CTNF 18/299,509 CTNF 73484 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Election/Restrictions 08-25-01 AIA Applicant’s election without traverse of Group I in the reply filed on 8/11/2025 is acknowledged. Claims 1-39 are pending. 08-06 AIA Claim 39 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention , there being no allowable generic or linking claim.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 8/11/2025 . Claims 1-38 are examined . Claim Rejections - 35 USC § 112 07-30-01 AIA The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. 07-31-01 Claims 1-38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection. The specification discloses NSE repressor agents that are nucleic acids based on SEQ ID NOS:23, 26, 37, 39, 51, and 53-55 and also targeted to SEQ ID NOS:58 and 60. NSE repressor agents based on the above, therefore have written description. However, the claims encompass a broad scope where the scope lacks adequate written description. The invention, for example is disclosed to encompass ANY NSE repressor agent may include ANY type of agent (not limited to nucleic acid agents, for example). The scope of the claims include small molecules or peptides or proteins or nucleic acid agents, for example. The specification as filed does not provide any description of ANY repressor agents other than those identified above other than defining them by function. One in the art would clearly not be appraised of the structure/sequence of these molecules based on the specification as filed and where the prior art does not appear to describe NSE repressor agent compounds. One in the art would clearly be required to determine, de novo, what compounds may be included. One in the art would be required to empirically determine the structure/sequence of other functional NSE repressor agents. One in the art would not know, based on the specification as filed, what the structure of any other of the broad scope “agonists” and “antagonists” may be. One in the art would need to make that determination de novo since it is not readily apparent that any of these compounds were described in the instant specification, other than those noted above, or were known in the prior art. One in the art would clearly not be capable or able to immediately envisage the sequence/structure of the claimed agonists or antagonists. The NSE repressor agents identified in the specification were identified empirically with the structure of those agents not providing a description of any other repressors that may function as claimed. Kralovicova et al (Nucleic Acids Research Vol.26(6):392-400,2016 at pages 393, 396, and 398) and Kralovicova et al (Scientific Reports www.nature.com/scientificreports, 06 January 2016,12 pages plus corrigendum, 1 page at page 2 discussion) have both described the claimed invention and have demonstrated that NSE repressor agents were determined empirically. The specification fails to provide sufficient description of NSE repressor agents such that one in the art would not be capable of immediately knowing a structure that would provide a specific NSE function. The specification provides insufficient written description to support the genus encompassed by the claim. Vas-Cath Inc. v. Mahurkar , 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed. " (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.) With the exception of the NSE repressor agents identified above, the skilled artisan cannot envision the detailed chemical structure of the encompassed claimed compounds, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel , 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird , 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Applicant is also directed to AbbVie Deeutchland GmbH v. Janssen BiotechnologyLtd., F.3 1285 (Fed. Cir. 2014) “ [A] sufficient description of a genus . . . requires the disclosure of either a representative number* of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus” ( AbbVie, 759 F.3d at 1299, reiterating Eli Lilly , 119 F.3d at 1568-69) (emphasis added). “The asserted claims attempt to claim every fully human IL-12 antibody that would achieve a desired result , i.e., high binding affinity and neutralizing activity, and cover an antibody as different as Stelara ® , whereas the patents do not describe representative examples to support the full scope of the claims.” Jury’s decision of invalidity for lack of adequate written description for the claimed genus affirmed (AbbVie, 759 F.3d at 1301) (emphasis added). The species specifically disclosed are not representative of the genus because the genus is highly variant. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC 112 is severable from its enablement provision. (See page 1115.) Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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. 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-15 AIA Claim s 1-16 and 22-35 are rejected under 35 U.S.C. 102( a)(1 )as being anticipated by Perez et al (2014) . Perez etal have disclosed the use of modified oligonucleotides that bind to a target motif corresponding to a pseudoexon or cryptic splice site, including LNA, PNA, morpholino, 2’-O-methyl, etc., modifications. The administration of the oligonucleotide represses the inclusion of a pseudoexon and provides for the expression of a functional and/or full length protein. It has also been disclosed the use of conjugates and complexes including cell penetrating peptides to deliver oligonucleotides to cells. See first full paragraph of “Introduction” and figure 1, for example). It has been taught that it was known that targeting pseudoexons via exon skipping to produce therapeutic oligonucleotides was known. It was known that forcing pseudoexon skipping, normal splicing is resumed and wild-type transcript and protein produced and that antisense oligonucleotide treatment of IMD patients carrying intronic pseudoexon activating mutation in different gene defects has resulted in complete recovery of protein and activity up to wild type levels. (See second full paragraph, page 49, left column). It has been disclosed that the use of cryptic splice sites and exon skipping are the two most frequent consequences of splicing mutations and thus constitute a potentially abundant source of candidates for splicing oligonucleotide therapy provided that the cryptic sites are located a reasonable distance from the natural splice sites . Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-21-aia AIA Claim s 17-21 are rejected under 35 U.S.C. 103 as being unpatentable over Perez et al (Human Gene Therapy Volume 25(7):587-598,2014) in view of Disterer et al (Human Gene Therapy Vol. 25 (7):18 pages, July 2014). Perez etal have disclosed the use of modified oligonucleotides that bind to a target motif corresponding to a pseudoexon or cryptic splice site, including LNA, PNA, morpholino, 2’-O-methyl, etc., modifications. The administration of the oligonucleotide represses the inclusion of a pseudoexon and provides for the expression of a functional and/or full length protein. It has also been disclosed the use of conjugates and complexes including cell penetrating peptides to deliver oligonucleotides to cells. See first full paragraph of “Introduction” and figure 1, for example). It has been taught that it was known that targeting pseudoexons via exon skipping to produce therapeutic oligonucleotides was known. It was known that forcing pseudoexon skipping, normal splicing is resumed and wild-type transcript and protein produced and that antisense oligonucleotide treatment of IMD patients carrying intronic pseudoexon activating mutation in different gene defects has resulted in complete recovery of protein and activity up to wild type levels. (See second full paragraph, page 49, left column). It has been disclosed that the use of cryptic splice sites and exon skipping are the two most frequent consequences of splicing mutations and thus constitute a potentially abundant source of candidates for splicing oligonucleotide therapy provided that the cryptic sites are located a reasonable distance from the natural splice sites. Perez et al have not taught the use of vectors to deliver splicing oligonucleotides. Disterer et al, however, have taught in a review article on therapeutic splice-switching oligonucleotides (SSO) that the use of viral vectors including AAV vectors was a known option for delivery of SSOs see Table 1, for example). It would have been obvious to one in the art to utilize vectors as a means of delivery since vectors, including viral vectors, were known in the art as an option for delivery with Disterer et al evidencing their use, for example. Disterer et al have also taught throughout the reference that modification of SSOs was known and have also provided teaching on how to select SSOs and to identify effective SSO target sequences (see Figure 4, for example). The invention as a whole would therefore have been prima facie obvious to one in the art at the time the application was effectively filed . Double Patenting 08-33 AIA 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. 08-34 AIA Claim s 1-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-20 of U.S. Patent No. 10,196,405 . Although the claims at issue are not identical, they are not patentably distinct from each other because both the patent and the instant application are drawn to the same methods utilizing the same components (e.g. oligonucleotides targeting a motif to affect cryptic splice cites/NSE (equivalents)) between two canonical exons, and steps that result in the same ends (e.g. increased protein expression of a target gene). See claims 1 and 7(ATM comprises and has targeted a pseudoexon, for example), and claims 1 and 5 of the application, for example . 08-34 AIA Claim s 1-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-20 of U.S. Patent No. 10,941,405 . Although the claims at issue are not identical, they are not patentably distinct from each other because both the patent and the instant application are drawn to the same methods utilizing the same components (e.g. oligonucleotides targeting a motif to affect cryptic splice cites/NSE (equivalents)) between two canonical exons, and steps that result in the same ends (e.g. increased protein expression of a target gene). See claims 1, 3 and 7(ATM comprises and has targeted a pseudoexon, for example), and claims 1 and 5 of the application, for example . 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /SEAN MCGARRY/Primary Examiner, Art Unit 1635 Application/Control Number: 18/299,509 Page 2 Art Unit: 1635 Application/Control Number: 18/299,509 Page 3 Art Unit: 1635 Application/Control Number: 18/299,509 Page 4 Art Unit: 1635 Application/Control Number: 18/299,509 Page 5 Art Unit: 1635 Application/Control Number: 18/299,509 Page 6 Art Unit: 1635 Application/Control Number: 18/299,509 Page 7 Art Unit: 1635 Application/Control Number: 18/299,509 Page 8 Art Unit: 1635 Application/Control Number: 18/299,509 Page 9 Art Unit: 1635 Application/Control Number: 18/299,509 Page 10 Art Unit: 1635 Application/Control Number: 18/299,509 Page 11 Art Unit: 1635 Application/Control Number: 18/299,509 Page 12 Art Unit: 1635 Application/Control Number: 18/299,509 Page 13 Art Unit: 1635 Application/Control Number: 18/299,509 Page 14 Art Unit: 1635