DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/10/2025 has been entered.
Effective Filing Date
The effective filing date of the instant claims is 9 April 2021. This was determined as follows:
Provisionals 63/059,860, 63/059,916, 63/059,813 and 63/059,963, all filed 31 July 2020, and 63/199,930, filed 3 February 2021, and 63/199,949 and 63/199,951, filed 2 February 2021 do not disclose SEQ ID NO:16 or 17.
Provisional 63/201,030, filed 9 April 2021, discloses SEQ ID NOs:16 and 17 and soybean plants comprising it.
Status of the Claims
Claims 1-4 are pending.
Claims 1-4 are examined herein.
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 of this title, 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 1-4 remain rejected under 35 U.S.C. 103 as being unpatentable over Cui et al. (2017, US 9,540,655) in view of Bernabé‐Orts, et al. "Assessment of Cas12a‐mediated gene editing efficiency in plants." Plant biotechnology journal 17.10 (2019): 1971-1984 and Finnigan, et al. "mCAL: a new approach for versatile multiplex action of Cas9 using one sgRNA and loci flanked by a programmed target sequence." G3: Genes, Genomes, Genetics 6.7 (2016): 2147-2156 and Lee, et al. "Activities and specificities of CRISPR/Cas9 and Cas12a nucleases for targeted mutagenesis in maize." Plant biotechnology journal 17.2 (2019): 362-372.
Applicant claims a DNA molecule comprising SEQ ID NO: 16 or 17 (Claim1), a processed transgenic soybean plant product comprising the DNA molecule of claim 1 (Claim2), the processed transgenic soybean plant product of claim 2, wherein said product comprises defatted or non-defatted soybean seed meal (Claim 3), a biological sample containing the DNA molecule of claim 1 (Claim 4).
Cui teaches soybean plants comprising event pDAB8264.44.06.1. Cui teaches the sequence of the event as SEQ ID NO:27, which includes 5’ flanking sequence, the insert, and 3’ flanking sequence of the event. Cui teaches that the event was selected for stability and expression in soybean plants from generation to generation and based on its unique characteristics such as single insertion site, normal Mendelian segregation and stable expression, and a superior combination of efficacy, including herbicide tolerance and agronomic performance. (col. 8 lines 16-26, Example 1). The instant SEQ ID NO:16 is identical to a portion of Cui SEQ ID NO:27, except for a single insertion of 27 bases between positions 11791 and 11792 of Cui et al. SEQ ID NO:27, 16 nucleotides from the 3’ junction of the event, which is between bases 11774 and 11775 (example 7) as shown in the following alignment:
US-13-991-246-27
; Sequence 27, Application US/13991246
; Patent No. 9540655
; GENERAL INFORMATION
; APPLICANT: Dow AgroSciences LLC; M.S. Technologis, Inc.
; TITLE OF INVENTION: STACKED HERBICIDE TOLERANCE EVENT 8264.44.06.1, RELATED
; TITLE OF INVENTION:TRANSGENIC SOYBEAN LINES, AND DETECTION THEREOF
; FILE REFERENCE: DAS-P0189-01
; CURRENT APPLICATION NUMBER: US/13/991,246
; CURRENT FILING DATE: 2013-06-03
; NUMBER OF SEQ ID NOS: 29
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 27
; LENGTH: 13659
; TYPE: DNA
; ORGANISM: Artificial Sequence
; FEATURE:
; OTHER INFORMATION: Event pDAB8264.44.06.1
US-13-991-246-27
Query Match 99.5%; Score 13622; DB 37; Length 13659;
Best Local Similarity 99.8%;
Matches 13659; Conservative 0; Mismatches 0; Indels 27; Gaps 1;
Qy 1 CCGCTGAAGAAGATCAAGTGTGTGAACCAAAGTGAAAATAATGTTTAGAAGCCAACACAG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CCGCTGAAGAAGATCAAGTGTGTGAACCAAAGTGAAAATAATGTTTAGAAGCCAACACAG 60
Qy 61 TGGACAATTTTGATTTCTGGTTAATGGGTGTATTAAAAATATCAGAAAACTTTCAAATAT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TGGACAATTTTGATTTCTGGTTAATGGGTGTATTAAAAATATCAGAAAACTTTCAAATAT 120
Qy 121 CTCGAGCAGGCAGTTGGGTTGCCTAATCCATCACTTGATCTCAAAGATTCTTGTTGTCAA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CTCGAGCAGGCAGTTGGGTTGCCTAATCCATCACTTGATCTCAAAGATTCTTGTTGTCAA 180
Qy 181 GCTTCGATGAGTAGCGAAACCTACCGTGTGGGCTCTAAGCTTTAGGTTGCCATTGACGAT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GCTTCGATGAGTAGCGAAACCTACCGTGTGGGCTCTAAGCTTTAGGTTGCCATTGACGAT 240
Qy 241 CTTGACACGACATATGACCTATGATAGCAATTCAAACATGGTTCATATCAGCTGAGTTGC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CTTGACACGACATATGACCTATGATAGCAATTCAAACATGGTTCATATCAGCTGAGTTGC 300
Qy 301 AGACTTAGCTGCTAGCATTTCACGTTGTGAATGCAAGAGGAAAAATACATAGAAAAAGAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 AGACTTAGCTGCTAGCATTTCACGTTGTGAATGCAAGAGGAAAAATACATAGAAAAAGAG 360
Qy 361 GGAACAAAATTGTTAACCCTCCATATGTACAGGTTTTAGCCTCAATTTTACCCATTGATT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GGAACAAAATTGTTAACCCTCCATATGTACAGGTTTTAGCCTCAATTTTACCCATTGATT 420
Qy 421 GATTTATTATTGAAAAGTAATCACTTATCAGAACCAGAGTTTGTAATTCAGCTTGTATCG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GATTTATTATTGAAAAGTAATCACTTATCAGAACCAGAGTTTGTAATTCAGCTTGTATCG 480
Qy 481 TACCATCTAATATCTTAGTCAAATTTGTGTATAATAAGTATTTAAATGTGAGTCTCTTTT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 TACCATCTAATATCTTAGTCAAATTTGTGTATAATAAGTATTTAAATGTGAGTCTCTTTT 540
Qy 541 ATTTAATTAGTTTAAATAATTGGAATACAATTGGCAAATGGGCACTTCAACTATAATTAG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 ATTTAATTAGTTTAAATAATTGGAATACAATTGGCAAATGGGCACTTCAACTATAATTAG 600
Qy 601 TGAATTGATTTAGTTGACTGTTATGAAGTATTTTACTTAAGTTAGTAATAGTAGAGTGAT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 TGAATTGATTTAGTTGACTGTTATGAAGTATTTTACTTAAGTTAGTAATAGTAGAGTGAT 660
Qy 661 GTTTGATGAATTAAACTTAAGATTGGTTGAAGTTATTGATCTCACTGGATCCATAGTTTG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GTTTGATGAATTAAACTTAAGATTGGTTGAAGTTATTGATCTCACTGGATCCATAGTTTG 720
Qy 721 GTCTGTGGGATTGCATCTGAAACGGATCATATGGTTTTGTTTTGTGACTGAATTGTGGCA 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GTCTGTGGGATTGCATCTGAAACGGATCATATGGTTTTGTTTTGTGACTGAATTGTGGCA 780
Qy 781 ATGTAACACCTGGACTTTTTCACAACTATTGTATAAATCCAGTATATCTCACGTGAATCT 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 ATGTAACACCTGGACTTTTTCACAACTATTGTATAAATCCAGTATATCTCACGTGAATCT 840
Qy 841 GAAATTAGTAGCATGCTTAACATATAAGTATCGATTTATCTAATCAGTTTCCATATTTAT 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 GAAATTAGTAGCATGCTTAACATATAAGTATCGATTTATCTAATCAGTTTCCATATTTAT 900
Qy 901 GAAAACTGCACTGTTGAAAATTGTGCAAGCTTAACATACAAGTAATGTAATCCACAGTAC 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GAAAACTGCACTGTTGAAAATTGTGCAAGCTTAACATACAAGTAATGTAATCCACAGTAC 960
Qy 961 GAAAAATGTGCAGGTTCTTATTTGTGCTCCATAATTGTTTCTTGATTCCGATCAAAGCAA 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 GAAAAATGTGCAGGTTCTTATTTGTGCTCCATAATTGTTTCTTGATTCCGATCAAAGCAA 1020
Qy 1021 GAGCATCCAGTCTCAAAATTTTGTCTTCTCAATTCACTCATTCATCAAAATCAGCAGTTT 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GAGCATCCAGTCTCAAAATTTTGTCTTCTCAATTCACTCATTCATCAAAATCAGCAGTTT 1080
Qy 1081 TATGCATCAACAAGCATGGAATGTTGAACCACCCATGATTAAGCCCCATATCGTTGTGTT 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 TATGCATCAACAAGCATGGAATGTTGAACCACCCATGATTAAGCCCCATATCGTTGTGTT 1140
Qy 1141 GAGATAACTATCACCTGAAGTTGTCTTATAAAAAACACATCTGAATACTTTTATAATCAT 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 GAGATAACTATCACCTGAAGTTGTCTTATAAAAAACACATCTGAATACTTTTATAATCAT 1200
Qy 1201 ACCTTTCTCGGCCTTTTGGCTAAGATCAAGTGTAGTATCTGTTCTTATCAGTTTAATATC 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 ACCTTTCTCGGCCTTTTGGCTAAGATCAAGTGTAGTATCTGTTCTTATCAGTTTAATATC 1260
