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 .
This office action is in response to an amendment filed 11/26/2025.
Claims 1-3, 19, 21, 27, 29, 31, 33, 37, 43, 48, 50-54, 56-58 and 61-66 are pending.
This application is a 35 U.S.C. §371 filing of International Patent Application No. PCT/US2019/016122, filed January 31, 2019, which claims priority to U.S. Provisional Patent Application Serial Nos. 62/625,145, filed February 1, 2018, 62/671,915, filed May 15, 2018, and 62/793,158, filed January 16, 2019.
Information Disclosure Statement
An IDS filed 11/25/2025 has been identified and the documents considered. The signed and initialed PTO Form 1449 has been mailed with this action. Applicants assert that no size fee is required.
Claim Objections
Claims 1, 3, 27, 48 and 52 are objected to because of the following informalities: upon reconsideration it is noted that the conclusion of both claim 1 and 2 recite “the dose provides expression of FVIII” which for consistency with the claim should be ---the at least one dose provides expression of the polypeptide with FVIII activity--. Also see claim 3, 27, 48 and 52. This mirrors grammatically the format of the established limitation in claims 1 and 2. Appropriate correction is required.
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 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.
Claims 1-3, 19, 21, 27, 29, 31, 33, 37, 43, 48, 50-54, 56-58 and 61-66 are rejected under 35 U.S.C. 103 as being unpatentable over Tan and Liu (U.S. 201900185543) in view of Cantore et al (Blood, 2017, pages 1-2). This rejection is maintained for reasons of record.
Tan and Liu teach a method of treating hemophilia A in a subject with a lentiviral vector (see abstract and figure 13). The dose is at least one at 5x1010 (see ¶0445) which in light of the dose used in claims 3 and 48 embraces the recited dose. The lentiviral vector comprises a promoter operably linked to the sequences from SEQ ID NO:71 at least that are recited in claims 1 and 2 as well as 27 and 52 LV-coFVIII-6 (see below and ¶0010).
RESULT 1
US-16-074-729-6
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
Sequence 6, US/16074729
Publication No. US20190185543A1
GENERAL INFORMATION
APPLICANT: BIOVERATIV THERAPEUTICS INC.
APPLICANT: TAN, SIYUAN
APPLICANT: LIU, TONGYAO
TITLE OF INVENTION: OPTIMIZED FACTOR VIII GENES
FILE REFERENCE: 4159.4690002/C-K/BMD
CURRENT APPLICATION NUMBER: US/16/074,729
CURRENT FILING DATE: 2018-08-01
PRIOR APPLICATION NUMBER: PCT/US17/015879
PRIOR FILING DATE: 2017-01-31
PRIOR APPLICATION NUMBER: 62/409,739
PRIOR FILING DATE: 2016-10-18
PRIOR APPLICATION NUMBER: 62/289,696
PRIOR FILING DATE: 2016-02-01
NUMBER OF SEQ ID NOS: 103
SEQ ID NO 6
LENGTH: 4374
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: coFVIII-26
Query Match 100.0%; Score 2220; Length 4374;
Best Local Similarity 100.0%;
