ME03544B - Supstance anтiтijela za liječenje tumora - Google Patents

Supstance anтiтijela za liječenje tumora

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Publication number
ME03544B
ME03544B MEP-2019-303A MEP2019303A ME03544B ME 03544 B ME03544 B ME 03544B ME P2019303 A MEP2019303 A ME P2019303A ME 03544 B ME03544 B ME 03544B
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Montenegro
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ser
val
pro
thr
leu
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MEP-2019-303A
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German (de)
English (en)
French (fr)
Inventor
Samuel Davis
Eric Smith
Bindu Varghese
Jessica R Kirshner
Gavin Thurston
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Regeneron Pharma
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Publication of ME03544B publication Critical patent/ME03544B/me

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Description

<br>SUPSTANCE ANTI?IJELA ZA LIJECENJE TUMORA <br>SPISAK SEKVENCI <br>[031 7] <br><11 > REGENERON PHARMACEUTICALS, INC. <br><120> POSTUPCI 1 SUPSTANCE ANTITIJELA ZA LIJECENJE TUMORA <br><130> A0015W001 <br><150> 62/033,460 <br><151 > 5.8.2014. <br>< 150> 62/007 ' 385 <br><151 > 3.6.2014. <br><150> 61/981 ,641 <br><151> 18.4.2014. <br><150> 61/955,663 <br><151> 19.3.2014 <br><160> 75 <br><170> Patentln verzija 3.5 <br><21 > 1 <br><211 > 382 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 1 <br><br>gaagtacagc <br>tcctgtgtag <br>ccagggaagg <br>gcggactctg <br>ctgcaaatgc <br>cactatggtt <br>accacggtca <br><21 > 2 <br><211> 127 <br><212> PRT <br>tggtggagtc <br>cctctggatt <br>gcctggaatg <br>tgaagggccg <br>acagtctgag <br>cggggagtta <br>ccgtctcctc <br>??311980881 <br>tgggggaggc ttggtacagc ctggcaggtc cctgagactc <br>cacctttaat gattatgcca tgcactgggt ccggcaagct <br>ggtctcagtt attagttgga atagtgatag cataggctat <br>attcaccatc tccagagaca acgccaagaa ctccctgtat <br>agctgaggac acggccttgt attactgtgc aaaagataat <br>ttactactac caatacggta tggacgtctg gggccaaggg <br>ag <br><21 > Vesta?ka sekvenca <br><220> <br><22?> Sinteti?ka <br><400> 2 <br>Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg <br>1 5 10 15 <br>Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Asn Asp Tyr <br>20 <br>25 <br>30 <br>Ala Met His ~rp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val <br>35 40 45 <br>Ser Val Ile Ser Trp Asn Ser Asp Ser Ile Gly Tyr Ala Asp Ser Val <br>50 55 60 <br>Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr <br>65 70 75 80 <br>Leu Gln Met His Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys <br>85 90 95 <br>Ala Lys Asp Asn His Tyr Gly Ser Gly Ser Tyr Tyr Tyr Tyr Gln Tyr <br>100 105 110 <br>Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser <br>115 120 125 <br><21 ?> ? <br><211> 24 <br><212> DNK <br>2 <br>60 <br>120 <br>180 <br>240 <br>300 <br>360 <br>382 ;? <br>, <br>?? 3119 808 81 <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> ? <br>ggattcacct ttaatgatta tgcc 24 <br><210> 4 <br><211 > 8 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 4 <br>Gly Phe Thr Phe Asn Asp Tyr Ala <br>1 5 <br><2 10> 5 <br><211> 24 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 5 <br>attagttgga atagtgatag cata 24 <br><210> 6 <br><211 > 8 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 6 <br>Ile Ser Trp Asn Ser Asp Ser Ile <br>1 5 <br><210> 7 <br><211> 60 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 7 <br>gcaaaagata atcactatgg ttcggggagt tattactact accaatacgg tatggacgtc 60 <br><21 ?> 8 <br><211>20 <br>? , <br>?? 3119 808 81 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 8 <br>Ala Lys Asp Asn His Tyr Gly Ser Gly Ser Tyr Tyr Tyr Tyr Gln Tyr <br>1 5 10 15 <br>Gly Met Asp Val <br>20 <br><21 0> 9 <br><211> ?69 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 9 <br>gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60 <br>tcctgtgcag cctctggatt cacctttgat gattatacca tgcactgggt ccggcaagct 120 <br>ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag tataggctat 180 <br>gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa gtccctgtat 240 <br>ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagataat 300 <br>agtggctacg gtcactacta ctacggaatg gacgtctggg gccaagggac cacggtcacc 360 <br>gtcgcctca 369 <br><210> 10 <br><211 > 12? <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 10 <br>4 , <br>?? ? 119 808 81 <br>Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg <br>1 5 10 15 <br>Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr <br>20 25 30 <br>Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val <br>35 40 45 <br>Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val <br>50 55 60 <br>Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Lys Ser Leu Tyr <br>65 70 75 80 <br>Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys <br>85 90 95 <br>Ala Lys Asp Asn Ser Gly Tyr Gly His Tyr Tyr Tyr Gly Met Asp Val <br>100 105 110 <br>Trp Gly Gln Gly Thr Thr Val Thr Val Ala Ser <br>115 120 <br><21 ?> 11 <br><211>24 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 11 <br>ggattcacct ttgatgatta tacc 24 <br><210> 12 <br><211 > 8 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 12 <br><210> 1? <br><211> 24 <br><212> DNK <br><21 ?> Vestacka sekvenca <br>Gly Phe Thr Phe Asp Asp Tyr Thr <br>1 5 <br>5 ?? 3119 808 81 <br><220> <br><22?> Sinteticka <br><400> 1? <br>attagttgga atagtggtag tata 24 <br><210> 14 <br><211 > 8 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 14 <br><210> 15 <br><211> 48 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 15 <br>Ile Ser Trp Asn Ser Gly Ser Ile <br>1 5 <br>gcaaaagata atagtggcta cggtcactac tactacggaa tggacgtc 48 <br><210> 16 <br><211 > 16 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 16 <br>Ala Lys Asp Asn Ser Gly Tyr Gly His Tyr Tyr Tyr Gly Met Asp Val <br>1 5 10 15 <br><210> 17 <br><211>?20 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 17 <br>6 gaaatagtga <br>ctctcctgca <br>ggccaggctc <br>aggttcagtg <br>gaagattttg <br>gggaccaagg <br><210> 18 <br><2 11 > 108 <br><212> PRT <br>tgacgcagtc <br>gggccagtca <br>ccaggctcct <br>gcagtgggtc <br>cagtttatta <br>tggagatcaa <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 18 <br>?? ? 119 808 81 <br>tccagccacc ctgtctgtgt ctccagggga aagagccacc <br>gagtgttagc agcaacttag cctggtacca gcaaaaacct <br>catctatggt gcatccacca gggccactgg tatcccagcc <br>tgggacagag ttcactctca ccatcagcag cctgcagtct <br>ctgtcagcac tatattaact ggcctctcac tttcggcgga <br>Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly <br>1 5 10 15 <br>Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn <br>20 25 30 <br>Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile <br>35 40 45 <br>Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser <br>65 70 75 80 <br>Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Ile Asn Trp Pro Leu <br>85 90 95 <br>Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg <br>100 105 <br><210> 19 <br><211> 18 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 19 <br>cagagtgtta gcagcaac 18 <br>7 <br>60 <br>120 <br>180 <br>240 <br>300 <br>320 • <br><210> 20 <br><211>6 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 20 <br><21 0>21 <br><2 11 > 9 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 21 <br>ggtgcatcc 9 <br><210> 22 <br><211 > ? <br><2 12> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 22 <br><210> 2? <br><211>27 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 2? <br>cagcactata ttaactggcc tctcact 27 <br><210> 24 <br><2 11 > 9 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 24 <br>?? 3119 808 81 <br>Gln Ser Val Ser Ser Asn <br>1 5 <br>Gly Ala Ser <br>1 <br>8 ??311980881 <br>.. <br>Gln His Tyr I le Asn Trp Pro Leu Thr <br>1 5 <br><210> 25 <br><211 > 981 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 25 <br>gccagcacaa aaggtcctag cgt ttttcca cttgccccat gttcaaggtc aacctccgaa 60 <br>agtaccgccg ctcttggctg tct cgtaaaa gattattttc ccgaacctgt aactgtctcc 120 <br>tggaactccg gcgcactcac ttccggcgta cataccttcc ccgctgtcct ccaatcttcc 180 <br>ggtctctact ccctgtcttc tgt tgtcact gttccatcat cctcactcgg ?????????? 240 <br>tatacctgca acgttgatca caagccaagt aataccaaag ttgataagcg cgtcgaatcc 300 <br>aaatacggtc ccccctgccc accgtgccca gcaccacctg tggcaggacc atcagtcttc 360 <br>ctgttccccc ?????????? ggacactctc atgatctccc ggacccctga ggtcacgtgc 420 <br>gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 480 <br>gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cacgtaccgt 540 <br>gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 600 <br>aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 660 <br>cagccccgag agccacaggt gtacaccctg cccccatccc aggaggagat gaccaagaac 720 <br>caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 780 <br>gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 840 <br>ggctccttct tcctctacag caggctcacc gtggacaaga gcaggtggca ggaggggaat 900 <br>gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagtccctc 960 <br>tccctgtctc tgggtaaatg ? 981 <br><210> 26 <br><21 1> ?26 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 26 <br>9 ?? ? 119 808 81 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arq <br>1 5 10 15 <br>Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser <br>50 55 60 <br>Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr <br>65 70 75 80 <br>Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys <br>85 90 95 <br>Arq Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro <br>100 105 110 <br>Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp <br>115 120 125 <br>Thr Leu Met Ile Ser Arq Thr Pro Glu Val Thr Cys Val Val Val Asp <br>130 135 140 <br>Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly <br>145 150 155 160 <br>Val Glu Val His Asn Ala Lys Thr Lys Pro Arq Glu Glu Gln Phe Asn <br>165 170 175 <br>Ser Thr Tyr Arq Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp <br>180 185 190 <br>Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro <br>195 200 205 <br>Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arq Glu <br>210 215 220 <br>Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn <br>225 230 235 240 <br>10 ?? 3119 808 81 <br>Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile <br>245 250 255 <br>Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr <br>260 265 270 <br>Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg <br>275 280 285 <br>Leu Thr Va l Asp Lys Ser Ar g Tr p Gln Glu Gly Asn Val Phe Ser Cys <br>290 295 300 <br>Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu <br>305 310 315 320 <br>Ser Leu Ser Leu Gly Lys <br>325 <br><210> 27 <br><211> 981 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 27 <br>11 ?? ? 119 808 81 <br>gccagcacaa aaggtcctag cgtttttcca cttgccccat gttcaaggtc aacctccgaa 60 <br>agtaccgccg ctcttggctg tctcgtaaaa gattattttc ccgaacctgt aactgtctcc 120 <br>tggaactccg gcgcactcac ttccggcgta cataccttcc ccgctgtcct ccaatcttcc 180 <br>ggtctctact ccctgtcttc tgttgtcact gttccatcat cctcactcgg ?????????? 240 <br>tatacctgca acgttgatca caagccaagt aataccaaag ttgataagcg cgtcgaatcc 300 <br>aaatacggtc ccccctgccc accgtgccca gcaccacctg tggcaggacc atcagtcttc 360 <br>ctgttccccc ?????????? ggacactctc atgatctccc ggacccctga ggtcacgtgc 420 <br>gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 480 <br>gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cacgtaccgt 540 <br>gtggtcagcg tcctcaccgt cct gcaccag gactggctga acggcaagga gtacaagtgc 600 <br>aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 660 <br>cagccccgag agccacaggt gtacaccctg cccccatccc aggaggagat gaccaagaac 720 <br>caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 780 <br>gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 840 <br>ggctccttct tcctctacag caggctcacc gtggacaaga gcaggtggca ggaggggaat 900 <br>gtcttctcat gctccgtgat gcatgaggct ctgcacaaca gattcacaca gaagtccctc 960 <br>tccctgtctc tgggtaaatg ? 981 <br><2 10> 28 <br><211> 326 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 28 <br>12 ?? ? 119 808 81 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg <br>1 5 10 15 <br>Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser <br>50 55 60 <br>Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr <br>65 70 75 80 <br>Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys <br>85 90 95 <br>Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro <br>100 105 110 <br>Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp <br>115 120 125 <br>Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp <br>130 135 140 <br>Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly <br>145 150 155 160 <br>Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn <br>165 170 175 <br>Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp <br>180 185 190 <br>13 ???11980881 <br>Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro <br>195 200 205 <br>Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu <br>210 215 220 <br>Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn <br>225 230 235 240 <br>Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile <br>245 250 255 <br>Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr <br>260 265 270 <br>Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg <br>275 280 285 <br>Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys <br>290 295 300 <br>Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser Leu <br>305 310 315 320 <br>Ser Leu Ser Leu Gly Lys <br>325 <br><210> 29 <br><211> 990 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 29 <br>14 ?? 3119 808 81 <br>gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 60 <br>ggcacagcgg ccctgggctg cct ggtcaag gactacttcc ccgaaccggt gacggtgtcg 120 <br>tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 180 <br>ggactctact ccctcagcag cgt ggtgacc gtgccctcca gcagcttggg cacccagacc 240 <br>tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 300 <br>aaatcttgtg acaaaactca cacatgccca ccgtgcccag caccacctgt ggcaggacca 360 <br>tcagtcttcc tgttcccccc aaaacccaag gacactctca tgatctcccg gacccctgag 420 <br>gtcacgtgcg tggtggtgga cgt gagccag gaagaccccg aggtccagtt caactggtac 480 <br>gtggatggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gttcaacagc 540 <br>acgtaccgtg tggtcagcgt cct caccgtc ctgcaccagg actggctgaa cggcaaggag 600 <br>tacaagtgca aggtctccaa caaaggcctc ccgtcctcca tcgagaaaac catctccaaa 660 <br>gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 720 <br>accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 780 <br>gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 840 <br>gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 900 <br>caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 960 <br>aagtccctct ccctgtctcc gggtaaatga 990 <br><21 0> 30 <br><211 > 329 <br><212> PRT <br><21 ?> Vesta?ka sekvenca <br><220> <br><223> Sinteti?ka <br><400> 30 <br>15 ?? 3119 808 81 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys <br>1 5 10 15 <br>Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser <br>50 55 60 <br>Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr <br>65 70 75 80 <br>Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys <br>85 90 95 <br>Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys <br>100 105 110 <br>Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys <br>115 120 125 <br>Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val <br>130 135 140 <br>16 ??3119808?1 <br>Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr <br>145 150 155 160 <br>Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu <br>165 170 175 <br>Gln Phe Asn Ser Th r Tyr Arg Val Val Ser Val Leu Thr Val Leu His <br>180 185 190 <br>Gln Asp Trp Leu Asn Gl y Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys <br>195 200 205 <br>Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln <br>210 215 220 <br>Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu <br>225 230 235 240 <br>Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro <br>245 250 255 <br>Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn <br>260 265 270 <br>Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu <br>275 280 285 <br>Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val <br>290 295 300 <br>Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln <br>305 310 315 320 <br>Lys Ser Leu Ser Leu Ser Pr o Gly Lys <br>32 5 <br><210> 31 <br><211> 990 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 31 <br>17 ?? 3119 808 81 <br>gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 60 <br>ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 120 <br>tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 180 <br>ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 240 <br>tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 300 <br>aaatcttgtg acaaaactca cacatgccca ccgtgcccag caccacctgt ggcaggacca 360 <br>tcagtcttcc tgttcccccc aaaacccaag gacactctca tgatctcccg gacccctgag 420 <br>gtcacgtgcg tggtggtgga cgtgagccag gaagaccccg aggtccagtt caactggtac 480 <br>gtggatggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gttcaacagc 540 <br>acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa cggcaaggag 600 <br>tacaagtgca aggtctccaa caaaggcctc ccgtcctcca tcgagaaaac catctccaaa 660 <br>gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 720 <br>accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 780 <br>gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 840 <br>gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 900 <br>caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacag attcacgcag 960 <br>aagtccctct ccctgtctcc gggtaaatga 990 <br><210> 32 <br><21 1> 329 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 32 <br>18 ?? ? 119 808 81 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys <br>1 5 10 15 <br>Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser <br>50 55 60 <br>Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr <br>65 70 75 80 <br>Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys <br>85 90 95 <br>19 ?? ? 119 808 81 <br>Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys <br>100 105 110 <br>Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys <br>115 12 0 125 <br>Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val <br>130 135 140 <br>Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr <br>145 150 155 160 <br>Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu <br>165 170 175 <br>Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His <br>180 185 190 <br>Gln Asp Trp Leu Asn Gl y Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys <br>195 200 205 <br>Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln <br>210 215 220 <br>Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu <br>225 230 235 240 <br>Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro <br>245 250 255 <br>Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn <br>260 265 270 <br>Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu <br>275 280 285 <br>Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val <br>290 295 300 <br>Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln <br>305 310 315 320 <br>Lys Ser Leu Ser Leu Ser Pro Gly Lys <br>325 <br><210> 33 <br><211> 981 <br>20 ?? ? 119 808 81 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> ?? <br>gccagcacaa aaggtcctag cgtttttcca cttgccccat gttcaaggtc aacctccgaa 60 <br>agtaccgccg ctcttggctg tctcgtaaaa gattattttc ccgaacctgt aactgtctcc 120 <br>tggaactccg gcgcact~ac ttccggcgta cataccttcc ccgctgtcct ccaatcttcc 180 <br>ggtctctact ccctgtcttc tgttgtcact gttccatcat cctcactcgg ?????????? 240 <br>tatacctgca acgttgatca caagccaagt aataccaaag ttgataagcg cgtcgaatcc 300 <br>aaatacggtc ccccctgccc cccatgtccc gctccacctg tggctggtcc ctctgttttc 360 <br>ctttttcccc ctaaacccaa agataccctc atgatttcca gaacccccga ggtcacctgc 420 <br>gtcgtcgttg atgtaagcca agaagatccc gaagtccagt tcaattggta tgtagacggt 480 <br>gttgaagtcc ataatgcaaa ?????????? agagaggaac agtttaattc aacctatcgt 540 <br>gtcgttagcg tactcaccgt tcttcatcaa gactggctca atggaaaaga atataaatgt 600 <br>aaagttagca acaaaggtct gcccagttca atcgaaaaaa caattagcaa agccaaaggc 660 <br>caacctcgcg aaccccaagt ctataccttg cccccttctc aggaagaaat gaccaaaaac 720 <br>caagtttcac tcacatgcct cgt aaaagga ttctatccat cagacattgc agtagaatgg 780 <br>gaatctaacg gccaacctga aaataattac aaaaccactc ctcctgtcct cgattctgac 840 <br>ggctcttttt tcctttactc cagattgact gttgataaat cccgctggca ggaaggtaac 900 <br>gttttttctt gttctgtgat gcacgaagcc ctccataaca gattcactca aaaatctctt 960 <br>tctctctccc tgggcaaata ? 981 <br><210> ?4 <br><211> 645 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> ?4 <br>21 ?? 3119 808 81 <br>gaaatagtga tgacgcagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc 60 <br>ctctcctgca gggccagtca gagtgttagc agcaacttag cctggtacca gcagaaacct 120 <br>ggccaggctc ccaggctcct catctatggt gcatccacca gggccactgg tatcccagcc 180 <br>aggttcagtg gcagtgggtc tgggacagag ttcactctca ccatcagcag cctgcagtct 240 <br>gaagattttg cagtttatta ctgtcagcac tatattaact ggcctctcac tttcggcgga 300 <br>gggaccaagg tggagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 <br>tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 <br>cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 <br>gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 <br>ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600 <br>ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645 <br><2 1 ?> 35 <br><211 >214 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 35 <br>22 ?? 3119 808 81 <br>Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly <br>1 5 10 15 <br>Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn <br>20 25 30 <br>Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile <br>35 40 45 <br>Tyr Gly Ala Ser Thr Arg Al a Thr Gly Ile Pro Ala Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser <br>65 70 75 80 <br>Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Ile Asn Trp Pro Leu <br>85 90 95 <br>Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala <br>100 105 110 <br>Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly <br>115 120 125 <br>Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala <br>130 135 140 <br>Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln <br>145 150 155 160 <br>Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser <br>1 65 170 175 <br>Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr <br>180 185 190 <br>Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser <br>195 200 205 <br>Phe Asn Arg Gly Glu Cys <br>210 <br><210> 36 <br><211 > 1362 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br>23 ??311980881 <br><223> Sinteticka <br><400> 36 <br>gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60 <br>tcctgtgtag cctctggatt cacctttaat gattatgcca tgcactgggt ccggcaagct 120 <br>ccagggaagg gcctggaatg ggtctcagtt attagttgga atagtgatag cataggctat 180 <br>gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240 <br>ctgcaaatgc acagtctgag agctgaggac acggccttgt attactgtgc aaaagataat 300 <br>cactatggtt cggggagtta ttactactac caatacggta tggacgtctg gggccaaggg 360 <br>accacggtca ccgtctcctc agccagcaca aaaggtccta gcgtttttcc acttgcccca 420 <br>tgttcaaggt caacctccga aagtaccgcc gctcttggct gtctcgtaaa agattatttt 480 <br>cccgaacctg taactgtctc ctggaactcc ggcgcactca cttccggcgt acataccttc 540 <br>cccgctgtcc tccaatcttc cggtctctac tccctgtctt ctgttgtcac tgttccatca 600 <br>tcctcactcg gcacaaaaac atatacctgc aacgttgatc acaagccaag taataccaaa 660 <br>gttgataagc gcgtcgaatc caaatacggt cccccctgcc caccgtgccc agcaccacct 720 <br>gtggcaggac catcagtctt cctgttcccc ?????????? aggacactct catgatctcc 780 <br>cggacccctg aggtcacgtg cgtggtggtg gacgtgagcc aggaagaccc cgaggtccag 840 <br>ttcaactggt acgtggatgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag 900 <br>cagttcaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg 960 <br>aacggcaagg agtacaagtg caaggtctcc aacaaaggcc tcccgtcctc catcgagaaa 1020 <br>accatctcca aagccaaagg gcagccccga gagccacagg tgtacaccct gcccccatcc 1080 <br>caggaggaga tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctacccc 1140 <br>agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg 1200 <br>cctcccgtgc tggactccga cggctccttc ttcctctaca gcaggctcac cgtggacaag 1260 <br>agcaggtggc aggaggggaa tgtcttctca tgctccgtga tgcatgaggc tctgcacaac 1320 <br>cactacacac agaagtccct ctccctgtct ctgggtaaat ga 1362 <br><21 ?> 37 <br><211> 453 <br><212> PRT <br><21 ?> Vesta?ka sekvenca <br><220> <br><223> Sinteticka <br><400> 37 <br>24 ?? ? 119 808 81 <br>Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arq <br>1 5 10 15 <br>Ser Leu Arq Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Asn Asp Tyr <br>20 25 30 <br>Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val <br>35 40 45 <br>Ser Val Ile Ser Trp Asn Ser Asp Ser Ile Gly Tyr Ala Asp Ser Val <br>50 55 60 <br>Lys Gly Arq Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr <br>65 70 75 80 <br>Leu Gln Met His Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys <br>85 90 95 <br>Ala Lys Asp Asn His Tyr Gly Ser Gly Ser Tyr Tyr Tyr Tyr Gln Tyr <br>100 105 110 <br>Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala <br>115 120 125 <br>Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser <br>130 135 140 <br>Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe <br>145 150 155 160 <br>Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly <br>165 170 175 <br>Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu <br>180 185 190 <br>25 ?? ? 