Qy 1261 TGATATGTGGGTCATTGGCCCACATGATATTAAATTTATTTTTTGAAGGGTGGGGCCTGA 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 TGATATGTGGGTCATTGGCCCACATGATATTAAATTTATTTTTTGAAGGGTGGGGCCTGA 1320
Qy 1321 CATAGTAGCTTGCTACTGGGGGTTCTTAAGCGTAGCCTGTGTCTTGCACTACTGCATGGG 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 CATAGTAGCTTGCTACTGGGGGTTCTTAAGCGTAGCCTGTGTCTTGCACTACTGCATGGG 1380
Qy 1381 CCTGGCGCACCCTACGATTCAGTGTATATTTATGTGTGATAATGTCATGGGTTTTTATTG 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 CCTGGCGCACCCTACGATTCAGTGTATATTTATGTGTGATAATGTCATGGGTTTTTATTG 1440
Qy 1441 TTCTTGTTGTTTCCTCTTTAGGAACTTACATGTAAACGGTAAGGTCATCATGGAGGTCCG 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 TTCTTGTTGTTTCCTCTTTAGGAACTTACATGTAAACGGTAAGGTCATCATGGAGGTCCG 1500
Qy 1501 AATAGTTTGAAATTAGAAAGCTCGCAATTGAGGTCTACAGGCCAAATTCGCTCTTAGCCG 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 AATAGTTTGAAATTAGAAAGCTCGCAATTGAGGTCTACAGGCCAAATTCGCTCTTAGCCG 1560
Qy 1561 TACAATATTACTCACCGGATCCTAACCGGTGTGATCATGGGCCGCGATTAAAAATCTCAA 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 TACAATATTACTCACCGGATCCTAACCGGTGTGATCATGGGCCGCGATTAAAAATCTCAA 1620
Qy 1621 TTATATTTGGTCTAATTTAGTTTGGTATTGAGTAAAACAAATTCGAACCAAACCAAAATA 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 TTATATTTGGTCTAATTTAGTTTGGTATTGAGTAAAACAAATTCGAACCAAACCAAAATA 1680
Qy 1681 TAAATATATAGTTTTTATATATATGCCTTTAAGACTTTTTATAGAATTTTCTTTAAAAAA 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 TAAATATATAGTTTTTATATATATGCCTTTAAGACTTTTTATAGAATTTTCTTTAAAAAA 1740
Qy 1741 TATCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATATGAAGTGCTCC 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 TATCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATATGAAGTGCTCC 1800
Qy 1801 ATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTATCAAGTGTTACTAAAA 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 ATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTATCAAGTGTTACTAAAA 1860
Qy 1861 TGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAACCTATCAAAATTCTTATATA 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1861 TGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAACCTATCAAAATTCTTATATA 1920
Qy 1921 TCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAAAATTAAATAGAACATATCATTAT 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1921 TCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAAAATTAAATAGAACATATCATTAT 1980
Qy 1981 TTAGGTATCATATTGATTTTTATACTTAATTACTAAATTTGGTTAACTTTGAAAGTGTAC 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1981 TTAGGTATCATATTGATTTTTATACTTAATTACTAAATTTGGTTAACTTTGAAAGTGTAC 2040
Qy 2041 ATCAACGAAAAATTAGTCAAACGACTAAAATAAATAAATATCATGTGTTATTAAGAAAAT 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2041 ATCAACGAAAAATTAGTCAAACGACTAAAATAAATAAATATCATGTGTTATTAAGAAAAT 2100
Qy 2101 TCTCCTATAAGAATATTTTAATAGATCATATGTTTGTAAAAAAAATTAATTTTTACTAAC 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2101 TCTCCTATAAGAATATTTTAATAGATCATATGTTTGTAAAAAAAATTAATTTTTACTAAC 2160
Qy 2161 ACATATATTTACTTATCAAAAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAA 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2161 ACATATATTTACTTATCAAAAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAA 2220
Qy 2221 AAAAAAAACCAGAAAATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGT 2280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2221 AAAAAAAACCAGAAAATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGT 2280
Qy 2281 TGGTTTGGTTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCAT 2340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2281 TGGTTTGGTTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCAT 2340
Qy 2341 AATAGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTTG 2400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2341 AATAGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTTG 2400
Qy 2401 CAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGTGGTGGT 2460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2401 CAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGTGGTGGT 2460
Qy 2461 AATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATTTCTGCTAGGAA 2520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2461 AATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATTTCTGCTAGGAA 2520
Qy 2521 GAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAATGAACCATAAAGTGATTGAAGC 2580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2521 GAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAATGAACCATAAAGTGATTGAAGC 2580
Qy 2581 TCGAAATATACGAAGGAACAAATATTTTTAAAAAAATACGCAATGACTTGGAACAAAAGA 2640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2581 TCGAAATATACGAAGGAACAAATATTTTTAAAAAAATACGCAATGACTTGGAACAAAAGA 2640
Qy 2641 AAGTGATATATTTTTTGTTCTTAAACAAGCATCCCCTCTAAAGAATGGCAGTTTTCCTTT 2700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2641 AAGTGATATATTTTTTGTTCTTAAACAAGCATCCCCTCTAAAGAATGGCAGTTTTCCTTT 2700
Qy 2701 GCATGTAACTATTATGCTCCCTTCGTTACAAAAATTTTGGACTACTATTGGGAACTTCTT 2760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2701 GCATGTAACTATTATGCTCCCTTCGTTACAAAAATTTTGGACTACTATTGGGAACTTCTT 2760
Qy 2761 CTGAAAATAGTGGCCACCGCTTAATTAAGGCGCGCCGACGAATGTCCCCGATCAAATCTG 2820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2761 CTGAAAATAGTGGCCACCGCTTAATTAAGGCGCGCCGACGAATGTCCCCGATCAAATCTG 2820
Qy 2821 AGGGACGTTAAAGCGATGATAAATTGGAACCAGAATATAGAATCTTTGTTCTGCTCTAGC 2880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2821 AGGGACGTTAAAGCGATGATAAATTGGAACCAGAATATAGAATCTTTGTTCTGCTCTAGC 2880
Qy 2881 TTTTCTTCTGTACATTTTTTACGATTAGACTATGATTTTCATTCAATAACCAAAATTCTG 2940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2881 TTTTCTTCTGTACATTTTTTACGATTAGACTATGATTTTCATTCAATAACCAAAATTCTG 2940
Qy 2941 AAGTTTGTCATCAAGTTGCTCAATCAAACTTGTACCGGTTTGTTTCGGTTTTATATCAGC 3000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2941 AAGTTTGTCATCAAGTTGCTCAATCAAACTTGTACCGGTTTGTTTCGGTTTTATATCAGC 3000
Qy 3001 TCACTGTTACACTTTAACCAAAATCGGTTTATGTCTTAATAAAGGAATTGAGTCGGTTTA 3060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3001 TCACTGTTACACTTTAACCAAAATCGGTTTATGTCTTAATAAAGGAATTGAGTCGGTTTA 3060
Qy 3061 ACTCATATCCGTACCAATGCGACGTCGTGTCCGCGTTTCAGTAGCTTTGCTCATTGTCTT 3120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3061 ACTCATATCCGTACCAATGCGACGTCGTGTCCGCGTTTCAGTAGCTTTGCTCATTGTCTT 3120
Qy 3121 CTACGGGAACTTTCCCGGACATAGGAACCGCCCTTTCGTTATCCTCATCCATCGTGAAAT 3180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3121 CTACGGGAACTTTCCCGGACATAGGAACCGCCCTTTCGTTATCCTCATCCATCGTGAAAT 3180
Qy 3181 CAGGAAATAAATGTTCGAAGATTTGAGGTCAAAAGTCGAATTTCATGTTGTCTCTTCTAT 3240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3181 CAGGAAATAAATGTTCGAAGATTTGAGGTCAAAAGTCGAATTTCATGTTGTCTCTTCTAT 3240
Qy 3241 TTAGATACAAAATTGAAGCAATTTTCACCAATTTAATGCCAAAATTTAAAACAACGCTGA 3300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3241 TTAGATACAAAATTGAAGCAATTTTCACCAATTTAATGCCAAAATTTAAAACAACGCTGA 3300
Qy 3301 TAAAGTGAAACTTGATTCGATTTATATTTCAACCGAAACTGCTGAAGCAAGAAGAAAAAG 3360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3301 TAAAGTGAAACTTGATTCGATTTATATTTCAACCGAAACTGCTGAAGCAAGAAGAAAAAG 3360
Qy 3361 CGTAATTACACATAACAAGAACGCTACCGCAAACTACTAAACGCCAAACCCAATACAAAA 3420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3361 CGTAATTACACATAACAAGAACGCTACCGCAAACTACTAAACGCCAAACCCAATACAAAA 3420
Qy 3421 GTAAAACGCAGACGCTTAAGTGAGAAACCCAGAAAACACAAACGCGGATCGGGGGATCCA 3480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3421 GTAAAACGCAGACGCTTAAGTGAGAAACCCAGAAAACACAAACGCGGATCGGGGGATCCA 3480
