COMPOUNDS AND METHODS FOR MODULATING SPLICING

§103 §112 §DOUBLEPATENT

DETAILED ACTION This office action is in response to applicant’s filing dated September 16, 2026. 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 . Status of claims Claims 1, 5, 7, 15, 25, 32, 40-41, 44, 47, 50-51, 56-57, 61, 63, 79, 81, 102, 116-118, 121, 125, 130-131 and 137 are pending in the instant application. Election/Restrictions Applicant’s election without traverse of Groups I and III, claims 1, 5, 7, 15, 25, 32, 40-41, 44, 47, 50-51, 56, 117-118, 121, and 125, drawn to compounds of Formula (I) and a method of altering the conformation of a nucleic acid comprising contacting the nucleic acid with a compound of Formula (I) in the reply filed on September 16, 2026 is acknowledged. Claims 57, 61, 63, 79, 81, 102, 116, 130-131 and 137 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 16, 2026. Applicant’s election without traverse of N-(8-methoxy-2-methylimidazo[1,2-a]pyrazin-6-yl)-5-(piperazin-1-yl)cinnoline-8- carboxamide: PNG media_image1.png 132 283 media_image1.png Greyscale (Specification, page 81, Ex. 179) as a single species of compound of Formula (I) in the reply filed on September 16, 2026 is acknowledged. Upon performing the search of prior art Examiner detected compounds related to non-elected species. Hence, the examination will expand to include non-elected species, compound of formula (I-f, claim 51). Claim 50 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 16, 2026. Claims 1, 5, 7, 15, 25, 32, 40-41, 44, 47, 51, 56, 117-118, 121, and 125 are under examination in the present office action. Priority The present application is a 371 of PCT/US2022/075683, filed August 30, 2022, and claims the benefits of priority to U.S. Application No. 63/238,687, filed on August 30, 2021; U.S. Application No. 63/238,693, filed on August 30, 2021; U.S. Application No. 63/238,424, filed on August 30, 2021; U.S. Application No. 63/282,902, filed on November 24, 2021; and U.S. Application No. 63/393,202, filed on July 28, 2022. Information Disclosure Statement The information disclosure statements (IDS) submitted on 02/29/2024 and 09/16/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. 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 121 and 125 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. Claims 121 and 125, reciting the term “e.g.” which is equivalent to the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claim 56 recites the limitation "compounds shown in Table 1" without a chemical name is ambiguous and indefinite. It is unclear what the scope of the limitation "compounds shown in Table 1" is. Claims must stand alone to define invention, and incorporation into claims by express reference to specification is not permitted, are properly rejected under 35 U.S.C. 112 (b), see Ex parte Fressola, No. 93-0828. Incorporation of the limitation "compounds shown in Table 1" with a chemical name or structure into claim 56 respectively would obviate the rejection. 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. Claims 1, 5, 7, 15, 25, 32, 40-41, 44, 47, 51, 56, 117-118, 121, and 125 are rejected under 35 U.S.C. 103 as being obvious over Reynolds et al (WO 2021/174164 A1, cited in IDS, filed 02/29/2024, hereinafter Reynolds). The applied reference has a common applicant and join inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). Regarding claims 1, 5, 7, 15, 25, 32, 40-41, 44, 47, 51, 56 and 117, drawn to a compound of Formula (I): PNG media_image2.png 106 191 media_image2.png Greyscale , such as compound of Formula (I-b): PNG media_image3.png 110 197 media_image3.png Greyscale or Formula (I-f): PNG media_image4.png 136 194 media_image4.png Greyscale , where W, X, Y, and Z are each independently C(R3a) or N, wherein at least one of W, X, Y, and Z is independently N, R3a is hydrogen; m is 0-2; A and B are each independently cycloalkyl, heterocyclyl (e.g. PNG media_image5.png 55 82 media_image5.png Greyscale or PNG media_image6.png 70 57 media_image6.png Greyscale ), aryl, or heteroaryl (e.g. PNG media_image7.png 49 86 media_image7.png Greyscale , PNG media_image8.png 66 109 media_image8.png Greyscale or PNG media_image9.png 93 106 media_image9.png Greyscale ) each of which is optionally substituted with one or more R1, R1 is hydrogen, C1-C6 alkyl; L1 is absent, C1-C6-alkylene, -O-, -C(O)-, -N(R4)-, -N(R4)C(O)-, or -C(O)N(R4)-, R4 is hydrogen. The exemplary compounds of Formula (I) are: PNG media_image1.png 132 283 media_image1.png Greyscale (Specification, page 81, Ex. 179), PNG media_image10.png 102 289 media_image10.png Greyscale (Specification, page 80, Ex. 170). The instant claims are further drawn to a pharmaceutical composition comprising a compound of Formula (I) and a pharmaceutically acceptable excipient. Reynolds teaches compounds of Formula (I-a): PNG media_image11.png 111 206 media_image11.png Greyscale ,where W, X, Y, and Z are each independently C(R3a) or N, R3a is hydrogen; m is 0-2; A and B are each independently cycloalkyl, heterocyclyl (e.g. PNG media_image5.png 55 82 media_image5.png Greyscale or PNG media_image6.png 70 57 media_image6.png Greyscale ), aryl, or heteroaryl (e.g. PNG media_image7.png 49 86 media_image7.png Greyscale , PNG media_image8.png 66 109 media_image8.png Greyscale or PNG media_image12.png 95 110 media_image12.png Greyscale ) each of which is optionally substituted with one or more R1, R1 is hydrogen, C1-C6 alkyl; L2 is absent, C1-C6-alkylene, -O-, -C(O)-, -N(R4)-, -N(R4)C(O)-, or -C(O)N(R4)-, R4 is hydrogen. The exemplary compounds of Formula (I) are: PNG media_image13.png 156 252 media_image13.png Greyscale (page 172, Ex. 113), PNG media_image14.png 139 259 media_image14.png Greyscale (page 167, Ex. 100). Reynolds further teaches A pharmaceutical composition comprising a compound of Formula (I-a) and a pharmaceutically acceptable excipient (page 5, 2nd paragraph). Thus, since Reynolds teaches structurally similar compounds of the same genus formula as instantly claimed, and where all the structural elements of the molecule are equivalent to those of instant claims, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to select and combine known structural elements of the molecule, and make various structural analogs acting as nucleic acid splicing modulators, to arrive at claimed compounds. The one of ordinary skills would be motivated to do so in search of an active agent, which is capable of modulating nucleic acid splicing and having improved desired properties, with the reasonable expectation of success. Regarding claims 118 and 121, drawn to a compound of Formula (I), where the compound is capable of altering a target nucleic acid, binding to a target nucleic acid or stabilizing a target nucleic acid, and where the compound increases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more, or the compound decreases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more, Reynolds teaches compounds of Formula (I-a), which alters a target nucleic acid or binds to a target nucleic acid, and where the compound increases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more, or the compound decreases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more (page 4, 3rd paragraph). Thus, compounds taught by Reynolds and instantly claimed compounds exhibit the same mechanism of action in the cell. Regarding claim 125, drawn to a method of altering the conformation of a nucleic acid (e.g., a DNA, RNA, e.g., a pre-mRNA) comprising contacting the nucleic acid with a compound of Formula (I), Reynolds teaches a method of altering the conformation of a nucleic acid (e.g., a DNA, RNA, e.g., a pre-mRNA) comprising contacting the nucleic acid with a compound of Formula (I). Thus, Reynolds teaches the same method, appling the same compounds, thereby rendeing the claimed method obvious. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02. Claims 1, 5, 7, 15, 40-41, 44, 47, 51, 117-118, 121, and 125 are rejected under 35 U.S.C. 103 as being unpatentable over Furet et al (WO 2009/141386 A1, cited in IDS, filed 02/29/2024, hereinafter Furet). Regarding claims 1, 5, 7, 15, 40-41, 44, 47, 51 and 117, drawn to a compound of Formula (I): PNG media_image2.png 106 191 media_image2.png Greyscale , such as compound of Formula (I-b): PNG media_image3.png 110 197 media_image3.png Greyscale or Formula (I-f): PNG media_image4.png 136 194 media_image4.png Greyscale , where W, X, Y, and Z are each independently C(R3a) or N, wherein at least one of W, X, Y, and Z is independently N, R3a is hydrogen; m is 0-2; A and B are each independently cycloalkyl, heterocyclyl (e.g. PNG media_image5.png 55 82 media_image5.png Greyscale or PNG media_image6.png 70 57 media_image6.png Greyscale ), aryl, or heteroaryl (e.g. PNG media_image7.png 49 86 media_image7.png Greyscale , PNG media_image8.png 66 109 media_image8.png Greyscale or PNG media_image9.png 93 106 media_image9.png Greyscale ) each of which is optionally substituted with one or more R1, R1 is hydrogen, C1-C6 alkyl; L1 is absent, C1-C6-alkylene, -O-, -C(O)-, -N(R4)-, -N(R4)C(O)-, or -C(O)N(R4)-, R4 is hydrogen. The exemplary compounds of Formula (I) are: PNG media_image1.png 132 283 media_image1.png Greyscale (Specification, page 81, Ex. 179), PNG media_image10.png 102 289 media_image10.png Greyscale (Specification, page 80, Ex. 170). The instant claims are further drawn to a pharmaceutical composition comprising a compound of Formula (I) and a pharmaceutically acceptable excipient. Furet teaches a compound of formula (I): PNG media_image15.png 137 470 media_image15.png Greyscale , such as a compound of formula IA: PNG media_image16.png 112 466 media_image16.png Greyscale or formula ID: PNG media_image17.png 108 448 media_image17.png Greyscale , where A and B is aryl or heteroaryl such as PNG media_image18.png 73 127 media_image18.png Greyscale pyrazolyl or imidazolyl, m is 0-3 and n is 0-5. The exemplary compounds taught by Furet are: PNG media_image19.png 100 237 media_image19.png Greyscale (page 75, Ex. 15), PNG media_image20.png 82 217 media_image20.png Greyscale (page 96, Ex. 60), PNG media_image21.png 100 228 media_image21.png Greyscale (page 165, Ex. 162), PNG media_image22.png 91 207 media_image22.png Greyscale (page 94, Ex. 55). Furet further teaches pharmaceutical composition, comprising a compound of formula (I) and may comprise excipients (pages 40 – 41). Thus, as illustrated above, the genus formulae IA and ID as well as exemplary compounds taught by Furet fall within the scope of Formula (I) of instant claims 1, 5, 7, 15, 40, 41, 44, 47 and 51. Thus, since Furet teaches a compound of similar structure, where all the structural elements of the molecule are equivalent of those of instant claims, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to select and combine known structural elements of the molecule, and make various structural analogs to arrive at claimed compounds. The one of ordinary skills would be motivated to do so in search of an active agent, able to treat conditions such as proliferative disease, autoimmune disease or metabolic disease with the reasonable expectation of success. Regarding claims 118 and 121, drawn to a compound of Formula (I), where the compound is capable of altering a target nucleic acid, binding to a target nucleic acid or stabilizing a target nucleic acid, and where the compound increases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more, or the compound decreases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more, Furet teaches compounds of formula (I), which is structurally identical or similar to the instantly claimed Formula (I), and is useful to treat the same conditions such as proliferative disease, autoimmune disease or metabolic disease (e.g. diabetes). Although Furet is silent about the compounds to be able to alter a target nucleic acid or increase splicing at splice site on a target nucleic acid, since Furet teaches compounds of the same structure, all the properties are necessarily present, even if prior art is silent as to those properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses (i.e. altering a target nucleic acid, binding to a target nucleic acid or stabilizing a target nucleic acid, and where the compound increases splicing at splice site on a target nucleic acid) and/or claims are necessarily present. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP 2112.01). Regarding claim 125, drawn to a method of altering the conformation of a nucleic acid (e.g., a DNA, RNA, e.g., a pre-mRNA) comprising contacting the nucleic acid with a compound of Formula (I), Furet teaches a method of treating proliferative disease (cancer), autoimmune disease or metabolic disease (e.g. diabetes), where the in vivo antitumor activity is tested, for example, using bladder carcinoma cell lines, such as the human urinary bladder transitional cell carcinoma RT112 cell line (page 19, lines 20 – 23). Thus, even Furet does not explicitly teach the method of altering the conformation of a nucleic acid, the “altering the conformation of a nucleic acid" will naturally flow from the teachings of (or method made obvious by) the prior art (see above rejection), since the same compound (compound of formula (I)) is being administered to the same subjects (treating proliferative disease (cancer), autoimmune disease or metabolic disease (e.g. diabetes)). In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. In other words, even though the prior art is silent regarding "altering the conformation of a nucleic acid", by practicing the method made obvious by the prior art: "the administration of an effective amount of compound of formula (I) to a patient suffering from proliferative disease (cancer), autoimmune disease or metabolic disease (e.g. diabetes)", one will also be " altering the conformation of a nucleic acid", even though the prior art was not aware of it. Apparently, Applicant has discovered a new property or advantage ("altering the conformation of a nucleic acid") of the method made obvious by the prior art ("the administration of an effective amount of compound of formula (I) to a patient suffering from proliferative disease (cancer), autoimmune disease or metabolic disease (e.g. diabetes)"). MPEP 2145 II states: "The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art, cannot be the basis for patentability when the differences would otherwise be obvious". Ex parte Obiaya, 227 USPQ 58, 60. (FP 7.37.07, MPEP 707.07(f)). Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. 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, 7, 15, 25, 32, 40-41, 44, 47, 51, 56 and 117 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 7, 8, 18, 20 and 22 - 25 of copending Application No. 17/802,863 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims are directed to a compound of Formula (I): PNG media_image2.png 106 191 media_image2.png Greyscale , such as compound of Formula (I-b): PNG media_image3.png 110 197 media_image3.png Greyscale or Formula (I-f): PNG media_image4.png 136 194 media_image4.png Greyscale , where W, X, Y, and Z are each independently C(R3a) or N, wherein at least one of W, X, Y, and Z is independently N, R3a is hydrogen; m is 0-2; A and B are each independently cycloalkyl, heterocyclyl (e.g. PNG media_image5.png 55 82 media_image5.png Greyscale or PNG media_image6.png 70 57 media_image6.png Greyscale ), aryl, or heteroaryl (e.g. PNG media_image7.png 49 86 media_image7.png Greyscale , PNG media_image8.png 66 109 media_image8.png Greyscale or PNG media_image9.png 93 106 media_image9.png Greyscale ) each of which is optionally substituted with one or more R1, R1 is hydrogen, C1-C6 alkyl; L1 is absent, C1-C6-alkylene, -O-, -C(O)-, -N(R4)-, -N(R4)C(O)-, or -C(O)N(R4)-, R4 is hydrogen. The exemplary compounds of Formula (I) are: PNG media_image23.png 124 278 media_image23.png Greyscale (Specification, page 71, Ex. 113), PNG media_image24.png 111 281 media_image24.png Greyscale (Specification, page 79, Ex. 166). The instant claims are further drawn to a pharmaceutical composition comprising a compound of Formula (I) and a pharmaceutically acceptable excipient. Claims of copending application are directed to a compound of formula (I-a): PNG media_image11.png 111 206 media_image11.png Greyscale , such as compounds: PNG media_image14.png 139 259 media_image14.png Greyscale , PNG media_image25.png 126 255 media_image25.png Greyscale (Ex. 124). Thus, the compounds of copending application would anticipate instantly claimed compounds. Claims 1, 5, 7, 15, 25, 32, 40-41, 44, 47, 51, 56, 117, 118, 121 and 125 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims: 1, 4, 6, 8, 11, 13, 18, 24, 32, 58 of copending Application No. 19/160,794 (reference application); 1 - 33 of copending Application No. 19/820,822 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims are directed to a compound of Formula (I): PNG media_image2.png 106 191 media_image2.png Greyscale , such as compound of Formula (I-b): PNG media_image3.png 110 197 media_image3.png Greyscale or Formula (I-f): PNG media_image4.png 136 194 media_image4.png Greyscale , where W, X, Y, and Z are each independently C(R3a) or N, wherein at least one of W, X, Y, and Z is independently N, R3a is hydrogen; m is 0-2; A and B are each independently cycloalkyl, heterocyclyl (e.g. PNG media_image5.png 55 82 media_image5.png Greyscale or PNG media_image6.png 70 57 media_image6.png Greyscale ), aryl, or heteroaryl (e.g. PNG media_image7.png 49 86 media_image7.png Greyscale , PNG media_image8.png 66 109 media_image8.png Greyscale or PNG media_image9.png 93 106 media_image9.png Greyscale ) each of which is optionally substituted with one or more R1, R1 is hydrogen, C1-C6 alkyl; L1 is absent, C1-C6-alkylene, -O-, -C(O)-, -N(R4)-, -N(R4)C(O)-, or -C(O)N(R4)-, R4 is hydrogen. The exemplary compounds of Formula (I) are: PNG media_image23.png 124 278 media_image23.png Greyscale (Specification, page 71, Ex. 113), PNG media_image24.png 111 281 media_image24.png Greyscale (Specification, page 79, Ex. 166). The instant claims are further drawn to a pharmaceutical composition comprising a compound of Formula (I) and a pharmaceutically acceptable excipient. Instant claims are further directed to a compound of Formula (I), where the compound is capable of altering a target nucleic acid, binding to a target nucleic acid or stabilizing a target nucleic acid, and where the compound increases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more, or the compound decreases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more. Instant claims are also directed to a method of altering the conformation of a nucleic acid (e.g., a DNA, RNA, e.g., a pre-mRNA) comprising contacting the nucleic acid with a compound of Formula (I). Claims of copending application No. 19/160,794 are directed to a compound of formula (I-c): PNG media_image26.png 114 196 media_image26.png Greyscale , such as compounds: PNG media_image27.png 95 211 media_image27.png Greyscale (Ex. 327), PNG media_image28.png 95 219 media_image28.png Greyscale (ex. 339). Claims of copending application are further directed to a compound of Formula (I-c), where the compound is capable of altering a target nucleic acid, binding to a target nucleic acid or stabilizing a target nucleic acid, and where the compound increases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more, or the compound decreases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more. Copending claims are also directed to a method of altering the conformation of a nucleic acid (e.g., a DNA, RNA, e.g., a pre-mRNA) comprising contacting the nucleic acid with a compound of Formula (I-c). Similarly, Claims of copending application No. 19/820,822 are directed to a compound of formula (I-a): PNG media_image11.png 111 206 media_image11.png Greyscale , such as compounds: PNG media_image29.png 128 237 media_image29.png Greyscale (Ex. 111), PNG media_image30.png 129 241 media_image30.png Greyscale (Ex. 103). Claims of copending application are further directed to a compound of Formula (I-a), where the compound is capable of altering a target nucleic acid, binding to a target nucleic acid or stabilizing a target nucleic acid, and where the compound increases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more, or the compound decreases splicing at splice site on a target nucleic acid, by about 0.5% to 95%, or more. Copending claims are also directed to a method of altering the conformation of a nucleic acid (e.g., a DNA, RNA, e.g., a pre-mRNA) comprising contacting the nucleic acid with a compound of Formula (I-a). Thus, the compounds and a method of copending applications would anticipate instantly claimed compounds and the method. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Conclusion Claims 1, 5, 7, 15, 25, 32, 40-41, 44, 47, 51, 56, 117-118, 121, and 125 are rejected. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELENA V VISHNYAKOVA whose telephone number is (571)272-3781. The examiner can normally be reached 7:30am - 5pm ET. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, RENEE CLAYTOR can be reached at (571)272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /E.V.V./Examiner, Art Unit 1691 /SAVITHA M RAO/Primary Examiner, Art Unit 1691