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    • 专利摘要:
    POLYPEPTIDE UNDERSTANDING A TENTH FIBRONECTIN TYPE III (10FN3) DOMAIN THAT LINKS TO HUMAN SERUM ALBUMIN DOMAIN I OR II, FUSION POLYPEPTIDE UNDERSTANDING THE SAME, METHOD OF PRODUCTION OF THE UNDERSTANDING OF THE UNDERSTANDING OF THE UNDERSTANDING HOSTING CELL UNDERSTANDING THE REFERRED NUCLEIC ACID.The present invention relates to an antibody-like protein based on the tenth domain of fibronectin type III (10Fn3) that binds to serum albumin. The invention further relates to fusion molecules comprising a 10Fn3 binding to serum albumin coupled with a heterologous protein for use in diagnostic and therapeutic applications.
    公开号:BR112012028162A2
    申请号:R112012028162-3
    申请日:2011-05-03
    公开日:2020-10-13
    发明作者:Michael L. Gosselin；Simeon I. Taylor；David Fabrizio；Joanna F. Swain；Tracy S. Mitchell；Ray Camphausen；Sharon T. Cload；Eric Furfine；Paul E. Morin；Ranjan Mukherjee
    申请人:Bristol-Myers Squibb Company；
    IPC主号:
    专利说明:

    [1858] [1858] CRE Doo Think TEA Sao o LID'NO: 7th Sequences fine | mistake en VU 160 SABA1- Variant 29 of SA- | MGVSDVPRDLEVVAATPTSLLISWHSY FGF21v28 | BAI-FGF21; see | YEQNSYYRITYGETGGNSPVQEFTVP similar description - | YSQTTATISGLKPGVDYTITVYAVYGSK for variant 1 YYYPISINYRTEIEKPSOHHHHHHPIPD SSPLLOFGGOVRORYLYTDDAQOTEA HLEIREDGTVGGAADOSPESLLOLKAL KPGVIQILGVKTSRFLCORPDGALYGS LHFDPEACSFRELLLEDGYNVYQSEA HGLPLHLPGNKSPHRDPAPRGPARFL PLPGLPPALPEPPGILAPQPPDVGSSD
    [1690] [1690] emus SNómeda ([0 1 ns SeguênciadeDNA 1D.NO: | ment aa |: Sequence | Dn + ERA VT LL 186 279 SABA1- atagocattagigatattcegcatgatctagaagitattgcageaacece FGF21viO0 | gaccagcctactgattagctagcatagctattatgaacagaatagetatt eatcgcattacctatggtgaaaccegatagtaatagtccagticaggaatita cegttoccatatagecagaccacegeaaccattagegatetgaaacegg gtattgattataccattaccgittatacagigtatageagcaaatatiatiat cegattagcatcaattategeacegaaategatagtageggtageceg attccgagatagcagtccactacitgcagtttagtagicagaticgtragegt tatctgtataccgatgatagcacagcagaccgaageacatciggaaatto glgaagatggcacegtiggtggigcageagatcagagtcoggaaage ctgctgcagctgaaagcactgaaacctagtgttaticagaticiaggtigtt aagaccagccegttttetatateagegtecggatagtacactatatagtag cctacatttigateeggaageatgtagcetttegtgaacigctgciggaaga M tagttataatotttalcagagegaageteatggtctgccgcitacatctacet ggtaataaaagtccgcategtgatceggcacegegiggtecageacgtt - tctgcetetacetagtitacetecgageactaccigaacegectagtattcta gceacegcagectecagatatiagtagcagegatecgctgageatagtto gtccgagecagagtegtagecegagetatacaagetga 187 274 SABA1- | atgggecgltagigatgticcacgatgatctagaagitatigcageaacece FGF21v11 | gaccagectactaattagetageatagetattataaacagaatagetatt atcgcattacctatagtaaaacceagtagtaatagtcegaticaggaatita cegttecgtatagecagaccacegeaaccattageggicigaaacegg gtatigattataccattacegtttatacgagtatatageageaaatattattat cegattagcateaattategcacegaaatecegatticeagatageagte cactactacagtttagtagtcagatticatcagegttatetatatacegatga tgcacagcagaccgaagcacatciggaaattcgtgaagatageaceg ttggtagigcagcagatcagagtceggaaagectacigcagetgaaag cactgaaacctggtattaticagattctggatattaaaaccagecatitict gigtcagegitceggatagigcactatatagtagectacatitigatecaga agcatgtagctticataaactgctactagaagatagitataatgatitatcag agegaagcicatggtctacegeigcatetacetygtaataaaagtecge atcgtgatceggeacegegtagtceggcacattttetacetetacetagttt acetceggcactacetgaacegectagtaticiggcacegeagecteca gatgattagtagcagegatcecgctgagcatggttagtrcegagecagggte gtagccegagetatgcaagetga
    SEQ Compri- DNA Sequence Name ID NO: | aa | Sequence
    188 288 SABA1- atgggcgttagtgatgttcegegtyatctagaagttattacageaacece FGF21v12 | gaccagcetgetgattagetggcatagetattataaacagaatagetatt atcgcattacctatagigaaaccggtagtaatagtccggttcaggaatita ccetticegtatagecageccacegeaaccattagegatetgaaacegoa grlgrtgattataccattacegrtitatacagtgtatageageaaatattattat ccgattageateaattategeacegaaatccateaccaccateateata gtageggtagegaticagatageccgattecggatageagtcegetget gcagtttagtagtcagattegteagcgttatetatataccgatgatgcaca gcagaccegaageacatetagaaaticgtaaagatageaccgttggtag tgcagcagatragagtecggaaagectactacagetgaaageactga aacctggtattattcagattcigogtattaaaaccagecgttttetatateag cgtecggatagtacactatatagtagcctgcattttaatceggaageatat * goteatagtetacegetacatetacetagtaataaaagicegeategigat agctitegtgaactgctgctggaagatagitataatatttatecagagegaa - ccogeacegegtagtecageacgttrttetgeetetacetagtttaceteca geactgcctgaacegectagtattctageacegeagectecagatgtig gtagcagegatcegetgagcatagtiggatecgagecagagtegtages cgagetatacaagetga 189,284 SABA1- atgggcgttagtgatgricegegteatetagaagitatigecageaaceco FGF21v13 | gaccagectgctgattagetageatagetattatgaacagaatagetatt | atcgcattacctatagtgaaaccogtggtaatagtccggticagaaatita | cegttecgtatagecagaceacegeaaceattageggtetgaaacegg gtgttgattataccattaccgtitatecggtatatageagcaaatattattat ccgattagcateaattategeacegaaatecatcaccaccateateatg gtageggtagecegattecggatagcagtcengctactacagtttagiagt caggttegteagegttatetatatacegatgatacacageagacegaag cacatctggaaaticalgaagatggcaccottigtagtgcageagatea gagtreggaaagectgctgcagetgaaageactigaaacctagtgttatt cagattctgggtattaaaaccagecattttetgtgteagegtceggatagt gractatatggtagcctgcatrttgateeggaageatgatagetttegtaaa ctgctgctagaagatgagttataatgtttateagegegaageteatagteto ccgretgcatetgectggtaataaaagtecgcategtgatceggcacege glggtccggcacgttttetgectetacetagittacetecggcactacetga accocctggtattetageacegeagectecggatgttagtagcagegat cegcetgagcatggttggtcegagecagagtogtagecegagetataca agetga
    SEQ Compri- DNA Sequence Name ID NO: | aa | Sequence 280 SABA1- atgggcgttagtgataticegegtaatctagaagitattgcageaacece FGF2ivi4 | gaccagccetactaattagetageatagetattatgaacagaatagetatt atcegcattacetatagigaaaceggltagtaatagtccgaticaggaattta cegttecgtatagecagaccacegeaaccattageggtetgaaacego gigttgattataccattaccgtitatacggtatatageageaaatattattat cegattagcatcaattategcacegaaatecatcaceaceateateatec gattceggatagcagtecactacigcagtttggtagtcagattcgateage gttatctgtatacegatgatgcacagcagaccegaageacatetagaaat tegtgaagatggcaccgttagtggtacagcagatcagagiceggaaag cetgctgcagetgaaageactgaaacctagtattattcagattctaggtat taaaaccagccgttttetatateagegtecacatagtacactatatagtag cetgcattttgateceggaagcatgatagetttegtgaactgctacigagaaga 'tagttataatgtitatcagagegaageteatagtetgcegetgcatetgect ggtaataaaagtcegeategigatecageacegegtagtecggcacatt. ttetacctetacetagtitacetecggeactgeetgaacegectagtattcta gcacegcagectecggatatiggtagcagegateegetgageatagtto gtcegagecagggtegtagecegagetatgcaagetga 191 284 SABA1- ataggacgacagagaggtactacatatatatatatatatatatatatatat gaccagectgetaattagetggeatagetattatgaacagaatagetatt ategcattacctatagtgaaaceggtagtaatagiccggttcaggaatita cegttecgtatagecagaccacegeaaccattageggtetgaaacegg gtgttgattataccattacecgtttatacggtatatagcagcaaatattattat ccgattagcatcaattategcacegaaateçaagataaagatgaggac gaagatgaggateegattecagatageagtecactgctacagtttagta gtcaggttegtcagegttatetatatacegatgatgcacageagacega agcacatctagaaattcgtaaagatagcaccatiggtggtacageagat cagagtceggaaagectgctgcagetgaaageactgaaacetagtatt attcagattctgggtattaaaaccagecgttttetatateagegtecagatag gtgcactatatagtagccetgcattttgateeggaageatgtagettitegtga actactgctggaagatggttataatgtitatcagagcgaagectoatagtet gecgcetgcatetgectagtaataaaagtccocategigatceggeaceg cgtggtceggcacgttttetacetetacetagtttacctecggeactacecta aaccgcectagtattetageacegcagectecagatattagtageagega tecgetagageatagttggtcegagecagagtegtagecegagetataea agctga
    XSEQE E Campriza [eENomeda | ENS ATE, TSequenicia de DINA ns, TE UNR ds.
    Pee EE AA ca Sud The RIMS 192 292 SABA1- atgggegttagigatgaticegegtgatctagaagitatigcageaacece FGF21vi6 gaccagoctgelgatiagetagcatagetatiatgaacagaatagetatt atcgcattacctatggtgaaaccagtagtaatagtecggticaggaattta cegttcegtatagccagaccaccgcaaccaltagcagtetgaaacega gtgttgattataccattaccgtitatacggtatalggcagcaaatattatiat cegattagcatcaattategeacegaaategâagatgaagatgaggac gaagatgaggatagtageggtagegaticagatagecogaticoggat ageagicegetactacagtttagiggtcaggticatcagegttatetgiata ccgaltgatgcacagcagacegaagceacatciggaaaticaigaagat ggcacegttggtggtacageagateagagtecagaaagectacigea gctgaaagcactgaaacctagigttaticagattctagglattaaaacca gecgtitictatateageatecagatagtgcacigtatagtagectgcatitt
    'gatccggaagcatgtagetttegigaacigctaciggaagatggttataa | tgtttalcagagegaageteatggtetacegeigcatetacetagtaataa
    . aagtccgcategtgatceggeacegegtagtêcageacatttictgecte tgcctggtitacetecggeactgecigaacegectagtattctageacege agectecggatatiggtagcagegatecgcigageatagitggtcogag ccagggtgtagagagagagagagagagagagagag
    193 287 SABA1- algggegttagigatgticogegtgatciggaagtigttigcageaacece FGF21vi17 | gaccagcctactgattagetageatagetattataaacagaatagetatt atcgcatiacctatagtgaaaccggtggtaatagiccggticaggaatita
    , Ceglicegtatagecagaccaccgcaaccatiageggtetgaaacega glgttgattataccattacegtttatgcagigtatagcagezaatattatiat cegattagcatcaattategcacegaaateggtagegeageageagea gecgetgcageagecagtagecegaticeggatageagtecactacta cagtitagtggicaggttogicagegttatetgtatacegatgataçacag cagacegaagceacatetggaaatticataaagatggcaccgtiggtagt gcagcagatcagagtceggaaagectactacagetgaaageactga aacctagigitaticagattctaggtgttaaaaccagecatitictatgtcag cgtccagatagtgcactatatagtagectacatitigatccggaageatgt agctitegtgaactactactgagaagatagttataatgtitateagagegaa getcatggtctacegetacatetgcetggtaataaaagicogcategigal ccggcacegegtggtccggeacgtitictigectetacetagitiaceteca gcactgcctgaaccgectagtattctagcaccgcagectocagatatta gtagcagcegatccgctgagcatggttggtecgagecagagtegtages cgagctatgcaagetga i |
    SEQ :. | - Compri- “f .. Name | ; - DNA sequencing
    ID.NO :. | “Ment aa | String | : = ão 184 SABA1- atgggcegttagtgatattcegcatgatctagaagttatigcagcaacece FGF21vi8 | gaccagcetactgattagetggcatagetatiatgaacagaatagetatt atcgcattacctatagigaaaccggigataatagiccoagttraggaattta cegttcegtatagecagaccacegeaaccattageggtetgaaacego glattgattataccattacegtitatacagtgtatageagecaaatatiatiat cegattageateaattategeacegaaateggtagigaagatagegaa gattcagaaggtticigaaggcagegaacegaticeggatageagicog clgctacagittagiggtcagattcateagegttatetatataccgataata cacagcagaccgaageacatetagaaaticgtgaagatggeacegtt gatagtacageagatcagagtceggaaagectgctgcagetaaaage actigaaacctggtattaticagattctaggtattaaaaccagecgttttetat Qgtcagegtceggatggtacactatatggtagectacattttgatceggaa
    'gceatgtagetttegigaactactactagaagatggttataatatitatecaga gegaagceteatggtetacegetacatetgacciggtaatazaagtccacat
    - cgtgatceggcacegegtagtecggcacatittetgcetetacetagttta cetecggeactgcetgaacegectagiaticiggeacegeagectcegg atgttggtagcagegatecgetgagratagttagtcegagecagagteg tagccegagcetatag
    195 289 SABA1- atgggcgtiagtgatgtticcgcgtaatciggaagitatigcageaacece FGF21v19 | gaccagcetgcigattagetggeatagetattataaacagaatagetatt atcgcattacctatagigaaaceggtagtaatagiccggttcaggaattta
    'Cegttcegtatagecagaccacegeaaccattagegatetgaaacegg gtattgattataccattaccgtitatacagtatatageagcaaatattatiat cegattagcatcaattategcacegaaatccetacaagtceggcatcac cogeaagtecggetagtecggeaagecegaticeggatagcagtecg ctactacagtttagtggicaggttegicagegttatetgtatacegatgata cacagcagaccgaageacatetggaaatticgtgaagatageacegtt gglggtgcageagateagagteeggaaagectactgcagetaaaage actgaaacctagigttaticagattctgggtatizaaaccagecatitictat gicagegtecggatagtacactatatagtagectacatitigatecggaa Qgcatgtagetttegtgaactactaciggaagatagitataatatitatcaga gegaageteatggtetacegetgcatetacetagtaataaaagtecgcat cgtgatceggcacegegtagteceggcacattttetacetetacetagitta ceteeggcactgeetgaacegectagiattctageacegcagectecgg atgttagtageagegatcegetgageatggttagtcegagecagggteg tagccegagctalgcaagetga section S ROOUEILE pNÓTe donates To Oo CT DNA Sendencia ATLAS the SLEEP) ment / yy | * strings, Plate, EAN REA
    1968 289 SABA1- atgggeagttagtgataticegcatgatctggaagttattgcagecaacece
    FGF21v20 | gaccagcctgctgattagetagratagetattatgaacagaatagetatt atcgcattacctatagigaaacceggtagtaatagiceggticaggaatita cegticegtatagecagaccacegeaaccattagegatetaaaacegg glgttgattataccattacegtttatacagtatatagcagcaaatattattat cegattageateaattategeacegaaateggtagtecgggtticacegg gtagecetagttcteegagtagteetecgattcoggatageagteegeta ctgcagtitagtagicagatticatcagegttatetatatacegatgatacac agcagaccgaagcacatctggaaaticgtaaagatagcaccgtigata gtgcagcagatcagagtceggaaagectaciacagetgaaageactg aaacctggtattaticagattetaggatattaaaaccagecattttetatatea gcegtecagatggtacactgtatagtagectacattttgatceggaageat
    | 'gtagctitegtgaacigetgciggaagatggitataatatitatcagageg | aagctcatggtetgcegctgcatetgectagiaataaaagtcegeategt - gatceggeacegegigatecgageacgtittetacetetacetagittacete cggcactgcctgaacegectagtaticiggcacegcagectecagattagtagagagagagtagagagagagagtaggag
    187 288 SABA1- atgggcgttagtgatgaticcacataatetagaagttattgcageaacece
    FGF21v21 | gaccagcctgactgattagelggeatagetatiatgaacagaatagetatt atcgcattacctatagigaaaccagtagtaatagtcegaticagaaatita
    'cegttecgtatagecagaccacegeaaccattagegatetgaaacegg gtgtigattataccatiaccatitatacagigtalggcagcaaatattatiat
    . cegattagcateaattategeacegaaatoggtageacegttacageac cgagcacegtigeegetecgtracegaticeggatageagicegetact gcagtttagiggtcaggttcgateagegttatetatataccegatgatacaca gcagacegaageacatetggaaattcataaagatageaccgtiggtag tgcagcagatcagagtccagaaagectacigcagetgaaageactga aacctagigttatticagatictaggtattaaaaccagecgtitictatateag
    . catccggatagtacactatatagiagcctacatttigatccagaageatat agctttegigaactgctactagaagatagttataatgtitatcagagegaa geteatggtetgcegetgcatetacetagiaataaaagtecacategtagat ceggcacegegtagteeggcacatttacetacetacetacetacetacetacetag
    | gcactgcctgaacegectagtaticiggcaccgcagectecagatatia
    ] gtagcagegatccgctgagcatagttagtcegagecagggtegtages cgagctatgcaagetga |
    "Gomnpri, [UNómeda [E 3 DNA Sequence. Coco“ ment aa: |. Sequence, [1 The 6 PMs EA
    198 282 SABA1- atgggcattagtgataticcacgtaatctagaagttattgcageaaceceo
    FGF21v22 | gaccagectactgatiagetageatagetattataaacagaatagctatt ategcattacctatggtgaaaceggtagtaatagtccggttcaggaatita cegticegtatagecagaccacegcaaccattageggtetgaaacego glgttgattataccattaccegtitatacagtatatagcageaaatatiatiat cegattagcatcaattategcacegaaateggtagtagegaagetagta gtgaacegattecggatagcagtecgetactacagitiggtagtcagatt cgtcagegttatetatatacegatgatgcacageagacegaageaçate tagaaaticataaagalggcaccatiggtggtgcageagatcagagtec ggaaagcctocigcagetgaaageactgaaacctagtattaticagati ctgggtgttaaaaccagecgtttictatatcagegtecagatagtacacta tatagtagectacattttgatceggaageatatagctttegtgaactactgc 'tagaagatggttataatatitateagagcgaagceteatagtetacegetae atctacetagtaataaaagicegeategtgatceggeacegegtagtec. ggcacgtittctgcctetgcetagittaccteeggcactgcctgaacegect gglatictggcacegeagectecggatattggtagcagegateegetga gcatggttagiccgagecagggitcgtagecegagcetatacaagetga
    281 SABA1- atgggcatiagigatgaticegegigatetggaagttgttacageaacece
    FGF21v23 | gaccagecetactagattagetageatagetattataaacagaatagetatt ategceattacctatagigaaacegatagtaatagtceggticaggaatita cegttecgtatagecagaccacegegacaceattageggtetaaaacegg
    'gtattgattataccattaccatttatacggtatatagcageaaatattattat Cecgaltagcateaattategcacegaaatcageaccageaceagtace
    . gateegatticeggatageagtecactactacagittagtagtcagattegt cagegttatetgtataccgatgatacacageagacegaageacatelg gaaattcataaagatageaccatiggtggtacageagatragagtecg gaaagcctgcetgcagelgaaageactgaaacctagtattaticagattct gggtattaaaaccagecgttttetatatcagegtceggatagitgcactata tggtagectgcattttgatceggaageatatagetttegtgaactactacta gaagatagitataatgtitateagagegaageteatagtetgcegetacat ctacctagtaataaaagtcogcategigatceggcacegegtagicega cacgttttetacetetacetagtitacctcegacacigectgaacegectag tattetggcacegeagectocggatgttggtageagegatcegetgage atogttagtcegagecagggtegiagecegagetatacaagetga
    FSEGTT, Buy | ENSMe dare FNESS 2 DNAP sequence RIA RES fióto.] Ce setaical AR Mao Madi 200 288 SABA1- atgggcgttagigatgttcegegatatetagaagitatigcageaaceco FGF21v24 | gaccagcctgctgattagetagcatagetattatgaacagaatagetatt atcgcattacctatagigaaaceggtggtaatagtccagttcaggaatita ccgticegtatagecagaccacegeaaccattagegatetgaaacegg Qgtgttgattataccattacegtttatacagigtatggcagcaaatattatiat cegattagcatcaattiategeacegaaatogaaaaacegagecaago tggtagecggtagegaticagatagecogaticoagatageagtecacta ctacagttiggtagtcaggticatcagegttatetatataccgataatacac agcagaccgaagcacatctagaaattcgtaaagatggeaceatigata gtgcagcagatcagagtceggaaagectactacagetaaaageacta aaacctagtattaticagattctaggtattaaaaccagecgtittetatatea gegtecggatagigeacigtatggtagectgcatitigatceggaageat "gtagctttegtgaactgctgctggaagatagttataatgtitateagageg aagctcatggtctacegetacatetgectagtaataaaagicegeategt. gatcegacacegegtggtecgagracgttttetacetetacetagtttacete cggcactgcectgaacegectagtatictageacogcagectecggatat tagtagcagegatccgctigageatagtitagtecgagecagggtegtag ccegagctatacaagetga
    201 SABA1- atgggegitagigatattcegegtyatctggaagtigttgcageaacece FGF21v25 | gaccagecctgctaattagctggcatagetattatgaácagaatagetatt atcgcattacctatagigaaaccagtggtaatagtccggticagaaatita cegitecgtatagecagaccacegcaaccattageggtetaaaacegg gtgtigattataccatiaccatitatgcagigtatggcagcaaatatiattat - cegattagcatcaattategcacegaaatcgaaaaacegagecaaga tagticaggtagecegattceagatagcagtccactactacagtttagta gtcagattcgteagegitatetatatacegatgatgcacagcagacega agcacatciggaaattcgtgaagatggcacegtiggtagigcagcagat cagagtceggasagectgctacagetgaaageactaaaacclagtatt aticagattctaggtattaaaaccagecgttttctatateagegtecagata glgcactatatggtagectacatitigatecggaageatgtagctttegtga aclgctgctagaagatagitataatatitateagagegaageteatagtet gecgcetacatetacetagtaataaaagicegeategigatcegacaces egtggtecageacgttttetacetetacetagtttacetecageactaceta aacegcectagtaticiggcacegcagectecagatgttagtagcagega tecgetgageatagttagtcegagecagggtegtagecegagetatgea
    |) agctga
    | 180/243 SEQ Compri- DNA Sequence Name ID NO: | aa | Sequence
    202 279 SABAT1- atgggcagttagigatgttccgcgtgatctggaagttatigcageaacece FGF21v26 | gaccagcctgctgattagetggcatagetattatagaacagaatagetatt atcgcattacctatggtgaaacceggatagtaatagtcegaticaggaatita cegtteegtatagecagaccacegeaaccattageggtetgaaacego gtattgattataccattaccotttatacgagtatatageagcaaatattattat cegattagcatcaattategeacegaaategaaaaacegagecaace gattceggatageagtecgetactacagittagtgagtcagatticateage gttatctatatacegatgatgcacagcagaccgaageacatetagaaat tegtgaagatageacegttggtagtacageagatcagagtceggaaag cetgetgcagetgaaageactgaaacctagtattaticagattctaggtot taaaaccageccgttttetatateagegtecagatggtacactatatagtag cclgcattttgateeggaageatgtagettiegraaactacigctggaaga
    : tagttataatgtitateagagegaagcteatggtetgcegctacatetgcet ggtaataaaagtccgcategtgatceggcacegegtagiceggcacatt
    - ttetgcctetgeetagtttacctecggeactgcetgaacegectagtatteta geacegeagectecagatatiggiageagegateegetgageatagttg gtcegagecagggtegtagecegagetatacaagelga
    203 293 SABAT1- ataggegttagigataticcgcgtyatctggaagitatigcageaacece FGF21v27 | gaccagcctaclgattagetageatagetattatgaacagaatagetatt atcgcattacctatggtgaaaccagtagtaatagtceggticaggaatita cegttcegtatagecagaccacegeaaccattageggtetaaaacegg
    , Gtatigattataccattaccgtttatacagtgtatageageaaatattatiat cegattagcatcaattategcacegaaalecgaaaaacegagecaacat caccaccatcatcatagtageggtageggticaggatagecegaticoga atagcagtcegetgcetacagtttggtagtcagattegteagegttatetata taccgatgatgcacagcagaccgaageacatctggasaticataaag atggcacegttggtagtgcageagatcagagtceggaaagectactae agctgaaagcaclgaaacctagigttaticagattctgggtattaaaace agceegttttetgtateagegtecggatggtacactatatggtagectacatt ttgatccggaageatgtagetttegtgaactactactggaagatagttata atgtttateagagegaageteatagtetgecgctacatetacetagtaata aaagtcegcategigatecgageacegegtagiceggcacgttticiget etgcetggtttacctecggeactgcetgaacegectagtatictggeaceg cagectceggatgttagtagcagegatcegetgageatggttagtcega
    Ggecagggtegtagecegagetatacaagetga
    HSEO E eSmoticA E Name safe FE Sa RATE sequence of ONA MIT.
    AGaaEniS [556 RCE Data EE tina A ro 204 289 SABA1- atgggcgttagigataticcgegigatctagaagitatigcagcaacece FGF21v28 | gaccagccetactyattagetageatagetattalgaacagaatagetatt atcgcattacctatagigaaacegatagtaatagtcegaticaggaattita cegttcegtatagecagaccaccegcaaccatiageggtetgaaacega gtgttgattataccattaccgtitatgoggtatatageageaaatattattat cegattagcateaattategeacegaaategaaaaaccgagecaacat caccaccatcatcatggiteaggtageccgaticcagatagcagicege tgctacagtitagtggtcageticatcagegliátetgtatacegatgatge acagcagaccegaageacatetagaaatticgtgaagatageacegtig gtagtacageagatcagagtccgagaaagectgcigcagetgaaagea ctgaaacctagtgattaticagattctggatattaaaaccagecagtittctgta tcagegtecggatagigcaciglatagtagecigcatitigatccggaag. calgtagetttogigaacigcigciggaagatggitataatgtitatcagag cgaagctcatagtetgcegetacatetgectggtaataasagtccgcate. gigatccageacegegtagiceggracgtiticigectetgcetggtitae. . ctecggcactacetgaacegectagtatictagcacegcagectccaga tgttggtageagegatecgctgagcatagttagtcegagecagggtegt agcccegagetatacaageliga 205 285 SABAT1- atgggcgttagtgatgticogegtgatctggaadgttattgcageaacece FGF21v29 gaccagectgctgattagetagcatagetattátgaacagaatagetatt atcgcattacctatggtgaaaccagiggtaatagtccgattcaggaattta, ccgltccatatagccagaccacegeaaccatiageggtctgaaacegg gtgttgattataccattaccgtitatacggigtatagcageaaatattatiat. cegattagcatcaattategcaccgaaategaaaaacegagecaaçat caccaccatcateatecgattceggatageagtcegetgctacagtttag tggtcagattegteagegttatetglatacegatgatgcacageagaceg aagcacatctggaaatticatgaagatageacegtigatagigcageag atcagagtccagaaagectgctacagetgasageacigaaacetgot gttattcagattctggglgttaaaaccagcegtitictgtgtcagegtecgg atggtgcactgtatggtagectacatttigatecagaagcatatagetiteg tgaacigctgctagaagatggttataatgtitatcagagegaageteata gtclgccgetgcatetgcclggtaataaagicegeategigatccagea cegegtagtceggcacgttttetacetetacetagtttacetecgageactae ctgaaccgcctagtattetagcacegcagectecagatattagtageag cgatccgctgagcatggtigatecgagecagggtegtagecegagetat = gcaagetga
    '182/243 .ESEQ | "Comprics. |" Name dajk [PESTE ST Sh sDNA Sequence: FESP OA te mal Sack IETAN LAN E ABEos 206 289 SABA1- atagacgttagigataticcgegtgatctagaagitgtigcageaacece FGF21v30 | gaccagcectgctgattagetageatagetatiatagaacagaatagetatt atcgcattacctatagigaaaccggtagtaatagtecagitraggaatita ceglicegtatagecagaccacegeaaceattagegatetgaaacega gtgttgattataccattaccgtitatgcagigtatagcagcaaatatiatiat cegattagcatcaattategcacegaaatogaaaaacegagecaaga agatgaggacgaggacgaagatgaggatcegattcoggatageagt cegetgctgcagttiggtagicagglicateagegttatetgtatacegata atgcacagcagaccgaageacatctagaaaticalgaagatggeace gtgg ggigcageagatcagagiceggaaagectgctgcagetgaaa gcactgaaacctagigttaticagattictagglattaaaaccagecatttio totateagegtecagatagtgcactatatagtágcctgcatitigatecgg: aagcatgtagectttegtgaactactgctagaagatggttataatgtitatea gagegaagcetcatagicigcegetgcatcigcctggtaataaaagtccg - categtgateeggcacegegtggtecageacatitictacetetacetagt ttacctceggcactgcetgaaccgcetggtaticiggcacegcagectes ggatgttagtagcagegatccactgageatagttagticegagecagegt cgtagccegagetatgcaagetga 207,297 SABA1- atgggcgttagtgatgtticegegtgatctagaagttattgcageaacece FGF21v31 gaccagcctgctgattagetggcatagetattatgaacagaatagetatt: atcgcattacctatagtgaaaccgg iggiaatagiccggticaggaatita glgtigattataccattaccgtitatacggigtatageageaaatatiatiat cegttecgtatagecagaccacegeaaccattagegatetaaaacegg 'cegattagcatcaatiategcaccgaaategaaaaaccgagecaaga agatgaggacgaggacgaagatgaggatagtageggtagegatica ggtagecegattceggatageagicegetactacagtttagiggicaga: tegicagegttatelgtatacegatgatacacageagacegaageacat ciggaaatticataaagatogcacegttggtggtgcagcagatcagagte cagaaagectacigcagetgaaageacigadacctagigttaticagat tcetagatgttaaaaccagecatittctatateagegtecggatagtacact gtatggtagoctgcatitigatccggaagcatgtagetitegigaacigcta clggaagatggtiataatgtitatcagagcgaagetratggictacegeta catctgcctggtaataaaagtcegeategigatceggcacegegiagte cggcacattttetacetetacetagtttacetecggcacigecigaacege ctggtattetageacegecagectecagatattagtagcagegatcegeta agcatggttggtccgagecagggtegtagecegagetatgcaagetga
    SEQUEL | “Compri-al | Name of) (ar.
    Ti Se ic DNA sequence Pruão, “ET ao [ÓNOA] ha al aeica Ea), Geil Caro ADA 208 292 SABAi- atgggcegttagtgatgttcegegtaatcetagaagitatigcageaacece FGF21v32 | gaccagcctgctgattagetageatagetattatgaacagaatagetatt ategcattacetatagigaaaccagiggtaatagtccggttcaggaattta cegttccgtatagecagaccacegeaaccattageggtetgaaacega gtattgattataccattacegtttatacggtatatagcagcaaatattatiat cegattagcatcaattategcacegaaatogaaaaaccegagecaagg tagegcageagcagcagecgctgcageagecagtagecegaticog gatagcagtecgctactacagtittagtagicagattegtcagegitatetat ataccgatgatgcacageagacegaageacatetggaaaticataaa gatagcacegttggtagtacageagatcagagtccggaaagectacta cagctgaaagcactgaaacctggtattaticagatictggatattaaaac cagcegtittetatateagegtecgagatagtgcactatatggtagectaca 'tittgatccggaagcatgtagetitegtaaactactactagaagatagttat aatgtttatcagagegaageteatggtetacegetacatetacetagtaat - aaaagtcegeategigateeggeaceacatagtecageacatittetac ctctgectagtttacetocggcactgecigaacegectagtaticiggeac cgcagceetecggatatiggtagcagegatcegetgageatagitagtee gagcceagggtegtagecegagetatacaagetga 209,294 SABA1- atgggegttagigataticegegigatctggaagitattacageaacece FGF21v33 | gaccagcctactaattagetageatagetatiataaacagaatagetatt alcgcattacctatagigaaaccggiggtaatagiceggttcaggaattta 'cegttocgtatagecagaccacegeaaccattageggtetgaaacegg gtatigattataccattacegttatatatagagatatatatatagat cegattagcatcaattategcacogaaatogaaaaacegagecaago tagegaagatagtgaagattcagaagaticigaagatagegaacegat tecagatagcagtecgctactacagittagtagtcagattcgtcagegtta tetgtatacegatgatgcacageagacegaageacatetaçaaaticot gaagatggcacegitagtagigcagcagalcagagtccagaaagect getgcagetgaaageactaaaacctagtattaticagattcigggtatias aaccagcecattttetatateagegtecagatggtacactgtatagtagect gcattttgatccggaageatgtagetttegtaaactactactggaagatag ttataatgtttatcagagegaageteatagictgcegetacatetgcetagt aataaaagtcegeategigatcegacacegegtggicegacacagtttct gectetgectagittacetecageactgcectgaacegectagtattictage accgceagectecagatgttggtageagegatecgcigageatagitagt cegagecaggagicatagecegagetatacaagetga
    SEQ Compri- DNA Sequence Name ID NO: | aa | Sequence 210 294 SABA1- atgggegttagigatgttecgcgtgatetagaagttatigcageaacece FGF21v34 | gaccagecctgcigattagetageatagetattatgaacagaatagetatt atcgceattacctatggigaaaceggtggtaatagtecagitcaggaattta Í Í cegttcegtatagecagaccacegeaacceattagegatetaaaacegg glgttgattataccattacegtttatacagtatatagcageaaatattattat cegattagcatcaattategcacegaaategaaaaacegagecaace ggcaagtceggcateaceggcatetecggetagticeggeaagecega ttecggatagcagtecgetactacagtttagtggtraggttegtragegt atctgtatacegatgatacacageagacegaagcacatetagaaatte gtgaagatggcaccegtiggtagtacageagatcagagtceggaaage ctgctgcagcetgaaageactgaaacctagigttattcagattetaggtgatt aaaaccagecattttetatatragegtecagatagtacactatatagtag i Í cetacatittigatceggaageatgtagetttegtgaactgcigctggaaga i | tagttataatatttatcagagegaageteatggtetacegctacatetaeet. ggtaataaaagtcegcategtgatceggeacegegiggtecggeacatt ttictgcctetacetagtttaceteeggeactacetagaacegectagtatteta gcacegeagectecggatgtiggtagcagegatcegetgageatggtta gtcegagetaggggggaggagaggagggggggg 211 294 SABA1- atgggcgttagtigatgttecgcatgatcetagaagitatigcageaacece FGF21iv35 | gaccagecctgetgattagetggeatagcetattataaacagaatagetatt atcgcattacctatagtyaaaccogtggtaatagiceggticaggaattta | 1 cegttecgtatagecagaccacegeaaccattageggtetaaaacegg gtgttgattataccattacegtitatacagtgtataggcagcaaatattattat. Cegattagcateaattategeacegaaatogaaaaacegagecaago tagecetagtagtecagattcacegagttetecgggtagecctecgatte | cagatagcagtecgetactacacgtttagtagtcagatticateagegttato tgtatacegatgatacacagcagacegaageacatctagaaattcata aagatggcaccegtiggtagtacagcagatcagagtceggaaagectg cilgcagctgaaageactgaaacctagtattaticagattctaggtattaaa accagcegttttetatateagegtecagatagtacactatatagtagecta: cattttgatceggaageatatagetttegtgaactgctaciggaagatagtt: ataatatttatcagagcgaagctcatagtetacegetacatetacetagta ataaaagtcegeategtgatecggeacegegtagtecageacgtitteta cetetgecetggtitacctecgageactgeetgaaccegcctagtattictagea cegeagectecagatattggtageagegatcegetaageatggtiggte cgagccagagitegtagecegagetatacaagetga s1D.NO: 1); aa ing, | iSequence; GARRA IE AA O E 212 293 SABA1- atgggcgitagtgatgaticcacatgatctiggaagitatigcageaacece FGF21v36 | gaccagcctgcetaattagctageatagetattataaacagaatagetatt atcgcattacclatagtgaaaccogtggtaatagticegaticaggaattta cegttcegtatagecagaccacegeaaccattageggtetgaaacegg gtattgattataccattaccgtitatacagigtatageageaaatattatiat cegattagcatcaattategcacegaaatrgaaaaacegagecaaga tagcaccgtigcageacegageacegtageageceetagecegatice ggatagcagteegetactacagtttggtagicaggttegtcagegttatet gtataccgatgatgcacagcagacegaageacatciggaaaticatga agatggcacegtiggtagtgcagcagatragagiceggaaagectact gcagctgaaageactgasacctagtattaticagattcigagtattaaaa creagoecgtttictatgateagegtecggatagigcactatatagtagectge l 'attttgatceggaageatgtagetttegtgaacigctgctggaagatggtt etaatgtttatcagagegaageteatagictgcegetgcatetacetagta. ataaaagicegcatogtgatcegacacegegiggtecageacatiticta cetetgectagtttaceteegacactgectgaacegectagtaticiagea cegcagectecagatgttagtagcagegatcegetgageatagttagte cgagccagggtgtaggggggggggggggggga- gaccagcctactgattagetageatagetattataaacagaatagetatt atcgcattacetatagigaaaceggtagtaatagtccagitcaggaatita 'cegtteegtatagecagaccacegraaccattagegatetaaaacegg gtgttgattataccattaccgtitatacggtatatggcageaaatattatiat 7 cegattagecateaattategcacegaaategaaaaacegagecaago tagtagegaaggtggtagigaaccgaticeggatageagicegetacta cagtitagtagicaggttcgtcagegttatetatataccgatgatacacag cagacegaagcacatctggaaattcgtgaagatageacegtigatag! gcagcagatcagagiceggaaagectactgcagetgaaageactga aacctggtgttaticagattctgggigttaaaaccagecgttttetatateag cgtecagatggtacactatatggtagectacattttgatceggaageatgt agctttegtgaactactactagaagatggttataatatitatecagagegaa geteatggtetgecgetacatetacctagtaataaaagicegcategigat ceggcacegegtggtecggeacatittetacctetacetagittaceteca gcactgectaaacegectagtatictageacegeagectcegyatattg gtagcagegatecgctgageatggttagtecgagecagggtegtages cgagctatacaagetga
    Compri- | “Nomeda | * DNA DNA sequence aa | String | : A 4 aqi 214 286 SABA1- atgggcattagtgataticcgacglgatctggaagitattgcageaacece FGF2iv38 | gaccagcctactaattagetggeatagetattataaacagaatagetatt 7 atcgcattacctatagtgaaaccagtagtaatagtceggticaggaattta cegttecgtatagecagaccacegeaaccattageggicigaaacegg. gtatigattataccattacegtttatacagigtatagcagcaaatatiatiat cegattagcatcaattalegcacegaaategaaaaacegagecaaag caccagcaccagtaceggtecgatticeggatageagtecgetactaca gtttagtagtcagaticatcagegttatctatatacegatgatacacagea gacecgaagcacatctggaaattcataaagatageaccatiggtagtac agcagatcagagtceggaaagectactgcagetgaaageacigaaa cetggigitaticagattctgggtattaaaaccagcegttitetatateageg tecggatggtacactatatagtagectacattttuatccggaageatatag. ctttegtgaactagctgctgagaagalagitataatigtttateagagegaage tcatggtetacegetacatetacotagtaataaaagtecgcategtgatce ggcacegegtagicegacacgttttacacetetetetagtttaceteegge: actgcetgaacegggggaggaggagggaggaggagg gctatacaagetga 437 187 FGF21vi | atogcatcatcatcatcaccatecgattecggatageagecegetaeige agtttggeggecagetacateagegitatetgtatacegatgatacacas -. cagaccgaagegcatetggaaaticataaagataggeacegiaggegs tgcggcggatcagageceggaaagectactgcagetgaaagegcta aaaccgggcgtgalticagattctaggacgtaaaaaccagecatittetata c gegtgcagetitegtgaactactactggaagatggctataacgtatatca gagcgaagegcatggectacegetacatetacegggeaacaaaage cegeategtgatecggeacegegigatecageacgttttetacegetace ccagegtecagatggegegctatatageagectacatitigatecggaa gggtctacegecageactgeeggaaceacegagtattetageacege agcegecggatgitagtageagegatecactatetatagtagatecgag ccagggtegtagecegagetatacgagetaataa. 398 187 FGF2iv2 | atgcatccgatticeggatageagecegetactgcagittggeggceagg tacgteagegttatetgtatacegatgatacgcageagacegaagege atctgagaaattcgtgaagatggcacegtaggacagtacageggatcaga geceggaaagectactacagetgaaagegetgaaacegagacalgatt cagattctagggcatgaaaaccagecgtitictatacragegtecagata gegegetatatageagectacattttyatreggaagegtacagetttegt gaactgctactagaagatagelataacgigtatcagagegaagegeat ggcelgecgctagcatetgcegageaacaaaagecegeategtgates ggcacegegtagtceggcacgtittetacegetacegggtetgcegeca gceactgceggaacegecagataticiggcaccacagecaceggatatt ggtagcagegatecactatetatagtaggtcegagecagggtegtage cegagetatgcgcatcatcateateaccattaataa
    权利要求:
    Claims (20)
    [1]
    1. Polypeptide comprising a tenth domain of fibronectin type III (ºFn3), characterized by the fact that the domain * ºFn3 binds to domain | or Il of human serum albumin with a Kp of 1 µM or less, and the half-life in the polypeptide serum in the presence of albumin is at least 5 times greater than the serum half-life of the polypeptide in the absence of serum albumin , and where the "Fn3 domain comprises an amino acid sequence modified in one or more loops BC, DE and FG with respect to the wild-type * ºFn3 domain.
    [2]
    2. Polypeptide according to claim 1, characterized by the fact that the domain "* Fn3 binds to serum albumin in a pH range of 5.5 to 7.4.
    [3]
    3. Polypeptide according to claim 1 or 2, characterized by the fact that the domain "º * Fn3 binds to HSA with a Kp of 200 nM or less than 5.5.
    [4]
    4. Polypeptide according to any one of claims 1 to 3, characterized by the fact that the BC, DE and FG loops of the * ºFn3 domain are selected from the group consisting of (a) a BC loop comprising the amino acid sequence shown in SEQ ID NO: 5, a DE loop comprising the amino acid sequence shown in SEQ ID NO: 6 and a FG loop comprising the amino acid sequence shown in SEQ ID NO: 7; (b) º a BC loop comprising the amino acid sequence shown in SEQ ID NO: 9, a DE loop comprising the amino acid sequence shown in SEQ ID NO: 10 and a FG loop comprising the sequence of amino acid shown in SEQ ID NO: 11; (c) a BC loop comprising the amino acid sequence shown in SEQ ID NO: 13, a DE loop comprising the amino acid sequence shown in SEQ ID NO: 14 and a FG loop comprising the amino acid sequence shown SEQ ID NO: 15; (d) a BC loop comprising the amino acid sequence shown in SEQ ID NO: 17, a DE loop comprising the amino acid sequence
    no acid shown in SEQ ID NO: 18 and a FG loop comprising the amino acid sequence shown in SEQ ID NO: 19; (e) a BC loop comprising the amino acid sequence shown in SEQ ID NO: 21, a DE loop comprising the amino acid sequence shown in SEQ ID NO: 22 and a FG loop comprising the amino acid sequence shown in SEQ ID NO: 23.
    [5]
    Polypeptide according to any one of claims 1 to 4, characterized in that the "Fn3 domain comprises: (i) an amino acid sequence at least 70% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs : 4, 8, 12, 16, 20, and 24-44; (ii) an amino acid sequence at least 80% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44; (ili) an amino acid sequence at least 85% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44; (iv ) an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4,8,12,16,20, and 24-44; (v) an amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44; (vi) an amino acid sequence at least 98% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44; or (vii) an amino acid sequence selected from the group consisting of SEQ ID NOs: 8, 12, 16, 20 and 24-44.
    [6]
    Polypeptide according to claim 5, characterized by the fact that the domain * Fn3 comprises SEQ ID NO: 4.
    [7]
    7. Polypeptide according to any one of claims 1-6, characterized by the fact that the * º * Fn3 domain also binds to one or more of rhesus serum albumin (RhSA), kinomologist monkey serum albumin (CySA) or murine serum albumin (MUSA).
    [8]
    8. Polypeptide comprising a tenth domain of fibronectin type III (ºFn3), characterized by the fact that the domain * ºFn3 (i) comprises a modified amino acid sequence in one or more of the AB, BC, CD, DE loops , EF and FG relative to the wild Ena domain, (ii) binds to a target molecule unbound by the wild * ºFn3 domain, and (iii) comprises a tail comprising a sequence (ED) ,, where n is an integer of 3 to 7.
    [9]
    9. Polypeptide comprising a tenth domain of type II fibronectin! (ºFn3), characterized by the fact that the domain "ºFn3 (i) comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 89-116 and 222-225.
    [10]
    10. Polypeptide according to any one of claims 1, characterized by the fact that the ** Fn3 domain still comprises an N-terminal sequence comprising any of SEQ ID NOs: 45-53.
    [11]
    11. Polypeptide according to claim 10, characterized in that the "º * Fn3 domain comprises an N-terminal sequence comprising SEQ ID NO: 47.
    [12]
    12. Polypeptide according to any one of claims 1 to 11, characterized in that the domain "º * Fn3 comprises a C terminal sequence comprising any one of SEQ ID NO: 54-64 and 215.
    [13]
    13. Polypeptide according to claim 12, characterized in that the "º * Fn3 domain comprises a C-terminal sequence comprising SEQ ID NO: 62.
    [14]
    14. Fusion polypeptide, characterized by the fact that it comprises a tenth domain of type II fibronectin! (ºFn3) as defined in any one of claims 1a 13 and a heterologous protein ,.
    [15]
    A fusion polypeptide according to claim 14, characterized by the fact that the heterologous protein is FGF21.
    [16]
    16. Pharmaceutical composition, characterized in that it comprises the fusion polypeptide or polypeptide as defined in any one of claims 1 to 15 and a vehicle.
    [17]
    17. Nucleic acid, characterized by the fact that it encodes a fusion polypeptide or polypeptide as defined in any one of claims 1 to 15.
    [18]
    18. Vector, characterized in that it comprises a nucleic acid as defined in claim 17.
    [19]
    19. Host cell, characterized by the fact that it comprises nucleic acid as defined in claim 17.
    [20]
    20. Method for producing a fusion polypeptide or polypeptide as defined in any one of claims 1 to 15, characterized in that it comprises expressing the nucleic acid as defined in claim 17 in a host cell as defined in claim19, isolating the cell fusion polypeptide or polypeptide.
    类似技术:
    公开号 | 公开日 | 专利标题
    US10934572B2|2021-03-02|Serum albumin binding molecules
    US11203630B2|2021-12-21|Serum albumin-binding fibronectin type III domains
    ES2781207T3|2020-08-31|Serum albumin-binding fibronectin type iii domains with rapid dissociation rate
    AU2016203044B2|2017-12-14|Serum albumin binding molecules
    AU2013202913B2|2016-06-16|Serum albumin binding molecules
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    法律状态:
    2020-10-27| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2021-04-06| B08F| Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette]|Free format text: REFERENTE A 10A ANUIDADE. |
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    优先权:
    申请号 | 申请日 | 专利标题
    US33067210P| true| 2010-05-03|2010-05-03|
    US61/330,672|2010-05-03|
    US13/098,851|2011-05-02|
    US13/098,851|US8969289B2|2010-05-03|2011-05-02|Serum albumin binding molecules|
    PCT/US2011/034998|WO2011140086A2|2010-05-03|2011-05-03|Serum albumin binding molecules|
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