or crRNA that are specificity-enhancing modifications, including modifications that encompass apurinic and apyrimidinic deoxyribose nucleotides, as taught by Dellinger.
The person of ordinary skill in the art would have been motivated to modify the spacer sequence of Hummel to include apurinic and apyrimidinic deoxyribose nucleotides for the predictable result of successfully enhancing specificity for target sequence, thus minimizing off-target effects of the gRNA:Cas nuclease complex, thus meeting the limitation of claims 51 and 54.
The skilled artisan would have had a reasonable expectation of success in combining the teachings of Hummel and Dellinger because each of these teachings are directed at CRISPR systems.
Claim(s) 53 is rejected under 35 U.S.C. 103 as being unpatentable over Hummel, as applied to claims 1, 3-4, 6, 33, 50 and 52, above, and further in view of May et al., (WO 2016/123230; previously cited) (“May”).
The teaching of Hummel is set forth above.
Regarding claims 53, Hummel does not specifically teach the CRISPR polynucleotide comprises an activating region comprising a DNA, or a mixture of RNA and DNA. However, May is directed to DNA-guided CRISPR polynucleotide systems comprising DNA, RNA and mixtures thereof for use with CRISPR systems (Abstract).
May teaches that CRISPR systems comprising single polynucleotides include a targeting region comprising deoxyribonucleic acid (DNA); and an activating region comprising ribonucleic acid (RNA), wherein the activating region comprises DNA, RNA or a mixture of DNA and RNA, said activating region reduces off-target effects or increases target-specific modification (page 2 and page 6, second paragraph).
Thus, May has established it was known prior to Applicant’s filing, that activating regions of CRISPR polynucleotides can be modified to reduce off-target effects and comprises a mixture of RNA and DNA.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the activating region of CRISPR polynucleotides to comprise a mixture of RNA and DNA, thus reducing off-target effects.
The person of ordinary skill in the art would have been motivated to modify the CRISPR composition of Hummel to include activating regions comprising a mixture of RNA and DNA, as taught by May, for the predictable result of successfully reducing off-target effects, thus meeting the limitation of claim 53.
The skilled artisan would have had a reasonable expectation of success in combining the teachings of Hummel and May because each of these teachings are directed at CRISPR systems.
Response to Remarks/Amendment
For the reasons set forth above, the previous rejections of record have been withdrawn in view of Applicant’s amendment submitted 7/13/2026.
Applicant’s arguments have been fully considered, but are not found persuasive in view of the new grounds of rejection set forth above, specifically addressing the newly amended claims.
Conclusion
No claim is allowed. No claim is free of prior art.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to E. YVONNE PYLA whose telephone number is (571)270-7366. The examiner can normally be reached M-F 9am - 6pm.
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E. YVONNE PYLA
Primary Examiner
Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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