PT1632574E - Homólogos do factor de crescimento fibroblástico - Google Patents

Homólogos do factor de crescimento fibroblástico Download PDF

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PT1632574E
PT1632574E PT05021714T PT05021714T PT1632574E PT 1632574 E PT1632574 E PT 1632574E PT 05021714 T PT05021714 T PT 05021714T PT 05021714 T PT05021714 T PT 05021714T PT 1632574 E PT1632574 E PT 1632574E
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human
polypeptide
residue
fhf
amino acid
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PT05021714T
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Thomas R Bukowski
Paul O Sheppard
Theresa A Deisher
Darrell C Conklin
Fenella C Raymond
Susan D Julien
Brigit Hansen
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Zymogenetics Inc
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    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/50—Fibroblast growth factor [FGF]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/119—Other fibroblast growth factors, e.g. FGF-4, FGF-8, FGF-10

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Claims (14)

  1. REIVINDICAÇÕES 1. Polipeptídeo seleccionado do grupo consistindo em: a) um polipeptídeo compreendendo uma sequência de aminoácidos, como mostrado na SEQ ID NO: 2 a partir de resíduo 28 (Glu) ao resíduo 175 (Met); e b) as moléculas de polipeptídeo que são pelo menos 80% idênticas à SEQ ID NO: 2 a partir do resíduo de aminoácido 28 (Glu) ao resíduo de aminoácido 175 (Met); para utilização na promoção da reparação de defeitos ósseo e deficiências; para uso na promoção da cicatrização óssea em cirurgia plástica; para uso no estímulo do crescimento ósseo em juntas não cimentadas protéticas e implantes dentários; para uso no aumento da formação óssea durante a distracção osteogénica; para uso no tratamento de outras doenças esqueléticas que podem ser tratadas por estimulação da actividade osteoblástica; para uso na reparação congénita, trauma-induzida, na ressecção oncológica do osso; ou para uso em reparação óssea após radiação induzida na osteonecrose.
  2. 2. Polipeptídeo seleccionado do grupo consistindo em: a) um polipeptídeo compreendendo uma sequência de aminoácidos, como mostrado na SEQ ID NO: 2 a partir de resíduo 28 (Glu) ao resíduo 196 (Lys); e b) as moléculas de polipeptídeos que são pelo menos 80% idênticas à SEQ ID NO: 2 a partir do resíduo de aminoácido 28 (Glu) ao resíduo de aminoácido 196 (Lys); para utilização na promoção da reparação de defeitos ósseo e deficiências; para uso na promoção da cicatrização óssea em cirurgia plástica; para uso no estímulo do crescimento ósseo em juntas não cimentadas protéticas e implantes dentários; para uso no aumento da formação óssea durante a distracção osteogénica; para uso no tratamento de outras doenças esqueléticas que podem ser tratadas por estimulação da actividade osteoblástica; para uso na reparação congénita, trauma-induzida, na ressecção oncológica do osso; ou para uso 1 em reparação óssea após radiação induzida na osteonecrose.
  3. 3. Polipeptideo seleccionado do grupo consistindo em: a) um polipeptideo compreendendo uma sequência de aminoácidos, como mostrado na SEQ ID NO: 2 a partir de resíduo 28 (Glu) ao resíduo 207 (Ala); e b) as moléculas de polipeptideos que são pelo menos 80% idênticas à SEQ ID NO: 2 a partir do resíduo de aminoácido 28 (Glu) ao resíduo de aminoácido 207 (Ala); para utilização na promoção da reparação de defeitos ósseo e deficiências; para uso na promoção da cicatrização óssea em cirurgia plástica; para uso no estímulo do crescimento ósseo em juntas não cimentadas protéticas e implantes dentários; para uso no aumento da formação óssea durante a distracção osteogénica; para uso no tratamento de outras doenças esqueléticas que podem ser tratadas por estimulação da actividade osteoblástica; para uso na reparação congénita, trauma-induzida, na ressecção oncológica do osso; ou para uso em reparação óssea após radiação induzida na osteonecrose.
  4. 4. Polipeptideo para uso de acordo com qualquer das reivindicações 1-3, em que o dito polipeptideo é seleccionado do grupo consistindo em: a) um polipeptideo composto por uma sequência de aminoácidos, como mostrado na SEQ ID NO: 2 a partir do resíduo 28 (Glu) ao resíduo 175 (Met); b) um polipeptideo composto por uma sequência de aminoácidos, como mostrado na SEQ ID NO: 2 a partir de resíduo 28 (Glu) ao resíduo 196 (Lys); c) um polipeptideo constituído de uma sequência de aminoácidos como mostrada em SEQ ID NO: 2 a partir de resíduo 28 (Glu) ao resíduo 207 (Ala).
  5. 5. Polipeptideo para uso de acordo com a reivindicação 4, para utilização na promoção da reparação de um defeito ósseo ou deficiência seleccionado entre fracturas fechadas, abertas e não-juntas. 2
  6. 6. Polipeptídeo para uso de acordo com qualquer das reivindicações 1-5, em que o dito polipeptídeo compreende ainda um residuo de metionina amino-terminal.
  7. 7. Polipeptídeo para uso de acordo com qualquer das reivindicações 1-5, em que o dito polipeptídeo ainda compreende uma sequência de sinal.
  8. 8. Polipeptídeo para uso de acordo com a reivindicação 7, em que o dita sequência de sinal é mostrada na SEQ ID NO: 2 a partir de um resíduo de aminoácido (Met) ao resíduo de aminoácido 27 (Ala).
  9. 9. Polipeptídeo para uso de acordo com a reivindicação 6, em que a desordem esquelética é a osteoporose ou artrite.
  10. 10. Polipeptídeo isolado seleccionado do grupo consistindo em: a) um polipeptídeo composto por uma sequência de aminoácidos, como mostrado na SEQ ID NO: 2 a partir do resíduo 28 (Glu) ao resíduo 175 (Met); acrescidos de um resíduo de metionina amino-terminal; b) um polipeptídeo consistindo numa sequência de aminoácidos como mostrada em SEQ ID NO: 2 a partir do resíduo 28 (Glu) ao resíduo 196 (Lys); além de um resíduo de metionina amino-terminal; c) um polipeptídeo consistindo numa sequência de aminoácidos como mostrada em SEQ ID NO: 2 a partir do resíduo 28 (Glu) ao resíduo 207 (Ala); acrescidos de um resíduo de metionina amino-terminal.
  11. 11. Polipeptídeo de acordo com a reivindicação 10, que compreende ainda uma sequência de sinal.
  12. 12. Polipeptídeo de acordo com a reivindicação 11, em que a dita sequência de sinal é mostrada na SEQ ID NO: 2a partir de um resíduo de aminoácido 1 (Met) ao resíduo de aminoácido 27 (Ala).
  13. 13. Polipeptídeo de acordo com qualquer das reivindicações 10-12 para o uso como um medicamento. 3
  14. 14. Composição farmacêutica compreendendo um polipeptídeo homólogo FGF purificado de acordo com qualquer das reivindicações 10-12, em combinação com um veículo farmaceuticamente aceitável. 4 FHF-2 -- -......- MAAAÍ AS5I. IRQKRQAfíESNS-DRVSASKSRSSPSKD5-R 38 FSF-10 -------------------------........................------ FHF-4 .......- - HAMIASGL IROKROAREOHk - DRPSASRRRSSPSKN * -R 37 FHF-2 ..........mMim WfWER--4fCSNACKCVSSPSKG^K 35 FHF-3 -.......- - MMt ASSLIRQKREVREPGB - SRPVSAQRRYCP - RGT - K 36 FSF4 mm ..........MS-GPGTMVALIPAVLLALL - APí-MGAAAPTAPN -G 37 FSFFHUMAN MAtGQKLF ÍTMSRGASRLQGTtWALVFLG IL -VGMVVP- - SPASTRAN - N 46 FSFrHUMAN -----.............- —............................ FSFiUUMWí .................................................. KSF-2 — -----MWKWI LTHCASAfPHLPGCCC-CCFLL LFLYSSVPVTC-Q 38 FSF? HUMAN -----------HHfâ(ILMLPTUYR-*S---*«CFHIiaveTISLAC-R 33 ZSI FRJZFGF ........-HV-SAPSACICLCLHFLLLCF-QVQ-.....VLVAEE-N 30 FSFB HUMAN -......- --HS-SPRSALSClUHLtVlCl-GAQEGPGRGPAL6R£L-A 37 FSF5“HUMAN -........MSISFLLLLFFSHULSA^AHGEKRLAPKGQPOPMTDRN 40 FGF9~Ht#IAN .................mGEVGMYFGVQCAVPFGNVPVLP- - VDSPVLLS-0 35 FGF3THUMAN —.............HGLIWLILL5UEP--------G.....WPAASPGA 23 FHF-l SLCERHV - - - LGVFSKVRFC5GR......—KRPVRRRFEPQLKGIVT 75 FGF-10 ................—---------------------MASKEPQLKSIVT 13 FHF-4 GLCMGNL—VD1FSKVRIR3LK..........KRRLRRQ-OPQLKGIVT 73 FHF-2 TSCDKNK-- -LNVFSRVKLFGSK..........KRRRRRP-EPQLKGIVT 73 ÍHF-3 SL CQKQL - - - L11LSK VRICGSRP -..........ARPDRGP-EPQLKSÍVT 73 FGF4 HUMAN TLEAEl£ RR-WESLVAl$LARL p WQPLE- AAVQSGAG9YLLG -1KRLR 84 FGF6“HUMAN TLLDS- -RG-WGTILSRSRAGl- --AG- -E- lAGVNWESSYLVG- IKRQR 36 FSF2~HUKAN -------- — - MAAGS1TTLPALPE * - * - *.....OSGSGAFPPSHFK0PK 30 ífiFlTilHAN ------------MAEGEITTFTALtE- - - — —KFíí— LPPGNYKKPK 27 K6F-2 ALeODHVSP-EAIRêSSSSFSSPSSAS------RHWYMHtGS-DVRWR 80 F5F7 HUMAN DMTPEÍ|M—ATNVNCS***5PE---------RHTRSY0Y(€G(2)IRVR 67 ZSI HUZFSF VOFSID--------------VEK- -—------- - - -QTRARODVSRKÍS.RLY 55 RSFB HUMAN SlFRAGR- - - EPGSVSQfWRF..............QSLTOSRRLIRTY 72 FGF5“HUMAN PISSSSR0SS$SAMS5SSASSSPAASIGSQSSSLE0SSFQ«SPS-GRRTS 89 FSF9“HUMAN HLfiQS---------E--AGGLPRGP...........AVTDLDHLKG-3UWR 64 FSF3IHUMAN RLRRO-----------------AGG............RGG7YEHLGG-APRRR 46 FHF-3 RLrSOQ'GYaWHP06TI0GTKDERSDYTLFNLIP76LR-VVAIQGW 122 FGF-10 RLFSOQ- -GYfLQMHPDGTIDGTKDENSDYTiFNLIP76LR-VVA1QGVK 60 FHF-4 RLYCR0-GYYlQMHPDGALDST!(OOSTRSTLFNLIP7GLR-V¥AlQGVt( 120 FHF-2 KLYSRQ--GYHLGLQAD6T1DGTKDE0STYTLFNLIP7GLR-WAIGGVQ 118 FHF-3 KLFCRQ--GF¥L0ANPE!GSiaGTPFDTSSFTHFNUP7G[R-WTIQSAK 120 FGF4 HUHAM RlYCíWGíGFHLQALPDGRISSAHADT - RD$Li£LSP>eS- WSÍ FGVA 132 FGF6“HUMAN RLYCNVGlGFHLGVLPDGRISâTHEEN - PYSLLEISTVERS-WSLFGVR 134 FGF2~HUMAN RLYCKNG-GFFlRIHPtíGRVDSVRFKSDPHIKLQLQAFERG-WSIKGVC 78 FSFrHUMAN LLYC5NG-GHFLRILPOGTYOSTRORSOQHIQLOISAESVS-EYYIK5TE 75 KGf-2 (ílFSFT-KYFLKIEWYSGTííKEfíCPYSILEITSYEIS-WAVKAlH 127 FSF7 HUMAN RLFCRT- -{^YLRIOKRGKVKGTQEMKNMYNÍMEIRTVAVG- IVA1KGVE 114 ZS! 8UZF6F QLYSRTS-GKHIQVlG-RRISARGEDGDKYAQLLVETDTFGSQVRIKGKt 103 FGFg HUMAN QLYSRTS-GKHVOVLAHKRHWtAEDGDPFMLIVtTDTFGSRVRVRGAE 121 FGF5“HUMAN SLYCRVSíGFHLQÍ YP06KW1SSHEWÍ-HLSVLEIFAV5QS- íVGJRSVF 137 FSFrHUMAN QIYCRT - -GFHLEIFPNQTIOSTRKOHSRFGILEFISIAVS-LVSIRSVD 111 FGF3“HUMAN KLYCAT--KYHLQLHPSGRVNSSL£MS-AYSÍLEÍTAYEVS-IVAIRSLF 92 *** - a* F1g. 1 FHF-1 FSF-1Q FHF-4 FHF-2 FHF-3 FGF4 HUMAN FGF6~MUMAN FSF2~HUMAN FGF1~HUMAN K8F-2 FGF7 HUMAN ZSí RUZFGF FSFB HUMAH FSF5“HliMAN F6E9~HUMAN FSF3"HUMAN TEFYLCMNRKGKLYGKPI^TSKECVntKVLEHHYTAlMSAKYSG.....148 TGLY ICHHKKGid IAKSNSKGKOCVFTE IVLENNYTALQNAKYEG.....166 FHF-1 FGF-10 FHF-4 FHF-2 FHF-3 F6F4 HUMAN FGF6~HUMAN FGF2”HUMAN FGFOUMAN KSF-2 F6F7 HUMAN ZSI HSJ7FGF FGF8 HUMAN FGF5~HIjMAM FSF9~HUMAN FGF3HUHAM MFIA15KN6KTKKG- -HRVSPTHKVTHFLPRL.....2Ô6 TYIALSKYGRVKRG- -SKVSPÍKmHFLPRI.......208 FHF-1 FGF-10 FHF-4 FHF-2 FHF-3 FGF4 HUMAN FGF6~HUMAN FGF2HUMAN FGFrHUHAM K6P-2 FGF7 HUMAíí 26! RUZFGF FGFB HUMAN fgfshuman FGF9~HUHAN FGF3~HUMAN MVRQLGSSLPRPPGKGVQPRRRRQKGSPDNt íPSHVGASRLGSQLSASAH 239 Fig. 2 ASL YVAMMGEGYLYSSDV - FTPEÇKFKESVFENYWI YSSÍl YRQGESG - 170 ASLYV/WNGEGYlY$$DV-FTP£CKFKESVFENWÍYSSTLYROQE$G- 108 TGLYlAHHGEGYLYFSEl-FTPECKFKESVFFNYWIYSSKLYRQQESG- 168 IXlYlAHNSEGYLYTSÉL-FTPECKFKESVFEHYYVTYSSMiYfiGQQSG* 166 tGHYHAHNAEGLLYSSPH-FTAECRFKECVFENYWLYASALYRQRRSG- 168 SRFFVAMSSKSKLYGSPF-FTDECTFKEILLPNNYNAYESYKYPG--— 176 SAtFVAHHSfCGRLYAFS-FQEECKFRETlLPHPÍYHAYESOlYíB.....178 ANR Y LAMKEDGRL LASKC-VTDECFFFERL ESNNYNTYRSRKYTS------ 122 TGQ YLAfiDTEfâLL YGSOT-PNEECLFLERLEENHYHTYI5KKHAEK --N - 121 SNYYLAMMííKGKLYGSKE-FMNOCKUCERIEEHGYHWASFNWQHH-G- 173 SFF Y LAMNKEEaCL YAKKE - CHEOCNFKEl IIENHYNTYASAKWTHN - -G - 160 SNKFLAHSFKGKLHASAK-FTGOCKFRERFOENSYHTYASAIHRTEKTG- 185 SGLYLGWEKGELYGSEK-UQECVFREQFEENWYNTY5SNLYKHVDT2- 159 SGRYLAHHiCRGRLYtôEH-YSAECEFVERIHElGYHTYASRLYRTVSSTP 141 «. * * * .* . * * * 1 * * » ► * * ---------RAWFIGINKEGÍHHKG--NRVKKTKPSSHFVPKFÍEVCMYR 209 .....- - - - RAWFLGL NKE6Q1MKG - - NRVEKTKPSSHF VPKPI EVCMYR 147 .........RAVJFIGLNKEGQAMKS- - NRVWCTKPAAHFLPKPLEVAMYR 207 .........RGWYlGtMEÔElHKG--NHYKKNKPAAHFLPKPLKVAMYK 205 .........RAWYLGIDKESQVMKG--NRVIQCTKAAAHFLPKLIEVAHYQ 207 - ..........WYVALKRTGQYKLG-- SKTGPGQKAÍLFLPMSAKS----155 .....-.....WFVGIKKNGSCKRG-PRTHYGQKAÍLFLPLPVSSD- - 155 - ------RQMYVALNGKGAPRRG - -GKTRRKNT5AHFLPMWHS- - - - 208 ——~ «GEMFVALNQKGÍPVRG - - KKTKKEQKTAHFLPMAIT.....194 ...........WYVQFTKKGRPRKG-PKTRENQQDVHFHKRYPKGQPEL 185 ...........WYMAFTRKGRPRK6- -SKTRQHQREVNFMKRlPRGHHTT 203 .......- -REWYVALHKRGKAKRGCSPRVKPCHISTHFLPRFKQSEO-P 225 -------- -RRYYVALM3GTPREG- -TRTKRHGKFTHFLPRPVDPOKVP 198 GARRQPSAERLWYVSVNSKGRPRRG- -FKTRRTQKS5LFIPRVLOHRDHE 189 ::,. * * ;·, *; EPSIHEÍGERQ- - - -GRS- -RKSSGTPTMHGGKVVNQD5T- ------ 243 EPSIBEIGENK—GVQ~ -GKFWTPP......................... 168 £PSLRDVGETVPKP-GVTPSKSTSASAIMNGGKPVNtôKTT--------- 247 EPSLHOlTEFSRSG-SGTPTKSRSVSGVLHGGKSNSIfliEST- ——- 245 EPSLHSVPEAS.......P--SSPPAP-...........-..........225 GKPFKYTTVTK.....RSRR-IRPTHPA.....................207 EOSLRFEFLNYPPF-TRSLRGSQRTWAPEPR...................233 ELSFTyTVPEKKNP-PSPIKSKIPLSAPRmsVKYRLKFRFG--------- 268 ELYKDILSQS—............................—-------- 208
    co D)
PT05021714T 1996-10-16 1997-10-16 Homólogos do factor de crescimento fibroblástico PT1632574E (pt)

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