PT1632574E - Homólogos do factor de crescimento fibroblástico - Google Patents
Homólogos do factor de crescimento fibroblástico Download PDFInfo
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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
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- 102000018233 Fibroblast Growth Factor Human genes 0.000 title abstract 3
- 108050007372 Fibroblast Growth Factor Proteins 0.000 title abstract 3
- 229940126864 fibroblast growth factor Drugs 0.000 title abstract 3
- 229920001184 polypeptide Polymers 0.000 claims abstract 31
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 31
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 31
- 125000000539 amino acid group Chemical group 0.000 claims abstract 12
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 10
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 14
- 210000000988 bone and bone Anatomy 0.000 claims 13
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims 10
- 102100035290 Fibroblast growth factor 13 Human genes 0.000 claims 9
- 108090000047 fibroblast growth factor 13 Proteins 0.000 claims 7
- 230000001737 promoting effect Effects 0.000 claims 7
- 102100028413 Fibroblast growth factor 11 Human genes 0.000 claims 5
- 108050003237 Fibroblast growth factor 11 Proteins 0.000 claims 5
- 102100035292 Fibroblast growth factor 14 Human genes 0.000 claims 5
- 108090000046 Fibroblast growth factor 14 Proteins 0.000 claims 5
- 102100028412 Fibroblast growth factor 10 Human genes 0.000 claims 4
- 108090001047 Fibroblast growth factor 10 Proteins 0.000 claims 4
- 102100028417 Fibroblast growth factor 12 Human genes 0.000 claims 4
- 108050003239 Fibroblast growth factor 12 Proteins 0.000 claims 4
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 claims 4
- 102100028075 Fibroblast growth factor 6 Human genes 0.000 claims 4
- 101001060274 Homo sapiens Fibroblast growth factor 4 Proteins 0.000 claims 4
- 101001060265 Homo sapiens Fibroblast growth factor 6 Proteins 0.000 claims 4
- 108010076504 Protein Sorting Signals Proteins 0.000 claims 4
- 230000007547 defect Effects 0.000 claims 4
- 230000007812 deficiency Effects 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 206010010356 Congenital anomaly Diseases 0.000 claims 3
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 claims 3
- 101001060267 Homo sapiens Fibroblast growth factor 5 Proteins 0.000 claims 3
- 206010031264 Osteonecrosis Diseases 0.000 claims 3
- 230000008468 bone growth Effects 0.000 claims 3
- 238000002316 cosmetic surgery Methods 0.000 claims 3
- 239000004053 dental implant Substances 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 230000002708 enhancing effect Effects 0.000 claims 3
- 230000035876 healing Effects 0.000 claims 3
- 208000014674 injury Diseases 0.000 claims 3
- 230000000771 oncological effect Effects 0.000 claims 3
- 230000011164 ossification Effects 0.000 claims 3
- 230000001582 osteoblastic effect Effects 0.000 claims 3
- 230000002188 osteogenic effect Effects 0.000 claims 3
- 230000005855 radiation Effects 0.000 claims 3
- 238000002271 resection Methods 0.000 claims 3
- 230000004936 stimulating effect Effects 0.000 claims 3
- 230000000638 stimulation Effects 0.000 claims 3
- 230000008733 trauma Effects 0.000 claims 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims 2
- 102100028043 Fibroblast growth factor 3 Human genes 0.000 claims 2
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 claims 2
- 101001060280 Homo sapiens Fibroblast growth factor 3 Proteins 0.000 claims 2
- 101001060261 Homo sapiens Fibroblast growth factor 7 Proteins 0.000 claims 2
- 102100037680 Fibroblast growth factor 8 Human genes 0.000 claims 1
- 102100037665 Fibroblast growth factor 9 Human genes 0.000 claims 1
- 101001027382 Homo sapiens Fibroblast growth factor 8 Proteins 0.000 claims 1
- 101001027380 Homo sapiens Fibroblast growth factor 9 Proteins 0.000 claims 1
- 208000001132 Osteoporosis Diseases 0.000 claims 1
- 206010003246 arthritis Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 abstract 6
- 125000003729 nucleotide group Chemical group 0.000 abstract 6
- 239000002157 polynucleotide Substances 0.000 abstract 4
- 102000040430 polynucleotide Human genes 0.000 abstract 4
- 108091033319 polynucleotide Proteins 0.000 abstract 4
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0657—Cardiomyocytes; Heart cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- A61K47/51—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
- A61K47/62—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 a protein, peptide or polyamino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- A61K47/51—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
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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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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- Health & Medical Sciences (AREA)
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- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Toxicology (AREA)
- Rheumatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cell Biology (AREA)
- Neurology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Peptides Or Proteins (AREA)
Claims (14)
- 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. 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. 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. 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. 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. 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. Polipeptídeo para uso de acordo com qualquer das reivindicações 1-5, em que o dito polipeptídeo ainda compreende uma sequência de sinal.
- 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. Polipeptídeo para uso de acordo com a reivindicação 6, em que a desordem esquelética é a osteoporose ou artrite.
- 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. Polipeptídeo de acordo com a reivindicação 10, que compreende ainda uma sequência de sinal.
- 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. Polipeptídeo de acordo com qualquer das reivindicações 10-12 para o uso como um medicamento. 3
- 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—............................—-------- 208co D)
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AU5103293A (en) | 1992-09-14 | 1994-04-12 | Oklahoma State University | Immortalized cells and uses therefor |
US5773252A (en) * | 1995-06-05 | 1998-06-30 | Human Genome Sciences, Inc. | Fibroblast growth factor 15 |
AU1158297A (en) | 1995-11-09 | 1997-05-29 | Zymogenetics Inc. | Production of gad65 in methylotrophic yeast |
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1997
- 1997-10-16 CN CN97199827A patent/CN1127568C/zh not_active Expired - Lifetime
- 1997-10-16 ES ES97910128T patent/ES2258788T3/es not_active Expired - Lifetime
- 1997-10-16 EP EP97910128A patent/EP0931148B1/en not_active Expired - Lifetime
- 1997-10-16 UA UA99042170A patent/UA75316C2/uk unknown
- 1997-10-16 DK DK05021714.0T patent/DK1632574T3/da active
- 1997-10-16 CA CA002269083A patent/CA2269083C/en not_active Expired - Lifetime
- 1997-10-16 EP EP05021714A patent/EP1632574B1/en not_active Expired - Lifetime
- 1997-10-16 PT PT97910128T patent/PT931148E/pt unknown
- 1997-10-16 US US08/951,822 patent/US5989866A/en not_active Expired - Lifetime
- 1997-10-16 EP EP10176653A patent/EP2264175B1/en not_active Expired - Lifetime
- 1997-10-16 PT PT05021714T patent/PT1632574E/pt unknown
- 1997-10-16 KR KR1019997003306A patent/KR100611063B1/ko not_active IP Right Cessation
- 1997-10-16 AT AT97910128T patent/ATE318906T1/de active
- 1997-10-16 JP JP51857798A patent/JP4091122B2/ja not_active Expired - Lifetime
- 1997-10-16 CZ CZ0131599A patent/CZ299288B6/cs not_active IP Right Cessation
- 1997-10-16 PL PL332851A patent/PL192537B1/pl unknown
- 1997-10-16 ES ES10176653T patent/ES2403880T3/es not_active Expired - Lifetime
- 1997-10-16 EP EP10185113A patent/EP2339002A1/en not_active Withdrawn
- 1997-10-16 AU AU47583/97A patent/AU725551B2/en not_active Expired
- 1997-10-16 DK DK97910128T patent/DK0931148T3/da active
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- 1997-10-16 BR BRPI9712348-0B1A patent/BR9712348B1/pt not_active IP Right Cessation
- 1997-10-16 DE DE69735352T patent/DE69735352T2/de not_active Expired - Lifetime
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- 1997-10-16 WO PCT/US1997/018635 patent/WO1998016644A1/en active IP Right Grant
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1999
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2001
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2006
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2011
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