DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/08/2026 has been entered.
Applicants’ amendments to the claims and arguments filed on June 8, 2026, have been received and entered. Claims 1-26, 28, 30-44, 46-51, 53-58, 61-64 are canceled, while Claims 65-66 are added. The Azzouz’s declaration under 37 CFR 1.132 filed June 8, 2026 is insufficient to overcome the rejection of claims based upon Behne et al (Human Molecular Genetics, 2020, Vol. 29, No. 2, 320-324)/ Scarrott et al (Human Gene Therapy, (August 2019) Vol. 30, No. 8, pp. A18. Abstract Number: P03, June 21, 2019) as set forth in the last Office action. The declaration will be discussed below as it pertains to the rejection.
Claims 27, 29, 45, 52, 59-60, 65 and 66 are pending in the instant application.
Election/Restrictions
Applicant’s election of claims 2, 6-13, 19-20, 24-26, 33, 36, 40, 44-50 (group I) in the reply filed on July 23, 2025, was acknowledged. Because applicants did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 27, 29 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 July 23, 2025.
Priority
This application is 371 of PCT/EP2021/059354 filed on 04/09/2021, which claims priority from foreign application 2005321.1 filed on 04/09/2020 and PCTEP2021057996 filed on 03/26/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claims 45, 52, 59-60, 65 and 66 are under consideration.
Withdrawn -Claim Rejections - 35 USC § 112-written description
Claims 45, 47-48, 51-57, 59-63 were 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. Applicants’ amendments to the claims obviate the basis of the rejection.
Withdrawn-Claim Rejections - 35 USC § 103
Claims 45, 47-48, 52, 59-64 are rejected under 35 U.S.C. 103 as being unpatentable over Lukashchuk et al ((Molecular Therapy, 2016, 3, 1-10), Behne et al (Human Molecular Genetics, 2020, Vol. 29, No. 2, 320-324)/ Scarrott et al (Human Gene Therapy, (August 2019) Vol. 30, No. 8, pp. A18. Abstract Number: P03, June 21, 2019) as evidenced by NCBI accession no NM_001253852.and Aldred et al (WO2008073303, dated 06/19/20). Applicants’ cancellation of claims 47-48, 61-64 renders their rejections moot. In view of applicant’s amendments to the claims “introducing promoter consisting of SEQ ID NO: 27”, the previous rejection is rendered moot and hereby withdrawn. Applicants’ arguments with respect to the withdrawn rejections are thereby rendered moot. The claims are, however, subject to new rejections over the prior art of record.
Maintained & New -Claim Rejections - 35 USC § 103-in modified form
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.
Claims 45, remain rejected and claims 65-66 are newly rejected under 35 U.S.C. 103 as being unpatentable over Scarrott et al (Human Gene Therapy, (August 2019) Vol. 30, No. 8, pp. A18. Abstract Number: P03, June 21, 2019) as evidenced by Behne et al (Human Molecular Genetics, 2020, Vol. 29, No. 2, 320-324), NCBI accession no NM_001253852.1., and further in view of Lukashchuk ((Molecular Therapy, 2016, 3, 1-10).
With respect to claims 45, 51, 59-64, Scarrott teaches an AAV9 vector comprising a nucleic acid encoding AP4B1 protein for expression in both in vitro and in vivo models (abstract). This is evidenced by Behne who teaches use of a vector comprising a transcription cassette comprising a ubiquitous promoter (PGK) that is adapted for expression ubiquitously, wherein said cassette further comprising a nucleic acid molecule comprising a nucleotide sequence NM_001253852.1 that encodes AP4B1 (see fig. 3, table 1and page 331, col. 1, para 3). AP4B1 (see fig. 3, table 1and page 331, col. 1, para 3). The accession number for AP4B1 disclosed in Behne has 100% sequence identity to SEQ ID NO: 1 and encodes amino acid as set forth in SEQ IDNO: 2 (see below).