119 808 81 <br>Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr <br>195 200 205 <br>Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg <br>210 215 220 <br>Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Pro <br>225 230 235 240 <br>Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr <br>245 250 255 <br>Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val <br>260 265 270 <br>Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val <br>275 280 285 <br>Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser <br>290 295 300 <br>Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu <br>305 310 315 320 <br>Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser <br>325 330 335 <br>Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro <br>340 345 350 <br>Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln <br>355 360 365 <br>Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala <br>370 375 380 <br>Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr <br>385 390 395 400 <br>Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu <br>405 410 415 <br>Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser <br>420 425 430 <br>Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser <br>26 <210> 38 <br><211 > 1350 <br><2 12> DNK <br>435 <br>Leu Ser Leu Gly Lys <br>450 <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 38 <br>?? 3 119 808 81 <br>440 445 <br>27 ?? ? 119 808 81 <br>gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60 <br>tcctgtgcag cctctggatt cacctttgat gattatacca tgcactgggt ccggcaagct 120 <br>c cagggaagg gcctggagtg ggt ctcaggt attagttgga atagtggtag tataggctat 180 <br>gcggactctg tgaagggccg att caccatc tccagagaca acgccaagaa gtccctgtat 240 <br>ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagataat 300 <br>agtggctacg gtcactacta ctacggaatg gacgtctggg gccaagggac cacggtcacc 360 <br>gtcgcctcag ccagcacaaa aggtcctagc gtttttccac ttgccccatg ttcaaggtca 420 <br>acctccgaaa gtaccgccgc tct tggctgt ctcgtaaaag attattttcc cgaacctgta 480 <br>actgtctcct ggaactccgg cgcactcact tccggcgtac ataccttccc cgctgtcctc 540 <br>caatcttccg gtctctactc cct gtcttct gttgtcactg ttccatcatc ctcactcggc 600 <br>acaaaaacat atacctg~aa cgt tgatcac aagccaagta ataccaaagt tgataagcgc 660 <br>gtcgaatcca aatacggtcc cccctgccca ccgtgcccag caccacctgt ggcaggacca 720 <br>tcagtcttcc tgttcccccc aaaacccaag gacactctca tgatctcccg gacccctgag 780 <br>gtcacgtgcg tggtggtgga cgtgagccag gaagaccccg aggtccagtt caactggtac 840 <br>gtggatggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gttcaacagc 900 <br>acgtaccgtg tggtcagcgt cct caccgtc ctgcaccagg actggctgaa cggcaaggag 960 <br>tacaagtgca aggtctccaa caaaggcctc ccgtcctcca tcgagaaaac catctccaaa 1020 <br>gccaaagggc agccccgaga gccacaggtg tacaccctgc ccccatccca ggaggagatg 1080 <br>accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctaccccag cgacatcgcc 1140 <br>gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200 <br>gactccgacg gctccttctt cctctacagc aggctcaccg tggacaagag caggtggcag 1260 <br>gaggggaatg tcttctcatg ctccgtgatg catgaggctc tgcacaacag attcacacag 1320 <br>aagtccctct ccctgtctct gggtaaatga 1350 <br><21 ?> 39 <br><211> 1350 <br><2 12> DNK <br><21 ?> V estacka sekvenca <br><220> <br><223> Sinteticka <br><400> 39 <br>28 ?? ? 119 808 81 <br>gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60 <br>tcctgtgcag cctctggatt cacctttgat gattatacca tgcactgggt ccggcaagct 120 <br>ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag tataggctat 180 <br>gcggactctg tgaagggccg att caccatc tccagagaca acgccaagaa gtccctgtat 240 <br>ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagataat 300 <br>agtggctacg gtcactacta ctacggaatg gacgtctggg gccaagggac cacggtcacc 360 <br>gtcgcctcag ccagcacaaa aggtcctagc gtttttccac ttgccccatg ttcaaggtca 420 <br>acctccgaaa gtaccgccgc tct tggctgt ctcgtaaaag attattttcc cgaacctgta 480 <br>actgtctcct ggaactccgg cgcactcact tccggcgtac ataccttccc cgctgtcctc 540 <br>caatcttccg gtctctactc cct gtcttct gttgtcactg ttccatcatc ctcactcggc 600 <br>acaaaaacat atacctgcaa cgt tgatcac aagccaagta ataccaaagt tgataagcgc 660 <br>gtcgaatcca aatacggtcc cccctgcccc ccatgtcccg ctccacctgt ggctggtccc 720 <br>tctgttttcc tttttccccc taaacccaaa gataccctca tgatttccag aacccccgag 780 <br>gtcacctgcg tcgtcgttga tgt aagccaa gaagatcccg aagtccagtt caattggtat 840 <br>gtagacggtg ttgaagtcca taatgcaaaa ?????????? gagaggaaca gtttaattca 900 <br>acctatcgtg tcgttagcgt act caccgtt cttcatcaag actggctcaa tggaaaagaa 960 <br>tataaatgta aagttagcaa caaaggtctg cccagttcaa tcgaaaaaac aattagcaaa 1020 <br>gccaaaggcc aacctcgcga accccaagtc tataccttgc ccccttctca ggaagaaatg 1080 <br>?????????? aagtttcact cacatgcctc gtaaaaggat tctatccatc agacattgca 1140 <br>gtagaatggg aatctaacgg ccaacctgaa aataattaca aaaccactcc tcctgtcctc 1200 <br>gattctgacg gctctttttt cctttactcc agattgactg ttgataaatc ccgctggcag 1260 <br>gaaggtaacg ttttttcttg ttctgtgatg cacgaagccc tccataacag attcactcaa 1320 <br>aaatctcttt ctctctccct gggcaaataa 1350 <br><210> 40 <br><211> 449 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 40 <br>29 ?? 3119 808 81 <br>Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arq <br>1 5 10 15 <br>Ser Leu Arq Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr <br>20 25 30 <br>Thr Met His Trp Val Arq Gln Ala Pro Gly Lys Gly Leu Glu Trp Val <br>35 40 45 <br>Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val <br>50 55 60 <br>Lys Gly Arq Phe Thr Ile Ser Arq Asp Asn Ala Lys Lys Ser Leu Tyr <br>65 70 75 80 <br>Leu Gln Met Asn Ser Leu Arq Ala Glu Asp Thr Ala Leu Tyr Tyr Cys <br>85 90 95 <br>Ala Lys Asp Asn Ser Gly Tyr Gly His Tyr Tyr Tyr Gly Met Asp Val <br>100 105 110 <br>Trp Gly Gln Gly Thr Thr Val Thr Val Ala Ser Ala Ser Thr Lys Gly <br>115 120 125 <br>Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arq Ser Thr Ser Glu Ser <br>130 135 140 <br>Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val <br>145 150 155 160 <br>Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe <br>165 170 175 <br>Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val <br>180 185 190 <br>Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val <br>195 200 205 <br>Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arq Val Glu Ser Lys <br>210 215 220 <br>Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro <br>225 230 235 240 <br>30 .. <br>?? ? 119 808 81 <br>Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser <br>245 250 255 <br>Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp <br>260 265 270 <br>Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn <br>275 280 285 <br>Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val <br>290 295 300 <br>Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu <br>305 310 315 320 <br>Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys <br>325 330 335 <br>Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr <br>340 345 350 <br>Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr <br>355 360 365 <br>Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu <br>370 375 380 <br>Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu <br>385 390 395 400 <br>Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys <br>405 410 415 <br>Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu <br>420 425 430 <br>Ala Leu His Asn Arg Phe Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly <br>435 440 445 <br>Lys <br><210> 41 <br><211> 1371 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br>31 ???11980881 <br><400> 41 <br>gaagtacagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60 <br>tcctgtgtag cctctggatt cacctttaat gattatgcca tgcactgggt ccggcaagct 120 <br>ccagggaagg gcctggaatg ggtctcagtt attagttgga atagtgatag cataggctat 180 <br>gcggactctg tgaaggg~cg attcaccatc tccagagaca acgccaagaa ctccctgtat 240 <br>ctgcaaatgc acagtctgag agctgaggac acggccttgt attactgtgc aaaagataat 300 <br>cactatggtt cggggagtta ttactactac caatacggta tggacgtctg gggccaaggg 360 <br>accacggtca ccgtctcctc agcctccacc aagggcccat cggtcttccc cctggcaccc 420 <br>tcctccaaga gcacctctgg gggcacagcg gccctgggct gcctggtcaa ggactacttc 480 <br>cccgaaccgg tgacggtgtc gtggaactca ggcgccctga ccagcggcgt gcacaccttc 540 <br>ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cgtgccctcc 600 <br>agcagcttgg gcacccagac ctacatctgc aacgtgaatc acaagcccag caacaccaag 660 <br>gtggacaaga aagttgagcc caaatcttgt gacaaaactc acacatgccc accgtgccca 720 <br>gcaccacctg tggcaggacc atcagtcttc ctgttccccc ?????????? ggacactctc 780 <br>atgatctccc ggacccctga ggtcacgtgc gtggtggtgg acgtgagcca ggaagacccc 840 <br>gaggtccagt tcaactggta cgt ggatggc gtggaggtgc ataatgccaa gacaaagccg 900 <br>cgggaggagc agttcaacag cacgtaccgt gtggtcagcg tcctcaccgt cctgcaccag 960 <br>gactggctga acggcaagga gtacaagtgc aaggtctcca acaaaggcct cccgtcctcc 1020 <br>atcgagaaaa ccatctccaa agccaaaggg cagccccgag aaccacaggt gtacaccctg 1080 <br>cccccatccc gggatgagct gaccaagaac caggtcagcc tgacctgcct ggtcaaaggc 1140 <br>ttctatccca gcgacatcgc cgtggagtgg gagagcaatg ggcagccgga gaacaactac 1200 <br>aagaccacgc ctcccgtgct ggactccgac ggctccttct tcctctacag caagctcacc 1260 <br>gtggacaaga gcaggtggca gcaggggaac gtcttctcat gctccgtgat gcatgaggct 1320 <br>ctgcacaacc actacacgca gaagtccctc tccctgtctc cgggtaaatg ? 1371 <br><210> 42 <br><211> 456 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 42 <br>32 ?? 3119 808 81 <br>Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg <br>1 5 10 15 <br>33 ?? ? 119 808 81 <br>Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Asn Asp Tyr <br>20 25 30 <br>Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val <br>35 40 45 <br>Ser Val Ile Ser Trp Asn Ser Asp Ser Ile Gly Tyr Ala Asp Ser Val <br>50 55 60 <br>Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr <br>65 70 75 80 <br>Leu Gln Met His Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys <br>85 90 95 <br>Ala Lys Asp Asn His Tyr Gly Ser Gly Ser Tyr Tyr Tyr Tyr Gln Tyr <br>100 105 110 <br>Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala <br>115 120 125 <br>Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser <br>130 135 140 <br>Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe <br>145 150 155 160 <br>Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly <br>165 170 175 <br>Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu <br>180 185 190 <br>Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr <br>195 200 205 <br>Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys <br>210 215 220 <br>Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro <br>225 230 235 240 <br>Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro <br>245 250 255 <br>Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val <br>260 265 270 <br>34 ??311980881 <br>Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val <br>275 280 285 <br>Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln <br>290 295 300 <br>Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln <br>305 310 315 320 <br>Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly <br>325 330 335 <br>Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro <br>340 345 350 <br>Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr <br>355 360 365 <br>Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser <br>370 375 380 <br>Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr <br>385 390 395 400 <br>Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr <br>405 410 415 <br>Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe <br>420 425 430 <br>Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys <br>435 440 445 <br>Ser Leu Ser Leu Ser Pro Gly Lys <br>450 455 <br><210> 43 <br><211 > 1359 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 43 <br>35 ?? 3119 808 81 <br>gaagtgcagc tggtggagtc t gggggaggc ttggtacagc ctggcaggtc cctgagactc 60 <br>tcctgtgcag cctctggatt cacctttgat gattatacca tgcactgggt ccggcaagct 120 <br>ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag tataggctat 180 <br>gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa gtccctgtat 240 <br>ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagataat 300 <br>agtggctacg gtcacta~ta ctacggaatg gacgtctggg gccaagggac cacggtcacc 360 <br>gtcgcctcag cctccaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc 420 <br>acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 480 <br>acggtgtcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 540 <br>cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgggc 600 <br>acccagacct acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaaa 660 <br>gttgagccca aatcttgtga caaaactcac acatgcccac cgtgcccagc accacctgtg 720 <br>gcaggaccat cagtcttcct gttcccccca aaacccaagg acactctcat gatctcccgg 780 <br>acccctgagg tcacgtgcgt ggtggtggac gtgagccagg aagaccccga ggtccagttc 840 <br>aactggtacg tggatggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 900 <br>ttcaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaac 960 <br>ggcaaggagt acaagtgcaa ggtctccaac aaaggcctcc cgtcctccat cgagaaaacc 1020 <br>atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1080 <br>gatgagctga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1140 <br>gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1200 <br>cccgtgctgg actccgacgg ctccttcttc ctctacagca agctcaccgt ggacaagagc 1260 <br>aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaacaga 1320 <br>ttcacgcaga agtccctctc cctgtctccg ggtaaatga 1359 <br><210> 44 <br><211> 452 <br><212> PRT <br><21 ?> V estacka sekvenca <br><220> <br><223> Sinteticka <br>< 400> 44 <br>36 ?? 3 119 808 81 <br>Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg <br>1 5 10 15 <br>Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr <br>20 25 30 <br>Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val <br>35 40 45 <br>37 ?? 3 119 808 81 <br>Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val <br>50 55 60 <br>Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Lys Ser Leu Tyr <br>65 70 75 80 <br>Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys <br>85 90 95 <br>Ala Lys Asp Asn Ser Gly Tyr Gly His Tyr Tyr Tyr Gly Met Asp Val <br>100 105 110 <br>Trp Gly Gln Gly Thr Thr Val Thr Val Ala Ser Ala Ser Thr Lys Gly <br>115 120 125 <br>Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly <br>130 135 140 <br>Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val <br>145 150 155 160 <br>Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe <br>165 170 175 <br>Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val <br>180 185 190 <br>Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile ??? Asn Val <br>195 200 205 <br>Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys <br>210 215 220 <br>Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val <br>225 230 235 240 <br>Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu <br>24 5 250 255 <br>Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser <br>260 265 270 <br>Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu <br>275 280 285 <br>Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr <br>290 295 300 <br>38 ?? ? 119 808 81 <br>Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn <br>305 310 315 320 <br>Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser <br>325 330 335 <br>Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln <br>340 345 350 <br>Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val <br>355 360 365 <br>Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val <br>370 375 380 <br>Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro <br>385 390 395 400 <br>Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr <br>405 410 415 <br>Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val <br>420 425 430 <br>Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser Leu Ser Leu <br>435 440 445 <br>Ser Pro Gly Lys <br>450 <br><210> 45 <br><211> 330 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 45 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys <br>1 5 10 15 <br>Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>39 ?? 3119 808 81 <br>Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser <br>50 55 60 <br>Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr <br>65 70 75 80 <br>Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys <br>85 90 95 <br>Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro ??? <br>100 105 110 <br>Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro <br>115 120 125 <br>Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys <br>130 135 140 <br>Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp <br>145 150 155 160 <br>Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu <br>165 170 175 <br>Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu <br>180 185 190 <br>His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn <br>195 200 205 <br>Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly <br>210 215 220 <br>Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu <br>225 230 235 240 <br>Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr <br>245 250 255 <br>Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn <br>260 265 270 <br>Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe <br>275 280 285 <br>Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn <br>290 295 300 <br>40 ?? 3119 808 81 <br>Val Phe Ser Cys Ser Val Met Hi s Glu Ala Leu His Asn His Tyr Thr <br>305 310 315 320 <br>Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys <br>325 330 <br><210> 46 <br><211> 326 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 46 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arq <br>1 5 10 15 <br>Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser <br>50 55 60 <br>Leu Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr <br>65 70 75 80 <br>Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys <br>85 90 95 <br>Thr Val Glu Arq Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro <br>100 105 110 <br>Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp <br>115 120 125 <br>Thr Leu Met Ile Ser Arq Thr Pro Glu Val Thr Cys Val Val Val Asp <br>130 135 140 <br>Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly <br>145 150 155 160 <br>Val Glu Val His Asn Ala Lys Thr Lys Pro Arq Glu Glu Gln Phe Asn <br>165 170 175 <br>41 <210> 47 <br>?? 3119 808 81 <br>Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp <br>180 185 190 <br>Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro <br>195 200 205 <br>Ala Pro Ile Glu Lys Thr I le Ser Lys Thr Lys Gly Gln Pro Arg Glu <br>210 215 220 <br>Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn <br>225 230 235 240 <br>Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile <br>24 5 250 255 <br>Ser Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr <br>260 265 270 <br>Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys <br>275 280 285 <br>Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys <br>290 295 300 <br>Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu <br>305 310 315 320 <br>Ser Leu Ser Pro Gly Lys <br>325 <br><211> 327 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteti cka <br>< 400> 47 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg <br>1 5 10 15 <br>Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>42 ?? 3 119 808 81 <br>G1y Va1 His Thr Phe Pro ?1? Va1 Leu G1n Ser Ser G1y Leu Tyr Ser <br>50 55 60 <br>Leu Ser Ser Va1 Va1 Thr Va1 Pro Ser Ser Ser Leu G1y Thr Lys Thr <br>65 70 75 80 <br>Tyr Thr Cys Asn Va1 Asp Hi s Lys Pro Ser Asn Thr Lys Va1 Asp Lys <br>85 90 95 <br>Arg Va1 G1u Ser Lys Tyr G1y Pro Pro Cys Pro Ser Cys Pro ?1? Pro <br>100 105 110 <br>G1u Phe Leu G1y G1y Pro Ser Va1 Phe Leu Phe Pro Pro Lys Pro Lys <br>115 120 125 <br>Asp Thr Leu Met I 1e Ser Arg Thr Pro G1u Va1 Thr Cys Va1 Va1 Va1 <br>130 135 140 <br>Asp Va1 Ser G1n G1u Asp Pro G1u Va1 G1n Phe Asn Trp Tyr Va1 Asp <br>145 150 155 160 <br>Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe <br>165 170 175 <br>Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp <br>180 185 190 <br>Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu <br>195 200 205 <br>Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg <br>210 215 220 <br>Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys <br>225 230 235 240 <br>Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp <br>245 250 255 <br>Ile Ala Val G1u Trp Glu Ser Asn G1y Gln Pro Glu Asn Asn Tyr Lys <br>260 265 270 <br>Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser <br>275 280 285 <br>Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser <br>290 295 300 <br>43 ?? ? 119 808 81 <br>Cys Ser Val Met His Glu Ala Leu Hi s Asn His Tyr Thr Gln Lys Ser <br>305 310 315 320 <br>Leu Ser Leu Ser Leu Gly Lys <br>325 <br><210> 48 <br><211 > 330 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 48 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys <br>1 5 10 15 <br>Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser <br>50 55 60 <br>Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr <br>65 70 75 80 <br>Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys <br>85 90 95 <br>Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys <br>100 105 110 <br>Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro <br>115 120 125 <br>Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys <br>130 135 140 <br>Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp <br>145 150 155 160 <br>Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu <br>165 170 175 <br>44 ?? ? 119 808 81 <br>G1u G1n Tyr Asn Ser Thr Tyr Arg Va1 Va1 Ser Va1 Leu Thr Va1 Leu <br>180 185 190 <br>His G1n Asp Trp Leu Asn G1y Lys G1u Tyr Lys Cys Lys Va1 Ser Asn <br>195 200 205 <br>Lys ?1? Leu Pro ?1? Pro I1e G1u Lys Thr I1e Ser Lys ?1? Lys G1y <br>210 215 220 <br>G1n Pro Arg G1u Pro G1n Va1 Tyr Thr Leu Pro Pro Ser Arg Asp G1u <br>225 230 235 240 <br>Leu Thr Lys Asn G1n Va1 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr <br>245 250 255 <br>Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn <br>260 265 270 <br>Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe <br>275 280 285 <br>Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn <br>290 295 300 <br>Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr <br>305 310 315 320 <br>Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys <br>325 330 <br><2 10> 49 <br><211> 327 <br><2 12> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 49 <br>45 ?? ? 119 808 81 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arq <br>1 5 10 15 <br>Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Gl u Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser <br>46 ?? ? 119 808 81 <br>50 55 60 <br>Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr <br>65 70 75 80 <br>Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys <br>85 90 95 <br>Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro <br>100 105 110 <br>Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys <br>115 120 125 <br>Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val <br>130 135 140 <br>Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp <br>145 150 155 160 <br>Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe <br>165 170 175 <br>Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp <br>180 185 190 <br>Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu <br>195 200 205 <br>Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg <br>210 215 220 <br>Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys <br>225 230 235 240 <br>Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp <br>245 250 255 <br>Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys <br>260 265 270 <br>Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser <br>275 280 285 <br>Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser <br>290 295 300 <br>47 ?? 3 119 808 81 <br>Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser <br>305 310 315 320 <br>Leu Ser Leu Ser Leu Gly Lys <br>325 <br><210> 50 <br><211> 12 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 50 <br>Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro <br>1 5 10 <br><21 ?> 51 <br><211 > 9 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 51 <br><210> 52 <br><211 > 8 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 52 <br><210> 53 <br><211> 20 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 53 <br>Glu Ser Lys Tyr Gly Pro Pro Cys Pro <br>1 5 <br>Pro Cys Pro Ala Pro Pro Val Ala <br>1 5 <br>Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala <br>1 5 10 15 <br>48 ?? ? 119 808 81 <br>Pro Pro Val Ala <br>20 <br><210> 54 <br><211> 17 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 54 <br>Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Pro Val <br>1 5 <br>10 <br>15 <br>Ala <br><210> 55 <br><211> 104 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 55 <br>Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met <br>1 5 10 15 <br>Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln <br>20 25 30 <br>Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val <br>35 40 45 <br>His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr <br>50 55 60 <br>Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly <br>65 70 75 80 <br>Lys Glu Tyr ~ys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile <br>85 90 95 <br>Glu Lys Thr Ile Ser Lys Ala Lys <br>100 <br><210> 56 <br><21 1> 107 <br>49 ?? ? 119 808 81 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 56 <br>Gly Gln Pro Arg Gl u Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp <br>1 5 10 15 <br>Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe <br>20 25 30 <br>Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu <br>35 40 45 <br>Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe <br>50 55 60 <br>Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly <br>65 70 75 80 <br>Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Hi s Tyr <br>85 90 95 <br>Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys <br>100 105 <br><210> 57 <br><211> 107 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 57 <br>50 ?? ? 119 808 81 <br>Gly Gln Pro Arg Glu Pro Gl n Val Tyr Thr Leu Pro Pro Ser Arg Asp <br>1 5 10 15 <br>Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe <br>20 25 30 <br>Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu <br>35 40 45 <br>Asn Asn Tyr ~ys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe <br>50 55 60 <br>Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly <br>65 70 75 80 <br>Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe <br>85 90 95 <br>Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys <br>100 105 <br><210> 58 <br><211> 107 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 58 <br>51 ?? 3 119 808 81 <br>Gly Gl n Pro Arg Glu Pro Gl n Val Tyr Thr Leu Pro Pro Ser Gln Glu <br>1 5 10 15 <br>Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe <br>20 25 30 <br>Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu <br>35 40 45 <br>Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe <br>50 55 60 <br>Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly <br>65 70 75 80 <br>Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr <br>85 90 95 <br>Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys <br>100 105 <br><2 10> 59 <br><211 > 107 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 59 <br>Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu <br>1 5 10 15 <br>52 ?? 3 119 808 81 <br>Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe <br>20 25 30 <br>Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu <br>35 40 45 <br>Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe <br>50 55 60 <br>Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly <br>65 70 75 80 <br>Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe <br>85 90 95 <br>Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys <br>100 105 <br><210> 60 <br><211> 98 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Sinteticka <br><400> 60 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys <br>1 5 10 15 <br>Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Glu Pro Va l Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser <br>50 55 60 <br>Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr <br>65 70 75 80 <br>Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys <br>85 90 95 <br>Lys Val <br><21 0>61 <br>53 ? <br>?? 3119 808 81 <br><211> 98 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 61 <br>Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg <br>1 5 10 15 <br>Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr <br>20 25 30 <br>Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser <br>35 40 45 <br>Gly Val His ~hr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser <br>50 55 60 <br>Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr <br>65 70 75 80 <br>Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys <br>85 90 95 <br>Arg Val <br><210> 62 <br><211 > 106 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 62 <br>Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln <br>1 5 10 15 <br>Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr <br>20 25 30 <br>Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser <br>35 40 45 <br>Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr <br>50 55 60 <br>54 r <br>?? 3119 808 81 <br>Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys <br>65 70 75 80 <br>His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro <br>85 90 95 <br>Val Thr Lys Ser Phe Asn Arg Gly Glu Cys <br><210> 6? <br><211> 60 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 6? <br>100 105 <br>ttcgcgcagc ttaggtttat gccagggggg acgggtggca cgggtcgtgg tggacaccgt 60 <br><210> 64 <br><211> 40 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 64 <br>aagcttatac tcgagctcta gattgggaac ccgggtctct 40 <br><210> 65 <br><211 > 58 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 65 <br>cccaccgtgc ccagcaccac ctgtggcagg accatcagtc ttcctgttcc ???????? 58 <br><210> 66 <br><211>44 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 66 <br>tgtgtcttca gggagaggga cagagaccca tttactcgcc ggcg 44 <br><210> 67 <br><211> 60 <br><212> DNK <br>55 .. <br>,. <br>?? ? 119 808 81 <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 67 <br>ctcgggttta gaacactgtt ttgagtgtgt acgggtggca cgggtcgtgg tggacaccgt 60 <br><210> 68 <br><211> 51 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 68 <br>aaatcttgtg acaaaactca cacatgccca ccgtgcccag caccacctgt g 51 <br><210> 69 <br><211> 54 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 69 <br>gagaaaacca tctccaaagc caaagggcag ccccgagaac cacaggtgta ???? 54 <br><21 ?> 70 <br><211>54 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 70 <br>ctcttttggt agaggtttcg gtttcccgtc. ggggctcttg gtgtccacat gtgg 54 <br><21 ?> 71 <br><211> ?9 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 71 <br>cttcagggag agggacagag gcccatttac tcgccggcg ?9 <br><210> 72 <br><211> 20 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br>56 , <br>• <br>?? ? 119 808 81 <br><22?> Sinteticka <br><400> 72 <br>gctgacagac taacagactg 20 <br><21 ?> 7? <br><211 > 26 <br><212> DNK <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 7? <br>atacattata cgaagttata ccggta 26 <br><210>74 <br><211> 105 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Sinteticka <br><400> 74 <br>Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu <br>1 5 10 15 <br>Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro <br>20 25 30 <br>Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly <br>35 40 45 <br>Asn Ser Gln Glu Se r Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr <br>50 55 60 <br>Ser Leu Ser Ser Thr Leu Thr Le u Ser Lys Ala Asp Tyr Glu Lys His <br>65 70 75 80 <br>Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val <br>85 90 95 <br>Thr Lys Ser Phe Asn Arg Gly Glu Cys <br>100 105 <br><210>75 <br><211 > 108 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br>57 ?? ? 119 808 81 <br><223> Sinteticka <br><400> 75 <br>Ala Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro <br>1 5 10 15 <br>Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser <br>20 25 30 <br>Asn Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu <br>35 40 45 <br>Ile Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser <br>50 55 60 <br>Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln <br>65 70 75 80 <br>Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Ile Asn Trp Pro <br>85 90 95 <br>Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys <br>100 105

Claims (14)

1. Bispecifično antitelo za upotrebu za lečenje ili poboljšanje kancera B ćelije kod subjekta, pri čemu to bispecifično antitelo obuhvata prvi domen koji vezuje antigen koji veže humani CD3, drugi domen koji vezuje antigen koji veže humani CD20, i himerni Fc domen je privezan na svaki od prvih i drugih domena koji vezuju antigen, pri čemu taj himerni Fc domen obuhvata: (a) sekvence aminokiseline gornjeg zgloba humanog lgG1 ili humanog lgG4 iz pozicija 216 do 227 (EU numeracija);(b) sekvenca aminokiseline donjeg zgloba humanog lgG2 obuhvata PCPAPPVA (SEK ID BR: 52) od pozicija 228 do 236 (EU numeracija); (e) CH1 domen humanog lgG1 i CH3 domen humanog lgG1, ili CHI domen humanog lgG4 i CH3 domen humanog lgG4; i(d) sekvencu aminokiseline CH2 domena humanog lgG4 od pozicija 237 do 340 (EU numeracija); pri čemu bispecifično antitelo ispoljava viši afinitet vezivanja za humani FcyRIIA u odnosu na humani FcyRIIB, i ispoljava mali ili nedektibilan afinitet vezivanja na humani FcyRI i humani FcyRIII, kako je izmereno u ogledu rezonance površinskog plazmona.
2.Bispecifično antitelo za upotrebu prema patentnom zahtevu 1, pri čemu se kancer B ćelije bira iz grupe koja obuhvata: folikularni limfom, hroničnu limfocitnu leukemiju B ćelije, limfoblastični limfom B ćelije, Hodžkinov limfom, ne-Hodžkinov limfom, difuzni limfom velike B ćelije, limfom marginalne zone, limfom ćelije plašta, leukemija dlakave ćelije i Burkov (Burkitt) limfom.
3.Bispecifično antitelo za upotrebu prema patentnom zahtevu 2, pri čemu je kancer B ćelije ne-Hodžkinov limfom.
4. Bispecifično an itelo za upotrebu prema patentnom zahtevu 1 ili 3, pri čemu je subjekat boluje od tumora koji je otporan na, ili potpuno neosetljiv na (a) monospecifičnu terapiju samo za anti-CD20, ili (b) rituksimab monoterapiju; i/ili pri čemu taj subjekat je primio terapiju monospecifičnog antitela anti-CD20 barem 1 dan do 1 godine pre isporuke bispecifičnog antitela.
5. Bispecifično antitelo za upotrebu prema jednom od patentnih zahteva 1 do 4, pri čemu to antitelo:(a) ispoljava smanjenu od antitela zavisnu ćelijsku citotoksičnost (ADCC) u poređenju sa antitelom koje obuhvata Fc domen divljeg tipa, kako je izmereno u in vitro ogledu citotoksičnosti;(b) ispoljava zanemarljiv ili nedektibilan ADCC;(e) ispoljava smanjenu citotoksičnost zavisnu od komplementa (CDC) u poređenju sa antitelom koje obuhvata Fc domen divljeg tipa, kako je izmereno u in vitro ogledu citotoksičnosti;(d) ispoljava manje od 50% citotoksičnosti, kako je detektovano merenjem lize ćelije u in vitro ogledu;(e) ispoljava zanemarljiv ili nedektibilan CDC;(f) indukuje smanjeno ubijanje posredovano T ćelijom ćelija koje nose Fc receptore, kao što su NK ćelije ili makrofagi, u poređenju sa antitelom koje obuhvata Fc domen divljeg tipa; ili(g) indukuje smanjeno T ćelijama posredovano ubijanje ćelijama koje nose Fc receptor, kao što su NK ćelije ili makrofagi, u poređenju sa antitelom koje obuhvata Fc domen divljeg tipa.
6. Bispecifično antitelo za upotrebu prema bilo kom od patentnih zahteva 1 do 4, pri čemu bispecifično antitelo obuhvata(a) himernu sekvencu aminokiseline zgloba EPKSCDKTHTCPPCPAPPVA (SEK ID BR: 53); ili(b) himernu sekvencu aminokiseline zgloba ESKYGPPCPPCPAPPVA (SEK ID BR: 54).
7. Bispecifično antitelo za upotrebu prema bilo kom od patentnih zahteva 1 do6, pri čemu prvi domen koji vezuje antigen koji specifično vezuje humani CD3 obuhvata promenljivi region teškog lanca (HCVR) sekvence aminokiseline koja obuhvata SEK ID BR: 10 i promenljivi region lakog lanca (LCVR) sa sekvencom aminokiseline iz SEK ID BR: 18.
8. Bispecifično antitelo za upotrebu prema bilo kom od patentnih zahteva 1 do7, pri čemu drugi domen koji vezuje antigen koji specifično vezuje humani CD20 obuhvata promenljivi region teškog lanca (HCVR) sekvence aminokiseline koja obuhvata SEK ID BR: 2 i promenljivi region lakog lanca (LCVR) sa sekvencom aminokiseline iz SEK ID BR: 18.
9. Bispecifično antitelo za upotrebu prema bilo kom od patentnih zahteva 1 do6, pri čemu prvi domen koji vezuje antigen (A1) koji specifično vezuje humani CD3 obuhvata tri regiona određivanja komplementarnosti teškog lanca (HCDR1, HCDR2, HCDR3) i tri regiona određivanja komplementarnosti lakog lanca (LCDR1, LCDR2, LCDR3), pri čemu(i) A1-HCDR1 obuhvata sekvencu aminokiseline od SEK ID BR: 12; (ii) A1-HCDR2 obuhvata sekvencu aminokiseline od SEK ID BR: 14; (iii) A1-HCDR3 obuhvata sekvencu aminokiseline od SEK ID BR. 16; (iv) A1-LCDR1 obuhvata sekvencu aminokiseline od SEK ID BR: 20; (v) A1-LCDR2 obuhvata sekvencu aminokiseline od SEK ID BR: 22; i(vi) A1-LCDR3 obuhvata sekvencu aminokiseline od SEK ID BR: 24.
10.Bispecifično antitelo za upotrebu prema bilo kom od patentnih zahteva 1 do6 ili 9, pri čemu drugi domen koji vezuje antigen (A2) koji specifično vezuje humani CD20, obuhvata tri regiona određivanja komplementarnosti teškog lanca (HCDR1,·HCDR2, HCDR3) i tri regiona određivanja komplementarnosti lakog lanca (LCDR1, LCDR2, LCDR3), pri čemu(i) A2-HCDR1 obuhvata sekvencu aminokiseline od SEK ID BR: 4; (ii) A2-HCDR2 obuhvata sekvencu aminokiseline od SEK ID BR: 6; (iii) A2-HCDR3 obuhvata sekvencu aminokiseline od SEK ID BR: 8; (iv) A2-LCDR1 obuhvata sekvencu aminokiseline od SEK ID BR: 20;(v) A2-LCDR2 obuhvata sekvencu aminokiseline od SEK ID BR. 22; i(vi) A2-LCDR3 obuhvata sekvencu aminokiseline od SEK ID BR: 24.
11. Bispecifično antitelo za upotrebu prema bilo kom od patentnih zahteva 1 do1O, pri čemu bispecifično antitelo obuhvata himerni Fc domen koji obuhvata sekvencu aminokiseline od SEK ID BR: 26.
12. Bispecifično antitelo za upotrebu prema bilo kom od patentnih zahteva 1 do10, pri čemu bispecifično antitelo obuhvata himerni Fc domen koji obuhvata sekvencu aminokiseline od SEK ID BR: 28.
13. Bispecifično antitelo za upotrebu prema bilo kom od patentnih zahteva 1 do1O, pri čemu bispecifično antitelo obuhvata himerni Fc domen koji obuhvata sekvencu aminokiseline od SEK ID BR: 30.
14. Bispecifično antitelo za upotrebu prema bilo kom od patentnih zahteva 1 do1O, pri čemu bispecifično antitelo obuhvata himerni Fc domen koji obuhvata sekvencu aminokiseline od SEK ID BR: 32.
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