Matches 2220; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GCCACCAGGAGATACTACCTGGGCGCCGTGGAGCTGAGCTGGGACTACATGCAGTCTGAC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 58 GCCACCAGGAGATACTACCTGGGCGCCGTGGAGCTGAGCTGGGACTACATGCAGTCTGAC 117
Qy 61 CTGGGCGAGCTGCCAGTGGACGCCAGGTTCCCCCCCAGAGTGCCCAAGAGCTTCCCCTTC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 118 CTGGGCGAGCTGCCAGTGGACGCCAGGTTCCCCCCCAGAGTGCCCAAGAGCTTCCCCTTC 177
Qy 121 AACACCAGCGTGGTGTACAAGAAGACCCTGTTCGTGGAGTTCACTGACCACCTGTTCAAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 178 AACACCAGCGTGGTGTACAAGAAGACCCTGTTCGTGGAGTTCACTGACCACCTGTTCAAC 237
Qy 181 ATCGCCAAGCCCAGGCCCCCCTGGATGGGCCTGCTGGGCCCCACCATCCAGGCCGAGGTG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 238 ATCGCCAAGCCCAGGCCCCCCTGGATGGGCCTGCTGGGCCCCACCATCCAGGCCGAGGTG 297
Qy 241 TACGACACCGTGGTCATCACCCTGAAGAACATGGCCAGCCACCCCGTCTCCCTGCACGCC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 298 TACGACACCGTGGTCATCACCCTGAAGAACATGGCCAGCCACCCCGTCTCCCTGCACGCC 357
Qy 301 GTGGGGGTGAGCTACTGGAAGGCCTCTGAGGGCGCCGAGTACGACGACCAGACCAGCCAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 358 GTGGGGGTGAGCTACTGGAAGGCCTCTGAGGGCGCCGAGTACGACGACCAGACCAGCCAG 417
Qy 361 AGGGAGAAGGAGGACGACAAGGTGTTCCCTGGGGGCAGCCACACCTACGTGTGGCAGGTC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 418 AGGGAGAAGGAGGACGACAAGGTGTTCCCTGGGGGCAGCCACACCTACGTGTGGCAGGTC 477
Qy 421 CTGAAGGAGAACGGCCCCATGGCCTCTGACCCCCTGTGCCTGACCTACAGCTACCTGAGC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 478 CTGAAGGAGAACGGCCCCATGGCCTCTGACCCCCTGTGCCTGACCTACAGCTACCTGAGC 537
Qy 481 CACGTGGACCTGGTGAAGGACCTGAACTCTGGCCTGATTGGGGCCCTGCTGGTGTGCAGG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 538 CACGTGGACCTGGTGAAGGACCTGAACTCTGGCCTGATTGGGGCCCTGCTGGTGTGCAGG 597
Qy 541 GAGGGCAGCCTGGCCAAGGAGAAGACCCAGACCCTGCACAAGTTCATCCTGCTGTTCGCC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 598 GAGGGCAGCCTGGCCAAGGAGAAGACCCAGACCCTGCACAAGTTCATCCTGCTGTTCGCC 657
Qy 601 GTGTTCGACGAGGGCAAGAGCTGGCACTCTGAAACCAAGAACAGCCTGATGCAGGACAGG 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 658 GTGTTCGACGAGGGCAAGAGCTGGCACTCTGAAACCAAGAACAGCCTGATGCAGGACAGG 717
Qy 661 GACGCCGCCTCTGCCAGGGCCTGGCCCAAGATGCACACCGTCAACGGCTACGTCAACAGG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 718 GACGCCGCCTCTGCCAGGGCCTGGCCCAAGATGCACACCGTCAACGGCTACGTCAACAGG 777
Qy 721 AGCCTGCCTGGCCTGATTGGCTGCCACAGGAAGAGCGTGTACTGGCATGTGATCGGCATG 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 778 AGCCTGCCTGGCCTGATTGGCTGCCACAGGAAGAGCGTGTACTGGCATGTGATCGGCATG 837
Qy 781 GGCACCACCCCTGAGGTGCACAGCATCTTCCTGGAGGGCCACACCTTCCTGGTCAGGAAC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 838 GGCACCACCCCTGAGGTGCACAGCATCTTCCTGGAGGGCCACACCTTCCTGGTCAGGAAC 897
Qy 841 CACAGGCAGGCCAGCCTGGAGATCAGCCCCATCACCTTCCTGACCGCCCAGACCCTGCTG 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 898 CACAGGCAGGCCAGCCTGGAGATCAGCCCCATCACCTTCCTGACCGCCCAGACCCTGCTG 957
Qy 901 ATGGACCTGGGCCAGTTCCTGCTGTTCTGCCACATCTCCAGCCACCAGCACGACGGCATG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 958 ATGGACCTGGGCCAGTTCCTGCTGTTCTGCCACATCTCCAGCCACCAGCACGACGGCATG 1017
Qy 961 GAGGCCTACGTGAAAGTGGACAGCTGCCCTGAGGAGCCCCAGCTGAGGATGAAGAACAAC 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1018 GAGGCCTACGTGAAAGTGGACAGCTGCCCTGAGGAGCCCCAGCTGAGGATGAAGAACAAC 1077
Qy 1021 GAGGAGGCCGAGGACTATGATGACGACCTGACCGACAGCGAGATGGACGTGGTCAGGTTC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1078 GAGGAGGCCGAGGACTATGATGACGACCTGACCGACAGCGAGATGGACGTGGTCAGGTTC 1137
Qy 1081 GACGACGACAACAGCCCCAGCTTCATCCAGATCAGGAGCGTGGCCAAGAAGCACCCCAAG 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1138 GACGACGACAACAGCCCCAGCTTCATCCAGATCAGGAGCGTGGCCAAGAAGCACCCCAAG 1197
Qy 1141 ACCTGGGTGCACTACATCGCTGCTGAGGAGGAGGACTGGGACTATGCCCCCCTGGTGCTG 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1198 ACCTGGGTGCACTACATCGCTGCTGAGGAGGAGGACTGGGACTATGCCCCCCTGGTGCTG 1257
Qy 1201 GCCCCTGATGACAGGAGCTACAAGAGCCAGTACCTGAACAATGGCCCCCAGAGGATTGGC 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1258 GCCCCTGATGACAGGAGCTACAAGAGCCAGTACCTGAACAATGGCCCCCAGAGGATTGGC 1317
Qy 1261 AGGAAGTACAAGAAAGTCAGGTTCATGGCCTACACTGATGAAACCTTCAAGACCAGGGAG 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1318 AGGAAGTACAAGAAAGTCAGGTTCATGGCCTACACTGATGAAACCTTCAAGACCAGGGAG 1377
Qy 1321 GCCATCCAGCATGAGTCTGGCATCCTGGGCCCCCTGCTGTACGGGGAGGTGGGGGACACC 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1378 GCCATCCAGCATGAGTCTGGCATCCTGGGCCCCCTGCTGTACGGGGAGGTGGGGGACACC 1437
Qy 1381 CTGCTGATCATCTTCAAGAACCAGGCCAGCAGGCCCTACAACATCTACCCCCATGGCATC 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1438 CTGCTGATCATCTTCAAGAACCAGGCCAGCAGGCCCTACAACATCTACCCCCATGGCATC 1497
Qy 1441 ACCGACGTGAGGCCCCTGTACAGCAGGAGGCTGCCTAAGGGGGTGAAGCACCTGAAAGAC 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1498 ACCGACGTGAGGCCCCTGTACAGCAGGAGGCTGCCTAAGGGGGTGAAGCACCTGAAAGAC 1557
Qy 1501 TTCCCCATCCTGCCTGGGGAGATCTTCAAGTACAAGTGGACTGTGACTGTGGAGGACGGC 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1558 TTCCCCATCCTGCCTGGGGAGATCTTCAAGTACAAGTGGACTGTGACTGTGGAGGACGGC 1617
Qy 1561 CCCACCAAGAGCGACCCCAGGTGCCTGACCAGATACTACAGCAGCTTCGTCAACATGGAG 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1618 CCCACCAAGAGCGACCCCAGGTGCCTGACCAGATACTACAGCAGCTTCGTCAACATGGAG 1677
Qy 1621 AGGGACCTGGCCTCTGGCCTGATTGGCCCCCTGCTGATCTGCTACAAGGAGTCTGTGGAC 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1678 AGGGACCTGGCCTCTGGCCTGATTGGCCCCCTGCTGATCTGCTACAAGGAGTCTGTGGAC 1737
Qy 1681 CAGAGGGGCAACCAGATCATGAGCGACAAGAGGAACGTGATCCTGTTCTCTGTCTTCGAC 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1738 CAGAGGGGCAACCAGATCATGAGCGACAAGAGGAACGTGATCCTGTTCTCTGTCTTCGAC 1797
Qy 1741 GAGAACAGGAGCTGGTACCTCACTGAAAACATCCAGAGGTTCCTCCCAAACCCCGCAGGA 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1798 GAGAACAGGAGCTGGTACCTCACTGAAAACATCCAGAGGTTCCTCCCAAACCCCGCAGGA 1857
Qy 1801 GTGCAACTGGAGGACCCTGAGTTTCAGGCCTCGAATATCATGCACTCGATTAACGGTTAC 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1858 GTGCAACTGGAGGACCCTGAGTTTCAGGCCTCGAATATCATGCACTCGATTAACGGTTAC 1917
Qy 1861 GTGTTCGACTCGCTGCAGCTGAGCGTGTGCCTCCATGAAGTCGCTTACTGGTACATTCTG 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1918 GTGTTCGACTCGCTGCAGCTGAGCGTGTGCCTCCATGAAGTCGCTTACTGGTACATTCTG 1977
Qy 1921 TCCATCGGCGCCCAGACTGACTTCCTGAGCGTGTTCTTTTCCGGTTACACCTTTAAGCAC 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1978 TCCATCGGCGCCCAGACTGACTTCCTGAGCGTGTTCTTTTCCGGTTACACCTTTAAGCAC 2037
Qy 1981 AAGATGGTGTACGAAGATACCCTGACCCTGTTCCCTTTCTCCGGCGAAACGGTGTTCATG 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2038 AAGATGGTGTACGAAGATACCCTGACCCTGTTCCCTTTCTCCGGCGAAACGGTGTTCATG 2097
Qy 2041 TCGATGGAGAACCCGGGTCTGTGGATTCTGGGATGCCACAACAGCGACTTTCGGAACCGC 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2098 TCGATGGAGAACCCGGGTCTGTGGATTCTGGGATGCCACAACAGCGACTTTCGGAACCGC 2157
Qy 2101 GGAATGACTGCCCTGCTGAAGGTGTCCTCATGCGACAAGAACACCGGAGACTACTACGAG 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2158 GGAATGACTGCCCTGCTGAAGGTGTCCTCATGCGACAAGAACACCGGAGACTACTACGAG 2217
Qy 2161 GACTCCTACGAGGATATCTCAGCCTACCTCCTGTCCAAGAACAACGCGATCGAGCCGCGC 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2218 GACTCCTACGAGGATATCTCAGCCTACCTCCTGTCCAAGAACAACGCGATCGAGCCGCGC 2277
RESULT 3
US-16-074-729-6
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
Sequence 6, US/16074729
Publication No. US20190185543A1
GENERAL INFORMATION
APPLICANT: BIOVERATIV THERAPEUTICS INC.
APPLICANT: TAN, SIYUAN
APPLICANT: LIU, TONGYAO
TITLE OF INVENTION: OPTIMIZED FACTOR VIII GENES
FILE REFERENCE: 4159.4690002/C-K/BMD
CURRENT APPLICATION NUMBER: US/16/074,729
CURRENT FILING DATE: 2018-08-01
PRIOR APPLICATION NUMBER: PCT/US17/015879
PRIOR FILING DATE: 2017-01-31
PRIOR APPLICATION NUMBER: 62/409,739
PRIOR FILING DATE: 2016-10-18
PRIOR APPLICATION NUMBER: 62/289,696
PRIOR FILING DATE: 2016-02-01
NUMBER OF SEQ ID NOS: 103
SEQ ID NO 6
LENGTH: 4374
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: coFVIII-26
Query Match 100.0%; Score 2055; Length 4374;
Best Local Similarity 100.0%;
Matches 2055; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAAATTACCCGGACCACCCTCCAATCGGATCAGGAGGAAATCGACTACGACGACACCATC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2320 GAAATTACCCGGACCACCCTCCAATCGGATCAGGAGGAAATCGACTACGACGACACCATC 2379
Qy 61 TCGGTGGAAATGAAGAAGGAAGATTTCGATATCTACGACGAGGACGAAAATCAGTCCCCT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2380 TCGGTGGAAATGAAGAAGGAAGATTTCGATATCTACGACGAGGACGAAAATCAGTCCCCT 2439
Qy 121 CGCTCATTCCAAAAGAAAACTAGACACTACTTTATCGCCGCGGTGGAAAGACTGTGGGAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2440 CGCTCATTCCAAAAGAAAACTAGACACTACTTTATCGCCGCGGTGGAAAGACTGTGGGAC 2499
Qy 181 TATGGAATGTCATCCAGCCCTCACGTCCTTCGGAACCGGGCCCAGAGCGGATCGGTGCCT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2500 TATGGAATGTCATCCAGCCCTCACGTCCTTCGGAACCGGGCCCAGAGCGGATCGGTGCCT 2559
Qy 241 CAGTTCAAGAAAGTGGTGTTCCAGGAGTTCACCGACGGCAGCTTCACCCAGCCGCTGTAC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2560 CAGTTCAAGAAAGTGGTGTTCCAGGAGTTCACCGACGGCAGCTTCACCCAGCCGCTGTAC 2619
Qy 301 CGGGGAGAACTGAACGAACACCTGGGCCTGCTCGGTCCCTACATCCGCGCGGAAGTGGAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2620 CGGGGAGAACTGAACGAACACCTGGGCCTGCTCGGTCCCTACATCCGCGCGGAAGTGGAG 2679
Qy 361 GATAACATCATGGTGACCTTCCGTAACCAAGCATCCAGACCTTACTCCTTCTATTCCTCC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2680 GATAACATCATGGTGACCTTCCGTAACCAAGCATCCAGACCTTACTCCTTCTATTCCTCC 2739
Qy 421 CTGATCTCATACGAGGAGGACCAGCGCCAAGGCGCCGAGCCCCGCAAGAACTTCGTCAAG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2740 CTGATCTCATACGAGGAGGACCAGCGCCAAGGCGCCGAGCCCCGCAAGAACTTCGTCAAG 2799
Qy 481 CCCAACGAGACTAAGACCTACTTCTGGAAGGTCCAACACCATATGGCCCCGACCAAGGAT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2800 CCCAACGAGACTAAGACCTACTTCTGGAAGGTCCAACACCATATGGCCCCGACCAAGGAT 2859
Qy 541 GAGTTTGACTGCAAGGCCTGGGCCTACTTCTCCGACGTGGACCTTGAGAAGGATGTCCAT 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2860 GAGTTTGACTGCAAGGCCTGGGCCTACTTCTCCGACGTGGACCTTGAGAAGGATGTCCAT 2919
Qy 601 TCCGGCCTGATCGGGCCGCTGCTCGTGTGTCACACCAACACCCTGAACCCAGCGCATGGA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2920 TCCGGCCTGATCGGGCCGCTGCTCGTGTGTCACACCAACACCCTGAACCCAGCGCATGGA 2979
Qy 661 CGCCAGGTCACCGTCCAGGAGTTTGCTCTGTTCTTCACCATTTTTGACGAAACTAAGTCC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2980 CGCCAGGTCACCGTCCAGGAGTTTGCTCTGTTCTTCACCATTTTTGACGAAACTAAGTCC 3039
Qy 721 TGGTACTTCACCGAGAATATGGAGCGAAACTGTAGAGCGCCCTGCAATATCCAGATGGAA 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3040 TGGTACTTCACCGAGAATATGGAGCGAAACTGTAGAGCGCCCTGCAATATCCAGATGGAA 3099
Qy 781 GATCCGACTTTCAAGGAGAACTATAGATTCCACGCCATCAACGGGTACATCATGGATACT 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3100 GATCCGACTTTCAAGGAGAACTATAGATTCCACGCCATCAACGGGTACATCATGGATACT 3159
Qy 841 CTGCCGGGGCTGGTCATGGCCCAGGATCAGAGGATTCGGTGGTACTTGCTGTCAATGGGA 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3160 CTGCCGGGGCTGGTCATGGCCCAGGATCAGAGGATTCGGTGGTACTTGCTGTCAATGGGA 3219
Qy 901 TCGAACGAAAACATTCACTCCATTCACTTCTCCGGTCACGTGTTCACTGTGCGCAAGAAG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3220 TCGAACGAAAACATTCACTCCATTCACTTCTCCGGTCACGTGTTCACTGTGCGCAAGAAG 3279
Qy 961 GAGGAGTACAAGATGGCGCTGTACAATCTGTACCCCGGGGTGTTCGAAACTGTGGAGATG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3280 GAGGAGTACAAGATGGCGCTGTACAATCTGTACCCCGGGGTGTTCGAAACTGTGGAGATG 3339
Qy 1021 CTGCCGTCCAAGGCCGGCATCTGGAGAGTGGAGTGCCTGATCGGAGAGCACCTCCACGCG 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3340 CTGCCGTCCAAGGCCGGCATCTGGAGAGTGGAGTGCCTGATCGGAGAGCACCTCCACGCG 3399
Qy 1081 GGGATGTCCACCCTCTTCCTGGTGTACTCGAATAAGTGCCAGACCCCGCTGGGCATGGCC 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3400 GGGATGTCCACCCTCTTCCTGGTGTACTCGAATAAGTGCCAGACCCCGCTGGGCATGGCC 3459
Qy 1141 TCGGGCCACATCAGAGACTTCCAGATCACAGCAAGCGGACAATACGGCCAATGGGCGCCG 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3460 TCGGGCCACATCAGAGACTTCCAGATCACAGCAAGCGGACAATACGGCCAATGGGCGCCG 3519
Qy 1201 AAGCTGGCCCGCTTGCACTACTCCGGATCGATCAACGCATGGTCCACCAAGGAACCGTTC 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3520 AAGCTGGCCCGCTTGCACTACTCCGGATCGATCAACGCATGGTCCACCAAGGAACCGTTC 3579
Qy 1261 TCGTGGATTAAGGTGGACCTCCTGGCCCCTATGATTATCCACGGAATTAAGACCCAGGGC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3580 TCGTGGATTAAGGTGGACCTCCTGGCCCCTATGATTATCCACGGAATTAAGACCCAGGGC 3639
Qy 1321 GCCAGGCAGAAGTTCTCCTCCCTGTACATCTCGCAATTCATCATCATGTACAGCCTGGAC 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3640 GCCAGGCAGAAGTTCTCCTCCCTGTACATCTCGCAATTCATCATCATGTACAGCCTGGAC 3699
Qy 1381 GGGAAGAAGTGGCAGACTTACAGGGGAAACTCCACCGGCACCCTGATGGTCTTTTTCGGC 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3700 GGGAAGAAGTGGCAGACTTACAGGGGAAACTCCACCGGCACCCTGATGGTCTTTTTCGGC 3759
Qy 1441 AACGTGGATTCCTCCGGCATTAAGCACAACATCTTCAACCCACCGATCATAGCCAGATAT 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3760 AACGTGGATTCCTCCGGCATTAAGCACAACATCTTCAACCCACCGATCATAGCCAGATAT 3819
Qy 1501 ATTAGGCTCCACCCCACTCACTACTCAATCCGCTCAACTCTTCGGATGGAACTCATGGGG 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3820 ATTAGGCTCCACCCCACTCACTACTCAATCCGCTCAACTCTTCGGATGGAACTCATGGGG 3879
Qy 1561 TGCGACCTGAACTCCTGCTCCATGCCGTTGGGGATGGAATCAAAGGCTATTAGCGACGCC 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3880 TGCGACCTGAACTCCTGCTCCATGCCGTTGGGGATGGAATCAAAGGCTATTAGCGACGCC 3939
Qy 1621 CAGATCACCGCGAGCTCCTACTTCACTAACATGTTCGCCACCTGGAGCCCCTCCAAGGCC 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3940 CAGATCACCGCGAGCTCCTACTTCACTAACATGTTCGCCACCTGGAGCCCCTCCAAGGCC 3999
Qy 1681 AGGCTGCACTTGCAGGGACGGTCAAATGCCTGGCGGCCGCAAGTGAACAATCCGAAGGAA 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4000 AGGCTGCACTTGCAGGGACGGTCAAATGCCTGGCGGCCGCAAGTGAACAATCCGAAGGAA 4059
Qy 1741 TGGCTTCAAGTGGATTTCCAAAAGACCATGAAAGTGACCGGAGTCACCACCCAGGGAGTG 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4060 TGGCTTCAAGTGGATTTCCAAAAGACCATGAAAGTGACCGGAGTCACCACCCAGGGAGTG 4119
Qy 1801 AAGTCCCTTCTGACCTCGATGTATGTGAAGGAGTTCCTGATTAGCAGCAGCCAGGACGGG 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4120 AAGTCCCTTCTGACCTCGATGTATGTGAAGGAGTTCCTGATTAGCAGCAGCCAGGACGGG 4179
Qy 1861 CACCAGTGGACCCTGTTCTTCCAAAACGGAAAGGTCAAGGTGTTCCAGGGGAACCAGGAC 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4180 CACCAGTGGACCCTGTTCTTCCAAAACGGAAAGGTCAAGGTGTTCCAGGGGAACCAGGAC 4239
Qy 1921 TCGTTCACACCCGTGGTGAACTCCCTGGACCCCCCACTGCTGACGCGGTACTTGAGGATT 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4240 TCGTTCACACCCGTGGTGAACTCCCTGGACCCCCCACTGCTGACGCGGTACTTGAGGATT 4299
Qy 1981 CATCCTCAGTCCTGGGTCCATCAGATTGCATTGCGAATGGAAGTCCTGGGCTGCGAGGCC 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4300 CATCCTCAGTCCTGGGTCCATCAGATTGCATTGCGAATGGAAGTCCTGGGCTGCGAGGCC 4359
Qy 2041 CAGGACCTGTACTGA 2055
|||||||||||||||
Db 4360 CAGGACCTGTACTGA 4374
Missing from these teachings are that the lentivirus comprises CD47 on the lipid coat. However, Cantore et al teach the increased efficacy and safety when the lentivirus is complexed with CD47. The CD47 ligand is human and MHC free as recited in claims 37 and 57 (see Cantore, page 2, line 18 for human CD47 as recited in claim 37 and MHC free in line 21).
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to incorporate the CD47 in the lipid coat as taught by Cantore et al. Such a modification would have resulted in a method encompassed by the claims. As noted above: 1) Tan and Liu teach methods of treating hemophilia A with FVIII in lentivirus at a dose encompassing 5x1010 and 2) Cantore teaches improved hemophilia A with CD47 embedded in the coat. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the expanded method would allow improved treatment.
As to subjects, claim 19 and 50 recites either a pediatric or adult subject which covers a subject of any age and hence is inherently encompassed by the subjects of Tan and Cantore. It is a liver tissue specific promoter as recited in claims 21 and 51 is mTTR (see e.g. ¶0085 and 0333). Administration as recited in claims 29 and 53 is intravenous (see ¶0100). It integrates into the genome as recited in claims 63 and 64 (see ¶ 481).
The sequence has a signal peptide corresponding to nucleotides 1-57 of SEQ ID NO:1. As recited in claims 31, 54, 61 and 62.
RESULT 1
US-16-074-729-1
(NOTE: this sequence has 7 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1, US/16074729
Publication No. US20190185543A1
GENERAL INFORMATION
APPLICANT: BIOVERATIV THERAPEUTICS INC.
APPLICANT: TAN, SIYUAN
APPLICANT: LIU, TONGYAO
TITLE OF INVENTION: OPTIMIZED FACTOR VIII GENES
FILE REFERENCE: 4159.4690002/C-K/BMD
CURRENT APPLICATION NUMBER: US/16/074,729
CURRENT FILING DATE: 2018-08-01
PRIOR APPLICATION NUMBER: PCT/US17/015879
PRIOR FILING DATE: 2017-01-31
PRIOR APPLICATION NUMBER: 62/409,739
PRIOR FILING DATE: 2016-10-18
PRIOR APPLICATION NUMBER: 62/289,696
PRIOR FILING DATE: 2016-02-01
NUMBER OF SEQ ID NOS: 103
SEQ ID NO 1
LENGTH: 4374
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: coFVIII-5
Query Match 100.0%; Score 57; Length 4374;
Best Local Similarity 100.0%;
Matches 57; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGCAAATCGAACTGAGCACCTGTTTCTTCCTCTGCCTGCTGAGATTCTGTTTCTCC 57
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGCAAATCGAACTGAGCACCTGTTTCTTCCTCTGCCTGCTGAGATTCTGTTTCTCC 57
The lentivirus further comprises XTEN (which is also instant SEQ ID NO:72) (see e.g. Figure 8) as recited in claim 33 and 57. This figure shows the sequence inserted between two amino acids.
Claims 43 and 58 recite products by process wherein the lentivirus of Cantore would be expected to be the same product.
Response to arguments
Applicants argue that Cantore et al does not teach hemophilia A or Factor VIII. Rather, applicants argue that Cantore is drawn to a different disease with a different gene.
This argument does not reflect the full meaning of the rejection. Tan teaches one how to treat hemophilia A with FVIII wherein using the lentivirus of Cantore one would improve treatment of this disorder with this disease given the success demonstrated by Cantore in treating a related disorder with a related gene. Both disorders are blood disorders and both are factors used to treat the related blood disorders. Tan teaches in fact the compositions can be used in hemophilia B or A.
[0149] Hemostatic disorder, as used herein, means a genetically inherited or acquired condition characterized by a tendency to hemorrhage, either spontaneously or as a result of trauma, due to an impaired ability or inability to form a fibrin clot. Examples of such disorders include the hemophilia. The three main forms are hemophilia A (factor VIII efficiency), hemophilia B (factor IX deficiency or “Christmas disease”) and hemophilia C (factor XI deficiency, mild bleeding tendency).
[0425] The nucleic acid molecules, vectors, or polypeptides of the disclosure can be used to treat hemostatic disorders known to be treatable with FVIII. The hemostatic disorders that can be treated using methods of the disclosure include, but are not limited to, hemophilia A, hemophilia B, von Willebrand's disease, Factor XI deficiency (PTA deficiency), Factor XII deficiency, as well as deficiencies or structural abnormalities in fibrinogen, prothrombin, Factor V, Factor VII, Factor X, or Factor XIII, hemarthrosis, muscle bleed, oral bleed, hemorrhage, hemorrhage into muscles, oral hemorrhage, trauma, trauma capitis, gastrointestinal bleeding, intracranial hemorrhage, intra-abdominal hemorrhage, intrathoracic hemorrhage, bone fracture, central nervous system bleeding, bleeding in the retropharyngeal space, bleeding in the retroperitoneal space, and bleeding in the illiopsoas sheath. Compositions for administration to a subject include nucleic acid molecules which comprise an optimized nucleotide sequence of the disclosure encoding a FVIII clotting factor (for gene therapy applications) as well as FVIII polypeptide molecules.
Tan teaches that the target for the agents is the liver
[0333] In one embodiment, the disclosure includes expression of a transgene under the control of a tissue specific promoter and/or enhancer. In another embodiment, the promoter or other expression control sequence selectively enhances expression of the transgene in liver cells.
Cantore teaches success for use of the lentivirus with increased levels of CD47 on the surface wherein the vector improves delivery in Cantore and would be expected to improve therapy for Tan with hemophilia A. Cantore teaches,
In this setting,CD47 proved to be a key player in reducing phagocytosis of LV, decreasing the inflammatory cytokine response following their administration, and increasing hepatocyte transduction and FIX output. We have now administered MHC-free or MHC-free/CD47high LV to 6 non-human primates (NHP, 3 for each LV version).
Upon necropsy, we measured vector copies in liver, spleen and major organs of treated animals and found between 0.5 and 1.5 LV copies in the liver accounting for 80-90% of all the retrieved LV copies, showing selective targeting and efficient gene transfer to the liver by LV in NHP. Overall, our studies support the efficacy and safety of these immune-stealth LV in NHP and position them to address some of the outstanding challenges in liver-directed gene therapy for hemophilia and conceivably other diseases.
Hence, the two reference are analogous art wherein the improvement shown in one could predictably be used to improve the method of Tan et al. A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention). Note that "same field of endeavor" and "reasonably pertinent" are two separate tests for establishing analogous art; it is not necessary for a reference to fulfill both tests in order to qualify as analogous art. In this case both are directed to treating related blood disorders and represent improvements through modifications of lentivirus (Cantore et al )and sequences (Tan et al).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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, Maria Leavitt can be reached on 571-272-1085. 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.
/MARIA MARVICH/Primary Examiner, Art Unit 1634