Query Match 100.0%; Score 2220; DB 1; Length 2723;
Best Local Similarity 100.0%;
Matches 2220; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGCCGTACCTTGGCTCCGAGGACGTGGTGAAGGAGCTGAAGAAGGCTCTGTGCAATCCT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 187 ATGCCGTACCTTGGCTCCGAGGACGTGGTGAAGGAGCTGAAGAAGGCTCTGTGCAATCCT 246
Qy 61 CACATTCAAGCTGATAGGCTGCGCTACCGGAATGTCATCCAGCGAGTGATTAGGTACATG 120 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 247 CACATTCAAGCTGATAGGCTGCGCTACCGGAATGTCATCCAGCGAGTGATTAGGTACATG 306
Qy 121 ACTCAAGGCTTGGACATGTCTGGTGTTTTTATGGAAATGGTGAAGGCCAGTGCCACTGTA 180 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 307 ACTCAAGGCTTGGACATGTCTGGTGTTTTTATGGAAATGGTGAAGGCCAGTGCCACTGTA 366
Qy 181 GATATTGTCCAGAAGAAGTTGGTTTATCTGTACATGTGCACATATGCTCCCCTGAAACCA 240 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 367 GATATTGTCCAGAAGAAGTTGGTTTATCTGTACATGTGCACATATGCTCCCCTGAAACCA 426
Qy 241 GATCTGGCTCTCCTGGCCATCAATACGCTGTGCAAAGACTGCTCAGACCCCAATCCAATG 300 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 427 GATCTGGCTCTCCTGGCCATCAATACGCTGTGCAAAGACTGCTCAGACCCCAATCCAATG 486
Qy 301 GTGCGAGGGCTGGCGTTACGGAGCATGTGTAGCCTCAGGATGCCTGGTGTGCAGGAGTAT 360 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 487 GTGCGAGGGCTGGCGTTACGGAGCATGTGTAGCCTCAGGATGCCTGGTGTGCAGGAGTAT 546
Qy 361 ATACAACAGCCTATTCTCAATGGTCTGCGGGATAAGGCTTCATATGTCAGGAGAGTGGCA 420 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 547 ATACAACAGCCTATTCTCAATGGTCTGCGGGATAAGGCTTCATATGTCAGGAGAGTGGCA 606
Qy 421 GTCCTTGGATGTGCCAAGATGCATAATCTTCATGGAGACTCTGAAGTAGATGGTGCCCTG 480 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 607 GTCCTTGGATGTGCCAAGATGCATAATCTTCATGGAGACTCTGAAGTAGATGGTGCCCTG 666
Qy 481 GTAAATGAATTATACAGTTTGCTGCGTGACCAGGATCCAATTGTAGTTGTGAACTGCTTG 540 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 667 GTAAATGAATTATACAGTTTGCTGCGTGACCAGGATCCAATTGTAGTTGTGAACTGCTTG 726
Qy 541 AGGTCTCTAGAGGAAATTCTGAAACAGGAAGGAGGCGTTGTCATCAATAAGCCCATTGCT 600 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 727 AGGTCTCTAGAGGAAATTCTGAAACAGGAAGGAGGCGTTGTCATCAATAAGCCCATTGCT 786
Qy 601 CACCATCTCTTAAATCGAATGTCAAAACTGGACCAATGGGGCCAGGCTGAAGTATTGAAC 660 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 787 CACCATCTCTTAAATCGAATGTCAAAACTGGACCAATGGGGCCAGGCTGAAGTATTGAAC 846
Qy 661 TTTCTGCTACGCTACCAACCCCGCAGTGAGGAAGAACTATTTGACATTCTCAATCTGTTG 720 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 847 TTTCTGCTACGCTACCAACCCCGCAGTGAGGAAGAACTATTTGACATTCTCAATCTGTTG 906
Qy 721 GATAGTTTCCTCAAGAGCAGTAGCCCAGGTGTGGTGATGGGAGCTACCAAACTTTTTCTG 780 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 907 GATAGTTTCCTCAAGAGCAGTAGCCCAGGTGTGGTGATGGGAGCTACCAAACTTTTTCTG 966
Qy 781 ATCTTGGCAAAAATGTTTCCCCACGTACAAACTGATGTCCTTGTGCGGGTCAAGGGACCT 840 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 967 ATCTTGGCAAAAATGTTTCCCCACGTACAAACTGATGTCCTTGTGCGGGTCAAGGGACCT 1026
Qy 841 TTGCTAGCTGCCTGTTCTTCAGAGAGCCGTGAGCTCTGTTTTGTTGCTCTTTGTCATGTA 900 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1027 TTGCTAGCTGCCTGTTCTTCAGAGAGCCGTGAGCTCTGTTTTGTTGCTCTTTGTCATGTA 1086
Qy 901 CGCCAGATCTTGCATAGTTTACCAGGTCACTTTAGCAGCCACTACAAAAAGTTTTTTTGC 960 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1087 CGCCAGATCTTGCATAGTTTACCAGGTCACTTTAGCAGCCACTACAAAAAGTTTTTTTGC 1146
Qy 961 TCCTACTCGGAGCCCCACTACATCAAACTACAGAAAGTGGAGGTGCTGTGTGAACTGGTG 1020 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1147 TCCTACTCGGAGCCCCACTACATCAAACTACAGAAAGTGGAGGTGCTGTGTGAACTGGTG 1206
Qy 1021 AACGATGAGAATGTGCAGCAGGTGCTAGAGGAGCTTCGAGGGTACTGCACGGATGTGTCT 1080 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1207 AACGATGAGAATGTGCAGCAGGTGCTAGAGGAGCTTCGAGGGTACTGCACGGATGTGTCT 1266
Qy 1081 GCGGACTTTGCACAGGCTGCCATCTTTGCCATAGGTGGCATTGCCAGGACTTACACAGAT 1140 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1267 GCGGACTTTGCACAGGCTGCCATCTTTGCCATAGGTGGCATTGCCAGGACTTACACAGAT 1326
Qy 1141 CAATGTGTTCAGATTTTAACAGAGTTGCTGGGTCTTCGACAAGAGCACATTACCACAGTG 1200 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1327 CAATGTGTTCAGATTTTAACAGAGTTGCTGGGTCTTCGACAAGAGCACATTACCACAGTG 1386
Qy 1201 GTGGTGCAGACTTTCCGAGACCTGGTTTGGTTGTGTCCTCAGTGTACTGAAGCTGTATGT 1260 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1387 GTGGTGCAGACTTTCCGAGACCTGGTTTGGTTGTGTCCTCAGTGTACTGAAGCTGTATGT 1446
Qy 1261 CAGGCCCTGCCCGGCTGTGAAGAGAACATTCAAGATAGTGAGGGGAAGCAAGCACTTATT 1320 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1447 CAGGCCCTGCCCGGCTGTGAAGAGAACATTCAAGATAGTGAGGGGAAGCAAGCACTTATT 1506
Qy 1321 TGGCTACTTGGTGTCCATGGGGAAAGAATTCCTAATGCTCCTTATGTGTTAGAGGACTTT 1380 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1507 TGGCTACTTGGTGTCCATGGGGAAAGAATTCCTAATGCTCCTTATGTGTTAGAGGACTTT 1566
Qy 1381 GTTGAGAATGTGAAGTCGGAAACATTTCCAGCTGTTAAGATGGAGCTGCTCACTGCTTTG 1440 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1567 GTTGAGAATGTGAAGTCGGAAACATTTCCAGCTGTTAAGATGGAGCTGCTCACTGCTTTG 1626
Qy 1441 CTGCGCCTTTTCCTCTCCCGACCTGCTGAGTGCCAGGACATGCTAGGACGTTTGTTGTAT 1500 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1627 CTGCGCCTTTTCCTCTCCCGACCTGCTGAGTGCCAGGACATGCTAGGACGTTTGTTGTAT 1686
Qy 1501 TACTGCATAGAGGAAGAAAAAGATATGGCTGTACGGGACCGAGGTCTCTTCTATTATCGC 1560 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1687 TACTGCATAGAGGAAGAAAAAGATATGGCTGTACGGGACCGAGGTCTCTTCTATTATCGC 1746
Qy 1561 CTCCTCTTAGTTGGCATTGATGAAGTTAAGCGGATTCTGTGTAGCCCTAAATCTGACCCT 1620 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1747 CTCCTCTTAGTTGGCATTGATGAAGTTAAGCGGATTCTGTGTAGCCCTAAATCTGACCCT 1806
Qy 1621 ACTCTTGGACTTTTGGAGGATCCGGCAGAAAGACCTGTGAATAGCTGGGCCTCAGACTTC 1680 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1807 ACTCTTGGACTTTTGGAGGATCCGGCAGAAAGACCTGTGAATAGCTGGGCCTCAGACTTC 1866
Qy 1681 AACACACTGGTGCCAGTGTATGGCAAAGCCCACTGGGCAACTATCTCTAAATGCCAGGGG 1740 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1867 AACACACTGGTGCCAGTGTATGGCAAAGCCCACTGGGCAACTATCTCTAAATGCCAGGGG 1926
Qy 1741 GCAGAGCGTTGTGACCCAGAGCTTCCTAAAACTTCATCCTTTGCCGCATCAGGACCCTTG 1800 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1927 GCAGAGCGTTGTGACCCAGAGCTTCCTAAAACTTCATCCTTTGCCGCATCAGGACCCTTG 1986
Qy 1801 ATTCCTGAAGAGAACAAGGAGAGGGTACAAGAACTCCCTGATTCTGGAGCCCTCATGCTA 1860 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1987 ATTCCTGAAGAGAACAAGGAGAGGGTACAAGAACTCCCTGATTCTGGAGCCCTCATGCTA 2046
Qy 1861 GTCCCCAATCGCCAGCTTACTGCTGATTATTTTGAGAAAACTTGGCTTAGCCTTAAAGTT 1920 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2047 GTCCCCAATCGCCAGCTTACTGCTGATTATTTTGAGAAAACTTGGCTTAGCCTTAAAGTT 2106
Qy 1921 GCTCATCAGCAAGTGTTGCCTTGGCGGGGAGAATTCCATCCTGACACCCTCCAGATGGCT 1980 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2107 GCTCATCAGCAAGTGTTGCCTTGGCGGGGAGAATTCCATCCTGACACCCTCCAGATGGCT 2166
Qy 1981 CTTCAAGTAGTGAACATCCAGACCATCGCAATGAGTAGGGCTGGGTCTCGGCCATGGAAA 2040 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2167 CTTCAAGTAGTGAACATCCAGACCATCGCAATGAGTAGGGCTGGGTCTCGGCCATGGAAA 2226
Qy 2041 GCATACCTCAGTGCTCAGGATGATACTGGCTGTCTGTTCTTAACAGAACTGCTATTGGAG 2100 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2227 GCATACCTCAGTGCTCAGGATGATACTGGCTGTCTGTTCTTAACAGAACTGCTATTGGAG 2286
Qy 2101 CCTGGAAACTCAGAAATGCAGATCTCTGTGAAACAAAATGAAGCAAGAACGGAGACGCTG 2160 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2287 CCTGGAAACTCAGAAATGCAGATCTCTGTGAAACAAAATGAAGCAAGAACGGAGACGCTG 2346
Qy 2161 AATAGTTTTATTTCTGTATTAGAAACTGTGATTGGAACAATTGAAGAAATAAAATCATAA 2220 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2347 AATAGTTTTATTTCTGTATTAGAAACTGTGATTGGAACAATTGAAGAAATAAAATCATAA 2406
Query Match 100.0%; Score 3836; DB 1; Length 739;
Best Local Similarity 100.0%;
Matches 739; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MPYLGSEDVVKELKKALCNPHIQADRLRYRNVIQRVIRYMTQGLDMSGVFMEMVKASATV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPYLGSEDVVKELKKALCNPHIQADRLRYRNVIQRVIRYMTQGLDMSGVFMEMVKASATV 60
Qy 61 DIVQKKLVYLYMCTYAPLKPDLALLAINTLCKDCSDPNPMVRGLALRSMCSLRMPGVQEY 120 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DIVQKKLVYLYMCTYAPLKPDLALLAINTLCKDCSDPNPMVRGLALRSMCSLRMPGVQEY 120
Qy 121 IQQPILNGLRDKASYVRRVAVLGCAKMHNLHGDSEVDGALVNELYSLLRDQDPIVVVNCL 180 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 IQQPILNGLRDKASYVRRVAVLGCAKMHNLHGDSEVDGALVNELYSLLRDQDPIVVVNCL 180
Qy 181 RSLEEILKQEGGVVINKPIAHHLLNRMSKLDQWGQAEVLNFLLRYQPRSEEELFDILNLL 240 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RSLEEILKQEGGVVINKPIAHHLLNRMSKLDQWGQAEVLNFLLRYQPRSEEELFDILNLL 240
Qy 241 DSFLKSSSPGVVMGATKLFLILAKMFPHVQTDVLVRVKGPLLAACSSESRELCFVALCHV 300 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 DSFLKSSSPGVVMGATKLFLILAKMFPHVQTDVLVRVKGPLLAACSSESRELCFVALCHV 300
Qy 301 RQILHSLPGHFSSHYKKFFCSYSEPHYIKLQKVEVLCELVNDENVQQVLEELRGYCTDVS 360 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RQILHSLPGHFSSHYKKFFCSYSEPHYIKLQKVEVLCELVNDENVQQVLEELRGYCTDVS 360
Qy 361 ADFAQAAIFAIGGIARTYTDQCVQILTELLGLRQEHITTVVVQTFRDLVWLCPQCTEAVC 420 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ADFAQAAIFAIGGIARTYTDQCVQILTELLGLRQEHITTVVVQTFRDLVWLCPQCTEAVC 420
Qy 421 QALPGCEENIQDSEGKQALIWLLGVHGERIPNAPYVLEDFVENVKSETFPAVKMELLTAL 480 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 QALPGCEENIQDSEGKQALIWLLGVHGERIPNAPYVLEDFVENVKSETFPAVKMELLTAL 480
Qy 481 LRLFLSRPAECQDMLGRLLYYCIEEEKDMAVRDRGLFYYRLLLVGIDEVKRILCSPKSDP 540 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 LRLFLSRPAECQDMLGRLLYYCIEEEKDMAVRDRGLFYYRLLLVGIDEVKRILCSPKSDP 540
Qy 541 TLGLLEDPAERPVNSWASDFNTLVPVYGKAHWATISKCQGAERCDPELPKTSSFAASGPL 600 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 TLGLLEDPAERPVNSWASDFNTLVPVYGKAHWATISKCQGAERCDPELPKTSSFAASGPL 600
Qy 601 IPEENKERVQELPDSGALMLVPNRQLTADYFEKTWLSLKVAHQQVLPWRGEFHPDTLQMA 660 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 IPEENKERVQELPDSGALMLVPNRQLTADYFEKTWLSLKVAHQQVLPWRGEFHPDTLQMA 660
Qy 661 LQVVNIQTIAMSRAGSRPWKAYLSAQDDTGCLFLTELLLEPGNSEMQISVKQNEARTETL 720 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 LQVVNIQTIAMSRAGSRPWKAYLSAQDDTGCLFLTELLLEPGNSEMQISVKQNEARTETL 720
Qy 721 NSFISVLETVIGTIEEIKS 739
|||||||||||||||||||
Db 721 NSFISVLETVIGTIEEIKS 739
The nucleotide sequence as set forth in NM_001253852.1 that encodes AP4B was known in accession no that has 100% sequence identity to SEQ ID NO: 1 and encodes amino acid as set forth in SEQ IDNO: 2 as discussed above.
Scarrott as evidenced by Behne differs from claimed invention by not disclosing the ubiquitous promoter selected from CAG promoter or AP-4 subunit specific promoter of AP$B1 as in SEQ ID NO: 27.
Lukashchuk cures the deficiency by disclosing such promoters that were known before the effective filing date in the context of CNS gene therapy. Lukashchuk teaches transcription cassette comprising a CAG or neuron specific promoter (Syn1 or Hb9) and a transgene that is regulated by said promoter (see fig. 1). It is further disclosed that the vector comprising a nucleic acid encoding reporter protein under the control of these promoters that are capable of expressing heterologous gene into motor neuron (see fig. 4). Lukashchuk teaches cells containing motor neurons and interneurons as well as glia were transduced AAV encoding GFP under the control of CAG resulted in the majority of the cells expressing GFP (see fig. 2, page 2, col. 1, para. 2) .
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the AAV9 vector of Scarrott as evidenced by Behne to incorporate CAG promoter as suggested in Lukashchuk, in order to express AP4B1 in neural cell, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification choice amounts to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to use CAG promoter for ubiquitous expression in non-neuronal cell required for different disease model (see page 7, col. 1). One of ordinary skill in the art would have been expected to have a reasonable expectation of success in using CAG promoter because the art teaches the successful incorporation of CAG promoter in AAV9 vector as evident from the teaching of Lukashchuk (see fig. 1). It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claims 45, 52, 59-60, 65-66 are rejected under 35 U.S.C. 103 as being unpatentable over Lukashchuk et al ((Molecular Therapy, 2016, 3, 1-10), Behne et al (Human Molecular Genetics, 2020, Vol. 29, No. 2, 320-324)/ Scarrott et al (Human Gene Therapy, (August 2019) Vol. 30, No. 8, pp. A18. Abstract Number: P03, June 21, 2019) as evidenced by NCBI accession no NM_001253852, GeneCard GH01J112906. as evidenced by GRCh38.p14 (Primary Assembly at NCBI accession no NC_000001.11, 2019) in view of Aldred et al (WO2008073303, dated 06/19/2008 art of record).
With respect to claims 45, 52, Lukashchuk teaches an AAV 9 vector comprising a transcription cassette comprising a neuronal promoter synapsin1 (SYN1) promoter or chicken beta actin hybrid and a gene of interest (GFP). Lukashchuk differs from claimed invention by not disclosing gene of interest is adaptor protein complex 4 subunit bl (AP4B1) and promoter is endogenous AP4B1 promoter as set forth in SEQ ID NO: 27.
Behne cures the deficiency by disclosing vector comprising a transcription cassette comprising a ubiquitous promoter (PGK) that is operably linked to a nucleic acid molecule comprising a nucleotide sequence NM_001253852.1 that encodes AP4B1 (see fig. 3, table 1and page 331, col. 1, para 3). The accession number for AP4B1 disclosed in Behne has 100% sequence identity to SEQ ID NO: 1 and encodes amino acid as set forth in SEQ IDNO: 2 (see above) (limitation of claims 53-58). Behne teaches deficiency of the adaptor protein complex 4 (AP-4) leads to childhood-onset hereditary spastic paraplegia (AP-4-HSP): SPG47) (abstract). (AP4B1), It is disclosed that re-expression of AP4B1 in fibroblasts from patients with AP4B1-associated HSP leads to a reduction of total ATG9A levels and redistribution from the trans-Golgi network to the cell periphery (see Fig. 3). The combination of references differs from claimed invention by not disclosing promoter comprises SEQ ID NO: 27 (Ap4B1 promoter).
GeneCard GH01J11290 identified endogenous promoter containing the region that is about ~600bp upstream of the hAP4B1 gene transcription start site. The NCBI accession number shows nt 196 to 795 has 100% sequence identity. Aldred discloses a transcription regulatory sequence operably linked with a heterologous sequence in an expression vector such that expression of the heterologous sequence is under transcriptional control of the transcription regulatory sequences, wherein the regulatory sequence is SEQ ID NO: 2673 (claim, 1 and 10 of ‘303) that has 100% sequence identity to SEQ ID NO: 27 (see sequence search result).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the construct of Lukashchuk by replacing the gene of interest with AP4B1 as disclosed in Behne, in order to express AP4B1 in neural cell using neuron specific promoter by substituting one disclosed in Lukashchuk with another regulatory sequence that is identified as region that is about ~600bp upstream of the hAP4B1 gene transcription start site.as shown in GeneCard and disclosed in Aldred , with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification choice amounts to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to study the over expression of AP4B1 because prior art recognized that deficiency of the adaptor protein complex 4 (AP-4) leads to childhood-onset hereditary spastic paraplegia. Absent evidence of any unexpected and/or superior expression, one of skill in the art would have been expected to have a reasonable expectation of success because substituting a coding sequence and one promoter with another regulatory region in a viral vector was routine and prior art successfully reported use of AAV9- vector delivery in targeting neurons throughout the brain (see fig. 1). It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support the finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Response to arguments
Applicant disagrees with the rejection by providing a Declaration removing Behne et al. as prior art under 35 U.S.C. § 102(b)(1)(A). In view of this, the rejection is moot. The remaining references do not teach or suggest all of the recited claim elements. Applicant argues that Lukashuchuk suggests using the Hb1 promoter and discourages using the chicken beta actin hybrid promoter. Applicant in part rely on Figure 5 illustrates that a transcription cassette encoding AP4-B1 under the control of the chicken beta actin hybrid promoter in a single delivery of adeno-associated virus serotype 9 expressing hAP4B1 (AAV9/hAP4B1) into the cisterna magna leads to widespread gene transfer and restoration of various hallmarks of disease, including AP-4 cargo (ATG9A) mislocalisation, calbindin- positive spheroids in the deep cerebellar nuclei, anatomical brain defects and motor dysfunction, in an SPG47 mouse model. Furthermore, AAV9/ hAP4-B1-basec gene therapy demonstrated a restoration of plasma neurofilament light (NfL) levels of treated mice when expressed from a chicken beta promoter. Applicants’ arguments have been fully considered but are not found persuasive.
In response, it should be noted that the Azzouz’s declaration filed June 8, 2026, is insufficient to overcome the rejection of claims based upon Behne et al or Scarrott as set forth in the last Office action. This is because declaration fails to show that: (1) the disclosure was made by the inventor or a joint inventor; and (2) the subject matter disclosed was obtained directly or indirectly from the inventor or a joint inventor (see MPEP 717.01(a)(1). In evaluating the declaration the authorship of the prior art disclosure includes the inventor or a joint inventor named in the application, an "unequivocal" statement from the inventor or a joint inventor that he/she (or some specific combination of named joint inventors) invented the subject matter of the disclosure, accompanied by a reasonable explanation of the presence of additional authors, may be acceptable in the absence of evidence to the contrary. See In re DeBaun, 687 F.2d 459, 463, 214 USPQ 933, 936 (CCPA 1982).
Applicant’s statement (see para. 4) that remaining co-authors on the Behne publications are not inventors of the present application and does not clarify contribution of co-authors in Behne and Scarrott publications. It is unclear if disclosure of the publication is solely made by the inventor or a joint inventor and not by others. The declaration is silent on any evidence or explaining on the involvement of other co-authors in the Behne or Scarrott publication.
In response to applicant's argument that Lukashuchuk suggest using the Hb1 promoter and discourage using the chicken beta promoter, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the instant case, it is Behne who teaches use of a weak ubiquitous PGK promoter and it would have been obvious for one of ordinary skill in the art to substitute ubiquitous PGK promoter with functionally equivalent another ubiquitous CAG promoter as suggested in Lukashuchuk . In fact, instant specification (see page 20 of the specification) and prior art of Lukashuchuk both recognize that these ubiquitous promoters are-recognized or obvious equivalent. It is relevant to note that claims are drawn to AAV and as such do not require any specific resulting outcome and therefore, it would be obvious for one of ordinary skill in the art to try using any ubiquitous or neuron specific promoter known in prior art that function in neuron and/or non-neuronal cells depending on desired intended use, with reasonable expectation of success.
On page 7 of the applicant’s argument, applicant assert that Lukashchuk, either alone or in combination, fail to teach or suggest each and every element of the pending claims and do not provide any rationale for one having ordinary skill in the art to combine or modify the teachings therein to arrive at the claimed subject matter with any reasonable expectation of success. Further claims uses a minimal SPG47 promoter (SEQ ID NO:27). This sequence is not disclosed in the prior art and there is no teaching or suggestion in the cited art to identify as a DNA sequence that has the control elements to regulate expression of APB4-B1. Applicants’ arguments have been fully considered but are not found persuasive.
In response, it is noted that newly cited reference of GeneCard GH01J112906 shows a putative endogenous promoter containing the region -600bp upstream of the hAP4B1 gene transcription start site. Absent evidence of any unexpected and/or superior expression, one of skill in the art would have been expected to have a reasonable expectation of success because substituting a coding sequence and a promoter with another regulatory region in a viral vector was routine and prior art successfully reported use of AAV9- vector delivery in targeting neurons throughout the brain (see fig. 1). It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support the finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Therefore, in view of the fact patterns of the instant case, and the ground of rejection outlined by the examiner, applicants' arguments are not compelling and do not overcome the rejection of record.
Examiner’s note: Applicant’s representative is requested to contact Examiner to resolve the pending issues related to declaration filed under 37C.F.R 1.132 to overcome the rejection of record.
Conclusion
No claims allowed.
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/ANOOP K SINGH/ Primary Examiner, Art Unit 1632
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