NO331690B1 - Forbindelse, og farmasoytisk kombinasjon av forbindelse, som har en aktivitet til a modulere signaloverforing formidlet av AILIM for forsterkning av virkningen av immunsupprimerende midler pa undertrykkelse, behandling eller forebyggelse av transplantatavstotning ved transplantasjon av et organ, del av et organ eller et vev. - Google Patents
Forbindelse, og farmasoytisk kombinasjon av forbindelse, som har en aktivitet til a modulere signaloverforing formidlet av AILIM for forsterkning av virkningen av immunsupprimerende midler pa undertrykkelse, behandling eller forebyggelse av transplantatavstotning ved transplantasjon av et organ, del av et organ eller et vev. Download PDFInfo
- Publication number
- NO331690B1 NO331690B1 NO20033839A NO20033839A NO331690B1 NO 331690 B1 NO331690 B1 NO 331690B1 NO 20033839 A NO20033839 A NO 20033839A NO 20033839 A NO20033839 A NO 20033839A NO 331690 B1 NO331690 B1 NO 331690B1
- Authority
- NO
- Norway
- Prior art keywords
- ailim
- antibody
- compound
- organ
- human
- Prior art date
Links
- 238000002054 transplantation Methods 0.000 title claims abstract description 57
- 210000000056 organ Anatomy 0.000 title claims abstract description 54
- 206010052779 Transplant rejections Diseases 0.000 title claims abstract description 39
- 238000011282 treatment Methods 0.000 title claims abstract description 32
- 101001042104 Homo sapiens Inducible T-cell costimulator Proteins 0.000 title claims abstract 16
- 102100021317 Inducible T-cell costimulator Human genes 0.000 title claims abstract 16
- 150000001875 compounds Chemical class 0.000 title claims description 70
- 239000003018 immunosuppressive agent Substances 0.000 title claims description 36
- 229940125721 immunosuppressive agent Drugs 0.000 title claims description 35
- 230000000694 effects Effects 0.000 title claims description 32
- 230000001629 suppression Effects 0.000 title claims description 17
- 230000001404 mediated effect Effects 0.000 title claims description 14
- 230000002265 prevention Effects 0.000 title claims description 10
- 230000008054 signal transmission Effects 0.000 title claims description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 64
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 63
- 229920001184 polypeptide Polymers 0.000 claims description 62
- 108060003951 Immunoglobulin Proteins 0.000 claims description 31
- 102000018358 immunoglobulin Human genes 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 24
- 230000004927 fusion Effects 0.000 claims description 23
- 229940079593 drug Drugs 0.000 claims description 20
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 16
- 238000011316 allogeneic transplantation Methods 0.000 claims description 16
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 15
- 230000019491 signal transduction Effects 0.000 claims description 13
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 12
- 238000002689 xenotransplantation Methods 0.000 claims description 11
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 10
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 10
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 9
- 229960002170 azathioprine Drugs 0.000 claims description 9
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 8
- 108010036949 Cyclosporine Proteins 0.000 claims description 8
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 claims description 8
- 229960001265 ciclosporin Drugs 0.000 claims description 8
- 229930182912 cyclosporin Natural products 0.000 claims description 8
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 claims description 8
- 229960000681 leflunomide Drugs 0.000 claims description 8
- 229950000844 mizoribine Drugs 0.000 claims description 8
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 claims description 8
- 229960004866 mycophenolate mofetil Drugs 0.000 claims description 8
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 8
- 229960002930 sirolimus Drugs 0.000 claims description 8
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 8
- -1 deoxyspergualine Chemical compound 0.000 claims description 6
- 229960000556 fingolimod Drugs 0.000 claims description 6
- 239000003470 adrenal cortex hormone Substances 0.000 claims description 5
- 108020004491 Antisense DNA Proteins 0.000 claims description 4
- 108020005544 Antisense RNA Proteins 0.000 claims description 4
- 239000003816 antisense DNA Substances 0.000 claims description 4
