EA011390B1 - Мутантные белки (мутеины) фактора роста фибробластов 21 - Google Patents
Мутантные белки (мутеины) фактора роста фибробластов 21 Download PDFInfo
- Publication number
- EA011390B1 EA011390B1 EA200700533A EA200700533A EA011390B1 EA 011390 B1 EA011390 B1 EA 011390B1 EA 200700533 A EA200700533 A EA 200700533A EA 200700533 A EA200700533 A EA 200700533A EA 011390 B1 EA011390 B1 EA 011390B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- mutein
- muteins
- type
- human
- amino acid
- Prior art date
Links
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 title description 2
- 108090000376 Fibroblast growth factor 21 Proteins 0.000 title description 2
- 208000008589 Obesity Diseases 0.000 claims abstract description 13
- 235000020824 obesity Nutrition 0.000 claims abstract description 13
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 12
- 208000001145 Metabolic Syndrome Diseases 0.000 claims abstract description 11
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims abstract description 11
- 239000013598 vector Substances 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 150000001413 amino acids Chemical class 0.000 claims description 52
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 8
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 4
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 4
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 4
- 206010022489 Insulin Resistance Diseases 0.000 claims description 4
- 201000001421 hyperglycemia Diseases 0.000 claims description 4
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 4
- 201000008980 hyperinsulinism Diseases 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000001963 growth medium Substances 0.000 claims description 3
- 239000002609 medium Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- 230000004989 O-glycosylation Effects 0.000 abstract description 28
- 240000004808 Saccharomyces cerevisiae Species 0.000 abstract description 26
- 210000004027 cell Anatomy 0.000 abstract description 19
- 108090000623 proteins and genes Proteins 0.000 abstract description 18
- 102000004169 proteins and genes Human genes 0.000 abstract description 15
- 241000894007 species Species 0.000 abstract description 2
- 101000846529 Homo sapiens Fibroblast growth factor 21 Proteins 0.000 abstract 2
- 150000007523 nucleic acids Chemical class 0.000 abstract 2
- 102000056713 human FGF21 Human genes 0.000 abstract 1
- 102000039446 nucleic acids Human genes 0.000 abstract 1
- 108020004707 nucleic acids Proteins 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 55
- 229940024606 amino acid Drugs 0.000 description 52
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 36
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 27
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 26
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 20
- 235000004279 alanine Nutrition 0.000 description 20
- 239000008103 glucose Substances 0.000 description 20
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 20
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 19
- 239000004471 Glycine Substances 0.000 description 18
- 238000006467 substitution reaction Methods 0.000 description 18
- 239000004475 Arginine Substances 0.000 description 17
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 17
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 16
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 14
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 14
- 108091033319 polynucleotide Proteins 0.000 description 13
- 239000002157 polynucleotide Substances 0.000 description 13
- 102000040430 polynucleotide Human genes 0.000 description 13
- 230000004071 biological effect Effects 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 11
- 229940009098 aspartate Drugs 0.000 description 11
- 235000018417 cysteine Nutrition 0.000 description 11
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 11
- 229920001184 polypeptide Polymers 0.000 description 11
- 102000004877 Insulin Human genes 0.000 description 10
- 108090001061 Insulin Proteins 0.000 description 10
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 10
- 229940125396 insulin Drugs 0.000 description 10
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 10
- 108091026890 Coding region Proteins 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 239000003755 preservative agent Substances 0.000 description 9
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 8
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 7
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 7
- 239000004472 Lysine Substances 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 125000003275 alpha amino acid group Chemical group 0.000 description 6
- 230000002335 preservative effect Effects 0.000 description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
- 229930195712 glutamate Natural products 0.000 description 5
- 238000006206 glycosylation reaction Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 150000003626 triacylglycerols Chemical class 0.000 description 5
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 210000001789 adipocyte Anatomy 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 150000001720 carbohydrates Chemical group 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 230000013595 glycosylation Effects 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 3
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- 108091029865 Exogenous DNA Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000013611 chromosomal DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 230000004190 glucose uptake Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 210000005253 yeast cell Anatomy 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- OYIFNHCXNCRBQI-UHFFFAOYSA-N 2-aminoadipic acid Chemical compound OC(=O)C(N)CCCC(O)=O OYIFNHCXNCRBQI-UHFFFAOYSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
- 108010025188 Alcohol oxidase Proteins 0.000 description 1
- 102100036826 Aldehyde oxidase Human genes 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 101150025129 POP1 gene Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- AFYNADDZULBEJA-UHFFFAOYSA-N bicinchoninic acid Chemical compound C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)O)=CC(C(O)=O)=C21 AFYNADDZULBEJA-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 150000001945 cysteines Chemical class 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 239000006160 differential media Substances 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- -1 for example Proteins 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 230000037219 healthy weight Effects 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000009655 industrial fermentation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000002614 leucines Chemical group 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 101150001396 oar gene Proteins 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008020 pharmaceutical preservative Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000007261 regionalization Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Animal Behavior & Ethology (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Child & Adolescent Psychology (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Emergency Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60680504P | 2004-09-02 | 2004-09-02 | |
| PCT/US2005/026398 WO2006028595A2 (en) | 2004-09-02 | 2005-07-26 | Muteins of fibroblast growth factor 21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200700533A1 EA200700533A1 (ru) | 2007-08-31 |
| EA011390B1 true EA011390B1 (ru) | 2009-02-27 |
Family
ID=36036790
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200700533A EA011390B1 (ru) | 2004-09-02 | 2005-07-26 | Мутантные белки (мутеины) фактора роста фибробластов 21 |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US7582607B2 (https=) |
| EP (2) | EP2161281A1 (https=) |
| JP (1) | JP4809352B2 (https=) |
| KR (1) | KR100854198B1 (https=) |
| CN (1) | CN101010338B (https=) |
| AT (1) | ATE444307T1 (https=) |
| AU (1) | AU2005283025B2 (https=) |
| BR (1) | BRPI0514790A (https=) |
| CA (1) | CA2575753A1 (https=) |
| DE (1) | DE602005016946D1 (https=) |
| DK (1) | DK1789442T3 (https=) |
| EA (1) | EA011390B1 (https=) |
| ES (1) | ES2332057T3 (https=) |
| HR (1) | HRP20090597T1 (https=) |
| IL (1) | IL181573A0 (https=) |
| MX (1) | MX2007002616A (https=) |
| NO (1) | NO20071327L (https=) |
| PL (1) | PL1789442T3 (https=) |
| PT (1) | PT1789442E (https=) |
| SI (1) | SI1789442T1 (https=) |
| WO (1) | WO2006028595A2 (https=) |
Families Citing this family (81)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7459540B1 (en) | 1999-09-07 | 2008-12-02 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
| US8981061B2 (en) | 2001-03-20 | 2015-03-17 | Novo Nordisk A/S | Receptor TREM (triggering receptor expressed on myeloid cells) and uses thereof |
| US9453251B2 (en) | 2002-10-08 | 2016-09-27 | Pfenex Inc. | Expression of mammalian proteins in Pseudomonas fluorescens |
| BRPI0513826A2 (pt) | 2004-07-26 | 2010-06-22 | Dow Global Technologies Inc | processo para expressão de proteìna melhorada através de engenharia de cepa |
| GB0426146D0 (en) | 2004-11-29 | 2004-12-29 | Bioxell Spa | Therapeutic peptides and method |
| CN107501407B (zh) | 2007-03-30 | 2022-03-18 | Ambrx公司 | 经修饰fgf-21多肽和其用途 |
| US9394571B2 (en) | 2007-04-27 | 2016-07-19 | Pfenex Inc. | Method for rapidly screening microbial hosts to identify certain strains with improved yield and/or quality in the expression of heterologous proteins |
| US9580719B2 (en) | 2007-04-27 | 2017-02-28 | Pfenex, Inc. | Method for rapidly screening microbial hosts to identify certain strains with improved yield and/or quality in the expression of heterologous proteins |
| US20110034373A1 (en) * | 2007-08-03 | 2011-02-10 | Eli Lilly And Company | Use of an fgf-21 compound and a glp-1 compound for the treatment of obesity |
| US8034770B2 (en) | 2008-06-04 | 2011-10-11 | Amgen Inc. | FGF21 polypeptides comprising two or more mutations |
| CA2739615C (en) * | 2008-10-10 | 2017-12-05 | Amgen Inc. | Fgf21 mutants comprising polyethylene glycol and uses thereof |
| US9120871B2 (en) | 2009-01-23 | 2015-09-01 | Novo Nordisk A/S | Process for preparing FGF21 with low degree of O-glycosylation |
| CN102361647B (zh) | 2009-01-23 | 2018-02-16 | 诺沃-诺迪斯克有限公司 | 具有白蛋白结合剂a‑b‑c‑d‑e‑的fgf21衍生物及其应用 |
| WO2010129503A1 (en) * | 2009-05-05 | 2010-11-11 | Amgen Inc. | Fgf21 mutants and uses thereof |
| WO2010129600A2 (en) * | 2009-05-05 | 2010-11-11 | Amgen Inc. | Fgf21 mutants and uses thereof |
| WO2011154349A2 (en) | 2010-06-08 | 2011-12-15 | Novo Nordisk A/S | Fgf21 analogues and derivatives |
| MX2011013903A (es) * | 2009-06-17 | 2012-05-08 | Amgen Inc | Polipeptidos quimericos y usos de los mismos. |
| CN101993485B (zh) | 2009-08-20 | 2013-04-17 | 重庆富进生物医药有限公司 | 促胰岛素分泌肽类似物同源二聚体及其用途 |
| EP2679234A3 (en) * | 2009-12-02 | 2014-04-23 | Amgen Inc. | Binding proteins that bind to human FGFR1C, human beta-klotho and both human FGFR1C and human beta-klotho |
| UA109888C2 (uk) * | 2009-12-07 | 2015-10-26 | ІЗОЛЬОВАНЕ АНТИТІЛО АБО ЙОГО ФРАГМЕНТ, ЩО ЗВ'ЯЗУЄТЬСЯ З β-КЛОТО, РЕЦЕПТОРАМИ FGF І ЇХНІМИ КОМПЛЕКСАМИ | |
| EP2460527A1 (en) | 2010-01-21 | 2012-06-06 | Sanofi | Pharmaceutical composition for treating a metabolic syndrome |
| ES2543634T3 (es) | 2010-01-22 | 2015-08-20 | Novo Nordisk A/S | Proceso para preparación de FGF-21 con grado de O-glicosilación bajo |
| CA2796055A1 (en) | 2010-04-15 | 2011-10-20 | Amgen Inc. | Human fgf receptor and .beta.-klotho binding proteins |
| WO2011130729A2 (en) | 2010-04-16 | 2011-10-20 | Salk Institute For Biological Studies | Methods for treating metabolic disorders using fgf |
| CN103415300B (zh) | 2010-07-20 | 2018-02-23 | 诺沃—诺迪斯克有限公司 | N‑末端修饰的fgf21化合物 |
| JP2014500248A (ja) | 2010-11-05 | 2014-01-09 | コヴェックス・テクノロジーズ・アイルランド・リミテッド | 抗糖尿病化合物 |
| US9023791B2 (en) * | 2010-11-19 | 2015-05-05 | Novartis Ag | Fibroblast growth factor 21 mutations |
| CN105601748B (zh) | 2011-07-01 | 2021-08-27 | 恩格姆生物制药公司 | 用于代谢病症和疾病治疗的组合物、应用和方法 |
| EP2548570A1 (en) | 2011-07-19 | 2013-01-23 | Sanofi | Pharmaceutical composition for treating a metabolic syndrome |
| TWI593708B (zh) * | 2011-09-26 | 2017-08-01 | 諾華公司 | 治療代謝病症之融合蛋白質 |
| AR087973A1 (es) * | 2011-10-04 | 2014-04-30 | Lilly Co Eli | Variantes del factor 21 del crecimiento de fibroblastos |
| BR112014014898A2 (pt) | 2011-12-22 | 2020-10-27 | Pfizer Inc. | processo para purificar uma amostra de anticorpo h38c2, ou variante do mesmo, e composição compreendendo o referido h38c2 |
| CN104203977A (zh) | 2012-02-15 | 2014-12-10 | 诺和诺德A/S（股份有限公司） | 结合肽聚糖识别蛋白1的抗体 |
| JP6411218B2 (ja) | 2012-02-15 | 2018-10-24 | ノヴォ ノルディスク アー／エス | 骨髄細胞で発現されるトリガー受容体１（ｔｒｅｍ−１）に結合し、それを遮断する抗体 |
| US9550830B2 (en) | 2012-02-15 | 2017-01-24 | Novo Nordisk A/S | Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1) |
| WO2013131091A1 (en) | 2012-03-02 | 2013-09-06 | New York University | Chimeric fgf21 proteins with enhanced binding affinity for beta-klotho for the treatment of type ii diabetes, obesity and related metabolic disorders |
| US9464126B2 (en) | 2012-06-07 | 2016-10-11 | New York University | Chimeric fibroblast growth factor 21 proteins and methods of use |
| US9657075B2 (en) | 2012-06-07 | 2017-05-23 | New York University | Chimeric fibroblast growth factor 23 proteins and methods of use |
| US9474785B2 (en) | 2012-06-07 | 2016-10-25 | New York University | Chimeric fibroblast growth factor 19 proteins and methods of use |
| CA2871656A1 (en) | 2012-06-11 | 2013-12-19 | Eli Lilly And Company | Fibroblast growth factor 21 variants |
| HK1214832A1 (zh) | 2012-11-28 | 2016-08-05 | 恩格姆生物制药公司 | 用於代謝病症和疾病治療的組合物和方法 |
| US9290557B2 (en) | 2012-11-28 | 2016-03-22 | Ngm Biopharmaceuticals, Inc. | Compositions comprising variants and fusions of FGF19 polypeptides |
| ES2915851T3 (es) | 2012-12-27 | 2022-06-27 | Ngm Biopharmaceuticals Inc | Péptidos quiméricos de FGF19 para usar en el tratamiento de trastornos de ácidos biliares |
| US9273107B2 (en) | 2012-12-27 | 2016-03-01 | Ngm Biopharmaceuticals, Inc. | Uses and methods for modulating bile acid homeostasis and treatment of bile acid disorders and diseases |
| US9550820B2 (en) | 2013-02-22 | 2017-01-24 | New York University | Chimeric fibroblast growth factor 23/fibroblast growth factor 19 proteins and methods of use |
| WO2015061331A1 (en) | 2013-10-21 | 2015-04-30 | Salk Institute For Biological Studies | Chimeric fibroblast growth factor (fgf) 2/fgf1 peptides and methods of use |
| AU2014340241B2 (en) | 2013-10-21 | 2018-11-01 | Salk Institute For Biological Studies | Mutated fibroblast growth factor (FGF) 1 and methods of use |
| CA2927592C (en) | 2013-10-28 | 2020-08-18 | Ngm Biopharmaceuticals, Inc. | Fgf-19 variants for treating a fgf-19 dependent cancer or tumor |
| PE20170256A1 (es) | 2014-01-24 | 2017-04-22 | Ngm Biopharmaceuticals Inc | Proteinas de union y sus metodos de uso |
| WO2015183890A2 (en) | 2014-05-28 | 2015-12-03 | Ngm Biopharmaceuticals, Inc. | Methods and compositions for the treatment of metabolic disorders and diseases |
| AU2015277438B2 (en) | 2014-06-16 | 2020-02-27 | Ngm Biopharmaceuticals, Inc. | Methods and uses for modulating bile acid homeostasis and treatment of bile acid disorders and diseases |
| EA037844B1 (ru) | 2014-07-17 | 2021-05-27 | Ново Нордиск А/С | Сайт-направленный мутагенез антител к trem-1 |
| RU2729161C2 (ru) | 2014-10-23 | 2020-08-04 | ЭнДжиЭм БАЙОФАРМАСЬЮТИКАЛЗ, ИНК. | Фармацевтические композиции, содержащие варианты пептидов, и способы их применения |
| CN114805532A (zh) | 2014-10-24 | 2022-07-29 | 百时美施贵宝公司 | 修饰的fgf-21多肽及其用途 |
| US10434144B2 (en) | 2014-11-07 | 2019-10-08 | Ngm Biopharmaceuticals, Inc. | Methods for treatment of bile acid-related disorders and prediction of clinical sensitivity to treatment of bile acid-related disorders |
| AR103246A1 (es) | 2014-12-23 | 2017-04-26 | Novo Nordiks As | Derivados de fgf21 y sus usos |
| WO2016187558A2 (en) | 2015-05-20 | 2016-11-24 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Method to improve neurologic outcomes in temperature managed patients |
| US10800843B2 (en) | 2015-07-29 | 2020-10-13 | Ngm Biopharmaceuticals, Inc. | Beta klotho-binding proteins |
| EP3368059A4 (en) | 2015-10-30 | 2019-03-27 | Salk Institute for Biological Studies | TREATMENT OF STEROID-INDUCED HYPERGLYCEMIA WITH FIBROBLAST GROWTH FACTOR (FGF) -1 ANALOGUE |
| JP6728352B2 (ja) | 2015-11-09 | 2020-07-22 | エヌジーエム バイオファーマシューティカルス，インコーポレーテッド | 胆汁酸に関係した障害の治療方法 |
| TW201731867A (zh) | 2015-12-02 | 2017-09-16 | 賽諾菲公司 | Ｆｇｆ２１變異體 |
| CN106279437B (zh) | 2016-08-19 | 2017-10-31 | 安源医药科技（上海）有限公司 | 高糖基化人凝血因子viii融合蛋白及其制备方法与用途 |
| US11123438B2 (en) | 2016-08-19 | 2021-09-21 | Ampsource Biopharma Shanghai Inc. | Linker peptide for constructing fusion protein |
| CN106317226B (zh) * | 2016-08-19 | 2017-09-05 | 安源医药科技（上海）有限公司 | 用于构建融合蛋白的连接肽 |
| CA3034399A1 (en) | 2016-08-26 | 2018-03-01 | Ngm Biopharmaceuticals, Inc. | Methods of treating fibroblast growth factor 19-mediated cancers and tumors |
| WO2018166461A1 (en) | 2017-03-14 | 2018-09-20 | Sunshine Lake Pharma Co., Ltd. | Dual-target fusion proteins comprising the fc portion of an immunoglobulin |
| SG11202001379WA (en) | 2017-09-08 | 2020-03-30 | Bristol Myers Squibb Co | Modified fibroblast growth factor 21 (fgf-21) for use in methods for treating nonalcoholic steatohepatitis (nash) |
| WO2019119673A1 (zh) | 2017-12-19 | 2019-06-27 | 北京吉源生物科技有限公司 | 一种双基因修饰的干细胞及其用途 |
| AU2019218147B2 (en) * | 2018-02-08 | 2023-06-08 | Sunshine Lake Pharma Co., Ltd. | FGF21 variant, fusion protein and application thereof |
| WO2019195126A1 (en) | 2018-04-02 | 2019-10-10 | Bristol-Myers Squibb Company | Anti-trem-1 antibodies and uses thereof |
| KR20210027426A (ko) | 2018-07-03 | 2021-03-10 | 브리스톨-마이어스 스큅 컴퍼니 | Fgf21 제제 |
| EP3935075A4 (en) | 2019-03-05 | 2023-01-18 | Sunshine Lake Pharma Co., Ltd. | POLYPEPTIDE MOLECULE AND APPLICATION THEREOF |
| US11542309B2 (en) | 2019-07-31 | 2023-01-03 | Salk Institute For Biological Studies | Fibroblast growth factor 1 (FGF1) mutant proteins that selectively activate FGFR1B to reduce blood glucose |
| US20220380426A1 (en) * | 2019-11-12 | 2022-12-01 | Technische Universitat Mu | Homogeneous muteins of the human il-27 alpha-subunit |
| EP4087612A1 (en) | 2020-01-08 | 2022-11-16 | Bristol-Myers Squibb Company | Fgf-21 conjugate formulations |
| CN113728013B (zh) | 2020-01-11 | 2022-06-14 | 北京质肽生物医药科技有限公司 | Glp-1和fgf21的融合蛋白的缀合物 |
| US11981718B2 (en) | 2020-05-27 | 2024-05-14 | Ampsource Biopharma Shanghai Inc. | Dual-function protein for lipid and blood glucose regulation |
| JP2023538533A (ja) | 2020-08-07 | 2023-09-08 | ブリストル－マイヤーズ スクイブ カンパニー | 線維症の処置のための、ｃｃｒ２／５拮抗剤と組み合わせたｆｇｆ２１ |
| US20240123031A1 (en) | 2020-11-25 | 2024-04-18 | Bristol-Myers Squibb Company | Methods of treating liver diseases |
| CN113633756A (zh) * | 2021-06-17 | 2021-11-12 | 温州医科大学 | Fgf21温敏缓释载体和基因修饰方法以及其制备方法 |
| WO2023284822A1 (en) | 2021-07-14 | 2023-01-19 | Beijing Ql Biopharmaceutical Co., Ltd. | Fusion polypeptides for metabolic disorders |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994026873A1 (en) * | 1993-05-07 | 1994-11-24 | Pharmacia Ab | Yeast strain and methods for expressing heterologous proteins in yeast |
| WO1996005224A1 (en) * | 1994-08-12 | 1996-02-22 | Washington University | Single-chain forms of the glycoprotein hormone quartet |
| WO2001036640A2 (en) * | 1999-11-18 | 2001-05-25 | Chiron Corporation | Human fgf-21 gene and gene expression products |
| WO2003011213A2 (en) * | 2001-07-30 | 2003-02-13 | Eli Lilly And Company | Method for treating diabetes and obesity |
| WO2005113606A2 (en) * | 2004-05-13 | 2005-12-01 | Eli Lilly And Company | Fgf-21 fusion proteins |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4334615B2 (ja) * | 1994-08-12 | 2009-09-30 | ワシントン・ユニバーシティ | 糖タンパク質ホルモンカルテットの一本鎖形態 |
| US7459540B1 (en) | 1999-09-07 | 2008-12-02 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
| AU7368100A (en) | 1999-09-10 | 2001-04-10 | Curagen Corporation | Fibroblast growth factor polypeptide and nucleic acids encoding same |
| US6716626B1 (en) | 1999-11-18 | 2004-04-06 | Chiron Corporation | Human FGF-21 nucleic acids |
| WO2001038357A2 (en) | 1999-11-22 | 2001-05-31 | Millennium Pharmaceuticals, Inc. | Jaffa, a novel fibroblast growth factor family member and uses therefor |
| US20050176631A1 (en) | 2002-01-15 | 2005-08-11 | Heuer Josef G. | Method for reducing morbidity and mortality in critically ill patients |
| EP2270163A1 (en) * | 2003-12-10 | 2011-01-05 | Eli Lilly and Company | Muteins of fibroblast growth factor 21 |
-
2005
- 2005-07-26 KR KR1020077004881A patent/KR100854198B1/ko not_active Expired - Fee Related
- 2005-07-26 PT PT05775749T patent/PT1789442E/pt unknown
- 2005-07-26 HR HR20090597T patent/HRP20090597T1/hr unknown
- 2005-07-26 BR BRPI0514790-5A patent/BRPI0514790A/pt not_active IP Right Cessation
- 2005-07-26 EA EA200700533A patent/EA011390B1/ru not_active IP Right Cessation
- 2005-07-26 MX MX2007002616A patent/MX2007002616A/es active IP Right Grant
- 2005-07-26 SI SI200530852T patent/SI1789442T1/sl unknown
- 2005-07-26 CN CN2005800294803A patent/CN101010338B/zh not_active Expired - Fee Related
- 2005-07-26 CA CA002575753A patent/CA2575753A1/en not_active Abandoned
- 2005-07-26 WO PCT/US2005/026398 patent/WO2006028595A2/en not_active Ceased
- 2005-07-26 ES ES05775749T patent/ES2332057T3/es not_active Expired - Lifetime
- 2005-07-26 AU AU2005283025A patent/AU2005283025B2/en not_active Ceased
- 2005-07-26 AT AT05775749T patent/ATE444307T1/de active
- 2005-07-26 US US11/574,332 patent/US7582607B2/en not_active Expired - Fee Related
- 2005-07-26 PL PL05775749T patent/PL1789442T3/pl unknown
- 2005-07-26 EP EP08162741A patent/EP2161281A1/en not_active Withdrawn
- 2005-07-26 EP EP05775749A patent/EP1789442B1/en not_active Expired - Lifetime
- 2005-07-26 DK DK05775749T patent/DK1789442T3/da active
- 2005-07-26 JP JP2007529870A patent/JP4809352B2/ja not_active Expired - Fee Related
- 2005-07-26 DE DE602005016946T patent/DE602005016946D1/de not_active Expired - Lifetime
-
2007
- 2007-02-26 IL IL181573A patent/IL181573A0/en unknown
- 2007-03-12 NO NO20071327A patent/NO20071327L/no not_active Application Discontinuation
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994026873A1 (en) * | 1993-05-07 | 1994-11-24 | Pharmacia Ab | Yeast strain and methods for expressing heterologous proteins in yeast |
| WO1996005224A1 (en) * | 1994-08-12 | 1996-02-22 | Washington University | Single-chain forms of the glycoprotein hormone quartet |
| WO2001036640A2 (en) * | 1999-11-18 | 2001-05-25 | Chiron Corporation | Human fgf-21 gene and gene expression products |
| WO2003011213A2 (en) * | 2001-07-30 | 2003-02-13 | Eli Lilly And Company | Method for treating diabetes and obesity |
| WO2005113606A2 (en) * | 2004-05-13 | 2005-12-01 | Eli Lilly And Company | Fgf-21 fusion proteins |
Non-Patent Citations (1)
| Title |
|---|
| HANSEN J. E. ET AL.: "NETOGLYC: PREDICTION OF MUCIN TYPE O-GLYCOSYLATION SITES BASED ON SEQUENCE CONTEXT AND SURFACE ACCESSIBILITY", GLYCOCONJUGATE JOURNAL, LUND, SE, vol. 15, no. 2, 1998, pages 115-130, XP001024941, ISSN: 0282-0080, the whole document * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005283025B2 (en) | 2011-06-30 |
| US20080103096A1 (en) | 2008-05-01 |
| US7582607B2 (en) | 2009-09-01 |
| CN101010338B (zh) | 2011-06-15 |
| EA200700533A1 (ru) | 2007-08-31 |
| BRPI0514790A (pt) | 2008-06-24 |
| KR20070050454A (ko) | 2007-05-15 |
| CA2575753A1 (en) | 2006-03-16 |
| JP4809352B2 (ja) | 2011-11-09 |
| KR100854198B1 (ko) | 2008-08-26 |
| MX2007002616A (es) | 2007-05-16 |
| ATE444307T1 (de) | 2009-10-15 |
| SI1789442T1 (sl) | 2010-01-29 |
| EP1789442A2 (en) | 2007-05-30 |
| HRP20090597T1 (hr) | 2009-12-31 |
| PT1789442E (pt) | 2009-11-11 |
| IL181573A0 (en) | 2007-07-04 |
| DK1789442T3 (da) | 2009-11-16 |
| WO2006028595A2 (en) | 2006-03-16 |
| DE602005016946D1 (de) | 2009-11-12 |
| ES2332057T3 (es) | 2010-01-25 |
| CN101010338A (zh) | 2007-08-01 |
| JP2008511323A (ja) | 2008-04-17 |
| AU2005283025A1 (en) | 2006-03-16 |
| WO2006028595A3 (en) | 2007-01-18 |
| NO20071327L (no) | 2007-05-29 |
| PL1789442T3 (pl) | 2010-02-26 |
| EP2161281A1 (en) | 2010-03-10 |
| EP1789442B1 (en) | 2009-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA011390B1 (ru) | Мутантные белки (мутеины) фактора роста фибробластов 21 | |
| US7655627B2 (en) | Muteins of fibroblast growth factor 21 | |
| US7622445B2 (en) | Muteins of fibroblast growth factor 21 | |
| JP4477013B2 (ja) | 線維芽細胞成長因子２１の突然変異タンパク質 | |
| FR2795734A1 (fr) | Conjugues d'erythropoietine,compositons les comprenant et procede pour leur preparation | |
| KR20150008137A (ko) | 지속성 옥신토모둘린 변이체 및 이의 생산 방법 | |
| KR20150110486A (ko) | 생식샘자극 호르몬 카복시 말단 펩타이드들과 부착하여 폴리펩타이드들의 유체역학적 부피를 증가시키는 방법 | |
| EP2194064A1 (en) | FGF-21 fusion proteins | |
| CZ98197A3 (cs) | Použití KGF nebo jeho analogu pro přípravu léčiva pro léčení cukrovky | |
| TWI777407B (zh) | 長效型多肽及其生產和給藥的方法 | |
| US20190284252A1 (en) | Engineered fgf1 and fgf2 compositions and methods of use thereof | |
| CN115916244A (zh) | 用于治疗戊二酸尿症的组合物及其给药方法 | |
| CN102336812B (zh) | 一种具有抑制血管生成活性的多肽 | |
| EP3870694A1 (en) | Compositions and methods for biodegrading alcohol | |
| HK1109408A (en) | Muteins of fibroblast growth factor 21 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM BY KZ KG MD TM |
|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AZ TJ RU |