CTNF 18/683,101 CTNF 100290 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. Priority The instant application is a national stage entry under 35 U.S.C. § 371 of PCT/US2022/077274 (filed 09/29/2022). Acknowledgement is made of Applicants’ claim for benefit of U.S. Provisional Application Nos. 63/364,655 (filed 05/13/2022) and 63/250,761 (filed 09/30/2021). Claim Objections Claim 13 is objected to because of the following informality: Line 2 of claim 13 recites, “...is administered intracisterna-magna.” This appears to be a typographical error. This limitation should read: “…is administered intracisterna-magna intracisternally .” Alternatively: “...is administered by intracisterna[[-]] magna injection .” Appropriate correction is required. 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. 08-36 AIA Claim s 1 and 7-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1, 5-6, and 13-16 of U.S. Patent No. 12,188,039 in view of Thevenon, et al. ( Am J Hum Genet . 2014) . U.S. Patent No. 12,188,039 (hereinafter Patent ‘039) teaches rAAV vectors and rAAV viral vectors comprising transgene nucleic acid molecules comprising nucleic acid sequences encoding for a SURF1 polypeptide (Abstract). Thevenon, et al. teaches mutations in SLC13A5 associated with early-onset epileptic encephalopathy (Abstract). Regarding claim 1: Patent ‘039 recites a recombinant adeno-associated virus (rAAV) vector comprising in 5’ to 3’ direction a first AAV inverted terminal repeat (ITR) sequence, a promoter sequence, a transgene nucleic acid molecule, a poly A sequence, and a second ITR sequence (claim 1); the first AAV ITR sequence comprises a nucleic acid sequence of SEQ ID NO: 12 (claim 5), and the second AAV ITR sequence comprises a nucleic acid sequence of SEQ ID NO: 12 (claim 6). Patented SEQ ID NO: 13 shares 100% sequence identity to the sequence set forth in SEQ ID NO: 7; patented SEQ ID NO: 12 shares 100% sequence identity to the sequence set forth in SEQ ID NO: 8. (Please see end of Office action for all sequence alignments.) Thus, these patented claims read on the limitations recited in the preamble, a), b), d), and e) of instant claim 1. Patent ‘039 does not teach the limitations recited in c) of instant claim 1. Thevenon, et al. teaches subject presenting with similar clinical presentations as early-onset epileptic encephalopathy (EOEE), wherein seizures first occurred within one week of birth (Table 1). It was hypothesized the clinical presentation was due to mutations in the same gene, and exome sequencing was performed (pg. 115; col. 2, par. 2), wherein a single gene mutated in affected individuals, SLC13A5, was identified; two individuals from a single family were compound heterozygous for two SLC13A5 missense changes, involving a glycine and threonine residue (pg. 116; col. 1, par. 2). A wider screen for SLC13A5 mutations in unrelated individuals with EOEE (pg. 116; col. 2, par. 2) identified additional subjects with SLC13A5 missense changes involving glycine and threonine residues (pg. 117; par. 1); SLC13A5 encodes a highly conserved homodimeric cytoplasmic sodium-dependent citrate carrier (pg. 117; par. 5). The mutation sites either affect the first sodium-binding site (p.Gly219Arg and p.Thr227Met in families 1 and 3, as seen in Table 2), or the second one (p.Leu488Pro in family 2); additionally, in silico predictions support a marked disruption of hydrogen bonds caused by the former mutations (pg. 118; col. 1, par. 1). Further, disruption of citrate metabolism and transport are associated with epilepsy (pg. 118; col. 1, par. 2). Thevenon, et al. additionally teaches non-mutated HsSLC13A5, comprising polypeptide NCBI Reference Sequence NP_808218.1 (Fig. S2), encoded by NCBI Reference Sequence NM_177550.3 (pg. 116; col. 1, par. 2). As NP_808218.1 shares 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, this reads on the limitations recited in c) of instant claim 1. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the rAAV have been motivated to do so in order to target the SLC13A5 mutations p.Gly219Arg and p.Thr227Met affecting the sodium-binding site, as taught by Thevenon, et al., for the association of citrate metabolism and transport dysfunction with epilepsy, as disclosed by the same. Further, as evidenced by Patent ‘039, including a nucleic acid sequence encoding a polypeptide is a well-known technique in the art; thus, a skilled artisan would have more than a reasonable expectation of success. The modification set forth above renders obvious the limitations of instant claim 1. Regarding claims 7-8: Following the above discussion, Patent ‘039 recites an rAAV viral vector comprising an AAV capsid protein and the rAAV vector (claim 13); this reads on the limitations of instant claim 7. Patent ‘039 recites an embodiment wherein the capsid protein is an AAV9 capsid protein (claim 14); this reads on the limitations recited in instant claim 8. Regarding claim 9: Following the above discussion, Patent ‘039 recites a pharmaceutical composition comprising the rAAV viral vector and at least one pharmaceutically acceptable excipient and/or additive (claim 16); this reads on the limitations recited in instant claim 9. Regarding claims 10-13: Following the above discussion, the claims of Patent ‘039 does not teach administration of the rAAV in a method for treating a subject having a disease and/or disorder involving an SLC13A5 gene, as required by the instant claims. However, in the specification, Patent ‘039 teaches the rAAV can be used for delivering transgenes to treat or prevent a disease or disorder (col. 1; lines 51-52), teaching .////, administration intrathecally and intracisternally (col. 3; lines 38-42). It has been held that a claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use . See Pfizer , 518 F.3d at 1363; Geneva , 349 F.3d at 1385-86, and Sun Pharmaceutical Industries v. Eli Lilly and Co ., 611 F. 3d 1381, 1387 (CAFC 2010). See MPEP 804(II)(B)(1). Therefore, as Patent ‘039 teaches intrathecal and intracisternal administration of the rAAV for the treatment or prevention of a disease or disorder (cols. 1 and 3), and as Thevenon, et al. teaches SLC13A5 mutations in subjects presenting with similar clinical presentations as EOEE wherein seizures first occur within one week of birth (Table 1), it would have been prima facie obvious to a person having ordinary skill in the art to have used the modified rAAV of Patent ‘039 in a method for treating a subject with neonatal epileptic encephalopathy involving SLC13A5, rendering the limitations recited in instant claims 10-13 obvious . 08-36 AIA Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1, 5-6, and 13-16 of U.S. Patent No. 12,188,039 in view of Thevenon, et al. ( Am J Hum Genet . 2014), further in view of Buck and Wijnholds ( Int J Mol Sci . 2020) . The teachings of Patent ‘039 and Thevenon, et al. are set forth above. Buck and Wijnholds (hereinafter Buck) teaches a library of rAAV vectors and elements that provide a workflow to design novel vectors (Abstract). Regarding claim 2: Following the above discussion, the claims of Patent ‘039 do not teach the nucleic acid sequence encoding the transgene as a codon optimized nucleic acid sequence. However, Buck teaches codon-optimization improves optimal expression of the transgene in the target cell and organism (pg. 24; par. 4). Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have further modified the rAAV vector by using a codon-optimized nucleic acid sequence. Further, as evidenced by the Buck disclosure, codon-optimization is a well-known and routine technique in the art; thus, a skilled artisan would have a reasonable expectation of success. This renders obvious the limitation recited in instant claim 2 . 08-37 AIA Claim s 1, 7-8, and 10-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 36, 41-42, 49-50 of copending Application No. 18/287,314 in view of Thevenon, et al. ( Am J Hum Genet . 2014). Copending Application No. 18/287,314 (hereinafter Application ‘314) teaches optimized AP4M1 polynucleotides and expression cassettes and their use (Title). The teachings of Thevenon, et al. is set forth above. Regarding claim 1: Application ‘314 recites a recombinant adeno-associated virus (rAAV) vector comprising in 5’ to 3’ direction a first AAV inverted terminal repeat (ITR) sequence, a promoter sequence, a transgene nucleic acid molecule, a poly A sequence, and a second ITR sequence (claim 36); the first AAV ITR sequence comprises a nucleic acid sequence of SEQ ID NO: 2 (claim 41), and the second AAV ITR sequence comprises a nucleic acid sequence of SEQ ID NO: 7 (claim 42). Copending SEQ ID NO: 2 shares 100% sequence identity to the sequence set forth in SEQ ID NO: 7; copending SEQ ID NO: 7 shares 100% sequence identity to the sequence set forth in SEQ ID NO: 8. (Please see end of Office action for all sequence alignments.) Thus, these copending claims read on the limitations recited in the preamble, a), b), d), and e) of instant claim 1. Application ‘314 does not teach the limitations recited in c) of instant claim 1. However, for the same reasons recited in the rejection of claim 1 over Patent ‘039, it would have been likewise prima facie obvious to a person having ordinary skill in the art to have modified the rAAV of Application ‘314 by including a nucleic acid sequence encoding an SLC13A5 polypeptide comprising the amino acid sequence set forth in NP_808218.1, as taught by Thevenon, et al., rendering obvious the remaining limitations recited in instant claim 1. Regarding claims 7-8: Following the above discussion, Application ‘314 recites an rAAV viral vector comprising an AAV capsid protein and the rAAV vector (claim 49); this reads on the limitations of instant claim 7. Application ‘314 further recites wherein the capsid protein is an AAV9 capsid protein (claim 50); this reads on the limitations recited in instant claim 8. Regarding claims 10-13: Following the above discussion, Application ‘314 does not teach administration of the rAAV in a method for treating a subject having a disease and/or disorder involving an SLC13A5 gene, as required by the instant claims. However, in the specification, Application ‘314 discloses a method of use for the rAAV, comprising administering the rAAV to a subject in need of treatment intrathecally and intracisternally (par. 0237). It has been held that a claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent or application disclosing the identical use . See Pfizer , 518 F.3d at 1363; Geneva , 349 F.3d at 1385-86, and Sun Pharmaceutical Industries v. Eli Lilly and Co ., 611 F. 3d 1381, 1387 (CAFC 2010). See MPEP 804(II)(B)(1). Therefore, as Application ‘314 teaches intrathecal and intracisternal administration of the rAAV for the treatment or prevention of a disease or disorder (par. 0237), and as Thevenon, et al. teaches SLC13A5 mutations in subjects presenting with similar clinical presentations as EOEE wherein seizures first occur within one week of birth (Table 1), it would have been prima facie obvious to a person having ordinary skill in the art to have used the modified rAAV of Application ‘314 in a method for treating a subject with neonatal epileptic encephalopathy involving SLC13A5, rendering the limitations recited in instant claims 10-13 obvious . This is a provisional nonstatutory double patenting rejection. 08-37 AIA Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 36, 41-42, 49-50 of copending Application No. 18/287,314 in view of Thevenon, et al. ( Am J Hum Genet . 2014), further in view of Buck and Wijnholds ( Int J Mol Sci . 2020). The teachings of copending Application ‘314, Thevenon, et al., and Buck are set forth above. Regarding claim 2: Following the above discussion, the claims of Application ‘314 do not teach the nucleic acid sequence encoding the transgene as a codon optimized nucleic acid sequence. However, Buck teaches codon-optimization improves optimal expression of the transgene in the target cell and organism (pg. 24; par. 4). Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have further modified the rAAV vector by using a codon-optimized nucleic acid sequence. Further, as evidenced by the Buck disclosure, codon-optimization is a well-known and routine technique in the art; thus, a skilled artisan would have a reasonable expectation of success. This renders obvious the limitation recited in instant claim 2 . This is a provisional nonstatutory double patenting rejection. 08-37 AIA Claim s 1 and 7-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1, 5-6, and 11-13 of copending Application No. 18/729,389 in view of Thevenon, et al. ( Am J Hum Genet . 2014). Copending Application No. 18/729,389 (hereinafter Application ‘389) teaches viral vectors comprising polynucleotides and methods of use (Abstract). The teachings of Thevenon, et al. are set forth above. Regarding claim 1: Application ‘389 recites a recombinant adeno-associated virus (rAAV) vector comprising in 5’ to 3’ direction a first AAV inverted terminal repeat (ITR) sequence, a promoter sequence, a transgene nucleic acid molecule, a poly A sequence, and a second ITR sequence (claim 1); the first AAV ITR sequence comprises a nucleic acid sequence of SEQ ID NO: 2 (claim 5), and the second AAV ITR sequence comprises a nucleic acid sequence of SEQ ID NO: 6 (claim 6). Copending SEQ ID NO: 2 shares 100% sequence identity to the sequence set forth in SEQ ID NO: 7; copending SEQ ID NO: 6 shares 100% sequence identity to the sequence set forth in SEQ ID NO: 8. (Please see end of Office action for all sequence alignments.) Thus, these copending claims read on the limitations recited in the preamble, a), b), d), and e) of instant claim 1. Application ‘389 does not teach the limitations recited in c) of instant claim 1. However, for the same reasons recited in the rejection of claim 1 over Patent ‘039, it would have been likewise prima facie obvious to a person having ordinary skill in the art to have modified the rAAV of Application ‘389 by including a nucleic acid sequence encoding an SLC13A5 polypeptide comprising the amino acid sequence set forth in NP_808218.1, as taught by Thevenon, et al., rendering obvious the remaining limitations recited in instant claim 1. Regarding claims 7-9: Following the above discussion, Application ‘389 recites an rAAV viral vector comprising an AAV capsid protein and the rAAV vector (claim 11), wherein the capsid protein is an AAV9 capsid protein (claim 12); Application ‘389 further recites an embodiment wherein the rAAV is in a pharmaceutical composition (claim 13). These copending claims render obvious the limitations recited in instant claims 7, 8, and 9. Regarding claims 10-13: Following the above discussion, Application ‘389 does not teach administration of the rAAV in a method for treating a subject having a disease and/or disorder involving an SLC13A5 gene, as required by the instant claims. However, in the specification, Application ‘389 teaches the rAAV can be used to repair a gene deficiency in a subject (par. 00146), disclosing administration intrathecally and intracisternally (par. 00145). It has been held that a claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent or application disclosing the identical use . See Pfizer , 518 F.3d at 1363; Geneva , 349 F.3d at 1385-86, and Sun Pharmaceutical Industries v. Eli Lilly and Co ., 611 F. 3d 1381, 1387 (CAFC 2010). See MPEP 804(II)(B)(1). Therefore, as Application ‘389 teaches intrathecal and intracisternal administration of the rAAV for the treatment or prevention of a disease or disorder (pars. 00145-00146), and as Thevenon, et al. teaches SLC13A5 mutations in subjects presenting with similar clinical presentations as EOEE wherein seizures first occur within one week of birth (Table 1), it would have been prima facie obvious to a person having ordinary skill in the art to have used the modified rAAV of Application ‘389 in a method for treating a subject with neonatal epileptic encephalopathy involving SLC13A5, rendering the limitations recited in instant claims 10-13 obvious . This is a provisional nonstatutory double patenting rejection. 08-37 AIA Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1, 5-6, and 11-13 of copending Application No. 18/729,389 in view of Thevenon, et al. ( Am J Hum Genet . 2014), further in view of Buck and Wijnholds ( Int J Mol Sci . 2020). The teachings of copending Application ‘389, Thevenon, et al., and Buck are set forth above. Regarding claim 2: Following the above discussion, the claims of Application ‘389do not teach the nucleic acid sequence encoding the transgene as a codon optimized nucleic acid sequence. However, Buck teaches codon-optimization improves optimal expression of the transgene in the target cell and organism (pg. 24; par. 4). Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have further modified the rAAV vector by using a codon-optimized nucleic acid sequence. Further, as evidenced by the Buck disclosure, codon-optimization is a well-known and routine technique in the art; thus, a skilled artisan would have a reasonable expectation of success. This renders obvious the limitation recited in instant claim 2 . This is a provisional nonstatutory double patenting rejection. Allowable Subject Matter 12-151-08 AIA 07-43 12-51-08 Claim s 3-6 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p 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, CHRISTOPHER BABIC can be reached at (571)272-8507. 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. /GINA PRONZATI/Examiner, Art Unit 1633 /ALLISON M FOX/Primary Examiner, Art Unit 1633 SEQUENCE ALIGNMENTS Query, ‘Qy’ (SEQ ID NO: 1) vs. Database, ‘Db’ (NCBI Reference Sequence NP_808218.1) PNG media_image1.png 378 695 media_image1.png Greyscale Query (SEQ ID NO: 7) vs. Subject (U.S. Patent No. 12,188,039; SEQ ID NO: 13) PNG media_image2.png 167 614 media_image2.png Greyscale Query, ‘Qy’ (SEQ ID NO: 8) vs. Database, ‘Db’ (U.S. Patent No. 12,188,039; SEQ ID NO: 12) PNG media_image3.png 366 683 media_image3.png Greyscale SEQUENCE ALIGNMENTS (continued) Query, ‘Qy’ (SEQ ID NO: 7) vs. Database, ‘Db’ (Application No. 18/287,314; SEQ ID NO: 2) PNG media_image4.png 259 681 media_image4.png Greyscale Query, ‘Qy’ (SEQ ID NO: 8) vs. Database, ‘Db’ (Application No. 18/287,314; SEQ ID NO: 7) PNG media_image5.png 338 685 media_image5.png Greyscale SEQUENCE ALIGNMENTS (continued) Query, ‘Qy’ (SEQ ID NO: 7) vs. Database, ‘Db’ (Application No. 18/729,389; SEQ ID NO: 2) PNG media_image6.png 261 678 media_image6.png Greyscale Query, ‘Qy’ (SEQ ID NO: 8) vs. Database, ‘Db’ (Application No. 18/729,389; SEQ ID NO: 6) PNG media_image7.png 346 685 media_image7.png Greyscale Application/Control Number: 18/683,101 Page 2 Art Unit: 1633 Application/Control Number: 18/683,101 Page 3 Art Unit: 1633 Application/Control Number: 18/683,101 Page 4 Art Unit: 1633 Application/Control Number: 18/683,101 Page 5 Art Unit: 1633 Application/Control Number: 18/683,101 Page 6 Art Unit: 1633 Application/Control Number: 18/683,101 Page 7 Art Unit: 1633 Application/Control Number: 18/683,101 Page 8 Art Unit: 1633 Application/Control Number: 18/683,101 Page 9 Art Unit: 1633 Application/Control Number: 18/683,101 Page 10 Art Unit: 1633 Application/Control Number: 18/683,101 Page 11 Art Unit: 1633 Application/Control Number: 18/683,101 Page 12 Art Unit: 1633 Application/Control Number: 18/683,101 Page 13 Art Unit: 1633 Application/Control Number: 18/683,101 Page 14 Art Unit: 1633 Application/Control Number: 18/683,101 Page 15 Art Unit: 1633 Application/Control Number: 18/683,101 Page 16 Art Unit: 1633
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