- 239000003184 complementary RNA Substances 0.000 claims description 4
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 claims 2
- 210000002216 heart Anatomy 0.000 abstract description 55
- 210000004185 liver Anatomy 0.000 abstract description 20
- 210000003734 kidney Anatomy 0.000 abstract description 10
- 210000004072 lung Anatomy 0.000 abstract description 8
- 210000000496 pancreas Anatomy 0.000 abstract description 6
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 206010060766 Heteroplasia Diseases 0.000 abstract 1
- 206010053159 Organ failure Diseases 0.000 abstract 1
- 241000282414 Homo sapiens Species 0.000 description 89
- 210000004027 cell Anatomy 0.000 description 60
- 108090000623 proteins and genes Proteins 0.000 description 59
- 241000700159 Rattus Species 0.000 description 52
- 241000699666 Mus <mouse, genus> Species 0.000 description 49
- 108020004414 DNA Proteins 0.000 description 47
- 238000000034 method Methods 0.000 description 41
- 241001465754 Metazoa Species 0.000 description 26
- 210000004408 hybridoma Anatomy 0.000 description 25
- 230000004083 survival effect Effects 0.000 description 25
- 230000001900 immune effect Effects 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 23
- 150000001413 amino acids Chemical group 0.000 description 23
- 239000002773 nucleotide Substances 0.000 description 23
- 125000003729 nucleotide group Chemical group 0.000 description 23
- 210000001519 tissue Anatomy 0.000 description 23
- 210000001744 T-lymphocyte Anatomy 0.000 description 21
- 102100034980 ICOS ligand Human genes 0.000 description 19
- 210000003491 skin Anatomy 0.000 description 19
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 14
- 102000004127 Cytokines Human genes 0.000 description 14
- 108090000695 Cytokines Proteins 0.000 description 14
- 241000124008 Mammalia Species 0.000 description 14
- 239000012634 fragment Substances 0.000 description 14
- 102000004169 proteins and genes Human genes 0.000 description 14
- 230000036961 partial effect Effects 0.000 description 12
- 239000002609 medium Substances 0.000 description 11
- 241000699800 Cricetinae Species 0.000 description 10
- 101001019455 Homo sapiens ICOS ligand Proteins 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 101710093458 ICOS ligand Proteins 0.000 description 9
- 239000000427 antigen Substances 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 239000012228 culture supernatant Substances 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 230000003053 immunization Effects 0.000 description 9
- 210000004698 lymphocyte Anatomy 0.000 description 9
- 206010035226 Plasma cell myeloma Diseases 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000013604 expression vector Substances 0.000 description 8
- 238000002649 immunization Methods 0.000 description 8
- 238000010253 intravenous injection Methods 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 201000000050 myeloid neoplasm Diseases 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 241000282898 Sus scrofa Species 0.000 description 7
- 230000000692 anti-sense effect Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 7
- 239000008177 pharmaceutical agent Substances 0.000 description 7
- 229960001967 tacrolimus Drugs 0.000 description 7
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- 241000700199 Cavia porcellus Species 0.000 description 6
- 101100179074 Homo sapiens ICOS gene Proteins 0.000 description 6
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- SWZTYAVBMYWFGS-UHFFFAOYSA-N fingolimod hydrochloride Chemical compound Cl.CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 SWZTYAVBMYWFGS-UHFFFAOYSA-N 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 241000701161 unidentified adenovirus Species 0.000 description 6
- 206010003445 Ascites Diseases 0.000 description 5
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 5
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 5
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 5
- 101001042093 Mus musculus ICOS ligand Proteins 0.000 description 5
- 101100179075 Mus musculus Icos gene Proteins 0.000 description 5
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 5
- 210000000988 bone and bone Anatomy 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 5
- 230000007969 cellular immunity Effects 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 210000004087 cornea Anatomy 0.000 description 5
- 230000001506 immunosuppresive effect Effects 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 108010074328 Interferon-gamma Proteins 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 230000001780 adrenocortical effect Effects 0.000 description 4
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 229940072221 immunoglobulins Drugs 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000008595 infiltration Effects 0.000 description 4
- 238000001764 infiltration Methods 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000009261 transgenic effect Effects 0.000 description 4
- 102000035160 transmembrane proteins Human genes 0.000 description 4
- 108091005703 transmembrane proteins Proteins 0.000 description 4
- 241001515965 unidentified phage Species 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 208000007204 Brain death Diseases 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 102000008070 Interferon-gamma Human genes 0.000 description 3
- 102000004388 Interleukin-4 Human genes 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 238000010824 Kaplan-Meier survival analysis Methods 0.000 description 3
- 206010028851 Necrosis Diseases 0.000 description 3
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 108090000526 Papain Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 210000000628 antibody-producing cell Anatomy 0.000 description 3
- 239000013602 bacteriophage vector Substances 0.000 description 3
- 230000008827 biological function Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 101150014721 cdr gene Proteins 0.000 description 3
- 238000007385 chemical modification Methods 0.000 description 3
- 230000000139 costimulatory effect Effects 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000012239 gene modification Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000005017 genetic modification Effects 0.000 description 3
- 235000013617 genetically modified food Nutrition 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 102000043321 human CTLA4 Human genes 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 229960003130 interferon gamma Drugs 0.000 description 3
- 229940028885 interleukin-4 Drugs 0.000 description 3
- 238000011694 lewis rat Methods 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 230000017074 necrotic cell death Effects 0.000 description 3
- 229940055729 papain Drugs 0.000 description 3
- 235000019834 papain Nutrition 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 229930024421 Adenine Natural products 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 101150111062 C gene Proteins 0.000 description 2
- 102000002110 C2 domains Human genes 0.000 description 2
- 108050009459 C2 domains Proteins 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 102000012410 DNA Ligases Human genes 0.000 description 2
- 108010061982 DNA Ligases Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 2
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 102000000646 Interleukin-3 Human genes 0.000 description 2
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 102000015636 Oligopeptides Human genes 0.000 description 2
- 108010038807 Oligopeptides Proteins 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 229940104302 cytosine Drugs 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 230000004727 humoral immunity Effects 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 206010024378 leukocytosis Diseases 0.000 description 2
- 229960004584 methylprednisolone Drugs 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 210000003240 portal vein Anatomy 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000010349 pulsation Effects 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 229940075420 xanthine Drugs 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 description 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
- 208000007788 Acute Liver Failure Diseases 0.000 description 1
- 206010000804 Acute hepatic failure Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 102100039496 Choline transporter-like protein 4 Human genes 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 206010018367 Glomerulonephritis chronic Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 101000889282 Homo sapiens Choline transporter-like protein 4 Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 101150075078 MEP10 gene Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100020679 Mus musculus Lcn5 gene Proteins 0.000 description 1
- 241000609499 Palicourea Species 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 208000016222 Pancreatic disease Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010037596 Pyelonephritis Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 102000005686 Serum Globulins Human genes 0.000 description 1
- 108010045362 Serum Globulins Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 231100000836 acute liver failure Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical class N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 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
- 239000002775 capsule Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 101150076615 ck gene Proteins 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical compound C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 description 1
- 238000012786 cultivation procedure Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000005980 lung dysfunction Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000033607 mismatch repair Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 208000024691 pancreas disease Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010972 statistical evaluation Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 210000000779 thoracic wall Anatomy 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000001131 transforming effect Effects 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
- 230000001960 triggered effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- 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
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Transplantation (AREA)
- Surgery (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Graft Or Block Polymers (AREA)
- External Artificial Organs (AREA)
- Transplanting Machines (AREA)
- Soil Working Implements (AREA)
- Cylinder Crankcases Of Internal Combustion Engines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001056209 | 2001-03-01 | ||
| JP2001056216 | 2001-03-01 | ||
| JP2002008028 | 2002-01-16 | ||
| PCT/JP2002/000930 WO2002070010A1 (fr) | 2001-03-01 | 2002-02-05 | Inhibiteurs de rejet du greffon |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20033839D0 NO20033839D0 (no) | 2003-08-29 |
| NO20033839L NO20033839L (no) | 2003-11-03 |
| NO331690B1 true NO331690B1 (no) | 2012-02-27 |
Family
ID=27346134
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20033839A NO331690B1 (no) | 2001-03-01 | 2003-08-29 | Forbindelse, og farmasoytisk kombinasjon av forbindelse, som har en aktivitet til a modulere signaloverforing formidlet av AILIM for forsterkning av virkningen av immunsupprimerende midler pa undertrykkelse, behandling eller forebyggelse av transplantatavstotning ved transplantasjon av et organ, del av et organ eller et vev. |
| NO20110218A NO20110218L (no) | 2001-03-01 | 2011-02-08 | Transplantatrejeksjonssuppressorer |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20110218A NO20110218L (no) | 2001-03-01 | 2011-02-08 | Transplantatrejeksjonssuppressorer |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US7438905B2 (fr) |
| EP (2) | EP1374901B9 (fr) |
| JP (1) | JP4212278B2 (fr) |
| KR (1) | KR100609444B1 (fr) |
| CN (1) | CN1518458B (fr) |
| AT (2) | ATE352318T1 (fr) |
| AU (1) | AU2002228435B2 (fr) |
| BR (1) | BR0207787A (fr) |
| CA (1) | CA2439858C (fr) |
| CY (1) | CY1110143T1 (fr) |
| CZ (1) | CZ20032406A3 (fr) |
| DE (2) | DE60217839T2 (fr) |
| DK (1) | DK1769807T3 (fr) |
| ES (1) | ES2344219T3 (fr) |
| HK (2) | HK1061531A1 (fr) |
| HU (2) | HU228045B1 (fr) |
| IL (2) | IL156845A0 (fr) |
| MX (1) | MXPA03006736A (fr) |
| NO (2) | NO331690B1 (fr) |
| NZ (1) | NZ527076A (fr) |
| PT (1) | PT1769807E (fr) |
| RU (1) | RU2263512C2 (fr) |
| SI (1) | SI1769807T1 (fr) |
| SK (1) | SK288048B6 (fr) |
| WO (1) | WO2002070010A1 (fr) |
Families Citing this family (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3521382B2 (ja) | 1997-02-27 | 2004-04-19 | 日本たばこ産業株式会社 | 細胞間接着及びシグナル伝達を媒介する細胞表面分子 |
| US7112655B1 (en) | 1997-02-27 | 2006-09-26 | Japan Tobacco, Inc. | JTT-1 protein and methods of inhibiting lymphocyte activation |
| DE19821060A1 (de) * | 1997-09-23 | 1999-04-15 | Bundesrepublik Deutschland Let | Ko-stimulierendes Polypeptid von T-Zellen, monoklonale Antikörper sowie die Herstellung und deren Verwendung |
| JP4210454B2 (ja) | 2001-03-27 | 2009-01-21 | 日本たばこ産業株式会社 | 炎症性腸疾患治療剤 |
| JP3871503B2 (ja) | 1999-08-30 | 2007-01-24 | 日本たばこ産業株式会社 | 免疫性疾患治療剤 |
| CZ20022000A3 (cs) * | 1999-12-16 | 2003-02-12 | Teva Pharmaceuticals Industries Ltd. | Způsoby přípravy a nová krystalická forma leflunomidu |
| JP3597140B2 (ja) | 2000-05-18 | 2004-12-02 | 日本たばこ産業株式会社 | 副刺激伝達分子ａｉｌｉｍに対するヒトモノクローナル抗体及びその医薬用途 |
| JP4212278B2 (ja) | 2001-03-01 | 2009-01-21 | 日本たばこ産業株式会社 | 移植片拒絶反応抑制剤 |
| GB0504544D0 (en) * | 2005-03-04 | 2005-04-13 | Novartis Ag | Organic compounds |
| JP2006321765A (ja) * | 2005-05-20 | 2006-11-30 | Mikiko Ueda | 肝移植における拒絶反応の予防又は治療薬、或いは拒絶反応とは断定できない肝機能異常の治療薬 |
| EP2703011A3 (fr) * | 2007-05-07 | 2014-03-26 | MedImmune, LLC | Anticorps anti-ICOS et leur utilisation dans le traitement de l'oncologie, la transplantation et les maladies auto-immunes |
| US9931386B2 (en) * | 2008-06-16 | 2018-04-03 | Atsuo Ochi | Recombinant multiple domain fusion protein mitogens and use thereof for inducing enhancement or repression of antigen-specific immunity |
| US20120114595A1 (en) * | 2009-07-16 | 2012-05-10 | Otsuka Chemical Co., Ltd. | Sugar chain-added ailim extracellular domain and method for producing same |
| US9420770B2 (en) | 2009-12-01 | 2016-08-23 | Indiana University Research & Technology Corporation | Methods of modulating thrombocytopenia and modified transgenic pigs |
| EP2558024B1 (fr) * | 2010-04-12 | 2017-03-08 | The University Of Miami | Échafaudages biotechnologiques macroporeux pour la transplantation de cellules |
| RU2456615C1 (ru) * | 2011-03-25 | 2012-07-20 | Федеральное государственное учреждение "Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова" Министерства здравоохранения и социального развития Российской Федерации | Способ профилактики отторжения трансплантата трупной почки |
| SG193428A1 (en) * | 2011-03-31 | 2013-10-30 | Inst Nat Sante Rech Med | Antibodies directed against icos and uses thereof |
| US20150139994A1 (en) * | 2013-11-12 | 2015-05-21 | The Regents Of The University Of California | Compositions and methods for preventing allogeneic immune rejection |
| ME03318B (fr) * | 2013-11-22 | 2019-10-20 | Shire Viropharma Inc | Méthodes de traitement de rejet médié par les anticorps chez des patients transplantés à l'aide d'un inhibiteur de c1-estérase |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| CN106461679B (zh) | 2014-03-12 | 2018-10-09 | 西奈山伊坎医学院 | 鉴定处于慢性损伤风险的肾异体移植物接受者的方法 |
| CN113444783B (zh) | 2014-06-26 | 2024-04-09 | 西奈山伊坎医学院 | 通过分析预示性基因集诊断亚临床和临床的急性排异的方法 |
| ES2897004T3 (es) * | 2014-06-26 | 2022-02-28 | Icahn School Med Mount Sinai | Métodos para diagnosticar el riesgo de fibrosis y rechazo de aloinjerto renal |
| MA41414A (fr) | 2015-01-28 | 2017-12-05 | Centre Nat Rech Scient | Protéines de liaison agonistes d' icos |
| CA3006930A1 (fr) | 2015-12-03 | 2017-06-08 | Glaxosmithkline Intellectual Property Development Limited | Dinucleotides cycliques de purine a titre de modulateurs du sting |
| WO2017098421A1 (fr) | 2015-12-08 | 2017-06-15 | Glaxosmithkline Intellectual Property Development Limited | Composés benzothiadiazine |
| WO2017153952A1 (fr) | 2016-03-10 | 2017-09-14 | Glaxosmithkline Intellectual Property Development Limited | Dérivés de 5-sulfamoyl-2-hydroxybenzamide |
| EA201892128A1 (ru) | 2016-04-07 | 2019-04-30 | Глаксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Гетероциклические амиды, полезные в качестве модуляторов |
| CN109608443B (zh) | 2016-04-07 | 2021-09-07 | 葛兰素史密斯克莱知识产权发展有限公司 | 用作蛋白质调节剂的杂环酰胺 |
| CA3023157A1 (fr) | 2016-05-05 | 2017-11-09 | Glaxosmithkline Intellectual Property (No.2) Limited | Activateur d'inhibiteurs de l'homologue 2 de zeste |
| EP3471754A1 (fr) | 2016-06-20 | 2019-04-24 | Kymab Limited | Anticorps anti-pd-l1 |
| US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
| WO2018029474A2 (fr) | 2016-08-09 | 2018-02-15 | Kymab Limited | Anticorps anti-icos |
| EP3487503A1 (fr) | 2016-07-20 | 2019-05-29 | GlaxoSmithKline Intellectual Property Development Limited | Dérivés d'isoquinoléine utilisés comme inhibiteurs de perk |
| BR112019002529A2 (pt) | 2016-08-09 | 2019-05-28 | Kymab Ltd | anticorpo isolado, composição, método para modular o equilíbrio de células t, método para tratar uma doença ou afecção tratável com terapia, método para tratar câncer, combinação de anticorpo igg1, anticorpo anti-icos, mamífero não humano transgênico, e método para produzir um anticorpo |
| WO2018083248A1 (fr) | 2016-11-03 | 2018-05-11 | Kymab Limited | Anticorps, combinaisons comprenant des anticorps, biomarqueurs, utilisations et procédés |
| BR112019017738A2 (pt) | 2017-02-27 | 2020-04-07 | Glaxosmithkline Ip Dev Ltd | combinação, composição farmacêutica, uso de uma combinação ou composição farmacêutica, método para tratar câncer em um humano, e, composto |
| WO2018225033A1 (fr) | 2017-06-09 | 2018-12-13 | Glaxosmithkline Intellectual Property Development Limited | Polythérapie |
| CN110709423A (zh) | 2017-06-09 | 2020-01-17 | 葛兰素史克知识产权开发有限公司 | 用icos激动剂和ox40激动剂治疗癌症的组合疗法 |
| WO2018225034A1 (fr) | 2017-06-09 | 2018-12-13 | Glaxosmithkline Intellectual Property Development Limited | Polythérapie avec un agoniste icos et un agoniste ox40 pour traiter le cancer |
| GB201709808D0 (en) | 2017-06-20 | 2017-08-02 | Kymab Ltd | Antibodies |
| WO2019021208A1 (fr) | 2017-07-27 | 2019-01-31 | Glaxosmithkline Intellectual Property Development Limited | Dérivés d'indazole utiles en tant qu'inhibiteurs de perk |
| WO2019053617A1 (fr) | 2017-09-12 | 2019-03-21 | Glaxosmithkline Intellectual Property Development Limited | Composés chimiques |
| CA3075717A1 (fr) | 2017-09-14 | 2019-03-21 | Glaxosmithkline Intellectual Property Development Limited | Polytherapie pour le traitement du cancer |
| BR112020006780A2 (pt) | 2017-10-05 | 2020-10-06 | Glaxosmithkline Intellectual Property Development Limited | moduladores do estimulador de genes do interferon (sting) |
| TW201927771A (zh) | 2017-10-05 | 2019-07-16 | 英商葛蘭素史密斯克藍智慧財產發展有限公司 | 可作為蛋白質調節劑之雜環醯胺及其使用方法 |
| GB201721338D0 (en) | 2017-12-19 | 2018-01-31 | Kymab Ltd | Anti-icos Antibodies |
| US11629189B2 (en) | 2017-12-19 | 2023-04-18 | Kymab Limited | Bispecific antibody for ICOS and PD-L1 |
| RU2688172C1 (ru) * | 2018-04-05 | 2019-05-20 | Государственное бюджетное учреждение здравоохранения Московской области "Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского" (ГБУЗ МО МОНИКИ им. М.Ф. Владимирского) | Способ профилактики отторжения трансплантата трупной почки |
| CA3095198A1 (fr) | 2018-04-16 | 2019-10-24 | Icahn School Of Medicine At Mount Sinai | Procede et kits pour la prediction d'un rejet aigu et d'une perte d'allogreffe renale a l'aide de signatures transcriptomiques de pre-transplantation dans le sang du receveur |
| GB201807924D0 (en) | 2018-05-16 | 2018-06-27 | Ctxt Pty Ltd | Compounds |
| CA3101553A1 (fr) | 2018-05-31 | 2019-12-05 | Glaxosmithkline Intellectual Property Development Limited | Association d'un inhibiteur des proteine arginine methyltransferases de type ii et d'une proteine se liant a icos pour traiter le cancer |
| CA3101561A1 (fr) | 2018-05-31 | 2019-12-05 | Glaxosmithkline Intellectual Property Development Limited | Polytherapie avec des proteines de liaison a icos et des inhibiteurs d'arginine methyltransferase |
| WO2020031087A1 (fr) | 2018-08-06 | 2020-02-13 | Glaxosmithkline Intellectual Property Development Limited | Polythérapie |
| WO2020086476A1 (fr) | 2018-10-22 | 2020-04-30 | Glaxosmithkline Intellectual Property Development Limited | Schéma posologique |
| US20200368369A1 (en) * | 2019-05-22 | 2020-11-26 | Wyvern Pharmaceuticals Inc. | Composition for endogenous production of checkpoint protein precursors |
| GB201910305D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| GB201910304D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| WO2021018941A1 (fr) | 2019-07-31 | 2021-02-04 | Glaxosmithkline Intellectual Property Development Limited | Méthodes de traitement du cancer |
| WO2021043961A1 (fr) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Schéma posologique pour le traitement du cancer avec un anticorps agoniste anti-icos et une chimiothérapie |
| WO2021046293A1 (fr) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Schéma posologique pour le traitement du cancer avec un anticorps agoniste anti-icos et du trémélimumab |
| JP7280387B2 (ja) | 2019-09-27 | 2023-05-23 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | 抗原結合タンパク質 |
| CN113294813B (zh) * | 2020-02-24 | 2022-09-02 | 宁波方太厨具有限公司 | 一种电磁灶 |
| EP4136112A1 (fr) | 2020-04-14 | 2023-02-22 | GlaxoSmithKline Intellectual Property Development Limited | Traitement combiné pour le cancer |
| WO2021209357A1 (fr) | 2020-04-14 | 2021-10-21 | Glaxosmithkline Intellectual Property Development Limited | Traitement combiné pour le cancer impliquant des anticorps anti-icos et anti-pd1, impliquant éventuellement en outre des anticorps anti-tim3 |
| US20230149543A1 (en) | 2020-04-14 | 2023-05-18 | Glaxosmithkline Intellectual Property Development Limited | Combination treatment for cancer based upon an icos antbody and a pd-l1 antibody tgf-bets-receptor fusion protein |
| GB202007099D0 (en) | 2020-05-14 | 2020-07-01 | Kymab Ltd | Tumour biomarkers for immunotherapy |
| EP4301733A1 (fr) | 2021-03-02 | 2024-01-10 | GlaxoSmithKline Intellectual Property Development Limited | Pyridines substituées utiles en tant qu'inhibiteurs de la dnmt1 |
| US20240166747A1 (en) | 2021-03-31 | 2024-05-23 | Glazosmithkline Intellectual Property Development Limited | Antigen binding proteins and combinations thereof |
| WO2022243378A1 (fr) | 2021-05-18 | 2022-11-24 | Kymab Limited | Utilisations d'anticorps anti-icos |
| GB202107994D0 (en) | 2021-06-04 | 2021-07-21 | Kymab Ltd | Treatment of cancer |
| WO2023222854A1 (fr) | 2022-05-18 | 2023-11-23 | Kymab Limited | Utilisations d'anticorps anti-icos |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5506126A (en) * | 1988-02-25 | 1996-04-09 | The General Hospital Corporation | Rapid immunoselection cloning method |
| US6075181A (en) * | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6641809B1 (en) * | 1990-03-26 | 2003-11-04 | Bristol-Myers Squibb Company | Method of regulating cellular processes mediated by B7 and CD28 |
| US5770197A (en) * | 1991-06-27 | 1998-06-23 | Bristol-Myers Squibb Company | Methods for regulating the immune response using B7 binding molecules and IL4-binding molecules |
| JP3162438B2 (ja) | 1991-09-12 | 2001-04-25 | 住友製薬株式会社 | 高感度特異的抗体測定法 |
| US5484892A (en) * | 1993-05-21 | 1996-01-16 | Dana-Farber Cancer Institute, Inc. | Monoclonal antibodies that block ligand binding to the CD22 receptor in mature B cells |
| US6719972B1 (en) * | 1994-06-03 | 2004-04-13 | Repligen Corporation | Methods of inhibiting T cell proliferation or IL-2 accumulation with CTLA4- specific antibodies |
| US5747461A (en) * | 1994-07-26 | 1998-05-05 | Markov; Angel K. | Synergistic administration of cyclosporine and fructose diphosphate |
| US5914112A (en) * | 1996-01-23 | 1999-06-22 | Genentech, Inc. | Anti-CD18 antibodies in stroke |
| ES2183131T3 (es) | 1996-01-23 | 2003-03-16 | Genentech Inc | Anticuerpos anti-cd18 utilizados contra el ictus cerebral. |
| CA2266346A1 (fr) | 1996-09-18 | 1998-03-26 | Zetesis S.P.A. | Utilisation de proteines comme agents actifs contre des maladies auto-immunes |
| ATE453406T1 (de) * | 1996-11-08 | 2010-01-15 | Biogen Idec Inc | Identifikation von bindungs- interaktionen zwischen gewissen antikorpern und den humanen costimulatorischen antigenen b7.1 (cd80) und b7.2 (cd28) |
| AU4145597A (en) | 1997-02-20 | 1998-09-09 | Cedars-Sinai Medical Center | Ulcerative colitis panca secretory vesicle antigen and methods of using sa me |
| FI107538B (fi) * | 1997-02-26 | 2001-08-31 | Raisio Benecol Oy | Menetelmä stanoliesterien valmistamiseksi |
| US7112655B1 (en) * | 1997-02-27 | 2006-09-26 | Japan Tobacco, Inc. | JTT-1 protein and methods of inhibiting lymphocyte activation |
| JP3521382B2 (ja) | 1997-02-27 | 2004-04-19 | 日本たばこ産業株式会社 | 細胞間接着及びシグナル伝達を媒介する細胞表面分子 |
| WO1998045331A2 (fr) | 1997-04-07 | 1998-10-15 | Genentech, Inc. | Anticorps anti-vegf |
| ES2279585T3 (es) * | 1997-09-23 | 2007-08-16 | Bundesrepublik Deutschland Letztvertreten Durch Den Direktor Des Robert-Koch-Instituts | Polipeptido coestimulante de celulas t, anticuerpos monoclonales, su preparacion y su uso. |
| DE19821060A1 (de) | 1997-09-23 | 1999-04-15 | Bundesrepublik Deutschland Let | Ko-stimulierendes Polypeptid von T-Zellen, monoklonale Antikörper sowie die Herstellung und deren Verwendung |
| JPH11228442A (ja) * | 1998-02-09 | 1999-08-24 | Cypros Pharmaceut Corp | 臓器移植後のシクロスポリン投与量を低減するためのフルクトース二リン酸の使用 |
| JP2000154151A (ja) * | 1998-09-14 | 2000-06-06 | Kyo Jo | 免疫抑制剤 |
| AU767241B2 (en) * | 1998-09-14 | 2003-11-06 | Qiang Xu | Immunosuppressive agents |
| EP1119253A4 (fr) * | 1998-10-07 | 2005-12-21 | Millennium Pharm Inc | NOUVELLES MOLECULES SPECIFIQUES DE Th2 ET LEURS UTILISATIONS |
| CN1309734C (zh) * | 1999-02-03 | 2007-04-11 | 安姆根有限公司 | 与免疫应答有关的新颖多肽 |
| IL146106A0 (en) | 1999-05-06 | 2002-07-25 | Genetics Inst | Use of soluble costimulatory molecules to enhance immune responses |
| WO2001008700A1 (fr) | 1999-07-28 | 2001-02-08 | Genetics Institute, Inc. | Prevention d'avortements d'origine immunologique par l'inhibition de signaux de costimulation |
| WO2001012658A2 (fr) | 1999-08-11 | 2001-02-22 | Isis Innovations Limited | Acides nucleiques, polypeptides, analyses, moyens et techniques therapeutiques |
| JP3871503B2 (ja) * | 1999-08-30 | 2007-01-24 | 日本たばこ産業株式会社 | 免疫性疾患治療剤 |
| JP4210454B2 (ja) | 2001-03-27 | 2009-01-21 | 日本たばこ産業株式会社 | 炎症性腸疾患治療剤 |
| JP2003508088A (ja) | 1999-09-03 | 2003-03-04 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | ５２個のヒト分泌タンパク質 |
| ES2290052T3 (es) | 1999-09-21 | 2008-02-16 | Genetics Institute, Llc | Moleculas gl50 y usos para las mismas. |
| EP1224201A4 (fr) | 1999-10-29 | 2005-03-02 | Human Genome Sciences Inc | 32 proteines humaines secretees |
| WO2001064704A1 (fr) | 2000-03-02 | 2001-09-07 | Mayo Foundation For Medical Education And Research | LA hB7-H2, NOUVELLE MOLECULE CO-STIMULANTE |
| JP3597140B2 (ja) * | 2000-05-18 | 2004-12-02 | 日本たばこ産業株式会社 | 副刺激伝達分子ａｉｌｉｍに対するヒトモノクローナル抗体及びその医薬用途 |
| EP1337634A2 (fr) | 2000-11-28 | 2003-08-27 | Amgen Inc. | Nouveaux polypeptides impliques dans la reponse immunitaire |
| JP4212278B2 (ja) | 2001-03-01 | 2009-01-21 | 日本たばこ産業株式会社 | 移植片拒絶反応抑制剤 |
-
2002
- 2002-01-22 JP JP2002013189A patent/JP4212278B2/ja not_active Expired - Fee Related
- 2002-02-05 SI SI200230901T patent/SI1769807T1/sl unknown
- 2002-02-05 EP EP02710508A patent/EP1374901B9/fr not_active Expired - Lifetime
- 2002-02-05 IL IL15684502A patent/IL156845A0/xx active IP Right Grant
- 2002-02-05 CA CA002439858A patent/CA2439858C/fr not_active Expired - Fee Related
- 2002-02-05 WO PCT/JP2002/000930 patent/WO2002070010A1/fr active IP Right Grant
- 2002-02-05 HU HU0303332A patent/HU228045B1/hu not_active IP Right Cessation
- 2002-02-05 PT PT06024523T patent/PT1769807E/pt unknown
- 2002-02-05 BR BR0207787-6A patent/BR0207787A/pt not_active IP Right Cessation
- 2002-02-05 HU HU1100018A patent/HU228108B1/hu not_active IP Right Cessation
- 2002-02-05 DE DE60217839T patent/DE60217839T2/de not_active Expired - Lifetime
- 2002-02-05 CN CN028058054A patent/CN1518458B/zh not_active Expired - Fee Related
- 2002-02-05 DK DK06024523.0T patent/DK1769807T3/da active
- 2002-02-05 AT AT02710508T patent/ATE352318T1/de not_active IP Right Cessation
- 2002-02-05 AU AU2002228435A patent/AU2002228435B2/en not_active Ceased
- 2002-02-05 MX MXPA03006736A patent/MXPA03006736A/es active IP Right Grant
- 2002-02-05 AT AT06024523T patent/ATE463256T1/de active
- 2002-02-05 SK SK1214-2003A patent/SK288048B6/sk not_active IP Right Cessation
- 2002-02-05 RU RU2003129166/15A patent/RU2263512C2/ru not_active IP Right Cessation
- 2002-02-05 CZ CZ20032406A patent/CZ20032406A3/cs unknown
- 2002-02-05 KR KR1020037011255A patent/KR100609444B1/ko not_active IP Right Cessation
- 2002-02-05 EP EP06024523A patent/EP1769807B1/fr not_active Expired - Lifetime
- 2002-02-05 DE DE60235928T patent/DE60235928D1/de not_active Expired - Lifetime
- 2002-02-05 ES ES06024523T patent/ES2344219T3/es not_active Expired - Lifetime
- 2002-02-05 NZ NZ527076A patent/NZ527076A/xx not_active IP Right Cessation
-
2003
- 2003-07-09 IL IL156845A patent/IL156845A/en not_active IP Right Cessation
- 2003-08-29 NO NO20033839A patent/NO331690B1/no not_active IP Right Cessation
-
2004
- 2004-03-04 US US10/793,171 patent/US7438905B2/en not_active Expired - Fee Related
- 2004-06-24 HK HK04104524A patent/HK1061531A1/xx not_active IP Right Cessation
-
2007
- 2007-09-27 HK HK07110465.8A patent/HK1102293A1/xx not_active IP Right Cessation
-
2008
- 2008-09-12 US US12/209,643 patent/US20090047292A1/en not_active Abandoned
-
2010
- 2010-06-04 CY CY20101100496T patent/CY1110143T1/el unknown
-
2011
- 2011-02-08 NO NO20110218A patent/NO20110218L/no not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO331690B1 (no) | Forbindelse, og farmasoytisk kombinasjon av forbindelse, som har en aktivitet til a modulere signaloverforing formidlet av AILIM for forsterkning av virkningen av immunsupprimerende midler pa undertrykkelse, behandling eller forebyggelse av transplantatavstotning ved transplantasjon av et organ, del av et organ eller et vev. | |
| TWI316546B (en) | Human monoclonal antibody against a costimulatory signal transduction molecule ailim and pharmaceutical use thereof | |
| US7465444B2 (en) | Methods of suppressing or treating an inflammatory bowel disease by administering an antibody or portion thereof that binds to AILIM | |
| KR100609441B1 (ko) | 면역성 질환 치료제 | |
| ZA200306516B (en) | Graft rejection inhibitors. | |
| JP3543966B2 (ja) | 副刺激伝達分子ａｉｌｉｍに対するヒトモノクローナル抗体及びその医薬用途 | |
| JP4234992B2 (ja) | 副刺激伝達分子ａｉｌｉｍに対するヒトモノクローナル抗体及びその医薬用途 | |
| JP2004261182A (ja) | 副刺激伝達分子ａｉｌｉｍに対するヒトモノクローナル抗体及びその医薬用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |