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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
Authority
ME
Montenegro
Prior art keywords
ser
val
pro
thr
leu
Prior art date
Application number
MEP-2019-303A
Other languages
German (de)
English (en)
French (fr)
Inventor
Samuel Davis
Eric Smith
Bindu Varghese
Jessica R Kirshner
Gavin Thurston
Original Assignee
Regeneron Pharma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Regeneron Pharma filed Critical Regeneron Pharma
Publication of ME03544B publication Critical patent/ME03544B/me

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    • C07K2317/526—CH3 domain
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    • C07K2317/00—Immunoglobulins specific features
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    • C07—ORGANIC CHEMISTRY
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

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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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Families Citing this family (189)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12466897B2 (en) 2011-10-10 2025-11-11 Xencor, Inc. Heterodimeric human IgG1 polypeptides with isoelectric point modifications
US10851178B2 (en) 2011-10-10 2020-12-01 Xencor, Inc. Heterodimeric human IgG1 polypeptides with isoelectric point modifications
JOP20200236A1 (ar) 2012-09-21 2017-06-16 Regeneron Pharma الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها
US10487155B2 (en) 2013-01-14 2019-11-26 Xencor, Inc. Heterodimeric proteins
US9605084B2 (en) 2013-03-15 2017-03-28 Xencor, Inc. Heterodimeric proteins
US10968276B2 (en) 2013-03-12 2021-04-06 Xencor, Inc. Optimized anti-CD3 variable regions
US11053316B2 (en) 2013-01-14 2021-07-06 Xencor, Inc. Optimized antibody variable regions
US9701759B2 (en) 2013-01-14 2017-07-11 Xencor, Inc. Heterodimeric proteins
US10131710B2 (en) 2013-01-14 2018-11-20 Xencor, Inc. Optimized antibody variable regions
CN110981964B (zh) 2013-01-14 2023-09-15 Xencor股份有限公司 新型异二聚体蛋白
TWI682941B (zh) 2013-02-01 2020-01-21 美商再生元醫藥公司 含嵌合恆定區之抗體
EP3421495A3 (en) 2013-03-15 2019-05-15 Xencor, Inc. Modulation of t cells with bispecific antibodies and fc fusions
US10519242B2 (en) 2013-03-15 2019-12-31 Xencor, Inc. Targeting regulatory T cells with heterodimeric proteins
US10106624B2 (en) 2013-03-15 2018-10-23 Xencor, Inc. Heterodimeric proteins
US10858417B2 (en) 2013-03-15 2020-12-08 Xencor, Inc. Heterodimeric proteins
AR095196A1 (es) 2013-03-15 2015-09-30 Regeneron Pharma Medio de cultivo celular libre de suero
KR20220116581A (ko) 2013-12-17 2022-08-23 제넨테크, 인크. 항-cd3 항체 및 이의 사용 방법
TWI680138B (zh) 2014-01-23 2019-12-21 美商再生元醫藥公司 抗ｐｄ-ｌ１之人類抗體
TWI681969B (zh) 2014-01-23 2020-01-11 美商再生元醫藥公司 針對ｐｄ-１的人類抗體
TWI701042B (zh) * 2014-03-19 2020-08-11 美商再生元醫藥公司 用於腫瘤治療之方法及抗體組成物
RS59907B1 (sr) 2014-03-28 2020-03-31 Xencor Inc Bispecifična antitela koja se vezuju za cd38 i cd3
WO2016040868A1 (en) 2014-09-12 2016-03-17 Genentech, Inc. Anti-cll-1 antibodies and immunoconjugates
HUE071048T2 (hu) * 2014-11-17 2025-07-28 Regeneron Pharma Daganatkezelési módszerek a CD3XCD20 bispecifikus antitest használatával
HUE052603T2 (hu) 2014-11-24 2021-05-28 Regeneron Pharma Humanizált CD3-komplexet expresszáló nem humán állatok
SG11201704283PA (en) 2014-11-26 2017-06-29 Xencor Inc Heterodimeric antibodies that bind cd3 and tumor antigens
US10526417B2 (en) 2014-11-26 2020-01-07 Xencor, Inc. Heterodimeric antibodies that bind CD3 and CD38
US10259887B2 (en) 2014-11-26 2019-04-16 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
US10428155B2 (en) 2014-12-22 2019-10-01 Xencor, Inc. Trispecific antibodies
CA2973159A1 (en) 2015-01-08 2016-07-14 Genmab A/S Bispecific antibodies against cd3 and cd20
WO2016141387A1 (en) 2015-03-05 2016-09-09 Xencor, Inc. Modulation of t cells with bispecific antibodies and fc fusions
ES2846748T3 (es) 2015-03-30 2021-07-29 Regeneron Pharma Regiones constantes de cadenas pesadas con unión reducida a receptores Fc gamma
EA039429B1 (ru) * 2015-05-13 2022-01-26 Ридженерон Фармасьютикалз, Инк. Способы лечения опухолей с применением биспецифического антитела cd3xcd20
WO2016204966A1 (en) 2015-06-16 2016-12-22 Genentech, Inc. Anti-cd3 antibodies and methods of use
TW201718647A (zh) 2015-06-16 2017-06-01 建南德克公司 抗-cll-1抗體及使用方法
RS64662B1 (sr) 2015-06-16 2023-11-30 Hoffmann La Roche Humanizovana i afinitetno sazrela antitela na fcrh5 i postupci upotrebe
WO2017010423A1 (ja) * 2015-07-10 2017-01-19 中外製薬株式会社 内因性ｃｄ３遺伝子をヒトｃｄ３遺伝子に置換した非ヒト動物
JOP20160154B1 (ar) 2015-07-31 2021-08-17 Regeneron Pharma أجسام ضادة مضاد لل psma، وجزيئات رابطة لمستضد ثنائي النوعية الذي يربط psma و cd3، واستخداماتها
TWI797060B (zh) 2015-08-04 2023-04-01 美商再生元醫藥公司 補充牛磺酸之細胞培養基及用法
US11623957B2 (en) 2015-12-07 2023-04-11 Xencor, Inc. Heterodimeric antibodies that bind CD3 and PSMA
US20170174781A1 (en) * 2015-12-22 2017-06-22 Regeneron Pharmaceuticals, Inc. Bispecific Anti-CD20/Anti-CD3 Antibodies to Treat Acute Lymphoblastic Leukemia
WO2017112775A1 (en) * 2015-12-22 2017-06-29 Regeneron Pharmaceuticals, Inc. Combination of anti-pd-1 antibodies and bispecific anti-cd20/anti-cd3 antibodies to treat cancer
JP7190901B2 (ja) * 2016-01-12 2022-12-16 クレッシェンド、バイオロジックス、リミテッド 前立腺特異的膜抗原（ｐｓｍａ）と結合する分子
TW201803981A (zh) 2016-04-20 2018-02-01 再生元醫藥公司 用於以使用增強表現基因座爲基礎製造抗體之組成物及方法
SG11201807885PA (en) 2016-04-20 2018-10-30 Regeneron Pharma Compositions and methods for making antibodies based on use of expression-enhancing loci
GB201607968D0 (en) 2016-05-06 2016-06-22 Crescendo Biolog Ltd Chimeric antigen receptor
TWI786044B (zh) 2016-05-13 2022-12-11 美商再生元醫藥公司 藉由投予ｐｄ-１抑制劑治療皮膚癌之方法
US20170349657A1 (en) * 2016-06-01 2017-12-07 Xencor, Inc. Bispecific antibodies that bind cd20 and cd3
LT3468586T (lt) 2016-06-14 2024-12-10 Xencor, Inc. Bispecifiniai antikūnai prieš imuninės sistemos kontrolės taškų inhibitorius
JP7432363B2 (ja) * 2016-06-21 2024-02-16 テネオバイオ， インコーポレイテッド Ｃｄ３結合抗体
MX2018016265A (es) 2016-06-28 2019-07-04 Xencor Inc Anticuerpos heterodimericos que se unen al receptor 2 de somatostatina.
WO2018038046A1 (ja) 2016-08-22 2018-03-01 中外製薬株式会社 ヒトｇｐｃ３ポリペプチドを発現する遺伝子改変非ヒト動物
EP3504328A1 (en) 2016-08-24 2019-07-03 Regeneron Pharmaceuticals, Inc. Host cell protein modification
US10793632B2 (en) 2016-08-30 2020-10-06 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
CR20220408A (es) 2016-09-14 2022-10-20 Teneobio Inc ANTICUERPOS DE UNIÓN A CD3(Divisional del Expediente 2019-198)
BR112019005670A2 (pt) * 2016-09-23 2019-06-04 Regeneron Pharmaceuticals, Inc. anticorpos anti-muc16 (mucina 16)
NZ793452A (en) 2016-10-14 2025-09-26 Xencor Inc IL15/IL15Rα HETERODIMERIC FC-FUSION PROTEINS
KR20190074300A (ko) * 2016-11-15 2019-06-27 제넨테크, 인크. 항-cd20/항-cd3 이중특이적 항체에 의한 치료를 위한 투약
BR112019012354A2 (pt) 2016-12-21 2019-11-26 Teneobio Inc anticorpos apenas de cadeia pesada anti-bcma
EP3565841A1 (en) 2017-01-06 2019-11-13 Crescendo Biologics Limited Single domain antibodies to programmed cell death (pd-1)
MA47604A (fr) 2017-02-21 2020-01-01 Regeneron Pharma Anticorps anti-pd-1 pour le traitement du cancer du poumon
US11603407B2 (en) 2017-04-06 2023-03-14 Regeneron Pharmaceuticals, Inc. Stable antibody formulation
JOP20190222A1 (ar) * 2017-04-11 2019-09-24 Zymeworks Inc الأجسام المضادة ثنائية النوعية المضادة لـ pd-l1 والمضادة لـ tim-3
JP7240335B2 (ja) 2017-06-20 2023-03-15 テネオワン， インコーポレイテッド 抗ｂｃｍａ重鎖のみ抗体
IL271194B2 (en) 2017-06-20 2024-10-01 Teneobio Inc Anti-bcma heavy chain-only antibodies
EP3642229A1 (en) 2017-06-21 2020-04-29 Gilead Sciences, Inc. Multispecific antibodies that target hiv gp120 and cd3
MA49517A (fr) 2017-06-30 2020-05-06 Xencor Inc Protéines de fusion fc hétérodimères ciblées contenant il-15/il-15ra et domaines de liaison à l'antigène
AU2018298039B2 (en) 2017-07-06 2023-02-02 Regeneron Pharmaceuticals, Inc. Cell culture process for making a glycoprotein
GB201711068D0 (en) 2017-07-10 2017-08-23 Crescendo Biologics Ltd Therapeutic molecules binding PSMA
TWI799432B (zh) * 2017-07-27 2023-04-21 美商再生元醫藥公司 抗ctla-4抗體及其用途
EP3658125A4 (en) * 2017-07-28 2021-04-28 National University of Singapore BIOMOLECULAR COMPOSITES INCLUDING MODIFIED CELL PHANTOMS
CN113896797B (zh) 2017-08-01 2023-05-09 Ab工作室有限公司 双特异性抗体及其用途
AU2018366199A1 (en) 2017-11-08 2020-05-28 Xencor, Inc. Bispecific and monospecific antibodies using novel anti-PD-1 sequences
US10981992B2 (en) 2017-11-08 2021-04-20 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
CA3082321A1 (en) 2017-11-13 2019-05-16 Crescendo Biologics Limited Single domain antibodies that bind to cd137
CN111655718B (zh) 2017-12-19 2025-07-22 Xencor股份有限公司 经过工程化的il-2 fc融合蛋白
CN111683966B (zh) 2017-12-22 2023-07-11 特尼奥生物股份有限公司 与cd22结合的重链抗体
JP7321159B2 (ja) 2017-12-22 2023-08-04 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 薬剤生成物不純物を特性決定するためのシステム及び方法
AU2019215363A1 (en) 2018-01-31 2020-07-23 Regeneron Pharmaceuticals, Inc. System and method for characterizing size and charge variant drug product impurities
TW202311746A (zh) 2018-02-02 2023-03-16 美商再生元醫藥公司 用於表徵蛋白質二聚合之系統及方法
WO2019157308A1 (en) 2018-02-08 2019-08-15 Genentech, Inc. Bispecific antigen-binding molecules and methods of use
GB201802573D0 (en) 2018-02-16 2018-04-04 Crescendo Biologics Ltd Therapeutic molecules that bind to LAG3
SG11202006310PA (en) 2018-02-28 2020-07-29 Regeneron Pharma Systems and methods for identifying viral contaminants
BR112020018618A2 (pt) 2018-03-13 2020-12-29 Zymeworks, Inc. Conjugados anticorpo anti-her2 biparatópico-droga e métodos de uso
US12253490B2 (en) 2018-03-19 2025-03-18 Regeneron Pharmaceuticals, Inc. Microchip capillary electrophoresis assays and reagents
US12259355B2 (en) 2018-03-19 2025-03-25 Regeneron Pharmaceuticals, Inc. Microchip capillary electrophoresis assays and reagents
PL3768709T3 (pl) 2018-03-19 2024-05-20 Regeneron Pharmaceuticals, Inc. Analizy mikroczipowej elektroforezy kapilarnej i stosowane w nich odczynniki
EP3773911A2 (en) 2018-04-04 2021-02-17 Xencor, Inc. Heterodimeric antibodies that bind fibroblast activation protein
EP3781598A1 (en) 2018-04-18 2021-02-24 Xencor, Inc. Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains
JP2021521784A (ja) 2018-04-18 2021-08-30 ゼンコア インコーポレイテッド ＩＬ−１５／ＩＬ−１５ＲａＦｃ融合タンパク質とＰＤ−１抗原結合ドメインを含むＰＤ−１標的化ヘテロダイマー融合タンパク質およびそれらの使用
TW202016125A (zh) 2018-05-10 2020-05-01 美商再生元醫藥公司 用於定量及調節蛋白質黏度之系統與方法
EP3569617A1 (en) * 2018-05-18 2019-11-20 Trion Research GmbH Pharmaceutical preparation for use in treating epstein- barr virus positive patients with reactivation phenomenon- associated diseases
CN110540593B (zh) * 2018-05-29 2022-05-17 上海药明生物技术有限公司 新型的抗cd3/抗cd20双特异性抗体
TW202504917A (zh) 2018-06-21 2025-02-01 美商再生元醫藥公司 用雙特異性抗CD3xMUC16抗體及抗PD-1抗體治療癌症之方法
BR112020024296A2 (pt) 2018-08-27 2021-03-09 Regeneron Pharmaceuticals, Inc. Métodos para produção de um intermediário de purificação de proteína concentrado, para monitoramento e controle dos atributos de qualidade críticos em um intermediário de purificação de proteína e para monitorar e controlar os níveis de excipientes no fluido de cultura de células colhido e/ou intermediário de purificação de proteína, e, intermediário de purificação de proteína
TWI866924B (zh) 2018-08-30 2024-12-21 美商再生元醫藥公司 用於將蛋白質複合物定特徵之方法
PL3844189T3 (pl) 2018-08-31 2025-03-31 Regeneron Pharmaceuticals, Inc. Strategia dawkowania, która łagodzi zespół uwalniania cytokin, dla przeciwciał dwuswoistych cd3/cd20
WO2020072821A2 (en) 2018-10-03 2020-04-09 Xencor, Inc. Il-12 heterodimeric fc-fusion proteins
CN109836502B (zh) * 2018-11-12 2021-09-07 浙江大学 一种双特异性抗体及其应用
SG11202104103XA (en) 2019-01-16 2021-05-28 Regeneron Pharma Methods for characterizing disulfide bonds
CN111484555B (zh) * 2019-01-28 2022-07-08 正大天晴药业集团股份有限公司 新型双特异性cd3/cd20多肽复合物
JP7261307B2 (ja) * 2019-01-28 2023-04-19 ウーシー バイオロジクス アイルランド リミテッド 新規二重特異性ｃｄ３／ｃｄ２０ポリペプチド複合体
US12463463B2 (en) 2019-01-28 2025-11-04 Ab Therapeutics, Inc. Bispecific antibodies and uses thereof
KR20210126641A (ko) 2019-02-12 2021-10-20 리제너론 파아마슈티컬스, 인크. 보체 및 표적 항원에 결합하기 위해 이중 특이적 항체를 사용하는 조성물 및 방법
CN114173875B (zh) 2019-03-01 2025-04-15 Xencor股份有限公司 结合enpp3和cd3的异二聚抗体
EA202192736A1 (ru) 2019-04-05 2022-01-27 Тенеобио, Инк. Антитела, содержащие только тяжелые цепи, которые связываются с псма
CN113785203A (zh) 2019-05-13 2021-12-10 里珍纳龙药品有限公司 改进的竞争性配体结合测定
BR112021024956A2 (pt) 2019-06-14 2022-01-25 Teneobio Inc Anticorpos multiespecíficos de cadeia pesada que se ligam a cd22 e cd3
TWI889320B (zh) 2019-07-05 2025-07-01 日商小野藥品工業股份有限公司 以pd-1/cd3雙特異性蛋白質所進行之血液性癌症治療
IL291020B2 (en) 2019-09-24 2025-04-01 Regeneron Pharma Systems and methods for use in chromatography and regeneration
US12297451B1 (en) 2019-10-25 2025-05-13 Regeneron Pharmaceuticals, Inc. Cell culture medium
EP4065086B1 (en) 2019-11-25 2026-01-28 Regeneron Pharmaceuticals, Inc. Sustained release formulations using non-aqueous emulsions
PE20221511A1 (es) 2019-12-13 2022-10-04 Genentech Inc Anticuerpos anti-ly6g6d y metodos de uso
JP7342279B2 (ja) 2020-01-21 2023-09-11 リジェネロン・ファーマシューティカルズ・インコーポレイテッド グリコシル化タンパク質の電気泳動のための脱グリコシル化方法
US20230203161A1 (en) 2020-04-29 2023-06-29 Teneobio, Inc Multispecific heavy chain antibodies with modified heavy chain constant regions
CA3180569A1 (en) 2020-05-01 2021-11-04 Regeneron Pharmaceuticals, Inc. Neutralizing antibody assay for therapeutic proteins
EP4146175A1 (en) 2020-05-08 2023-03-15 Genmab A/S Bispecific antibodies against cd3 and cd20
WO2021231976A1 (en) 2020-05-14 2021-11-18 Xencor, Inc. Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3
EP4190352A4 (en) 2020-07-27 2024-08-14 Chia Tai Tianqing Pharmaceutical Group Co., Ltd. NEW FORMULATION OF BISPECIFIC ANTI-CD3/CD20 POLYPEPTIDE COMPLEX
MX2023001962A (es) 2020-08-19 2023-04-26 Xencor Inc Composiciones anti-cd28.
US12163122B2 (en) 2020-08-31 2024-12-10 Regeneron Pharmaceuticals, Inc. Asparagine feed strategies to improve cell culture performance and mitigate asparagine sequence variants
KR20230066391A (ko) 2020-09-10 2023-05-15 젠맵 에이/에스 여포성 림프종을 치료하기 위한 조합 요법에서의 cd3 및 cd20에 대한 이중특이적 항체
WO2022053655A1 (en) 2020-09-10 2022-03-17 Genmab A/S Bispecific antibody against cd3 and cd20 in combination therapy for treating follicular lymphoma
MX2023002545A (es) 2020-09-10 2023-03-14 Genmab As Anticuerpo biespecifico contra cumulo de diferenciacion 3 (cd3) y cumulo de diferenciacion 20 (cd20) en terapia de combinacion para el tratamiento de linfoma difuso de celulas b grandes.
IL301102A (en) 2020-09-10 2023-05-01 Genmab As Bispecific antibody against cd3 and cd20 in combination therapy for treating diffuse large b-cell lymphoma
MX2023002546A (es) 2020-09-10 2023-03-14 Genmab As Anticuerpos biespecificos contra cumulo de diferenciacion 3 (cd3) y contra cumulo de diferenciacion 20 (cd20) para tratar leucemia linfocitica cronica.
WO2022072762A1 (en) 2020-10-02 2022-04-07 Regeneron Pharmaceuticals, Inc. Combination of antibodies for treating cancer with reduced cytokine release syndrome
WO2022098628A2 (en) 2020-11-04 2022-05-12 Genentech, Inc. Subcutaneous dosing of anti-cd20/anti-cd3 bispecific antibodies
AU2021374592A1 (en) 2020-11-04 2023-06-01 Genentech, Inc. Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies
EP4240493A2 (en) 2020-11-04 2023-09-13 Genentech, Inc. Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies and anti-cd79b antibody drug conjugates
IL303027A (en) 2020-11-25 2023-07-01 Regeneron Pharma Sustained release formulations by creating a non-aqueous membrane emulsion
EP4262757A1 (en) 2020-12-17 2023-10-25 Regeneron Pharmaceuticals, Inc. Fabrication of protein-encapsulating microgels
JP2024503408A (ja) 2021-01-20 2024-01-25 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 細胞培養におけるタンパク質力価の改善方法
HRP20250696T1 (hr) 2021-01-28 2025-08-01 Regeneron Pharmaceuticals, Inc. Sastavi i postupci za liječenje sindroma oslobađanja citokina
EP4302098A1 (en) 2021-03-03 2024-01-10 Regeneron Pharmaceuticals, Inc. Systems and methods for quantifying and modifying protein viscosity
CN117157319A (zh) 2021-03-09 2023-12-01 Xencor股份有限公司 结合cd3和cldn6的异二聚抗体
JP2024509274A (ja) 2021-03-10 2024-02-29 ゼンコア インコーポレイテッド Ｃｄ３及びｇｐｃ３に結合するヘテロ二量体抗体
MX2023010567A (es) 2021-03-12 2023-09-21 Genmab As Variantes de anticuerpos no activadoras.
IL305731A (en) 2021-03-26 2023-11-01 Regeneron Pharma Methods and systems for developing mixing protocols
IL306111A (en) 2021-04-30 2023-11-01 Hoffmann La Roche Dosage for combined treatment with BISPIFIC ANTI-CD20/ANTI-CD3 antibody and anti-CD79B antibody for antiretroviral drugs
IL308417A (en) 2021-05-14 2024-01-01 Genentech Inc Methods for the treatment of CD20-positive proliferative disorder with musuntozumab and folatuzumab and dotin
AU2022286340A1 (en) 2021-06-01 2024-01-04 Regeneron Pharmaceuticals, Inc. Microchip capillary electrophoresis assays and reagents
EP4355785A1 (en) 2021-06-17 2024-04-24 Amberstone Biosciences, Inc. Anti-cd3 constructs and uses thereof
TW202326138A (zh) 2021-09-08 2023-07-01 美商再生元醫藥公司 用於定量抗體及其他含Ｆｃ蛋白之高通量及基於質譜之方法
AU2022348521A1 (en) 2021-09-20 2024-04-04 Regeneron Pharmaceuticals, Inc. Methods of controlling antibody heterogeneity
MX2024004107A (es) 2021-10-07 2024-04-19 Regeneron Pharma Sistemas y metodos para modelar y controlar el ph.
KR20240090312A (ko) 2021-10-07 2024-06-21 리제너론 파아마슈티컬스, 인크. Ph 미터 보정 및 교정
CN118176167A (zh) 2021-10-26 2024-06-11 瑞泽恩制药公司 用于产生实验室用水和分配处于不同温度的实验室用水的系统和方法
EP4437003A1 (en) 2021-11-24 2024-10-02 Regeneron Pharmaceuticals, Inc. Methods for treating cancer with bispecific anti-cd3 x muc16 antibodies and anti-ctla-4 antibodies
MX2024008055A (es) 2022-01-07 2024-09-06 Regeneron Pharma Métodos para tratar el cáncer ovarico recurrente con anticuerpos biespecificos anti-muc16 x anti-cd3 solos o en combinación con anticuerpos anti-pd-1.
IL315405A (en) 2022-03-17 2024-11-01 Regeneron Pharma Methods for treating recurrent epithelioid sarcoma using bispecific anti-MUC16 and anti-CD3 antibodies alone or in combination with anti-PD-1 antibodies
EP4493921A1 (en) 2022-03-18 2025-01-22 Regeneron Pharmaceuticals, Inc. Methods and systems for analyzing polypeptide variants
AU2023254191A1 (en) 2022-04-11 2024-10-17 Regeneron Pharmaceuticals, Inc. Compositions and methods for universal tumor cell killing
AU2023254206A1 (en) 2022-04-13 2024-10-17 Genentech, Inc. Pharmaceutical compositions of mosunetuzumab and methods of use
EP4519679A1 (en) 2022-05-02 2025-03-12 Regeneron Pharmaceuticals, Inc. Biochemical assays for therapeutic proteins
CN119451985A (zh) 2022-05-12 2025-02-14 健玛保 在组合疗法中能够结合cd27的结合剂
WO2023224912A1 (en) 2022-05-16 2023-11-23 Regeneron Pharmaceuticals, Inc. Methods of treating metastatic castration-resistant prostate cancer with bispecific anti-psma x anti-cd3 antibodies alone or in combination with anti-pd-1 antibodies
AU2023271827A1 (en) 2022-05-18 2024-12-05 Regeneron Pharmaceuticals, Inc. Multispecific antigen binding molecules that bind cd38 and 4-1bb, and uses thereof
IL318426A (en) 2022-08-02 2025-03-01 Regeneron Pharma Methods for treating metastatic castration-resistant prostate cancer using bispecific antibodies against PSMA and CD28 in combination with anti-PD-1 antibodies
EP4573128A2 (en) * 2022-08-19 2025-06-25 Eli Lilly and Company Pd-1 agonist antibodies and methods of treating autoimmune diseases with a pd-1 agonist antibody
KR20250124178A (ko) 2022-12-16 2025-08-19 리제너론 파아마슈티컬스, 인크. 크로마토그래피 칼럼의 무결성을 평가하기 위한 방법 및 시스템
WO2024158880A1 (en) 2023-01-25 2024-08-02 Regeneron Pharmaceuticals, Inc. Methods of modeling liquid protein composition stability
US20240248097A1 (en) 2023-01-25 2024-07-25 Regeneron Pharmaceuticals, Inc. Mass spectrometry-based characterization of antibodies co-expressed in vivo
WO2024163708A1 (en) 2023-02-01 2024-08-08 Regeneron Pharmaceuticals, Inc. Asymmetrical flow field-flow fractionation with mass spectrometry for biomacromolecule analysis
IL322545A (en) 2023-02-17 2025-10-01 Regeneron Pharma Induced NK cells responding to bispecific CD3/TAA antibodies
TW202446462A (zh) 2023-02-22 2024-12-01 美商再生元醫藥公司 系統適用性參數及管柱老化
KR20250155062A (ko) * 2023-03-10 2025-10-29 조인트 스탁 컴퍼니 "바이오케드" Cd3 및 종양 항원에 특이적으로 결합하는 분리된 이중 특이성 항체 및 그 용도
TW202508625A (zh) 2023-05-01 2025-03-01 美商再生元醫藥公司 使用苯酚或苯甲醇之多劑量抗體藥物產品
WO2025030044A1 (en) 2023-08-02 2025-02-06 Regeneron Pharmaceuticals, Inc. Methods of treating clear cell renal cell carcinoma with bispecific anti-psma x anti-cd28 antibodies
WO2025030041A1 (en) 2023-08-02 2025-02-06 Regeneron Pharmaceuticals, Inc. Methods of treating metastatic castration-resistant prostate cancer with bispecific anti-psma x anti-cd28 antibodies
US20250086164A1 (en) 2023-09-08 2025-03-13 Regeneron Pharmaceuticals, Inc. Methods and systems for assessing chromatographic column integrity
US20250095773A1 (en) 2023-09-18 2025-03-20 Regeneron Pharmaceuticals, Inc. Methods and systems for developing chromatography protocols
WO2025072597A2 (en) 2023-09-29 2025-04-03 Regeneron Pharmaceuticals, Inc. Lyophilization using controlled nucleation
WO2025085594A1 (en) 2023-10-18 2025-04-24 Regeneron Pharmaceuticals, Inc. Rapid purification of monoclonal antibody from in-process upstream cell culture material
US20250145662A1 (en) 2023-11-02 2025-05-08 Regeneron Pharmaceuticals, Inc. Methods for reducing lipase activity using stress
TW202539732A (zh) 2023-11-29 2025-10-16 美商再生元醫藥公司 以雙特異性抗muc16×抗cd28抗體與抗pd-1抗體之組合或與雙特異性抗muc16×抗cd3抗體之組合治療復發性卵巢癌及子宮內膜癌之方法
WO2025128652A1 (en) 2023-12-12 2025-06-19 Regeneron Pharmaceuticals, Inc. Methods of treating endometrial cancer with bispecific anti-muc16 x anti-cd3 antibodies alone or in combination with anti-pd-1 antibodies
WO2025160340A2 (en) 2024-01-26 2025-07-31 Regeneron Pharmaceuticals, Inc. Combination immunosuppression for inhibiting an immune response and enabling immunogen administration and re-administration
WO2025160324A2 (en) 2024-01-26 2025-07-31 Regeneron Pharmaceuticals, Inc. Methods and compositions for using plasma cell depleting agents and/or b cell depleting agents to suppress host anti-aav antibody response and enable aav transduction and re-dosing
WO2025166281A1 (en) 2024-02-01 2025-08-07 Regeneron Pharmaceuticals, Inc. Platform for charge-detection mass spectrometry analysis of aavs
WO2025171124A1 (en) 2024-02-07 2025-08-14 Regeneron Pharmaceuticals, Inc. Methods of treating prostate cancer with bispecific anti-psma x anti-cd3 antibodies and bispecific anti-psma x anti-cd28 antibodies
WO2025175164A1 (en) 2024-02-16 2025-08-21 Regeneron Pharmaceuticals, Inc. Methods of producing concentrated formulated drug substances comprising proteins, and concentrated formulated drug substance made by the methods
WO2025184567A1 (en) 2024-03-01 2025-09-04 Regeneron Pharmaceuticals, Inc. Methods and compositions for re-dosing aav using anti-cd40 antagonistic antibody to suppress host anti-aav antibody response
WO2025194043A1 (en) 2024-03-15 2025-09-18 Regeneron Pharmaceuticals, Inc. Polysorbate and polyoxyethylene sorbitan as excipients for stable protein formulations
WO2025240287A1 (en) 2024-05-13 2025-11-20 Regeneron Pharmaceuticals, Inc. Methods of treating light chain amyloidosis with bispecific bcma x cd3 antibodies
WO2025244973A1 (en) 2024-05-20 2025-11-27 Regeneron Pharmaceuticals, Inc. Methods of treating multiple myeloma with bispecific bcma x cd3 antibodies
WO2025259840A1 (en) 2024-06-13 2025-12-18 Regeneron Pharmaceuticals, Inc. Methods and systems for scaled chromatography
WO2026006495A1 (en) 2024-06-25 2026-01-02 Alloy Therapeutics, Inc. Anti-wt1/hla-a2 antibody and uses thereof
WO2026006492A2 (en) 2024-06-25 2026-01-02 Ypsilon Therapeutics, Inc. Anti-prame/hla-a2 antibodies and uses thereof
WO2026015612A1 (en) 2024-07-10 2026-01-15 Regeneron Pharmaceuticals, Inc. Methods of treating smarcb1-deficient cancers

Family Cites Families (140)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4361549A (en) 1979-04-26 1982-11-30 Ortho Pharmaceutical Corporation Complement-fixing monoclonal antibody to human T cells, and methods of preparing same
FR2593830B1 (fr) 1986-02-06 1988-04-08 Snecma Superalliage a matrice a base de nickel notamment elabore en metallurgie des poudres et disque de turbomachine constitue en cet alliage
US6893625B1 (en) 1986-10-27 2005-05-17 Royalty Pharma Finance Trust Chimeric antibody with specificity to human B cell surface antigen
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
EP0307434B2 (en) 1987-03-18 1998-07-29 Scotgen Biopharmaceuticals, Inc. Altered antibodies
WO1989007142A1 (en) 1988-02-05 1989-08-10 Morrison Sherie L Domain-modified constant region antibodies
DE122004000008I1 (de) 1991-06-14 2005-06-09 Genentech Inc Humanisierter Heregulin Antikörper.
IE922437A1 (en) 1991-07-25 1993-01-27 Idec Pharma Corp Recombinant antibodies for human therapy
PL174721B1 (pl) 1992-11-13 1998-09-30 Idec Pharma Corp Przeciwciało monoklonalne anty-CD20
US5736137A (en) 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US6180377B1 (en) 1993-06-16 2001-01-30 Celltech Therapeutics Limited Humanized antibodies
US6750334B1 (en) 1996-02-02 2004-06-15 Repligen Corporation CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor
DK0826696T3 (da) 1996-09-03 2002-09-23 Gsf Forschungszentrum Umwelt Anvendelse af bi- og trispecifikke antistoffer til inducering af en tumorimmunitet
AU758240B2 (en) 1998-02-25 2003-03-20 Merck Patent Gmbh Enhancing the circulating half-life of antibody-based fusion proteins
US6528624B1 (en) 1998-04-02 2003-03-04 Genentech, Inc. Polypeptide variants
HRP20000714B1 (en) 1998-04-21 2006-03-31 Micromet Ag NOVEL CD19xCD3 SPECIFIC POLYPEPTIDES AND USES THEREOF
GB9809951D0 (en) 1998-05-08 1998-07-08 Univ Cambridge Tech Binding molecules
WO2000009160A1 (en) 1998-08-11 2000-02-24 Idec Pharmaceuticals Corporation Combination therapies for b-cell lymphomas comprising administration of anti-cd20 antibody
US6224866B1 (en) 1998-10-07 2001-05-01 Biocrystal Ltd. Immunotherapy of B cell involvement in progression of solid, nonlymphoid tumors
US7183387B1 (en) 1999-01-15 2007-02-27 Genentech, Inc. Polypeptide variants with altered effector function
KR100887482B1 (ko) 1999-01-15 2009-03-10 제넨테크, 인크. 효과기 기능이 변화된 폴리펩티드 변이체
ES2569919T3 (es) 1999-04-09 2016-05-13 Kyowa Hakko Kirin Co., Ltd. Procedimiento para controlar la actividad de una molécula inmunofuncional
MXPA01011279A (es) 1999-05-07 2002-07-02 Genentech Inc Tratamiento de enfermedades autoinmunes con antagonistas que se unene a los marcadores de superficie, de celulas b.
US7087411B2 (en) 1999-06-08 2006-08-08 Regeneron Pharmaceuticals, Inc. Fusion protein capable of binding VEGF
ITMI991299A1 (it) 1999-06-11 2000-12-11 Consiglio Nazionale Ricerche Uso di anticorpi contro antigeni di superficie per il trattamento della malattia trapianto contro ospite
US7396917B2 (en) 2000-12-05 2008-07-08 Alexion Pharmaceuticals, Inc. Rationally designed antibodies
AU2002250293B2 (en) 2001-03-09 2007-10-11 Arnason, Barry G. Mr Polymeric immunoglobulin fusion proteins that target low-affinity FCGammaReceptors
WO2003026490A2 (en) 2001-09-28 2003-04-03 Elusys Therapeutics, Inc. Methods and compositions for prevention, diagnosis, and treatment of cancer using bispecific molecules
US20040093621A1 (en) 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
EP1519959B1 (en) 2002-02-14 2014-04-02 Immunomedics, Inc. Anti-cd20 antibodies and fusion proteins thereof and methods of use
US20040132101A1 (en) 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US8673589B2 (en) 2002-05-29 2014-03-18 Regeneron Pharmaceuticals, Inc. Inducible eukaryotic expression system
EP1400534B1 (en) 2002-09-10 2015-10-28 Affimed GmbH Human CD3-specific antibody with immunosuppressive properties
US7820166B2 (en) 2002-10-11 2010-10-26 Micromet Ag Potent T cell modulating molecules
CA2502552C (en) 2002-10-17 2019-02-12 Genmab A/S Human monoclonal antibodies against cd20
US7608260B2 (en) 2003-01-06 2009-10-27 Medimmune, Llc Stabilized immunoglobulins
US7355008B2 (en) 2003-01-09 2008-04-08 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
US7960512B2 (en) 2003-01-09 2011-06-14 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
US8084582B2 (en) 2003-03-03 2011-12-27 Xencor, Inc. Optimized anti-CD20 monoclonal antibodies having Fc variants
EP2960251A1 (en) 2003-05-09 2015-12-30 Duke University CD20-specific antibodies and methods of employing same
AR044388A1 (es) 2003-05-20 2005-09-07 Applied Molecular Evolution Moleculas de union a cd20
US20070041972A1 (en) 2003-05-30 2007-02-22 Alexion Pharmaceuticals, Inc. Antibodies and fusion proteins that include engineered constant regions
RU2005137325A (ru) 2003-05-31 2006-09-10 Микромет Аг (De) Фармацевтическая композиция, содержащая конструкт, специфичный к ерсам
ATE455127T1 (de) 2003-05-31 2010-01-15 Micromet Ag Humane anti-humane cd3-bindungsmoleküle
JP5091476B2 (ja) 2003-06-27 2012-12-05 バイオジェン・アイデック・エムエイ・インコーポレイテッド 均質な抗体溶液の生成のための疎水性相互作用クロマトグラフィーまたはヒンジ領域改変の使用
ZA200601218B (en) 2003-08-29 2007-05-30 Genentech Inc Anti-CD20 therapy of ocular disorders
US8399618B2 (en) 2004-10-21 2013-03-19 Xencor, Inc. Immunoglobulin insertions, deletions, and substitutions
JP4948174B2 (ja) 2003-10-16 2012-06-06 マイクロメット アクツィエン ゲゼルシャフト 多重特異的脱免疫ｃｄ３−結合物質
CA2549237A1 (en) 2003-12-19 2005-07-07 Genentech, Inc. Detection of cd20 in transplant rejection
EP1737890A2 (en) 2004-03-24 2007-01-03 Xencor, Inc. Immunoglobulin variants outside the fc region
NZ549872A (en) 2004-04-13 2009-09-25 Hoffmann La Roche Anti-P-selectin antibodies
WO2005103081A2 (en) 2004-04-20 2005-11-03 Genmab A/S Human monoclonal antibodies against cd20
RU2006142857A (ru) 2004-05-05 2008-06-10 Дженентек, Инк. (Us) Профилактика аутоиммунного заболевания
US7728114B2 (en) * 2004-06-03 2010-06-01 Novimmune S.A. Anti-CD3 antibodies and methods of use thereof
AR049292A1 (es) 2004-06-04 2006-07-12 Genentech Inc Metodo para tratar lupus con un anticuerpo cd20
WO2006041680A2 (en) 2004-10-05 2006-04-20 Genentech, Inc. Method for treating vasculitis
US20120189643A1 (en) 2004-11-30 2012-07-26 Carton Jill M Toll Like Receptor 3 Antagonists, Methods and Uses
TWI487535B (zh) 2004-11-30 2015-06-11 Centocor Inc 類鐸受體３（ｔｏｌｌ ｌｉｋｅ ｒｅｃｅｐｔｏｒ３）拮抗劑，方法及用途
WO2006074399A2 (en) 2005-01-05 2006-07-13 Biogen Idec Ma Inc. Multispecific binding molecules comprising connecting peptides
US7700099B2 (en) 2005-02-14 2010-04-20 Merck & Co., Inc. Non-immunostimulatory antibody and compositions containing the same
TW200714289A (en) 2005-02-28 2007-04-16 Genentech Inc Treatment of bone disorders
AR053579A1 (es) 2005-04-15 2007-05-09 Genentech Inc Tratamiento de la enfermedad inflamatoria intestinal (eii)
MX2007012989A (es) 2005-04-22 2008-01-11 Genentech Inc Metodo para tratar la demencia o la enfermedad de alheimer.
US20070014720A1 (en) 2005-06-02 2007-01-18 Gadi Gazit-Bornstein Antibodies directed to CD20 and uses thereof
EP2500355A3 (en) 2005-08-19 2012-10-24 Abbott Laboratories Dual variable domain immunoglobulin and uses thereof
BRPI0615026A8 (pt) 2005-08-19 2018-03-06 Abbott Lab imunoglobulina de domínio variável duplo e seus usos
AU2006301492B2 (en) 2005-10-11 2011-06-09 Amgen Research (Munich) Gmbh Compositions comprising cross-species-specific antibodies and uses thereof
EP1943332A4 (en) 2005-10-14 2011-04-13 Medimmune Inc CELLULAR DISPLAY OF ANTIBODY LIBRARIES
BRPI0707126A2 (pt) 2006-01-12 2011-04-19 Alexion Pharma Inc anticorpos para ox-2/cd200 e uso destes
EP1820513A1 (en) 2006-02-15 2007-08-22 Trion Pharma Gmbh Destruction of tumor cells expressing low to medium levels of tumor associated target antigens by trifunctional bispecific antibodies
EP4316465A3 (en) 2006-03-15 2024-04-24 Alexion Pharmaceuticals, Inc. Treatment of paroxysmal nocturnal hemoglobinuria patients by an inhibitor of complement
JP4294082B2 (ja) 2006-03-23 2009-07-08 協和発酵キリン株式会社 ヒトトロンボポエチン受容体に対するアゴニスト抗体
AU2007254831B2 (en) 2006-06-02 2012-03-22 Regeneron Pharmaceuticals, Inc. High affinity antibodies to human IL-6 receptor
NO347649B1 (no) 2006-12-14 2024-02-12 Regeneron Pharma Humant antistoff eller antistoff fragment som spesifikt binder human deltaliknende ligand 4 (hDII4), nukleinsyremolekyl som koder for slike og vektor og vert-vektorsystemer, samt fremgangsmåte for fremstilling, sammensetning og anvendelse.
CN101802015B (zh) 2007-03-29 2015-05-06 根马布股份公司 双特异性抗体及其制造方法
HRP20120759T1 (hr) 2007-04-03 2012-10-31 Amgen Research (Munich) Gmbh Bispecifična veziva specifična između vrsta
ES2432792T5 (es) 2007-04-03 2023-01-16 Amgen Res Munich Gmbh Dominio de unión a CD3-épsilon específico de especies cruzadas
AU2008254951A1 (en) 2007-05-14 2008-11-27 Biogen Idec Ma Inc. Single-chain Fc (ScFc) regions, binding polypeptides comprising same, and methods related thereto
JP5577243B2 (ja) 2007-05-30 2014-08-20 ポステク アカデミー−インダストリー ファウンデイション 免疫グロブリン融合タンパク質
US20100267934A1 (en) 2007-05-31 2010-10-21 Genmab A/S Stable igg4 antibodies
EP2170951A2 (en) 2007-05-31 2010-04-07 Genmab A/S Recombinant non glycosylated monovalent half-antibodies obtained by molecular engineering
WO2009006520A1 (en) 2007-07-03 2009-01-08 Medimmune, Llc Hinge domain engineering
NZ583019A (en) 2007-07-31 2011-05-27 Regeneron Pharma Human antibodies to human cd20 and method of using thereof
SI2187964T1 (sl) 2007-08-10 2015-01-30 Regeneron Pharmaceuticals, Inc. Visokoafinitetna humana protitelesa proti humanemu živčnemu rastnemu faktorju
WO2009030368A1 (en) 2007-09-05 2009-03-12 F. Hoffmann-La Roche Ag Combination therapy with type i and type ii anti-cd20 antibodies
PE20140132A1 (es) 2007-09-26 2014-02-14 Chugai Pharmaceutical Co Ltd Anticuerpo anti-receptor de il-6
CN101874041B (zh) 2007-09-26 2013-06-19 中外制药株式会社 抗体恒定区修饰体
US8268972B2 (en) 2008-02-20 2012-09-18 G2 Inflammation Pty Ltd Humanized anti-C5aR antibodies
WO2009106096A1 (en) 2008-02-27 2009-09-03 Fresenius Biotech Gmbh Treatment of resistant tumors with trifunctional antibodies
AU2009313389A1 (en) 2008-11-06 2010-05-14 Alexion Pharmaceuticals, Inc. Engineered antibodies with reduced immunogenicity and methods of making
ES2535257T3 (es) 2008-11-07 2015-05-07 Amgen Research (Munich) Gmbh Tratamiento de leucemia linfoblástica aguda pediátrica
AR074438A1 (es) 2008-12-02 2011-01-19 Pf Medicament Proceso para la modulacion de la actividad antagonista de un anticuerpo monoclonal
JP5746040B2 (ja) 2008-12-03 2015-07-08 ゲンマブ エー／エス 定常領域の中に改変を有する抗体変種
EP2389192A4 (en) 2009-01-23 2013-01-16 Biogen Idec Inc STABILIZED FC POLYPEPTIDES WITH REDUCED EFFECTOR FUNCTION AND METHOD OF USE
WO2010107110A1 (ja) 2009-03-19 2010-09-23 中外製薬株式会社 抗体定常領域改変体
EP3674317B1 (en) 2009-03-19 2024-12-11 Chugai Seiyaku Kabushiki Kaisha Antibody constant region variant
MY164121A (en) * 2009-06-26 2017-11-30 Regeneron Pharma Readily isolated bispecific antibodies with native immunoglobulin format
JO3182B1 (ar) 2009-07-29 2018-03-08 Regeneron Pharma مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2
US10150808B2 (en) 2009-09-24 2018-12-11 Chugai Seiyaku Kabushiki Kaisha Modified antibody constant regions
CA2782218C (en) 2009-11-30 2018-07-31 Janssen Biotech, Inc. Antibody fc mutants with ablated effector functions
US20130129723A1 (en) 2009-12-29 2013-05-23 Emergent Product Development Seattle, Llc Heterodimer Binding Proteins and Uses Thereof
CN105693861A (zh) 2009-12-29 2016-06-22 新兴产品开发西雅图有限公司 异二聚体结合蛋白及其应用
JP5955781B2 (ja) 2010-02-08 2016-07-20 リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 共通の軽鎖のマウス
CN102167741B (zh) * 2010-02-25 2014-05-14 上海百迈博制药有限公司 一种全人源抗TNF-α单克隆抗体、其制备方法及用途
EP2543730B1 (en) 2010-03-04 2018-10-31 Chugai Seiyaku Kabushiki Kaisha Antibody constant region variant
CA2794708C (en) 2010-03-29 2021-11-16 Zymeworks Inc. Antibodies with enhanced or suppressed effector function
US20140206849A1 (en) 2010-04-30 2014-07-24 Alexion Pharmaceuticals, Inc. Antibodies having reduced immunogenicity in a human
GB201014033D0 (en) 2010-08-20 2010-10-06 Ucb Pharma Sa Biological products
JP6105472B2 (ja) 2010-09-16 2017-03-29 バリオファルム・アクチェンゲゼルシャフト 抗ｈｕＴＮＦＲ１抗体
CA2819530C (en) * 2010-11-30 2023-01-10 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing therapeutic agent
PH12013501332B1 (en) 2010-12-23 2019-01-16 Janssen Biotech Inc Active protease-resistant antibody fc mutants
HUE040734T2 (hu) 2011-02-08 2019-03-28 Medimmune Llc Antitestek, amelyek specifikusan kötik staphylococcus aureus alfatoxinját és alkalmazási eljárások
FI2691417T4 (fi) 2011-03-29 2025-01-14 Roche Glycart Ag Vasta-aineen Fc-variantteja
JP2014514314A (ja) * 2011-04-20 2014-06-19 ゲンマブ エー／エス Ｈｅｒ２およびｃｄ３に対する二重特異性抗体
WO2013012733A1 (en) 2011-07-15 2013-01-24 Biogen Idec Ma Inc. Heterodimeric fc regions, binding molecules comprising same, and methods relating thereto
US20130058936A1 (en) 2011-08-23 2013-03-07 Peter Bruenker Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use
CA2899433A1 (en) 2012-01-27 2013-08-01 Gliknik Inc. Fusion proteins comprising igg2 hinge domains
JO3820B1 (ar) 2012-05-03 2021-01-31 Regeneron Pharma أجسام مضادة بشرية لـ fel d1وطرق لاستخدامها
RU2014153674A (ru) 2012-06-05 2016-07-27 Регенерон Фармасьютикалз, Инк. Способ получения полностью человеческих биспецифических антител с применением общей легкой цепи
KR20150036606A (ko) * 2012-07-13 2015-04-07 자임워크스 인코포레이티드 항-cd3 구조체를 포함하는 이중특이적 비대칭 이형이합체
US20150203591A1 (en) * 2012-08-02 2015-07-23 Regeneron Pharmaceuticals, Inc. Mutivalent antigen-binding proteins
JOP20200236A1 (ar) * 2012-09-21 2017-06-16 Regeneron Pharma الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها
PT2900694T (pt) 2012-09-27 2018-11-13 Merus Nv Anticorpos de igg biespecíficos como ativadores de células t
WO2014054804A1 (ja) 2012-10-05 2014-04-10 協和発酵キリン株式会社 ヘテロダイマータンパク質組成物
BR112015007120A2 (pt) 2012-10-08 2017-12-12 Roche Glycart Ag anticorpo biespecífico, composição farmacêutica, uso, célula hospedeira e método de produção de um anticorpo
TWI682941B (zh) 2013-02-01 2020-01-21 美商再生元醫藥公司 含嵌合恆定區之抗體
NZ715896A (en) * 2013-07-05 2022-02-25 Genmab As Humanized or chimeric cd3 antibodies
BR112016000666A2 (pt) * 2013-07-12 2017-10-03 Zymeworks Inc Constructos de ligação de antígeno cd3 e cd19 biespecíficos
KR20220116581A (ko) * 2013-12-17 2022-08-23 제넨테크, 인크. 항-cd3 항체 및 이의 사용 방법
EP3327038B1 (en) 2013-12-20 2020-09-23 F. Hoffmann-La Roche AG Bispecific her2 antibodies and methods of use
TWI681969B (zh) 2014-01-23 2020-01-11 美商再生元醫藥公司 針對ｐｄ-１的人類抗體
TWI701042B (zh) 2014-03-19 2020-08-11 美商再生元醫藥公司 用於腫瘤治療之方法及抗體組成物
HUE071048T2 (hu) 2014-11-17 2025-07-28 Regeneron Pharma Daganatkezelési módszerek a CD3XCD20 bispecifikus antitest használatával
ES2846748T3 (es) 2015-03-30 2021-07-29 Regeneron Pharma Regiones constantes de cadenas pesadas con unión reducida a receptores Fc gamma
GB201506407D0 (en) 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
ES2901133T3 (es) 2015-09-23 2022-03-21 Regeneron Pharma Anticuerpos biespecíficos anti-CD3 optimizados y usos de los mismos
WO2017112775A1 (en) * 2015-12-22 2017-06-29 Regeneron Pharmaceuticals, Inc. Combination of anti-pd-1 antibodies and bispecific anti-cd20/anti-cd3 antibodies to treat cancer
US20170174781A1 (en) 2015-12-22 2017-06-22 Regeneron Pharmaceuticals, Inc. Bispecific Anti-CD20/Anti-CD3 Antibodies to Treat Acute Lymphoblastic Leukemia
KR20190074300A (ko) 2016-11-15 2019-06-27 제넨테크, 인크. 항-cd20/항-cd3 이중특이적 항체에 의한 치료를 위한 투약
PL3844189T3 (pl) * 2018-08-31 2025-03-31 Regeneron Pharmaceuticals, Inc. Strategia dawkowania, która łagodzi zespół uwalniania cytokin, dla przeciwciał dwuswoistych cd3/cd20

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