Qy 3481 CTAGTTCTAGAGCTTAATTCTTGACGAAAGTGCTCAGCACATCGAAGTAGTCGGGGAAGG 3540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3481 CTAGTTCTAGAGCTTAATTCTTGACGAAAGTGCTCAGCACATCGAAGTAGTCGGGGAAGG 3540
Qy 3541 TCTTCCGGGTGCACCCAGGGTCCCGGATGGTGACGGGGACCTCGGCACAGGCGGCAAGGG 3600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3541 TCTTCCGGGTGCACCCAGGGTCCCGGATGGTGACGGGGACCTCGGCACAGGCGGCAAGGG 3600
Qy 3601 AGAAAGCCATCGCCATCCTGTGGTCGTCGTACGTGTCGATCGCCGTCACGTTCAGCTTCT 3660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3601 AGAAAGCCATCGCCATCCTGTGGTCGTCGTACGTGTCGATCGCCGTCACGTTCAGCTTCT 3660
Qy 3661 CCGGCGGCGTGATGATGCAGTAGTCCGGCCCTTCCTCAACAGATGCTCCCAGCTTGGTTA 3720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3661 CCGGCGGCGTGATGATGCAGTAGTCCGGCCCTTCCTCAACAGATGCTCCCAGCTTGGTTA 3720
Qy 3721 GCTCCGTCCGGATCGCAACCATCCTCTCGGTCTCCTTTACTCTCCAGGAAGCCACGTCTC 3780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3721 GCTCCGTCCGGATCGCAACCATCCTCTCGGTCTCCTTTACTCTCCAGGAAGCCACGTCTC 3780
Qy 3781 TGATGGCTGTCGGGCCATCGGCAAAGAGGGCAACCACAGCAAGAGTCATGGCGACATCAG 3840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3781 TGATGGCTGTCGGGCCATCGGCAAAGAGGGCAACCACAGCAAGAGTCATGGCGACATCAG 3840
Qy 3841 GCATCTTGTTCATGTTGACATCAATCGCCTTGAGGTGTTTCCTCCCAAATGGCTCCCGCG 3900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3841 GCATCTTGTTCATGTTGACATCAATCGCCTTGAGGTGTTTCCTCCCAAATGGCTCCCGCG 3900
Qy 3901 GTGGGCCAGTAACAGTTACGCTAGTCTCGGTCCATGTAACCTTCGCTCCCATCATCTCCA 3960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3901 GTGGGCCAGTAACAGTTACGCTAGTCTCGGTCCATGTAACCTTCGCTCCCATCATCTCCA 3960
Qy 3961 GTACCTCAGCAAACTTCACATCACCCTGCAAACTGGTGGTGCCACAACCTTCCACAGTCA 4020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3961 GTACCTCAGCAAACTTCACATCACCCTGCAAACTGGTGGTGCCACAACCTTCCACAGTCA 4020
Qy 4021 CAGTCCCTCCAGTAATTGCAGCACCAGCCAAGAAATAGCTTGCGCTTGAGGCATCACCTT 4080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4021 CAGTCCCTCCAGTAATTGCAGCACCAGCCAAGAAATAGCTTGCGCTTGAGGCATCACCTT 4080
Qy 4081 CAACATAGGCATTTTTAGGGGACTTGTATTTTTGACCTCCCTTAATGTAGAATCTGTCCC 4140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4081 CAACATAGGCATTTTTAGGGGACTTGTATTTTTGACCTCCCTTAATGTAGAATCTGTCCC 4140
Qy 4141 AGCTATCAGAATGCTCTGCTTTCACACCAAAACGCTCCATCAATCTCAATGTCATTTCGA 4200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4141 AGCTATCAGAATGCTCTGCTTTCACACCAAAACGCTCCATCAATCTCAATGTCATTTCGA 4200
Qy 4201 CGTACGGAATGGAGATTAATTTATCAATGATTTCAATCTCCACATCCCCAAGAGCCAAAG 4260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4201 CGTACGGAATGGAGATTAATTTATCAATGATTTCAATCTCCACATCCCCAAGAGCCAAAG 4260
Qy 4261 GAGCAGCCATCAGCAAGGCACTCAAGTACTGACTGCTGATGGAGCCAGACAGCTTGACCT 4320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4261 GAGCAGCCATCAGCAAGGCACTCAAGTACTGACTGCTGATGGAGCCAGACAGCTTGACCT 4320
Qy 4321 TGCCACCAGGTAGCCCTCCGATTCCATTGACACGAACAGGTGGGCAGTCAGTGCCAAGGA 4380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4321 TGCCACCAGGTAGCCCTCCGATTCCATTGACACGAACAGGTGGGCAGTCAGTGCCAAGGA 4380
Qy 4381 AACAATCAACATCTGCACCAAGCTGCTTCAATCCGACAACCAAGTCGCCAATGGGTCTCT 4440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4381 AACAATCAACATCTGCACCAAGCTGCTTCAATCCGACAACCAAGTCGCCAATGGGTCTCT 4440
Qy 4441 CCCTCATTCTTGGTACTCCATCAAGCACGTAAGTTGCATTTCCACCAGCAGCAGTAACAG 4500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4441 CCCTCATTCTTGGTACTCCATCAAGCACGTAAGTTGCATTTCCACCAGCAGCAGTAACAG 4500
Qy 4501 CTGCTGTCAAGGACCGCATTGCGATTCCAGCATTCCCCAAGAAGAGCTGCACTTCCTCTT 4560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4501 CTGCTGTCAAGGACCGCATTGCGATTCCAGCATTCCCCAAGAAGAGCTGCACTTCCTCTT 4560
Qy 4561 TAGCATCCTCAACTGGGAACTTTCCACCACAGCCAACAACTACAGCTCTTTTGGCAGCTT 4620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4561 TAGCATCCTCAACTGGGAACTTTCCACCACAGCCAACAACTACAGCTCTTTTGGCAGCTT 4620
Qy 4621 TGTCCGCTTCGACAGAGAGACCAAGAGTCCTCAAGGCCCCGAGCATGTAGTGGACATCCT 4680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4621 TGTCCGCTTCGACAGAGAGACCAAGAGTCCTCAAGGCCCCGAGCATGTAGTGGACATCCT 4680
Qy 4681 CACTGTTCAGCAGGTTATCAACCACTGTTGTCCCCTCGGACAGGGCGGCGAGTAGGAGGA 4740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4681 CACTGTTCAGCAGGTTATCAACCACTGTTGTCCCCTCGGACAGGGCGGCGAGTAGGAGGA 4740
Qy 4741 TCCGGTTGGAAAGCGACTTGGACCCCGGCAGCTTGACGGTGCCGGAGATCTCCTTGATGG 4800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4741 TCCGGTTGGAAAGCGACTTGGACCCCGGCAGCTTGACGGTGCCGGAGATCTCCTTGATGG 4800
Qy 4801 GCTGCAGCACGATCTCCTCGGCGCCGGCCATGCACCGGATCCTTCCGCCGTTGCTGACGT 4860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4801 GCTGCAGCACGATCTCCTCGGCGCCGGCCATGCACCGGATCCTTCCGCCGTTGCTGACGT 4860
Qy 4861 TGCCGAGGCTTCTGGAGGAGCGGCGGGCGACGGGGAGGCTGGCGGTGGACTTGAGCCCCT 4920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4861 TGCCGAGGCTTCTGGAGGAGCGGCGGGCGACGGGGAGGCTGGCGGTGGACTTGAGCCCCT 4920
Qy 4921 GGAACGGAGCGACGGCGGTGGCCGACGAGGCCATCATCACGGTGGGCGCCATAGACAGCG 4980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4921 GGAACGGAGCGACGGCGGTGGCCGACGAGGCCATCATCACGGTGGGCGCCATAGACAGCG 4980
Qy 4981 GCGGCAGGTACGACAGCGTCTCGAACTTCTTGTTGCCGTAGGCCGGCCACACCTGCATAC 5040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4981 GCGGCAGGTACGACAGCGTCTCGAACTTCTTGTTGCCGTAGGCCGGCCACACCTGCATAC 5040
Qy 5041 ATTGAACTCTTCCACCGTTGCTGGGAAGGGTGGAGAAGTCGTTAGCCTTCTTGGTGGTGG 5100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5041 ATTGAACTCTTCCACCGTTGCTGGGAAGGGTGGAGAAGTCGTTAGCCTTCTTGGTGGTGG 5100
Qy 5101 GGAAGGCGGCGTTGGACTTAAGGCCGGTGAACGGAGCCACCATGTTGGCCTGAGCAGGGG 5160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5101 GGAAGGCGGCGTTGGACTTAAGGCCGGTGAACGGAGCCACCATGTTGGCCTGAGCAGGGG 5160
Qy 5161 CGGTCCGGCTAACGGTCGCGACTGAGGAGGAGATCGAAGCCATGGGGATCTGCGCATTTA 5220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5161 CGGTCCGGCTAACGGTCGCGACTGAGGAGGAGATCGAAGCCATGGGGATCTGCGCATTTA 5220
Qy 5221 ACAAGAAATTGAACAGTCAATTGGGGATTTTCATTATCCATAACTAAATTTTGAAGAAAT 5280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5221 ACAAGAAATTGAACAGTCAATTGGGGATTTTCATTATCCATAACTAAATTTTGAAGAAAT 5280
Qy 5281 TGGAATACTAAACGTCACCACTTAAAACCCTAATCCAGATGAATCGTTATCGAACCAGAT 5340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5281 TGGAATACTAAACGTCACCACTTAAAACCCTAATCCAGATGAATCGTTATCGAACCAGAT 5340
Qy 5341 ATAACCAAAAGGGGCAAAATTGACTCGAAAACCCTAGTTCTCGATACACGGCTAGGTAAT 5400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5341 ATAACCAAAAGGGGCAAAATTGACTCGAAAACCCTAGTTCTCGATACACGGCTAGGTAAT 5400
Qy 5401 GACAATCGCACACAGACAAATCTGGTTATACAGAACTTCGAAGCAAGAAAAAAACGATGA 5460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5401 GACAATCGCACACAGACAAATCTGGTTATACAGAACTTCGAAGCAAGAAAAAAACGATGA 5460
Qy 5461 AGAATGGATCATCCAATAAATCGACTAGACTCAATCTTCACAGGTTTATCGATCCAGCAA 5520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5461 AGAATGGATCATCCAATAAATCGACTAGACTCAATCTTCACAGGTTTATCGATCCAGCAA 5520
Qy 5521 ACTTAAAAGACGGACCTTTATTTTCAAACTGGAATGGGACAAAACCCGAAACTCTATTGT 5580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5521 ACTTAAAAGACGGACCTTTATTTTCAAACTGGAATGGGACAAAACCCGAAACTCTATTGT 5580
Qy 5581 CGTAAAATCAGATCGCGGAGACAGTAACAGAAAAAACATTAAAAAGTAATGGAAAGACCT 5640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5581 CGTAAAATCAGATCGCGGAGACAGTAACAGAAAAAACATTAAAAAGTAATGGAAAGACCT 5640
Qy 5641 AAACCCCTGATCTAATTACAAACAAATCATACCTGTTCTTCGCCTGAGGGGTTCGAAATC 5700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5641 AAACCCCTGATCTAATTACAAACAAATCATACCTGTTCTTCGCCTGAGGGGTTCGAAATC 5700
