JP4255618B2 - 単鎖二官能性糖タンパク質ホルモン - Google Patents
単鎖二官能性糖タンパク質ホルモン Download PDFInfo
- Publication number
- JP4255618B2 JP4255618B2 JP2000521213A JP2000521213A JP4255618B2 JP 4255618 B2 JP4255618 B2 JP 4255618B2 JP 2000521213 A JP2000521213 A JP 2000521213A JP 2000521213 A JP2000521213 A JP 2000521213A JP 4255618 B2 JP4255618 B2 JP 4255618B2
- Authority
- JP
- Japan
- Prior art keywords
- subunit
- protein
- linker
- amino acid
- hormone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 229940088597 hormone Drugs 0.000 title claims description 62
- 239000005556 hormone Substances 0.000 title claims description 62
- 108090000288 Glycoproteins Proteins 0.000 title claims description 22
- 102000003886 Glycoproteins Human genes 0.000 title claims description 22
- 230000001588 bifunctional effect Effects 0.000 title description 11
- 108090000623 proteins and genes Proteins 0.000 claims description 62
- 125000005647 linker group Chemical group 0.000 claims description 56
- 102000004169 proteins and genes Human genes 0.000 claims description 54
- 101800005309 Carboxy-terminal peptide Proteins 0.000 claims description 39
- 150000001413 amino acids Chemical class 0.000 claims description 34
- 230000000694 effects Effects 0.000 claims description 34
- 102000011022 Chorionic Gonadotropin Human genes 0.000 claims description 24
- 108010062540 Chorionic Gonadotropin Proteins 0.000 claims description 24
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 21
- 239000005557 antagonist Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 21
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 claims description 17
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 claims description 17
- 239000000556 agonist Substances 0.000 claims description 17
- 229940028334 follicle stimulating hormone Drugs 0.000 claims description 17
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 13
- 108010073521 Luteinizing Hormone Proteins 0.000 claims description 12
- 229940040129 luteinizing hormone Drugs 0.000 claims description 12
- 102000009151 Luteinizing Hormone Human genes 0.000 claims description 11
- 239000002773 nucleotide Substances 0.000 claims description 11
- 125000003729 nucleotide group Chemical group 0.000 claims description 11
- 102000011923 Thyrotropin Human genes 0.000 claims description 9
- 108010061174 Thyrotropin Proteins 0.000 claims description 9
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims description 8
- 229940015047 chorionic gonadotropin Drugs 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 8
- 238000012217 deletion Methods 0.000 claims description 7
- 230000037430 deletion Effects 0.000 claims description 7
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 230000003993 interaction Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 230000035772 mutation Effects 0.000 claims 3
- 238000012258 culturing Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 229960000874 thyrotropin Drugs 0.000 claims 1
- 230000001748 thyrotropin Effects 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 38
- 235000001014 amino acid Nutrition 0.000 description 32
- 150000001875 compounds Chemical class 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 28
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 16
- 102000005962 receptors Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 230000027455 binding Effects 0.000 description 13
- 230000004048 modification Effects 0.000 description 13
- 238000012986 modification Methods 0.000 description 13
- 230000013595 glycosylation Effects 0.000 description 10
- 238000006206 glycosylation reaction Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 102000023108 LH Receptors Human genes 0.000 description 9
- 108010011942 LH Receptors Proteins 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 108091026890 Coding region Proteins 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 239000000833 heterodimer Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229960003067 cystine Drugs 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 241000282412 Homo Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 150000004985 diamines Chemical class 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 102000008175 FSH Receptors Human genes 0.000 description 2
- 108010060374 FSH Receptors Proteins 0.000 description 2
- 102000017357 Glycoprotein hormone receptor Human genes 0.000 description 2
- 108050005395 Glycoprotein hormone receptor Proteins 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 150000001990 dicarboxylic acid derivatives Chemical class 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 101710116299 Choriogonadotropin subunit beta Proteins 0.000 description 1
- 101710166590 Choriogonadotropin subunit beta 3 Proteins 0.000 description 1
- 102100031196 Choriogonadotropin subunit beta 3 Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- IECPWNUMDGFDKC-UHFFFAOYSA-N Fusicsaeure Natural products C12C(O)CC3C(=C(CCC=C(C)C)C(O)=O)C(OC(C)=O)CC3(C)C1(C)CCC1C2(C)CCC(O)C1C IECPWNUMDGFDKC-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000776619 Homo sapiens Choriogonadotropin subunit beta 3 Proteins 0.000 description 1
- 101000893054 Homo sapiens Follitropin subunit beta Proteins 0.000 description 1
- 102000003864 Human Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010082302 Human Follicle Stimulating Hormone Proteins 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 230000004989 O-glycosylation Effects 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003388 anti-hormonal effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 102000035824 beta Subunit Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010081485 beta Subunit Follicle Stimulating Hormone Proteins 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 1
- 230000022811 deglycosylation Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 229960003983 diphtheria toxoid Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical compound O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- 229960004675 fusidic acid Drugs 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 1
- 229940055742 indium-111 Drugs 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000012216 screening Methods 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
- 229940126586 small molecule drug Drugs 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940124598 therapeutic candidate Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Images
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
- C07K14/575—Hormones
- C07K14/59—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Reproductive Health (AREA)
- Toxicology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/971,439 US6103501A (en) | 1997-11-17 | 1997-11-17 | Single chain glycoprotein hormones comprising two β and one α subunits and recombinant production thereof |
| US08/971,439 | 1997-11-17 | ||
| PCT/US1998/023744 WO1999025849A1 (en) | 1997-11-17 | 1998-11-09 | Single-chain bifunctional glycoprotein hormones |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2001523465A JP2001523465A (ja) | 2001-11-27 |
| JP2001523465A5 JP2001523465A5 (enExample) | 2006-01-05 |
| JP4255618B2 true JP4255618B2 (ja) | 2009-04-15 |
Family
ID=25518394
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000521213A Expired - Fee Related JP4255618B2 (ja) | 1997-11-17 | 1998-11-09 | 単鎖二官能性糖タンパク質ホルモン |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6103501A (enExample) |
| EP (1) | EP1032688B1 (enExample) |
| JP (1) | JP4255618B2 (enExample) |
| KR (1) | KR20010032147A (enExample) |
| CN (1) | CN1173037C (enExample) |
| AU (1) | AU754296B2 (enExample) |
| BR (1) | BR9814880A (enExample) |
| CA (1) | CA2308571C (enExample) |
| CZ (1) | CZ299742B6 (enExample) |
| DE (1) | DE69839779D1 (enExample) |
| HU (1) | HUP0004394A3 (enExample) |
| IL (2) | IL135995A0 (enExample) |
| NO (1) | NO20002527L (enExample) |
| PL (1) | PL342853A1 (enExample) |
| TR (1) | TR200001406T2 (enExample) |
| WO (1) | WO1999025849A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014159813A1 (en) | 2013-03-13 | 2014-10-02 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6319504B1 (en) | 1996-06-24 | 2001-11-20 | University Of Maryland Biotechnology Institute | Treatment and prevention of HIV infection by administration of derivatives of human chorionic gonadotropin |
| US6583109B1 (en) | 1997-06-24 | 2003-06-24 | Robert C. Gallo | Therapeutic polypeptides from β-hCG and derivatives |
| US6635256B1 (en) * | 1998-10-19 | 2003-10-21 | Washington University | Glycoprotein hormone compositions comprising two β subunits and methods of use thereof |
| US7994278B1 (en) | 1999-08-06 | 2011-08-09 | Nobel Biosciences Llc | Biologically active polypeptides derived from a novel early stage pregnancy factor designated maternin (MA) |
| JP2003511077A (ja) * | 1999-10-08 | 2003-03-25 | バイオフォーカス・ディスカバリー・リミテッド | 細胞ターゲティングのための方法および組成物 |
| GB9924351D0 (en) | 1999-10-14 | 1999-12-15 | Brennan Frank | Immunomodulation methods and compositions |
| JP2001333772A (ja) * | 2000-04-25 | 2001-12-04 | Washington Univ | 可変性の活性を有する単鎖稔性ホルモン |
| EP1276765B1 (en) * | 2000-04-25 | 2011-06-08 | Washington University | Single-chain fertility hormones with variable lh activity |
| US6987172B2 (en) * | 2001-03-05 | 2006-01-17 | Washington University In St. Louis | Multifunctional single chain glycoprotein hormones comprising three or more β subunits |
| US7081446B2 (en) * | 2002-01-31 | 2006-07-25 | The Trustees Of Columbia University In The City Of New York | Long-acting follicle stimulating hormone analogues and uses thereof |
| NZ542549A (en) | 2003-03-04 | 2008-11-28 | Aspenbio Pharma Inc | Methods and kits for maintaining pregnancy, treating follicular cysts, and synchronizing ovulation using single-chain luteinizing hormone |
| JP4412989B2 (ja) * | 2003-12-15 | 2010-02-10 | 株式会社日立製作所 | 複数の記憶システムを有するデータ処理システム |
| US20080039372A1 (en) * | 2005-07-21 | 2008-02-14 | The Trustees Of Columbia University In The City Of New York | Human chorionic gonadotropin antagonists and methods to prevent ovarian hyperstimulation |
| AU2006316838B2 (en) * | 2005-11-15 | 2012-04-12 | Glycofi, Inc | Production of glycoproteins with reduced O-glycosylation |
| US10221228B2 (en) | 2006-02-03 | 2019-03-05 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US8048848B2 (en) | 2006-02-03 | 2011-11-01 | Prolor Biotech Ltd. | Long-acting interferons and derivatives thereof and methods thereof |
| US8759292B2 (en) | 2006-02-03 | 2014-06-24 | Prolor Biotech, Llc | Long-acting coagulation factors and methods of producing same |
| US8946155B2 (en) | 2006-02-03 | 2015-02-03 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US9458444B2 (en) | 2006-02-03 | 2016-10-04 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| US8048849B2 (en) | 2006-02-03 | 2011-11-01 | Modigene, Inc. | Long-acting polypeptides and methods of producing same |
| US7553941B2 (en) | 2006-02-03 | 2009-06-30 | Modigene Inc | Long-acting polypeptides and methods of producing same |
| US20140113860A1 (en) | 2006-02-03 | 2014-04-24 | Prolor Biotech Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US20150038413A1 (en) | 2006-02-03 | 2015-02-05 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US8450269B2 (en) | 2006-02-03 | 2013-05-28 | Prolor Biotech Ltd. | Long-acting growth hormone and methods of producing same |
| US10351615B2 (en) | 2006-02-03 | 2019-07-16 | Opko Biologics Ltd. | Methods of treatment with long-acting growth hormone |
| US9249407B2 (en) | 2006-02-03 | 2016-02-02 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| CA2721459A1 (en) | 2008-05-20 | 2009-11-26 | Merck Sharp & Dohme Corp. | Efficient production of heterologous proteins using mannosyl transferase inhibitors |
| JP2011530311A (ja) | 2008-08-12 | 2011-12-22 | グライコフィ, インコーポレイテッド | タンパク質製造のための改良されたベクターおよび酵母株:Ca2+ATPアーゼ過剰発現 |
| US12203113B2 (en) | 2009-07-09 | 2025-01-21 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| US9663778B2 (en) | 2009-07-09 | 2017-05-30 | OPKO Biologies Ltd. | Long-acting coagulation factors and methods of producing same |
| RU2014103185A (ru) | 2011-07-18 | 2015-08-27 | Артс Байолоджикс А/С | Биологически активное соединение на основе лютеинизирующего гормона (lh) с пролонгированным действием |
| MX2014012625A (es) | 2012-04-19 | 2015-05-15 | Opko Biolog Ltd | Variantes de oxintomodulina de accion prolongada y metodos para su produccion. |
| BR112015011583B1 (pt) | 2012-11-20 | 2023-03-14 | Opko Biologics Ltd | Métodos para aumentar o tamanho ou volume hidrodinâmico de hormônio de crescimento humano, método para aumentar o peso molecular aparente de um polipeptídeo e método para aumentar a meia-vida de um polipeptídeo |
| US20150158926A1 (en) | 2013-10-21 | 2015-06-11 | Opko Biologics, Ltd. | Long-acting polypeptides and methods of producing and administering same |
| SG11201704706RA (en) | 2014-12-10 | 2017-07-28 | Opko Biologics Ltd | Methods of producing long acting ctp-modified growth hormone polypeptides |
| PL3310347T3 (pl) | 2015-06-19 | 2021-12-27 | Opko Biologics Ltd. | Długo działające czynniki krzepnięcia i sposoby wytwarzania |
| WO2018011799A1 (en) | 2016-07-11 | 2018-01-18 | Opko Biologics Ltd. | Long-acting coagulation factor vii and methods of producing same |
| CN106279436B (zh) * | 2016-08-19 | 2017-10-31 | 安源医药科技(上海)有限公司 | 活化的人凝血因子vii融合蛋白及其制备方法与用途 |
| 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 |
| CN107759694B (zh) * | 2016-08-19 | 2023-01-13 | 安源医药科技(上海)有限公司 | 双特异性抗体及其制备方法与用途 |
| EP3502143A4 (en) * | 2016-08-19 | 2020-07-15 | Ampsource Biopharma Shanghai Inc. | BINDING PEPTIDE FOR THE CONSTRUCTION OF A FUSION PROTEIN |
| CN106256835A (zh) * | 2016-08-19 | 2016-12-28 | 安源医药科技(上海)有限公司 | 高糖基化人生长激素融合蛋白及其制备方法与用途 |
| CN107827987B (zh) * | 2017-01-04 | 2021-04-27 | 华侨大学 | 一种促黄体激素类似物及其制备方法 |
| CN113105562B (zh) * | 2018-09-26 | 2023-12-01 | 安源医药科技(上海)有限公司 | 突变型单链人凝血因子viii在制备融合蛋白中的应用 |
| BR102019004147A2 (pt) | 2019-02-28 | 2020-10-06 | Ouro Fino Saude Animal Participacoes S.A. | Gonadotrofina coriônica equina recombinante (recg) biologicamente ativa e processo para obtenção da mesma, composição veterinária e uso |
| CA3140267A1 (en) | 2019-05-16 | 2020-11-19 | Ceva Sante Animale | Compositions and methods for increasing reproduction performance in non-human mammals using recombinant luteinizing hormone |
| KR20220053003A (ko) * | 2019-08-30 | 2022-04-28 | 신텍스 에세.아. | 재조합 융모막 고나도트로핀, 그의 제조방법, 의약 조성물 및 용도 |
| US11981718B2 (en) | 2020-05-27 | 2024-05-14 | Ampsource Biopharma Shanghai Inc. | Dual-function protein for lipid and blood glucose regulation |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE169334T1 (de) * | 1983-11-02 | 1998-08-15 | Applied Research Systems | Herstellung heterodimirer menschlicher fruchtbarkeitshormone |
| CA1213537A (en) * | 1984-05-01 | 1986-11-04 | Canadian Patents And Development Limited - Societe Canadienne Des Brevets Et D'exploitation Limitee | Polypeptide expression method |
| EP0461200B1 (en) * | 1989-02-21 | 1997-01-22 | Washington University | Modified forms of reproductive hormones |
| WO1991016922A1 (en) * | 1990-05-08 | 1991-11-14 | University Of Medicine & Dentistry Of New Jersey | Analogs of glycoprotein hormones having altered immunological characteristics, efficacy and/or receptor specificity |
| JPH06504438A (ja) * | 1990-12-13 | 1994-05-26 | イミュネックス・コーポレーション | 白血病抑制因子受容体 |
| ZA942206B (en) * | 1993-04-01 | 1994-10-31 | Amgen Inc | Biologically active polypeptide fusion dimers |
| ES2251731T3 (es) * | 1994-02-18 | 2006-05-01 | Washington University | Gonadotropina monocatenaria. |
| KR960704932A (ko) * | 1994-08-12 | 1996-10-09 | 에이치. 에스. 리헤이 | 당단백질 호르몬 4개조의 단일-사슬 형태(single-chain forms of the glycoprotein hormone quartet) |
-
1997
- 1997-11-17 US US08/971,439 patent/US6103501A/en not_active Expired - Lifetime
-
1998
- 1998-11-09 TR TR2000/01406T patent/TR200001406T2/xx unknown
- 1998-11-09 JP JP2000521213A patent/JP4255618B2/ja not_active Expired - Fee Related
- 1998-11-09 CN CNB988112353A patent/CN1173037C/zh not_active Expired - Fee Related
- 1998-11-09 PL PL98342853A patent/PL342853A1/xx not_active IP Right Cessation
- 1998-11-09 CZ CZ20001774A patent/CZ299742B6/cs not_active IP Right Cessation
- 1998-11-09 IL IL13599598A patent/IL135995A0/xx active IP Right Grant
- 1998-11-09 KR KR1020007005334A patent/KR20010032147A/ko not_active Abandoned
- 1998-11-09 EP EP98956662A patent/EP1032688B1/en not_active Expired - Lifetime
- 1998-11-09 HU HU0004394A patent/HUP0004394A3/hu unknown
- 1998-11-09 DE DE69839779T patent/DE69839779D1/de not_active Expired - Lifetime
- 1998-11-09 AU AU13131/99A patent/AU754296B2/en not_active Ceased
- 1998-11-09 WO PCT/US1998/023744 patent/WO1999025849A1/en not_active Ceased
- 1998-11-09 CA CA2308571A patent/CA2308571C/en not_active Expired - Fee Related
- 1998-11-09 BR BR9814880-0A patent/BR9814880A/pt not_active Application Discontinuation
-
2000
- 2000-05-05 IL IL135995A patent/IL135995A/en not_active IP Right Cessation
- 2000-05-16 NO NO20002527A patent/NO20002527L/no not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014159813A1 (en) | 2013-03-13 | 2014-10-02 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2308571A1 (en) | 1999-05-27 |
| AU754296B2 (en) | 2002-11-14 |
| PL342853A1 (en) | 2001-07-16 |
| CN1173037C (zh) | 2004-10-27 |
| CZ20001774A3 (cs) | 2000-10-11 |
| EP1032688B1 (en) | 2008-07-23 |
| HUP0004394A2 (hu) | 2001-09-28 |
| AU1313199A (en) | 1999-06-07 |
| US6103501A (en) | 2000-08-15 |
| NO20002527L (no) | 2000-07-10 |
| HUP0004394A3 (en) | 2003-04-28 |
| WO1999025849A1 (en) | 1999-05-27 |
| NO20002527D0 (no) | 2000-05-16 |
| CN1290301A (zh) | 2001-04-04 |
| JP2001523465A (ja) | 2001-11-27 |
| EP1032688A1 (en) | 2000-09-06 |
| DE69839779D1 (de) | 2008-09-04 |
| IL135995A (en) | 2007-03-08 |
| BR9814880A (pt) | 2000-10-03 |
| CZ299742B6 (cs) | 2008-11-05 |
| IL135995A0 (en) | 2001-05-20 |
| CA2308571C (en) | 2013-04-23 |
| TR200001406T2 (tr) | 2000-12-21 |
| KR20010032147A (ko) | 2001-04-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4255618B2 (ja) | 単鎖二官能性糖タンパク質ホルモン | |
| US6987172B2 (en) | Multifunctional single chain glycoprotein hormones comprising three or more β subunits | |
| IL114859A (en) | Glycoproteins, pharmaceutical and veterinary compositions containing the same and methods for the production thereof | |
| FI120150B (fi) | Glykoproteiinihormonikvartetin yksiketjumuotoja | |
| US6635256B1 (en) | Glycoprotein hormone compositions comprising two β subunits and methods of use thereof | |
| US5883073A (en) | Single-chain double-alpha peptide | |
| US6689365B1 (en) | Single-chain fertility hormones with fsh and LH activity | |
| JP2009050278A (ja) | 糖タンパク質ホルモンカルテットの一本鎖形態 | |
| EP1276765B1 (en) | Single-chain fertility hormones with variable lh activity | |
| MXPA00004761A (en) | Single-chain bifunctional glycoprotein hormones | |
| MXPA01003947A (en) | Multiple domain glycoprotein hormones and methods of using |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20051027 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20051027 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080806 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20081105 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20081112 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081202 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090105 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20081202 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090128 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120206 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120206 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130206 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130206 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140206 Year of fee payment: 5 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |