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 .
Claim Status
Claims 2, 4, 14, 16, 18-19, 25, 27, 29-31, 35, 36, 43, 47-50 are pending.
Claims 2, 4, 14, 16, 18-19, 25, 27, 29-31, 35, 36, 43 of Group II and the miRNA, CRISPR, endogenous species are examined here, while claims 47-50 stand withdrawn.
Priority
The priority to foreign applications UK 1715116.8, UK 1715113.5, both filed on 09/19/2017, and UK 1719516.5, filed on 11/23/2017 via their 371 PCT/IB2018/057143, filed on 09/18/2018, is recognized. All examined claims enjoy the priority date of 09/19/2017.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 03/27/2026, along with its fee, after the mailing date of the prior non-final office Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
35 U.S.C. 112(d):
Rejection of cl. 16 under 112(d) is withdrawn. TasiRNA is deleted from the claim.
Claim Rejections - 35 USC § 103
All the examined claims are rejected under 103, as noted below.
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.
Claims 2, 4, 14, 16, 18, 19, 25, 27, 29-31, 35, 36 are rejected under 35 U.S.C. 103 as being unpatentable over Lataniotis et al. (8/2017, Scientific Reports, 7, 8585, 1-14, referred as Lataniotis) and further in view of Liu et al. (2008, Nucleic Acids Research, 36, 2811-2824, referred as Liu) and Senis et al. (2017, Nucleic Acid Research, 45, pg. 1-17, in IDS).
Regarding instant cl. 2, 18, 36, Lataniotis discloses a method of modifying several miRNA genome sites encoding miRNAs that targets mRNA in vascular smooth muscle cells (VSMCs). VSMCs were transduced with lentiviral expressing Cas9 (LentiCRISPRv2 vector) that encodes Streptococcus pyogenes Cas9 (SpCas9) (pg. 2) and transfected with sgRNA designated “sg18” (pg. 10, Fig. 5a). The expression product of Cas9/sg18 targeted the miR-17-92 cluster, see Fig. 5, which also demonstrates deletion/insertion of nucleotides within the MiR-18a genomic locus of the miR-17-92 cluster and demonstrates the loss of miR-18a expression (Fig. 5d, e, pg. 10; relevant to instant cl. 2, “the original specificity of the RNA silencing molecule is destroyed”).
However, Lataniotis does not disclose a RNAi molecule modified to recognize a new, second target while preserving its secondary RNA structure, nor introducing a donor oligonucleotide sequence, nor a second target associated with an infectious disease.
Liu discloses siRNAs/shRNA molecules targeting HIV that are inserted into pri-miR backbones of polycistronic miR-17-92 (abstract, see Fig. 1). Liu designed a polycistronic transcript based on the miR-17-92 backbone to simultaneously express four anti-HIV siRNAs and mimicked the structural features of natural pre-miRNA (pg. 2813-2814, Fig. 1, Fig. 2, relevant to instant cl. 18). An example modification detailed in Fig. 2 is below: r/t5 siRNA targeting HIV (blue color sequence) is incorporated into the Dwt pre-miRNA (red color sequence) of mir-17-19b polycistron. Thus exemplifying, first, that the original specificity of the RNA silencing molecule is destroyed, since the red sequence, a mature mir-20 sequence, is removed, and second, that a new specificity towards the second target RNA is gained. The newly incorporated blue sequence is directed towards a second target, specifically HIV. The figure also illustrates mimicking original structural features (mismatches, bulges, and thermodynamic stability) (pg. 2815).
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Liu demonstrated that expression of shRNA/miRNAs is greatly enhanced in multiplex hairpin transcripts that are properly processed into functional miRNAs and demonstrate potent inhibition of HIV-1 replication by simultaneous expression of four antiviral siRNAs/shRNAs or miRNAs, and “a promising therapeutic approach against escape-prone viral pathogens” (i.e. multiple siRNA binding sites on a viral target to overcome rapid emergence of escape mutants; abstract, pg. 2811-2812, relevant to instant cl. 36). Both a plasmid construct and lentiviral vector plasmids (pLV) comprising modified miR-17-92 with siRNA/shRNA targeting HIV were created (pg. 2812, relevant to instant cl. 2).
Senis teaches a method of using a donor vector to insert a foreign DNA into an excision site generated by CRISPR/Cas9 by a homologous DNA replication process (See pg. 2, “Methods with TALEN/CRISPR/Cas9 expression plasmids together with the homologous recombination template pSSV9-hcr-donor-shmiRHCV318”, relevant to instant cl. 2). Further Senis discloses that the use of TALEN and CRISPR/Cas9 nucleases to insert a shmiRNA against a viral pathogen (HCV) stably integrates a minimal promoterless shmiRNA hairpin into an endogenous miRNA locus, in order to hijack the cellular miRNA promoter for long-term shmiRNA expression at robust yet non-toxic levels (pg. 2). Senis also provides concerns for use of imprecise integrating vectors, such as retro- or lentiviruses, that permit long-term RNAi expression, but due to their promiscuity bear a risk of insertional mutagenesis and a risk of progression to clonal expansion or oncogenesis, and imprecise insertion also does not provide sufficient control over the number of insertion and over governing RNAi expression levels (pg. 2).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Based on the teachings of Senis, which highlights the drawbacks of promiscuous integration by the use of lentivirus, and noting improved, precise insertion of CRISPR/Cas9 nuclease that is robust yet non-toxic, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have modified the CRISPR/Cas9 process of Lataniotis in view of Liu and arrived at the claimed invention with a reasonable expectation of success. Based on the success of using sg18 to modify miR-17-92 site using CRISPR/Cas9 nuclease of Lataniotis, and using a plasmid DNA construct of miR-17-92 backbone that incorporates siRNA targeting HIV and was successful in reducing HIV expression levels as taught by Liu, one of ordinary skill in the art would expect reasonable success by combining the method of editing the miR-17-92 cluster backbone by using CRISPR/Cas9 of Lataniotis with the method of using a donor vector with miR-17-92 backbone modified with siRNAs targeting HIV as taught by Liu and Senis as a therapeutic approach to attack escape-prone viral pathogens, thus combating infectious disease. Thus, claims 2, 18, 36 are obvious.
Regarding instant claim 4, Lataniotis discloses the gene encoding the RNA silencing molecule is endogenous to VSMC (pg. 2).
Regarding instant claim 14, Lataniotis discloses the RNA silencing molecule miR17-92b is edited at its precursor site, see Fig. 5A and thus a mature miRNA sequence would be processed from a precursor. Further, Liu also discloses that the miR sequences would be processed from a precursor and discloses maintaining the “natural pri-miRNA structures” (pg. 2812, see also Fig. 2 above of post-incorporation blue sequence 2d structure mimicking pre-incorporation red sequence structure)
Regarding instant claim 16, Lataniotis discloses the RNAi molecule is a miR-17-92b cluster.
Regarding instant claim 19, Lataniotis discloses a modifying gene whereby some products are produced by insertion of either 1 or 3 nt., and some products are the result of deletion (see Fig. 5d, pg. 10). Liu discloses insertion of siRNA with length of at most 200 nt. targeting HIV (see Fig. 2 above of blue sequence insertion in wild-type red sequence).
Regarding instant claim 25, Lataniotis discloses a modification by insertion of 1 or 3 nt. or deletion of up to 26 nt. (see Fig. 5d, pg. 10).
Regarding instant claim 27, Lataniotis discloses sg18 (Fig. 5a, pg. 10), also design of single guide RNA in the method section (pg. 2) along with sequence in supplemental material (Supplemental Figure S10-B for Sg145m2).
Regarding claim 29, 30, 31, Lataniotis discloses the endonuclease is Cas9 (see lentiviral particle transduction/infection of LentiCRISPRv2 vector, pg. 2).
Regarding instant claim 35, the second target RNA is endogenous to said VSMCs (see Fig. 3e of 13 nt. indel).
Claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over Lataniotis et al. (8/2017, Scientific Reports, 7, 8585, 1-14, referred as Lataniotis) and Liu et al. (2008, Nucleic Acids Research, 36, 2811-2824, referred as Liu) and Senis et al. (2017, Nucleic Acid Research, 45, pg. 1-17, in IDS) as applied to claims 2, 4, 14, 16, 18, 19, 25, 27, 29-31, 35, 36 above, and further in view of Musinova et al. (2016, Cellular and Molecular Life Sciences, 73, pg. 589-601) and Yang et al. (2014, Nature Protocols, 9, 1956-1968).
Rejection of claims 2, 4, 14, 16, 18, 19, 25, 27, 29-31, 35, 36 are noted above.
Lataniotis, Liu and Senis do not teach a method of treating a cancerous disease in a subject in need thereof where the second target RNA is associated with onset or progression of the cancerous disease .
Musinova discloses that Tat protein expressed by HIV is associated with increased incidence of neoplasms and urge that the Tat protein be considered an oncogene since its expression is involved with lymphoma and other tumors (see pg. 593-594).
Further, modifying a genome of a mice, a rat, and a primate subjects using CRISPR/Cas9 with DNA donor oligonucleotide is known in the art as disclosed by Yang (pg. 1956-1968). Yang discloses a method of using of Cas9 and donor templates to modify genome in vivo, see Fig. 1 and 2 (pg. 1957, 1958, respectively; discloses that with a single stranded oligo donor DNA, efficiency of HDR varies from 10-80%, while of double-stranded plasmid donor DNA it’s 10 to 30% (pg. 1968)).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have combined the method of editing the miR19-72 cluster using Cas9/sg18 of Lataniotis, with a template comprising the miR19-72 backbone with siRNAs targeting viral pathogens of Liu and use of donor template and of CRISPR editing instead of imprecise lentiviral integration of Senis in view of Yang and arrive at the claimed invention of treating a cancerous disease in a subject with a reasonable expectation of success. Based on the success of using sg18 to modify miR-17-92 site using CRISPR/Cas9 nuclease of Lataniotis, and using a plasmid DNA construct of miR-17-92 backbone that incorporates siRNA targeting HIV that successfully reduced HIV expression levels as taught by Liu, one of ordinary skill in the art would expect a reasonable success combining the methods of editing miR19-72 backbone with siRNAs targeting viral pathogens of Lataniotis, Liu and Senis with the method of editing a genome of a subject in vivo as taught by Yang to treat a HIV-induced cancerous disease as taught by Musinova.
Response to Arguments
Applicant's arguments filed 03/27/2026 (referred as “the Remarks”) have been fully considered but they are not persuasive.
The Remarks argue the following as a basis that the rejection has not met its obviousness burden and failed to articulate proper reasons for combining the references:
The teaching of the references have inherent contradictions:
Purpose and aim of Lataniotis is completely different from that of Liu (i.e. unrelated technical fields, "technically irrationally for one having ordinary skill in the art to combine these references") (pg. 8).
Lataniotis is "focused on dissecting the regulation and function of clustered miRNAs in living cells"
Liu is "introduction of artificial and extracellular synthetic miRNA polycistronic construct" and goal is "appropriateness of using an effector miRNA molecular as a gene therapy against HIV-1" (pg. 8).
Thus a skilled artisan would have no reason "to introduce artificial RNA into the eukaryotic genome" since "such a construct [artificial RNA] could not have helped to understand the regulation and function of native miRNA in the eukaryotic genome" (pg. 8). WHAT?)
Then adds, citing prior Remarks of 3/28/25, that "purpose of Lataniotis is to interrogate the use of gene editing as a tool to understand the regulation and function of miRNA" (pg. 9). Then concludes that the references purpose "are completely different and the POSITA using CRISPR/Cas9 editing to study miRNA regulation (as in Lataniotis) would not have consulted a document aiming to develop a gene therapy against HIV (such as Liu)" (pg. 8, 9)
Senis is also incompatible, since it is "concerned with introducing an artificial miRNA into a genomic locus comprising an endogenous miRNA, without altering the endogenous miRNA" (pg. 9).
Further a skilled artisan "would not have combined Senis with Liu at all because they are performed in different contexts (artificially constructed effector miRNA molecules versus miRNA gene editing in a genomic context)" (pg. 9).Even if the method of Liu was performed in a genomic context as per Senis, a POSITA would not have thought to replace or swap a native miRNA sequence with a new artificial sequence (as in Liu), because Senis specifically teaches introducing exogenous shmiRNA sequences upstream of an endogenous miRNA gene without compromising the function of the endogenous miRNA (see final paragraph of Results, Design and validation of an anti-HCV shmiRNA for integration into the hcr locus, on page 5 of Senis) (pg. 9).
Even if using flexible approach, need to provide articulated reasoning that is grounded in fact (pg. 10).
The "obviousness theory improperly relies on the introduction of an artificial and extracellular synthetic miRNA polycistron construct (as taught in Liu) and the introduction of an artificial miRNA into a genomic locus comprising an endogenous miRNA, without altering the endogenous miRNA (as taught in Senis) to supply the missing limitations in Lataniotis acknowledged by the Examiner (see Non-final Office Action, pg. 5)."
The obviousness analysis is "contaminated with impermissible hindsight" (pg. 11).
Liu's procedure is cumbersome: "complicated 4-step fusion PCR" (pg. 12).
The references of Senis/Lataniotis discussing CRISPR is more contemporary than Liu reference, which "was published in 2008, almost 10 years earlier and before CRISPR/Cas9 editing" (pg. 13).
The argument is not persuasive.
The rejection has met the prima facie obviousness requirement.
The unrelated technical fields argument is not persuasive because KSR has implemented a flexible approach to obviousness. Here, the action has articulated clear reasoning for combining the prior art references. The goal of the reference(s) does not have to be the same goal as instant specification. Lataniotis teaches cleavage within the “highly studied” miR-17-92 cluster into the miR-18a expression genomic locus using a specific guide RNA “sg18”, and Liu discloses modifying the miR-17-92 backbone to express four anti-HIV siRNAs to target HIV virus. The sufficient, common sense rationale is to modify the miR-17-92 backbone to anti-HIV siRNAs to target anti-HIV, to address the escape-prone viral pathogens by using multiple siRNAs. The field is to modify the original genomic sequence to that of another, i.e. here, both references are using the miR-17-92 miRNA cluster sequence (addressing argument 1a, and both are addressing miRNA sequences; see juxtaposition of Fig. 5a of Lataniotis (top) and Fig. 1A of Liu (below “A”)).
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Further Senis discloses the ability to insert a desired donor vector into an excision site generated by CRISPR/Cas9, wherein the donor vector is a shmiRNA that targets a viral pathogen. Here, Senis teaches that lentiviral, as used by Liu, has a drawback (i.e. imprecision integration may cause insertional mutagenesis) and thus using CRISPR/Cas9 system to insert a donor vector, i.e. a donor vector taught by Liu, in a minimal promoterless shmiRNA in an endogenous miRNA locus will produce shmiRNA at non-toxic levels. Thus, the references teach a less-toxic method of inserting a DNA construct of miR-17-92 backbone incorporating siRNA targeting HIV and is successful in reducing HIV expression levels as taught by Liu. Further, the CRISPR/Cas9 modification of Senis overcomes, as the Remarks argue, a cumbersome “complicated 4-step fusion PCR” taught by Liu.
The Remarks do not provide a sufficient rationale for why a POSITA would not have thought to replace or swap a native miRNA sequence with a new artificial sequence (as in Liu). Here, the action has provided sufficient articulated reasoning for combining the references with reasonable likelihood of success, thus addressing argument 1b and 1c.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, it is not relevant the time periods of each reference as long as they are prior to the disclosure of instant specification. Each reference predates disclosure of instant specification.
The rejection of examined claims is maintained.
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 2, 4, 14, 16, 18, 19, 25, 27, 29, 30, 31, 35, 36, 43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4, 14, 12, 19, 52, 23, 25, 28, 30, 55, 37, 58 of copending Application No. 17/438,920 (referred as ‘920) in view of Hui et al. (2014, Nature Protocols, 9, pg. 1956-1968) and Liu et al. (2008, Nucleic Acids Research, 36, pg. 2811-2824).
This is a provisional nonstatutory double patenting rejection.
Regarding instant cl. 2, claims 4 and 14 of ‘920 teach the following:
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Claims 4 and 14 of ‘920 do not teach a donor oligonucleotide nor the seed sequence binding to second target RNA.
Hui teaches the use of donor template as a repair template to generate a desired modification to obtain precise gene modification (Table 1, pg. 1959).
Claims of ‘920 and Hui do not teach that seed sequence of the RNA silencing molecule binds to the second target RNA.
Liu discloses designing a vector template comprising a siRNAs/shRNA molecules targeting HIV that are inserted into pri-miR backbones of polycistronic miR-17-92 (abstract, see Fig. 1). Liu’s siRNA/shRNA seed sequence binds to the HIV mRNA. Liu demonstrated that expression of shRNA/miRNAs is greatly enhanced in multiplex hairpin transcripts that are properly processed into functional miRNAs and demonstrate potent inhibition of HIV-1 replication by simultaneous expression of four antiviral siRNAs/shRNAs or miRNAs, and “a promising therapeutic approach against escape-prone viral pathogens” (i.e. multiple siRNA binding sites on a viral target to overcome rapid emergence of escape mutants; abstract, pg. 2811-2812).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have combined the teachings of claims 4 and 14 of ‘920 in view of Hui and Liu and arrive at the claimed invention with a reasonable expectation of success. Based on the obtaining a more precise gene modification with the use of donor template of Hui and use of Liu’s donor template comprising siRNA/shRNA nucleotide sequence targeting HIV inserted into pri-miRNA backbone of polycistronic miR-17-92 to degrade HIV mRNA, one of ordinary skill in the art would expect reasonable success by combining a claimed subject matter of claims 4 and 14 of ‘920 with a donor template comprising siRNA/shRNA whose seed sequence bind to second target RNA as taught by Hui and Lui to achieve precise base editing and have sufficient binding to second target RNA. Thus, claim 2 is obvious.
Claim 12 of ‘920, teaching gene encoding or process into the RNA silencing molecule is endogenous to the eukaryotic cell, corresponds to instant cl. 4.
Claim 19 of ‘920, teaching said RNA silencing molecule is processed from a precursor, corresponds to instant cl. 14, 18. Regarding instant cl. 18, claim 19 of ‘920 teaches wherein said RNA silencing molecule is processed from a precursor, and small RNA engaged with RISC, which is a cellular RNAi factor and inherently its secondary RNA structure would need to be preserved to engage with RISC.
Claim 52 of ‘920, teaching small RNA is miRNA, corresponds to instant cl. 16.
Claim 23 of ‘920, teaching said gene is effected by one or more point mutations, corresponds to instant cl. 19.
Claim 25 of ‘920, teaching modification comprises a modification of at most 200 nt., corresponds to instant cl. 25.
Claim 28 of ‘920, teaching DNA editing agent comprises at least one sgRNA, corresponds to instant cl. 27. sgRNA is a species of or is gRNA.
Claim 30 of ‘920, teaching DNA editing agent comprises an endonuclease, corresponds to instant cl. 29.
Claim 55 of ‘920, teaching endonuclease comprises Cas9, corresponds to instant cl. 30 and 31.
Claim 37(c) of ‘920, teaching second target RNA is endogenous to said eukaryotic cell, corresponds to instant cl. 35.
Claim 58 of ‘920, teaching gene associated with apoptosis is BAX, PUMA or NOXA, corresponds to instant cl. 36 and 43. BAX, PUMA, or NOXA is associated with cancer and its modification may treat cancer.
Response to Arguments
Applicant's arguments filed 03/27/2026 have been fully considered but they are not persuasive. Here, the Remarks argue to hold the rejection in abeyance (pg. 14). The argument is not persuasive and the rejection is maintained.
Allowable Subject Matter
No claim allowed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEYUR A. VYAS whose telephone number is (571)272-0924. The examiner can normally be reached M-F 9am - 4 pm (EST).
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/KEYUR A VYAS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
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