Qy 5701 GATAAGCTTGGATCCTCTAGAGTCGAGAGAAATTGATGTCTGTAGAAGAAGAAGAACGGT 5760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5701 GATAAGCTTGGATCCTCTAGAGTCGAGAGAAATTGATGTCTGTAGAAGAAGAAGAACGGT 5760
Qy 5761 TAAGAGTAGATTTGGGTGAGAAAGATGTGAAATTGTTTTTATAGGCAAAGACGGAGAGTC 5820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5761 TAAGAGTAGATTTGGGTGAGAAAGATGTGAAATTGTTTTTATAGGCAAAGACGGAGAGTC 5820
Qy 5821 TATTTTTTGAGCAATCAGATCGCATATTAAATCTAACGGCTGAGATATCGATCCGTGTGT 5880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5821 TATTTTTTGAGCAATCAGATCGCATATTAAATCTAACGGCTGAGATATCGATCCGTGTGT 5880
Qy 5881 ACAATAAAATGATGTATAAACCGTCGATCTGTTTTAATCGACGGTTCATATTAGTGATCC 5940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5881 ACAATAAAATGATGTATAAACCGTCGATCTGTTTTAATCGACGGTTCATATTAGTGATCC 5940
Qy 5941 GCGTGATGGCAGTGATAGCCACTAAGAATCGTCTTTTGTTTTACATGTGGCGCCACAAAT 6000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5941 GCGTGATGGCAGTGATAGCCACTAAGAATCGTCTTTTGTTTTACATGTGGCGCCACAAAT 6000
Qy 6001 TAGGGTAATGAAGCGGCAATATTTTGGAACTCGGAAAATAAAATTGCGCCATCACATTAT 6060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6001 TAGGGTAATGAAGCGGCAATATTTTGGAACTCGGAAAATAAAATTGCGCCATCACATTAT 6060
Qy 6061 TTGAAAATTTTCACATGCTTTTATTTTAAAAACCCACGAATTACAAGTTACAACCGAAAA 6120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6061 TTGAAAATTTTCACATGCTTTTATTTTAAAAACCCACGAATTACAAGTTACAACCGAAAA 6120
Qy 6121 AGATTTATAATATAGTGATTTATACTAATTTTGTAGTAGCTTAATGTATATTGATACTGG 6180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6121 AGATTTATAATATAGTGATTTATACTAATTTTGTAGTAGCTTAATGTATATTGATACTGG 6180
Qy 6181 AAAAACAATGACAATCATATGTTAGTATTATCAAGTTATCGTATTGATATTGATATTGGA 6240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6181 AAAAACAATGACAATCATATGTTAGTATTATCAAGTTATCGTATTGATATTGATATTGGA 6240
Qy 6241 ACATACAATGGGTATTGCCTTCTTTCGACCATAAATATCACCAAATTTACAAAGTTTGTG 6300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6241 ACATACAATGGGTATTGCCTTCTTTCGACCATAAATATCACCAAATTTACAAAGTTTGTG 6300
Qy 6301 TATACCAAGTTATCAATTGTAAATGGGATGTCAACATTTTAATTTCCCTTTGAGAAACTA 6360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6301 TATACCAAGTTATCAATTGTAAATGGGATGTCAACATTTTAATTTCCCTTTGAGAAACTA 6360
Qy 6361 TAGACCACAAGAACACACTTCAATAGATAAAGTAACTATTTACATAAGAGGTTTTAAAAT 6420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6361 TAGACCACAAGAACACACTTCAATAGATAAAGTAACTATTTACATAAGAGGTTTTAAAAT 6420
Qy 6421 CACATTAACAAAAATAATTACCAACCGGCACTCACAAATACAAACAGAGCACACGACATG 6480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6421 CACATTAACAAAAATAATTACCAACCGGCACTCACAAATACAAACAGAGCACACGACATG 6480
Qy 6481 TCAAAGCCACAAGTAAATTCGTTGAGTGGTGGTTTCATTACAATTGTGTCACTTGCAGCA 6540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6481 TCAAAGCCACAAGTAAATTCGTTGAGTGGTGGTTTCATTACAATTGTGTCACTTGCAGCA 6540
Qy 6541 CAAACTATCTTGCTCTGGGAATCATCTCAGCATCAAAGATCATGCTCACTTCAGGGGAAC 6600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6541 CAAACTATCTTGCTCTGGGAATCATCTCAGCATCAAAGATCATGCTCACTTCAGGGGAAC 6600
Qy 6601 TTAGTGTATCCATGCCTCGACTCATATTTCTCCTCGACATGCATCCTGCAGGGGCGCGCC 6660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6601 TTAGTGTATCCATGCCTCGACTCATATTTCTCCTCGACATGCATCCTGCAGGGGCGCGCC 6660
Qy 6661 ATGCCCGGGCAAGCGGCCGCACAAGTTTGTACAAAAAAGCAGGCTCCGCGGTGACTGACT 6720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6661 ATGCCCGGGCAAGCGGCCGCACAAGTTTGTACAAAAAAGCAGGCTCCGCGGTGACTGACT 6720
Qy 6721 GAAAAGCTTGTCGACCTGCAGGTCAACGGATCAGGATATTCTTGTTTAAGATGTTGAACT 6780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6721 GAAAAGCTTGTCGACCTGCAGGTCAACGGATCAGGATATTCTTGTTTAAGATGTTGAACT 6780
Qy 6781 CTATGGAGGTTTGTATGAACTGATGATCTAGGACCGGATAAGTTCCCTTCTTCATAGCGA 6840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6781 CTATGGAGGTTTGTATGAACTGATGATCTAGGACCGGATAAGTTCCCTTCTTCATAGCGA 6840
Qy 6841 ACTTATTCAAAGAATGTTTTGTGTATCATTCTTGTTACATTGTTATTAATGAAAAAATAT 6900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6841 ACTTATTCAAAGAATGTTTTGTGTATCATTCTTGTTACATTGTTATTAATGAAAAAATAT 6900
Qy 6901 TATTGGTCATTGGACTGAACACGAGTGTTAAATATGGACCAGGCCCCAAATAAGATCCAT 6960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6901 TATTGGTCATTGGACTGAACACGAGTGTTAAATATGGACCAGGCCCCAAATAAGATCCAT 6960
Qy 6961 TGATATATGAATTAAATAACAAGAATAAATCGAGTCACCAAACCACTTGCCTTTTTTAAC 7020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6961 TGATATATGAATTAAATAACAAGAATAAATCGAGTCACCAAACCACTTGCCTTTTTTAAC 7020
Qy 7021 GAGACTTGTTCACCAACTTGATACAAAAGTCATTATCCTATGCAAATCAATAATCATACA 7080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7021 GAGACTTGTTCACCAACTTGATACAAAAGTCATTATCCTATGCAAATCAATAATCATACA 7080
Qy 7081 AAAATATCCAATAACACTAAAAAATTAAAAGAAATGGATAATTTCACAATATGTTATACG 7140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7081 AAAATATCCAATAACACTAAAAAATTAAAAGAAATGGATAATTTCACAATATGTTATACG 7140
Qy 7141 ATAAAGAAGTTACTTTTCCAAGAAATTCACTGATTTTATAAGCCCACTTGCATTAGATAA 7200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7141 ATAAAGAAGTTACTTTTCCAAGAAATTCACTGATTTTATAAGCCCACTTGCATTAGATAA 7200
Qy 7201 ATGGCAAAAAAAAACAAAAAGGAAAAGAAATAAAGCACGAAGAATTCTAGAAAATACGAA 7260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7201 ATGGCAAAAAAAAACAAAAAGGAAAAGAAATAAAGCACGAAGAATTCTAGAAAATACGAA 7260
Qy 7261 ATACGCTTCAATGCAGTGGGACCCACGGTTCAATTATTGCCAATTTTCAGCTCCACCGTA 7320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7261 ATACGCTTCAATGCAGTGGGACCCACGGTTCAATTATTGCCAATTTTCAGCTCCACCGTA 7320
Qy 7321 TATTTAAAAAATAAAACGATAATGCTAAAAAAATATAAATCGTAACGATCGTTAAATCTC 7380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7321 TATTTAAAAAATAAAACGATAATGCTAAAAAAATATAAATCGTAACGATCGTTAAATCTC 7380
Qy 7381 AACGGCTGGATCTTATGACGACCGTTAGAAATTGTGGTTGTCGACGAGTCAGTAATAAAC 7440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7381 AACGGCTGGATCTTATGACGACCGTTAGAAATTGTGGTTGTCGACGAGTCAGTAATAAAC 7440
Qy 7441 GGCGTCAAAGTGGTTGCAGCCGGCACACACGAGTCGTGTTTATCAACTCAAAGCACAAAT 7500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7441 GGCGTCAAAGTGGTTGCAGCCGGCACACACGAGTCGTGTTTATCAACTCAAAGCACAAAT 7500
Qy 7501 ACTTTTCCTCAACCTAAAAATAAGGCAATTAGCCAAAAACAACTTTGCGTGTAAACAACG 7560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7501 ACTTTTCCTCAACCTAAAAATAAGGCAATTAGCCAAAAACAACTTTGCGTGTAAACAACG 7560
Qy 7561 CTCAATACACGTGTCATTTTATTATTAGCTATTGCTTCACCGCCTTAGCTTTCTCGTGAC 7620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7561 CTCAATACACGTGTCATTTTATTATTAGCTATTGCTTCACCGCCTTAGCTTTCTCGTGAC 7620
Qy 7621 CTAGTCGTCCTCGTCTTTTCTTCTTCTTCTTCTATAAAACAATACCCAAAGCTTCTTCTT 7680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7621 CTAGTCGTCCTCGTCTTTTCTTCTTCTTCTTCTATAAAACAATACCCAAAGCTTCTTCTT 7680
Qy 7681 CACAATTCAGATTTCAATTTCTCAAAATCTTAAAAACTTTCTCTCAATTCTCTCTACCGT 7740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7681 CACAATTCAGATTTCAATTTCTCAAAATCTTAAAAACTTTCTCTCAATTCTCTCTACCGT 7740
Qy 7741 GATCAAGGTAAATTTCTGTGTTCCTTATTCTCTCAAAATCTTCGATTTTGTTTTCGTTCG 7800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7741 GATCAAGGTAAATTTCTGTGTTCCTTATTCTCTCAAAATCTTCGATTTTGTTTTCGTTCG 7800
Qy 7801 ATCCCAATTTCGTATATGTTCTTTGGTTTAGATTCTGTTAATCTTAGATCGAAGACGATT 7860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7801 ATCCCAATTTCGTATATGTTCTTTGGTTTAGATTCTGTTAATCTTAGATCGAAGACGATT 7860
Qy 7861 TTCTGGGTTTGATCGTTAGATATCATCTTAATTCTCGATTAGGGTTTCATAAATATCATC 7920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7861 TTCTGGGTTTGATCGTTAGATATCATCTTAATTCTCGATTAGGGTTTCATAAATATCATC 7920
Qy 7921 CGATTTGTTCAAATAATTTGAGTTTTGTCGAATAATTACTCTTCGATTTGTGATTTCTAT 7980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7921 CGATTTGTTCAAATAATTTGAGTTTTGTCGAATAATTACTCTTCGATTTGTGATTTCTAT 7980
Qy 7981 CTAGATCTGGTGTTAGTTTCTAGTTTGTGCGATCGAATTTGTCGATTAATCTGAGTTTTT 8040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 7981 CTAGATCTGGTGTTAGTTTCTAGTTTGTGCGATCGAATTTGTCGATTAATCTGAGTTTTT 8040
Qy 8041 CTGATTAACAGAGATCTCCATGGCTCAGACCACTCTCCAAATCACACCCACTGGTGCCAC 8100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8041 CTGATTAACAGAGATCTCCATGGCTCAGACCACTCTCCAAATCACACCCACTGGTGCCAC 8100
Qy 8101 CTTGGGTGCCACAGTCACTGGTGTTCACCTTGCCACACTTGACGATGCTGGTTTCGCTGC 8160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8101 CTTGGGTGCCACAGTCACTGGTGTTCACCTTGCCACACTTGACGATGCTGGTTTCGCTGC 8160
Qy 8161 CCTCCATGCAGCCTGGCTTCAACATGCACTCTTGATCTTCCCTGGGCAACACCTCAGCAA 8220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8161 CCTCCATGCAGCCTGGCTTCAACATGCACTCTTGATCTTCCCTGGGCAACACCTCAGCAA 8220
Qy 8221 TGACCAACAGATTACCTTTGCTAAACGCTTTGGAGCAATTGAGAGGATTGGCGGAGGTGA 8280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8221 TGACCAACAGATTACCTTTGCTAAACGCTTTGGAGCAATTGAGAGGATTGGCGGAGGTGA 8280
Qy 8281 CATTGTTGCCATATCCAATGTCAAGGCAGATGGCACAGTGCGCCAGCACTCTCCTGCTGA 8340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8281 CATTGTTGCCATATCCAATGTCAAGGCAGATGGCACAGTGCGCCAGCACTCTCCTGCTGA 8340
Qy 8341 GTGGGATGACATGATGAAGGTCATTGTGGGCAACATGGCCTGGCACGCCGACTCAACCTA 8400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8341 GTGGGATGACATGATGAAGGTCATTGTGGGCAACATGGCCTGGCACGCCGACTCAACCTA 8400
Qy 8401 CATGCCAGTCATGGCTCAAGGAGCTGTGTTCAGCGCAGAAGTTGTCCCAGCAGTTGGGGG 8460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8401 CATGCCAGTCATGGCTCAAGGAGCTGTGTTCAGCGCAGAAGTTGTCCCAGCAGTTGGGGG 8460
Qy 8461 CAGAACCTGCTTTGCTGACATGAGGGCAGCCTACGATGCCCTTGATGAGGCAACCCGTGC 8520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8461 CAGAACCTGCTTTGCTGACATGAGGGCAGCCTACGATGCCCTTGATGAGGCAACCCGTGC 8520
Qy 8521 TCTTGTTCACCAAAGGTCTGCTCGTCACTCCCTTGTGTATTCTCAGAGCAAGTTGGGACA 8580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8521 TCTTGTTCACCAAAGGTCTGCTCGTCACTCCCTTGTGTATTCTCAGAGCAAGTTGGGACA 8580
Qy 8581 TGTCCAACAGGCCGGGTCAGCCTACATAGGTTATGGCATGGACACCACTGCAACTCCTCT 8640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8581 TGTCCAACAGGCCGGGTCAGCCTACATAGGTTATGGCATGGACACCACTGCAACTCCTCT 8640
Qy 8641 CAGACCATTGGTCAAGGTGCATCCTGAGACTGGAAGGCCCAGCCTCTTGATCGGCCGCCA 8700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8641 CAGACCATTGGTCAAGGTGCATCCTGAGACTGGAAGGCCCAGCCTCTTGATCGGCCGCCA 8700
Qy 8701 TGCCCATGCCATCCCTGGCATGGATGCAGCTGAATCAGAGCGCTTCCTTGAAGGACTTGT 8760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8701 TGCCCATGCCATCCCTGGCATGGATGCAGCTGAATCAGAGCGCTTCCTTGAAGGACTTGT 8760
Qy 8761 TGACTGGGCCTGCCAGGCTCCCAGAGTCCATGCTCACCAATGGGCTGCTGGAGATGTGGT 8820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8761 TGACTGGGCCTGCCAGGCTCCCAGAGTCCATGCTCACCAATGGGCTGCTGGAGATGTGGT 8820
Qy 8821 TGTGTGGGACAACCGCTGTTTGCTCCACCGTGCTGAGCCCTGGGATTTCAAGTTGCCACG 8880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8821 TGTGTGGGACAACCGCTGTTTGCTCCACCGTGCTGAGCCCTGGGATTTCAAGTTGCCACG 8880
Qy 8881 TGTGATGTGGCACTCCAGACTCGCTGGACGCCCAGAAACTGAGGGTGCTGCCTTGGTTTG 8940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8881 TGTGATGTGGCACTCCAGACTCGCTGGACGCCCAGAAACTGAGGGTGCTGCCTTGGTTTG 8940
Qy 8941 AGTAGTTAGCTTAATCACCTAGAGCTCGGTCACCAGCATAATTTTTATTAATGTACTAAA 9000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 8941 AGTAGTTAGCTTAATCACCTAGAGCTCGGTCACCAGCATAATTTTTATTAATGTACTAAA 9000
Qy 9001 TTACTGTTTTGTTAAATGCAATTTTGCTTTCTCGGGATTTTAATATCAAAATCTATTTAG 9060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9001 TTACTGTTTTGTTAAATGCAATTTTGCTTTCTCGGGATTTTAATATCAAAATCTATTTAG 9060
Qy 9061 AAATACACAATATTTTGTTGCAGGCTTGCTGGAGAATCGATCTGCTATCATAAAAATTAC 9120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9061 AAATACACAATATTTTGTTGCAGGCTTGCTGGAGAATCGATCTGCTATCATAAAAATTAC 9120
Qy 9121 AAAAAAATTTTATTTGCCTCAATTATTTTAGGATTGGTATTAAGGACGCTTAAATTATTT 9180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9121 AAAAAAATTTTATTTGCCTCAATTATTTTAGGATTGGTATTAAGGACGCTTAAATTATTT 9180
Qy 9181 GTCGGGTCACTACGCATCATTGTGATTGAGAAGATCAGCGATACGAAATATTCGTAGTAC 9240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9181 GTCGGGTCACTACGCATCATTGTGATTGAGAAGATCAGCGATACGAAATATTCGTAGTAC 9240
Qy 9241 TATCGATAATTTATTTGAAAATTCATAAGAAAAGCAAACGTTACATGAATTGATGAAACA 9300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9241 TATCGATAATTTATTTGAAAATTCATAAGAAAAGCAAACGTTACATGAATTGATGAAACA 9300
Qy 9301 ATACAAAGACAGATAAAGCCACGCACATTTAGGATATTGGCCGAGATTACTGAATATTGA 9360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9301 ATACAAAGACAGATAAAGCCACGCACATTTAGGATATTGGCCGAGATTACTGAATATTGA 9360
Qy 9361 GTAAGATCACGGAATTTCTGACAGGAGCATGTCTTCAATTCAGCCCAAATGGCAGTTGAA 9420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9361 GTAAGATCACGGAATTTCTGACAGGAGCATGTCTTCAATTCAGCCCAAATGGCAGTTGAA 9420
Qy 9421 ATACTCAAACCGCCCCATATGCAGGAGCGGATCATTCATTGTTTGTTTGGTTGCCTTTGC 9480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9421 ATACTCAAACCGCCCCATATGCAGGAGCGGATCATTCATTGTTTGTTTGGTTGCCTTTGC 9480
Qy 9481 CAACATGGGAGTCCAAGGTTGCGGCCGCGCGCCGACCCAGCTTTCTTGTACAAAGTGGTT 9540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9481 CAACATGGGAGTCCAAGGTTGCGGCCGCGCGCCGACCCAGCTTTCTTGTACAAAGTGGTT 9540
Qy 9541 GCGGCCGCTTAATTAAATTTAAATGCCCGGGCGTTTAAACGCGGCCGCTTAATTAAGGCC 9600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9541 GCGGCCGCTTAATTAAATTTAAATGCCCGGGCGTTTAAACGCGGCCGCTTAATTAAGGCC 9600
Qy 9601 GGCCTGCAGCAAACCCAGAAGGTAATTATCCAAGATGTAGCATCAAGAATCCAATGTTTA 9660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9601 GGCCTGCAGCAAACCCAGAAGGTAATTATCCAAGATGTAGCATCAAGAATCCAATGTTTA 9660
Qy 9661 CGGGAAAAACTATGGAAGTATTATGTAAGCTCAGCAAGAAGCAGATCAATATGCGGCACA 9720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9661 CGGGAAAAACTATGGAAGTATTATGTAAGCTCAGCAAGAAGCAGATCAATATGCGGCACA 9720
Qy 9721 TATGCAACCTATGTTCAAAAATGAAGAATGTACAGATACAAGATCCTATACTGCCAGAAT 9780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9721 TATGCAACCTATGTTCAAAAATGAAGAATGTACAGATACAAGATCCTATACTGCCAGAAT 9780
Qy 9781 ACGAAGAAGAATACGTAGAAATTGAAAAAGAAGAACCAGGCGAAGAAAAGAATCTTGAAG 9840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9781 ACGAAGAAGAATACGTAGAAATTGAAAAAGAAGAACCAGGCGAAGAAAAGAATCTTGAAG 9840
Qy 9841 ACGTAAGCACTGACGACAACAATGAAAAGAAGAAGATAAGGTCGGTGATTGTGAAAGAGA 9900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9841 ACGTAAGCACTGACGACAACAATGAAAAGAAGAAGATAAGGTCGGTGATTGTGAAAGAGA 9900
Qy 9901 CATAGAGGACACATGTAAGGTGGAAAATGTAAGGGCGGAAAGTAACCTTATCACAAAGGA 9960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9901 CATAGAGGACACATGTAAGGTGGAAAATGTAAGGGCGGAAAGTAACCTTATCACAAAGGA 9960
Qy 9961 ATCTTATCCCCCACTACTTATCCTTTTATATTTTTCCGTGTCATTTTTGCCCTTGAGTTT 10020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 9961 ATCTTATCCCCCACTACTTATCCTTTTATATTTTTCCGTGTCATTTTTGCCCTTGAGTTT 10020
Qy 10021 TCCTATATAAGGAACCAAGTTCGGCATTTGTGAAAACAAGAAAAAATTTGGTGTAAGCTA 10080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10021 TCCTATATAAGGAACCAAGTTCGGCATTTGTGAAAACAAGAAAAAATTTGGTGTAAGCTA 10080
Qy 10081 TTTTCTTTGAAGTACTGAGGATACAACTTCAGAGAAATTTGTAAGTTTGTAGATCTCCAT 10140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10081 TTTTCTTTGAAGTACTGAGGATACAACTTCAGAGAAATTTGTAAGTTTGTAGATCTCCAT 10140
Qy 10141 GTCTCCGGAGAGGAGACCAGTTGAGATTAGGCCAGCTACAGCAGCTGATATGGCCGCGGT 10200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10141 GTCTCCGGAGAGGAGACCAGTTGAGATTAGGCCAGCTACAGCAGCTGATATGGCCGCGGT 10200
Qy 10201 TTGTGATATCGTTAACCATTACATTGAGACGTCTACAGTGAACTTTAGGACAGAGCCACA 10260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10201 TTGTGATATCGTTAACCATTACATTGAGACGTCTACAGTGAACTTTAGGACAGAGCCACA 10260
Qy 10261 AACACCACAAGAGTGGATTGATGATCTAGAGAGGTTGCAAGATAGATACCCTTGGTTGGT 10320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10261 AACACCACAAGAGTGGATTGATGATCTAGAGAGGTTGCAAGATAGATACCCTTGGTTGGT 10320
Qy 10321 TGCTGAGGTTGAGGGTGTTGTGGCTGGTATTGCTTACGCTGGGCCCTGGAAGGCTAGGAA 10380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10321 TGCTGAGGTTGAGGGTGTTGTGGCTGGTATTGCTTACGCTGGGCCCTGGAAGGCTAGGAA 10380
Qy 10381 CGCTTACGATTGGACAGTTGAGAGTACTGTTTACGTGTCACATAGGCATCAAAGGTTGGG 10440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10381 CGCTTACGATTGGACAGTTGAGAGTACTGTTTACGTGTCACATAGGCATCAAAGGTTGGG 10440
Qy 10441 CCTAGGATCCACATTGTACACACATTTGCTTAAGTCTATGGAGGCGCAAGGTTTTAAGTC 10500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10441 CCTAGGATCCACATTGTACACACATTTGCTTAAGTCTATGGAGGCGCAAGGTTTTAAGTC 10500
Qy 10501 TGTGGTTGCTGTTATAGGCCTTCCAAACGATCCATCTGTTAGGTTGCATGAGGCTTTGGG 10560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10501 TGTGGTTGCTGTTATAGGCCTTCCAAACGATCCATCTGTTAGGTTGCATGAGGCTTTGGG 10560
Qy 10561 ATACACAGCCCGGGGTACATTGCGCGCAGCTGGATACAAGCATGGTGGATGGCATGATGT 10620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10561 ATACACAGCCCGGGGTACATTGCGCGCAGCTGGATACAAGCATGGTGGATGGCATGATGT 10620
Qy 10621 TGGTTTTTGGCAAAGGGATTTTGAGTTGCCAGCTCCTCCAAGGCCAGTTAGGCCAGTTAC 10680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10621 TGGTTTTTGGCAAAGGGATTTTGAGTTGCCAGCTCCTCCAAGGCCAGTTAGGCCAGTTAC 10680
Qy 10681 CCAGATCTGAGGTACCCTGAGCTTGAGCTTATGAGCTTATGAGCTTAGAGCTCGGATCCA 10740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10681 CCAGATCTGAGGTACCCTGAGCTTGAGCTTATGAGCTTATGAGCTTAGAGCTCGGATCCA 10740
Qy 10741 CTAGTAACGGCCGCCAGTGTGCTGGAATTCGCCCTTGACTAGATAGGCGCCCAGATCGGC 10800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10741 CTAGTAACGGCCGCCAGTGTGCTGGAATTCGCCCTTGACTAGATAGGCGCCCAGATCGGC 10800
Qy 10801 GGCAATAGCTTCTTAGCGCCATCCCGGGTTGATCCTATCTGTGTTGAAATAGTTGCGGTG 10860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10801 GGCAATAGCTTCTTAGCGCCATCCCGGGTTGATCCTATCTGTGTTGAAATAGTTGCGGTG 10860
Qy 10861 GGCAAGGCTCTCTTTCAGAAAGACAGGCGGCCAAAGGAACCCAAGGTGAGGTGGGCTATG 10920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10861 GGCAAGGCTCTCTTTCAGAAAGACAGGCGGCCAAAGGAACCCAAGGTGAGGTGGGCTATG 10920
Qy 10921 GCTCTCAGTTCCTTGTGGAAGCGCTTGGTCTAAGGTGCAGAGGTGTTAGCGGGATGAAGC 10980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10921 GCTCTCAGTTCCTTGTGGAAGCGCTTGGTCTAAGGTGCAGAGGTGTTAGCGGGATGAAGC 10980
Qy 10981 AAAAGTGTCCGATTGTAACAAGATATGTTGATCCTACGTAAGGATATTAAAGTATGTATT 11040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 10981 AAAAGTGTCCGATTGTAACAAGATATGTTGATCCTACGTAAGGATATTAAAGTATGTATT 11040
Qy 11041 CATCACTAATATAATCAGTGTATTCCAATATGTACTACGATTTCCAATGTCTTTATTGTC 11100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11041 CATCACTAATATAATCAGTGTATTCCAATATGTACTACGATTTCCAATGTCTTTATTGTC 11100
Qy 11101 GCCGTATGTAATCGGCGTCACAAAATAATCCCCGGTGACTTTCTTTTAATCCAGGATGAA 11160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11101 GCCGTATGTAATCGGCGTCACAAAATAATCCCCGGTGACTTTCTTTTAATCCAGGATGAA 11160
Qy 11161 ATAATATGTTATTATAATTTTTGCGATTTGGTCCGTTATAGGAATTGAAGTGTGCTTGCG 11220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11161 ATAATATGTTATTATAATTTTTGCGATTTGGTCCGTTATAGGAATTGAAGTGTGCTTGCG 11220
Qy 11221 GTCGCCACCACTCCCATTTCATAATTTTACATGTATTTGAAAAATAAAAATTTATGGTAT 11280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11221 GTCGCCACCACTCCCATTTCATAATTTTACATGTATTTGAAAAATAAAAATTTATGGTAT 11280
Qy 11281 TCAATTTAAACACGTATACTTGTAAAGAATGATATCTTGAAAGAAATATAGTTTAAATAT 11340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11281 TCAATTTAAACACGTATACTTGTAAAGAATGATATCTTGAAAGAAATATAGTTTAAATAT 11340
Qy 11341 TTATTGATAAAATAACAAGTCAGGTATTATAGTCCAAGCAAAAACATAAATTTATTGATG 11400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11341 TTATTGATAAAATAACAAGTCAGGTATTATAGTCCAAGCAAAAACATAAATTTATTGATG 11400
Qy 11401 CAAGTTTAAATTCAGAAATATTTCAATAACTGATTATATCAGCTGGTACATTGCCGTAGA 11460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11401 CAAGTTTAAATTCAGAAATATTTCAATAACTGATTATATCAGCTGGTACATTGCCGTAGA 11460
Qy 11461 TGAAAGACTGAGTGCGATATTATGGTGTAATACATAGCGGCCGGGTTTCTAGTCACCGGT 11520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11461 TGAAAGACTGAGTGCGATATTATGGTGTAATACATAGCGGCCGGGTTTCTAGTCACCGGT 11520
Qy 11521 TAGGATCCGTTTAAACTCGAGGCTAGCGCATGCACATAGACACACACATCATCTCATTGA 11580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11521 TAGGATCCGTTTAAACTCGAGGCTAGCGCATGCACATAGACACACACATCATCTCATTGA 11580
Qy 11581 TGCTTGGTAATAATTGTCATTAGATTGTTTTTATGCATAGATGCACTCGAAATCAGCCAA 11640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11581 TGCTTGGTAATAATTGTCATTAGATTGTTTTTATGCATAGATGCACTCGAAATCAGCCAA 11640
Qy 11641 TTTTAGACAAGTATCAAACGGATGTGACTTCAGTACATTAAAAACGTCCGCAATGTGTTA 11700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11641 TTTTAGACAAGTATCAAACGGATGTGACTTCAGTACATTAAAAACGTCCGCAATGTGTTA 11700
Qy 11701 TTAAGTTGTCTAAGCGTCAATTTGATTTACAATTGAATATATCCTGCCCCAGCCAGCCAA 11760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11701 TTAAGTTGTCTAAGCGTCAATTTGATTTACAATTGAATATATCCTGCCCCAGCCAGCCAA 11760
Qy 11761 CAGCTCGATTTACAGAGAACGAATGTCGTGTTTTAGGAACTTACATGTAAACGGTAAGGA 11820
||||||||||||||||||||||||||||||| ||
Db 11761 CAGCTCGATTTACAGAGAACGAATGTCGTGT---------------------------GA 11793
Qy 11821 TATGTGGAACAAGGCAACGACAACAACATACATGAATCTCACAATAGAGTCGGGGTCGCC 11880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11794 TATGTGGAACAAGGCAACGACAACAACATACATGAATCTCACAATAGAGTCGGGGTCGCC 11853
Qy 11881 GAGTTGTGATGTAATCCATGGCATGGACATGGTGGCCGATCGAAAAAGAAAAAAGAAATG 11940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11854 GAGTTGTGATGTAATCCATGGCATGGACATGGTGGCCGATCGAAAAAGAAAAAAGAAATG 11913
Qy 11941 CATGTATATGTGTGAAAATGAGAGTTTTTTTTATCCAAATAATAAAAAAAAATTAATTAT 12000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11914 CATGTATATGTGTGAAAATGAGAGTTTTTTTTATCCAAATAATAAAAAAAAATTAATTAT 11973
Qy 12001 TTACCCAAAAAATTATTTACATGACCGATACGTACACTTTTTTCCTTAGTTAAGAAACAC 12060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 11974 TTACCCAAAAAATTATTTACATGACCGATACGTACACTTTTTTCCTTAGTTAAGAAACAC 12033
Qy 12061 CGATTTCTTAATTACATTTTTTTATACATTTAGAAATTGGTTTCCTTGGAACCGATTTCA 12120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12034 CGATTTCTTAATTACATTTTTTTATACATTTAGAAATTGGTTTCCTTGGAACCGATTTCA 12093
Qy 12121 AAATGTTCATTTTTTTTTTCAAAACCAAGTTAAGAAATCGGTTCCTTGGAAAACGACTTC 12180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12094 AAATGTTCATTTTTTTTTTCAAAACCAAGTTAAGAAATCGGTTCCTTGGAAAACGACTTC 12153
Qy 12181 TTAATTGCTTTTTTTTTTGTTTTGTTTTAAAATTGTTTGTATTTTTATTTTTTTTGTTAT 12240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12154 TTAATTGCTTTTTTTTTTGTTTTGTTTTAAAATTGTTTGTATTTTTATTTTTTTTGTTAT 12213
Qy 12241 TAATTGTCTATATTTGTGTTCTGTTTAAATTGAAAACAATATTATTTTTCATATGTTGTT 12300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12214 TAATTGTCTATATTTGTGTTCTGTTTAAATTGAAAACAATATTATTTTTCATATGTTGTT 12273
Qy 12301 AATTCTTAATTTCTTATGCATATTTTATGTTTTATCATTTTTTAAGAGTTGAAATCCTTT 12360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12274 AATTCTTAATTTCTTATGCATATTTTATGTTTTATCATTTTTTAAGAGTTGAAATCCTTT 12333
Qy 12361 GTATTTTTATTTTATTTGATTATTATAATACATAATTAAACAACAACTTAATTGAAATTA 12420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12334 GTATTTTTATTTTATTTGATTATTATAATACATAATTAAACAACAACTTAATTGAAATTA 12393
Qy 12421 AAAAATATATATTTAACTGACAAGTTGACTTGAACTAAAATATTTAAATTACAAAATAGA 12480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12394 AAAAATATATATTTAACTGACAAGTTGACTTGAACTAAAATATTTAAATTACAAAATAGA 12453
Qy 12481 TATGAAATTACAAACAATAGAACAAAATATTTAAATTTGAAATAATACAACAAAAATTTT 12540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12454 TATGAAATTACAAACAATAGAACAAAATATTTAAATTTGAAATAATACAACAAAAATTTT 12513
Qy 12541 AAAATACAAACAATATGGCATAAAATTAATGTTGTTGGCCTGAGCCTACACAATGGGGGG 12600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12514 AAAATACAAACAATATGGCATAAAATTAATGTTGTTGGCCTGAGCCTACACAATGGGGGG 12573
Qy 12601 AATGCGACACATGGAACATCATTTTGGTTTACCTGATTCTTGGATATCCATTTTGGTGTG 12660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12574 AATGCGACACATGGAACATCATTTTGGTTTACCTGATTCTTGGATATCCATTTTGGTGTG 12633
Qy 12661 TATACGAGAGGAGACATGACAACCTTTAGAATTTCTTTTCATTTTTGGGTTGGGGCAAAT 12720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12634 TATACGAGAGGAGACATGACAACCTTTAGAATTTCTTTTCATTTTTGGGTTGGGGCAAAT 12693
Qy 12721 TCTTGGCTTGTGACATGGTGACCAACATGCTTCATTGCACAATTTCCCAAGTAATCATTT 12780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12694 TCTTGGCTTGTGACATGGTGACCAACATGCTTCATTGCACAATTTCCCAAGTAATCATTT 12753
Qy 12781 GTACATGTTATAGATACTTTTCAGCGTATACACAAGATGTATGTAGTTCCTATACTCATG 12840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12754 GTACATGTTATAGATACTTTTCAGCGTATACACAAGATGTATGTAGTTCCTATACTCATG 12813
Qy 12841 GTGAGCATGCTTATAAACAACAACATGAGAACAAAACATGTGCATTTTTTGAAATTTGTC 12900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12814 GTGAGCATGCTTATAAACAACAACATGAGAACAAAACATGTGCATTTTTTGAAATTTGTC 12873
Qy 12901 ACAGTCACACTACCTTTCATCTAGCTTGACCATGAAATTTCTCACTAGTTGAATCTCTCT 12960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12874 ACAGTCACACTACCTTTCATCTAGCTTGACCATGAAATTTCTCACTAGTTGAATCTCTCT 12933
Qy 12961 CTCCAGTTAATTGTCTCCTAGACTAAGAATTGTATGTCGCATTAATCGAACTCAAGAACA 13020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12934 CTCCAGTTAATTGTCTCCTAGACTAAGAATTGTATGTCGCATTAATCGAACTCAAGAACA 12993
Qy 13021 ATGTGAGAGTTTGCCTTTTTCTGTATGTCTTTCATAGCCTTGTTTAATACTTTTGTATAA 13080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12994 ATGTGAGAGTTTGCCTTTTTCTGTATGTCTTTCATAGCCTTGTTTAATACTTTTGTATAA 13053
Qy 13081 ACTTCACCAAATGTAATCACTCTTGCGACTTCTCTCCCCCTTTGGTTGAACAATGCATTA 13140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 13054 ACTTCACCAAATGTAATCACTCTTGCGACTTCTCTCCCCCTTTGGTTGAACAATGCATTA 13113
Qy 13141 CACCTAGTATAGGTTGATTTTACCAACACACATTGCCAGATTTTGTGTTTTCTTGAGTAC 13200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 13114 CACCTAGTATAGGTTGATTTTACCAACACACATTGCCAGATTTTGTGTTTTCTTGAGTAC 13173
Qy 13201 CAAATTAATTAACTCAGTGTCCCCATCGCCAGCCACCATCCCATGCGAGAGTCCACTTTT 13260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 13174 CAAATTAATTAACTCAGTGTCCCCATCGCCAGCCACCATCCCATGCGAGAGTCCACTTTT 13233
Qy 13261 CTTGTGGAATCTTCCTAAGCTAATTAATTGTTAGTTCAGCTTGGCCTTAAAACACACATG 13320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 13234 CTTGTGGAATCTTCCTAAGCTAATTAATTGTTAGTTCAGCTTGGCCTTAAAACACACATG 13293
Qy 13321 ACAAATATTTTTATTATAAAACAAACACCCAGTGATACAACAATGAACAACACACATGAC 13380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 13294 ACAAATATTTTTATTATAAAACAAACACCCAGTGATACAACAATGAACAACACACATGAC 13353
Qy 13381 AACTACAAATCATTAAATAATACAATTACAATCAAATAATTTGGGGAGGGGGTCTTCAAA 13440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 13354 AACTACAAATCATTAAATAATACAATTACAATCAAATAATTTGGGGAGGGGGTCTTCAAA 13413
Qy 13441 ACTTGATTCAAGGTTCATTGTATCATCGAGGTATTCACCCAAACCCTCCAAATTCAAAGA 13500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 13414 ACTTGATTCAAGGTTCATTGTATCATCGAGGTATTCACCCAAACCCTCCAAATTCAAAGA 13473
Qy 13501 GCTTGCAGAAACTGGTGGTGGTTGTGCATATGTTTATGTGGGTGTGTCTACGGTGATAAC 13560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 13474 GCTTGCAGAAACTGGTGGTGGTTGTGCATATGTTTATGTGGGTGTGTCTACGGTGATAAC 13533
Qy 13561 ATAAAACTCAAGGCATGTGAAGTTGAAGAGTTTCCCAAATATAGAAAACATAGTAATTAT 13620
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Db 13534 ATAAAACTCAAGGCATGTGAAGTTGAAGAGTTTCCCAAATATAGAAAACATAGTAATTAT 13593
Qy 13621 TTCCTCATCATCTTGCAGCATACATGCCCTGTACTGAAAACAATCACCAACAAATGATAC 13680
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Db 13594 TTCCTCATCATCTTGCAGCATACATGCCCTGTACTGAAAACAATCACCAACAAATGATAC 13653
Qy 13681 GGGACA 13686
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Db 13654 GGGACA 13659
The 5’ junction of the pDAB8264.44.06.1 event is between Cui et al. SEQ ID NO:27 bases 1494 and 1495 and the 3’ junction is between bases 11774 and 11775 (example 7). The DNA before the 5’ junction, i.e., bases 1-1494, and the DNA after the 3’ junction i.e., bases 11775-13659, are non-transgenic genomic soybean DNAs. The DNA spanning bases 1495 to 11774 is the transgenic DNA inserted into the soybean genome (the “event”).
The 27 nucleotides that distinguish the instant SEQ ID NO:16 from Cui SEQ ID NO:27 appear at positions 1457 to 1483 of Cui SEQ ID NO:27, representing the closest Cas12a PAM sequence (TTTA) that is 5’ of the insertion site followed by 23 more nucleotides.
Cui teaches soybean plant cells, seeds and plants comprising the event (claims 1-10). Cui et al. teaches food and feed products made from the soybean plants, which necessarily require processing the soybean plants to make the feed, and otherwise reasonably reads on defatted or non-defatted meal. (¶ 0019). Cui teaches that transgenic plants comprising the event were selfed (example 9.1). Cui teaches that the plants comprising the event can be detected using PCR primers or labelled probes to detect, among other elements, border or junction sequences. (¶ 0099, 0105, 0109-0132).
Cui teaches it is desirable to excise polynucleotide sequence from a transgenic event using zing finger nuclease to remove polynucleotide consisting of a gene expression cassette, from chromosomally integrated transgenic event, where the polynucleotide removed can be a selectable marker. Where upon excision and removal of a polynucleotide sequence the modified transgenic event can be retargeted by the insertion of a polynucleotide sequence. The excision of a polynucleotide sequence and subsequent retargeting of the modified transgenic event provides advantages such as re-use of a selectable marker or the ability to overcome unintended changes to the plant transcriptome which results from the expression of specific genes (Cui, col 16, lines 1-16).
Cui does not teach transgenic soybean plants comprising SEQ ID NO:16 or 17.
Bernabe-Orts teaches a method of making deletions in a target Arabidopsis thaliana DNA (a PDS3 gene) by inserting a Cas12a endonuclease gene under the transcriptional control of the Ubiquitin10 (UBQ10) promoter and two crRNAs directed towards two target sites flanking the Arabidopsis PDS3 locus. (p. 1977 left col. ¶ 1). Bernabe-Orts teaches that the system resulted in deletions of various sizes to the PDS3 gene (resulting in an easily scoreable albino phenotype) and that in at least one instance, the entire PDS3 gene was deleted, indicative of concomitant activity in both target sites flanking the gene. (p. 1977 left col. ¶ 1, Figure 5). Bernabe-Orts teaches that the targets were endogenous sequences comprising a PAM sequence (either TTTA or TTTC) and that the targets further comprised 20 nucleotides following the PAM sequences. (Table 1).
Cui and Bernabe-Orts do not expressly teach using the same junction sequence in 5’ and 3’ of their disclosed transgene of interest to excise the locus of interest.
However, flanking the gene of interest upstream and downstream with a single unique target sequence that does not normally exist in the genome for excision of the locus is known in the art for higher editing efficiency for manipulating loci. Finnigan teaches their scheme—dubbed mCAL for “Multiplexing of Cas9 at Artificial Loci”—can be applied to any organism in which the CRISPR/Cas9 methodology is currently being utilized. Finnigan teaches their method can be applied to install synthetic sequences into the genome, to generate genomic libraries, and to program strains or cell lines so that they can be conveniently (and repeatedly) manipulated at multiple loci with extremely high efficiency (Page 2147, Abstract). Finnigan teaches flanking any number of selected genes with the same unique target sequence expression of just a single sgRNA initiates multiplex Cas9-mediated removal and scarless replacement and excision of these targeted genes (page 2151, right last paragraph). Finnigan teaches Installation of programmed non-yeast Cas9 target sites at multiple loci wherein the endogenous CDC11 gene were flanked by an identical 23 sequence containing a Cas9 target site (including a 59- NGG-39 PAM sequence) from the human SEPT9 gene, designated “unique Cas9 site 1,” u1 (see figure below).
Hence someone skilled in art would use the same target sequence flanking the locus of interest for efficient excision.
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Lee teaches a method of using Cas12a in maize plants to generate targeted mutations, including small deletions and comparing the system to a Cas9 system at the same locus. Lee teaches that the Cas12a guide sequences were 23 nucleotides in length corresponding to sequences in the genome following PAM sequences recognized by the Cas12a nuclease (TTTG). (Figure 2). Lee teaches that while the Cas12a system was able to generate targeted mutations including much larger deletions than a Cas9 system, it was less efficient compared to the Cas9 system in maize. (p. 365 right col. ¶ 2).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to modify the soybean plants comprising event pDAP8264.44.06.1, taught by Cui, to create Cas12a target sites at approximately the 5’ and 3’ junctions using the method described in Bernabe-Orts. One of ordinary skill in the art would have been motivated to do so because Cui suggest excising all or a portion of the transgenic insert and/or flanking sequences of event DAS-8264.44.06.1, then targeting another insert to the chromosomal site of event DAS-8264.44.06.1 (column 4, line 52, to column 5, line 10). Creating Cas12a target sites at approximately the 5’ and 3’ junctions would allow Cui’s suggested excision of the transgenic insert.
Lee teaches a method of using guide sequences of about 23 nucleotides in length. As there is already a TTTA PAM sequence just before the 5’ junction of the DAS-8264.44.06.1 event, it would be simplest for one of ordinary skill in the art to choose the next 23 nucleotides of the pDAP8264.44.06.1 event, i.e., GGAACTTACATGTAAACGGTAAG as a target sequence. While the exact sequence used is a design choice, the next 23 nucleotides of the pDAP8264.44.06.1 event would allow the removal of the entire event while deleting a minimal portion of flanking genomic DNA.
One of ordinary skill in the art would then adapt Finnigan’s method of inserting DNA sequences into a genomic site of interest flanking the insertion to introduce the 27 bp TTTAAGGAACTTACATGTAAACGGTAAG (i.e., to match the sequence just before the 5’ junction of the DAS-8264.44.06.1 event) at or just after the 3’ junction of a soybean plant with the pDAP8264.44.06.1 event. While the exact point of insertion for the 27 nucleotide targeting sequence 3’ of the event site is a mere matter of design choice, the instant 3’ targeting sequence is inserted 16 nucleotides from the event site, which is reasonably similar to the distance of the 5’ targeting sequence from the event – 12 nucleotides. As such the selected site for the 3’ insertion is obvious – as would any be any site within several nucleotides of the event site. As such the claims are obvious in view of the teachings of the prior art.
Response to Remarks
Applicant argues that Examiner errs in maintaining the rejection under 35 USC 103 because Examiner has not demonstrated that the combination of teachings would predictably lead one of ordinary skill to arrive at Applicant’s claimed invention. Applicant cites the affidavit of inventor Michael Nuccio for the assertion that CRISPR editing was largely focused on the production of small indels or nucleotide substitutions at the time of filing. Nuccio also asserts that Finnegan was incorrect in assuming that the types of DNA break repair observed in yeast would translate to other eukaryotes because, in particular, HDR was infrequent, rare or technically inefficient in plants and that >10kb dropouts were ever more rare. Nuccio argues that large scale sequence removal using such dropouts was not suited to solving specific technical agricultural problems. Nuccio asserts that there is a gap between published research and scalable agricultural solutions. (Remarks p. 8-9).
This is not found persuasive. Applicant employs the affidavit of Nuccio here to dispute the explicit teachings of Finnegan. However, the specific remarks by Nuccio when carefully considered fail to outweigh those teachings. The assertion that the CRISPR field was largely directed to small DNA alterations merely states the aim of most researchers at the time. Regarding the assertion that HDR was infrequent or rare in plants appears to disregard the fact that Finnegan does not merely rely on older HDR gene replacement/removal techniques but instead proposes a new technique using CRISPR/Cas nuclease complexes that are taught to be efficient in yeast. Further, even if there would have been a predicted low efficiency the removal of the expression cassette as taught by Cui needed only be achieved once to produce a plant wherein the cassette has been excised as taught by Cui. As such, low efficiency itself is not a bar to combining the teachings of the art. Nuccio’s remaining arguments concerning whether the technique was suited to solving specific technical agricultural problems that there is a gap between published research and scalable agricultural solutions are reasonably interpreted to be general opinions that ignore the specific teachings of the art.
Applicant further argues that Examiner has incorrectly asserted that the sequence selected by Appellant in the soybean genome as disclosed by Cui is a matter of design choice. Applicant argues that the art does not teach any insertions in the genome as specifically claimed by Applicant and that the choice was non-trivial. Specifically Applicant argues that the choice was non-trivial because the site selected for duplication results in a novel feature and that such selection required innovation. (Remarks p. 10-11).
This is not found persuasive. As set forth in the rejection, the rationale for selecting the duplicated sequence would have been obvious – the sequence starts with the closest endogenous PAM sequence 5’ of the expression cassette, thus minimizing the amount of sequence that is excised and the length following is obvious in view of the teachings of the art. The matter of design choice presented in view of the teachings of the art set forth previously herein is which upstream PAM sequence to supplicate and here Applicant picked the fist one in line.
Applicant’s argues that the rejection under 35 USC 103 should be withdrawn because Finnigan teaches away from the use of endogenous sequences in a CRISPR gene deletion/replacement system as asserted by Examiner in the rejection. Applicant argues that the standard for review cited in MPEP 2145 from In re Gurley is inapposite to the instant analysis because the art in Gurley disclosed and disparaged an embodiment identical to that claimed by Applicant. (Remarks p. 11-12).
It is unclear where Applicant has obtained this rule because neither the MPEP or In re Gurley states that the disparaged embodiment must be identical to that claimed. Indeed the analysis at issue in Gurley was under 35 USC 103 – it would seem that the issue would have been one of anticipation if the embodiment had to be identical. Here, Finnegan is cited in combination with the other cited art to form a 103 rejection. The elements Finnegan are cited for are set forth explicitly in the rejection – primarily the excision system using a single sgRNA. The other cited art teaches missing elements such as using endogenous sequences for excision.
Applicant argues that Examiner erred in stating that Finnegan does not teach any fundamental incompatibility between the system as taught by Finnegan and the use of endogenous sequences. Applicant focuses on the difference between the traditional embodiments disparaged by Finnegan – using multiple endogenous sequences – and the system as taught by Finnegan. Applicant argues that the only alternative disparaged embodiment of Finnegan is limited to using more than one endogenous sequence. (Remarks p. 12-13).
This is not found persuasive. Noting again that while Applicant appears to misstate the rule of Gurley, Applicant further ignores the fact the rejection was made using a combination of teachings from different items of the prior art. Indeed, if Finnegan can only disparage the particular embodiment of using multiple different endogenous sequences, then it should be held that it says nothing about a system using a duplicated endogenous sequence other than to suggest the existence of systems using endogenous sequences. Finnegan does indicate that using endogenous sequences can pose technical problems such as off-target activity, but the other cited art shows that similar systems can operate in plants using endogenous sequences. As such one having ordinary skill would reasonably believe that the system rendered obvious by the teachings of the prior art could be operable and effective in plants.
Applicant’s argument is heavily directed to the inventiveness of using duplicated endogenous sequences as targets for a CRISPR/Cas-based excision system. Indeed, this appears to be the inventive concept as the site that Applicant seeks to excise from the soybean genome was undoubtedly discovered and disclosed in detail by Cui as one that was specifically selected for stable expression, and a superior combination of efficacy, including herbicide tolerance and agronomic performance over generations. In view of the combination of teachings, and considering each in the entirety and in combination, the invention is deemed to be obvious.
Applicant further argues along the same lines in asserting that Examiner has not properly considered the teachings of Finnegan as a whole. Applicant argues that Finnegan teaches its system is superior and an improvement over traditional systems and that Finnegan teaches that such traditional systems “require” multiple different endogenous sequences. Applicant argues that Examiner has improperly cherry-picked the teachings of Finnegan.(Remarks p. 13-14).
This is not found persuasive. Applicant again focuses on a single alternative embodiment discussed by Finnegan as inferior and discounts the capacity of one of ordinary skill in the art to consider the totality of the teachings and language of Finnegan in view of the other teachings of the prior art. It is Examiner’s position that one of ordinary skill in the art would have recognized the teachings of Bernabe-Orts – using two different flaking endogenous sequences with endogenous PAM sites in a Crispr/Cas9 system – could be modified by recognizing the advantage of using a single sequence as taught by Finnegan. Innovation necessarily requires modification of “traditional” systems and as such one would not have been confined by the strict bounds of the alternative embodiments discussed by Finnegan.
Conclusion
No Claims are allowed.
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/CHARLES LOGSDON/Primary Examiner, Art Unit 1662