NO319867B1 - Humaniserte antistoffer mot leukocytt-adhesjonsmolekyl VLA-4, bindingsfragment derav, farmasoytisk preparat omfattende det humaniserte antistoffet eller et bindingsfragment derav, samt anvendelser av det humaniserte antistoff. - Google Patents
Humaniserte antistoffer mot leukocytt-adhesjonsmolekyl VLA-4, bindingsfragment derav, farmasoytisk preparat omfattende det humaniserte antistoffet eller et bindingsfragment derav, samt anvendelser av det humaniserte antistoff. Download PDFInfo
- Publication number
- NO319867B1 NO319867B1 NO19963097A NO963097A NO319867B1 NO 319867 B1 NO319867 B1 NO 319867B1 NO 19963097 A NO19963097 A NO 19963097A NO 963097 A NO963097 A NO 963097A NO 319867 B1 NO319867 B1 NO 319867B1
- Authority
- NO
- Norway
- Prior art keywords
- humanized
- mouse
- human
- immunoglobulin
- variable region
- Prior art date
Links
- 230000027455 binding Effects 0.000 title claims description 57
- 239000012634 fragment Substances 0.000 title claims description 36
- 108010008212 Integrin alpha4beta1 Proteins 0.000 title description 39
- 239000008194 pharmaceutical composition Substances 0.000 title description 4
- 150000001413 amino acids Chemical class 0.000 claims description 70
- 108060003951 Immunoglobulin Proteins 0.000 claims description 61
- 102000018358 immunoglobulin Human genes 0.000 claims description 61
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 52
- 238000011282 treatment Methods 0.000 claims description 28
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 17
- 201000006417 multiple sclerosis Diseases 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 13
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 10
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 108700004676 Bence Jones Proteins 0.000 claims description 3
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims description 3
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 claims description 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 2
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 claims description 2
- 108010041012 Integrin alpha4 Proteins 0.000 claims description 2
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 claims 1
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 claims 1
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 claims 1
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 claims 1
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 claims 1
- 102100022949 Immunoglobulin kappa variable 2-29 Human genes 0.000 claims 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 138
- 235000001014 amino acid Nutrition 0.000 description 74
- 229940024606 amino acid Drugs 0.000 description 66
- 210000004027 cell Anatomy 0.000 description 47
- 108020004414 DNA Proteins 0.000 description 33
- 238000006467 substitution reaction Methods 0.000 description 33
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 32
- 241001465754 Metazoa Species 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 22
- 238000000034 method Methods 0.000 description 22
- 239000000427 antigen Substances 0.000 description 21
- 108091033319 polynucleotide Proteins 0.000 description 20
- 102000040430 polynucleotide Human genes 0.000 description 20
- 239000002157 polynucleotide Substances 0.000 description 20
- 108091007433 antigens Proteins 0.000 description 19
- 102000036639 antigens Human genes 0.000 description 19
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 18
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 18
- 239000013604 expression vector Substances 0.000 description 18
- 229940072221 immunoglobulins Drugs 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 210000001519 tissue Anatomy 0.000 description 17
- 201000010099 disease Diseases 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 16
- 239000013598 vector Substances 0.000 description 14
- 239000002299 complementary DNA Substances 0.000 description 12
- 238000010276 construction Methods 0.000 description 12
- 210000000265 leukocyte Anatomy 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 210000004556 brain Anatomy 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- 102000004196 processed proteins & peptides Human genes 0.000 description 11
- 210000002889 endothelial cell Anatomy 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 241000700198 Cavia Species 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- 108010044426 integrins Proteins 0.000 description 9
- 102000006495 integrins Human genes 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 229920001184 polypeptide Polymers 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 8
- 241001529936 Murinae Species 0.000 description 8
- 230000008595 infiltration Effects 0.000 description 8
- 238000001764 infiltration Methods 0.000 description 8
- 230000004054 inflammatory process Effects 0.000 description 8
- 150000007523 nucleic acids Chemical class 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 108091035707 Consensus sequence Proteins 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- 238000010171 animal model Methods 0.000 description 7
- 230000001413 cellular effect Effects 0.000 description 7
- 210000003169 central nervous system Anatomy 0.000 description 7
- 201000002491 encephalomyelitis Diseases 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 210000000278 spinal cord Anatomy 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 6
- 239000004475 Arginine Substances 0.000 description 6
- 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 6
- 206010033799 Paralysis Diseases 0.000 description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 241000700199 Cavia porcellus Species 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 230000003449 preventive effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 241000282412 Homo Species 0.000 description 4
- 101000622304 Homo sapiens Vascular cell adhesion protein 1 Proteins 0.000 description 4
- 238000012408 PCR amplification Methods 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000021164 cell adhesion Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 210000003141 lower extremity Anatomy 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000000302 molecular modelling Methods 0.000 description 4
- 231100000350 mutagenesis Toxicity 0.000 description 4
- 238000002703 mutagenesis Methods 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 3
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 3
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 101001002508 Homo sapiens Immunoglobulin-binding protein 1 Proteins 0.000 description 3
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 3
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 3
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 3
- 102100021042 Immunoglobulin-binding protein 1 Human genes 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 108020005067 RNA Splice Sites Proteins 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 230000003302 anti-idiotype Effects 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 239000012148 binding buffer Substances 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 231100000219 mutagenic Toxicity 0.000 description 3
- 230000003505 mutagenic effect Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- OOIBFPKQHULHSQ-UHFFFAOYSA-N (3-hydroxy-1-adamantyl) 2-methylprop-2-enoate Chemical compound C1C(C2)CC3CC2(O)CC1(OC(=O)C(=C)C)C3 OOIBFPKQHULHSQ-UHFFFAOYSA-N 0.000 description 2
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 2
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 206010065042 Immune reconstitution inflammatory syndrome Diseases 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 102000047918 Myelin Basic Human genes 0.000 description 2
- 101710107068 Myelin basic protein Proteins 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 241000276498 Pollachius virens Species 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000012754 cardiac puncture Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000005094 computer simulation Methods 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000012938 design process Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 206010014599 encephalitis Diseases 0.000 description 2
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000005534 hematocrit Methods 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- NWXMGUDVXFXRIG-NAOJVREFSA-N (4s,4as,5as,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2C(O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-NAOJVREFSA-N 0.000 description 1
- MNRDNGRAKFSUSO-KHEUVVEUSA-N 2-aminoacetic acid;(2s)-2-amino-3-phenylpropanoic acid;(2s)-2,4-diamino-4-oxobutanoic acid Chemical group NCC(O)=O.OC(=O)[C@@H](N)CC(N)=O.OC(=O)[C@@H](N)CC1=CC=CC=C1 MNRDNGRAKFSUSO-KHEUVVEUSA-N 0.000 description 1
- BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
- OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
- 229940117976 5-hydroxylysine Drugs 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 101710125089 Bindin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000958041 Homo sapiens Musculin Proteins 0.000 description 1
- 101000926206 Homo sapiens Putative glutathione hydrolase 3 proenzyme Proteins 0.000 description 1
- 108010058683 Immobilized Proteins Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 101100370002 Mus musculus Tnfsf14 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241001049988 Mycobacterium tuberculosis H37Ra Species 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
- JJIHLJJYMXLCOY-BYPYZUCNSA-N N-acetyl-L-serine Chemical compound CC(=O)N[C@@H](CO)C(O)=O JJIHLJJYMXLCOY-BYPYZUCNSA-N 0.000 description 1
- PYUSHNKNPOHWEZ-YFKPBYRVSA-N N-formyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC=O PYUSHNKNPOHWEZ-YFKPBYRVSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 102100034060 Putative glutathione hydrolase 3 proenzyme Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 108010041332 Very Late Antigen Receptors Proteins 0.000 description 1
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 108010058966 bacteriophage T7 induced DNA polymerase Proteins 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- RIIWUGSYXOBDMC-UHFFFAOYSA-N benzene-1,2-diamine;hydron;dichloride Chemical compound Cl.Cl.NC1=CC=CC=C1N RIIWUGSYXOBDMC-UHFFFAOYSA-N 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 208000025698 brain inflammatory disease Diseases 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- UHBYWPGGCSDKFX-UHFFFAOYSA-N carboxyglutamic acid Chemical compound OC(=O)C(N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-UHFFFAOYSA-N 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001983 electron spin resonance imaging Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 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
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 238000012333 histopathological diagnosis Methods 0.000 description 1
- 102000046949 human MSC Human genes 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 230000009916 joint effect Effects 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000003287 lymphocyte surface marker Substances 0.000 description 1
- 101150030901 mab-21 gene Proteins 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 239000008268 mayonnaise Substances 0.000 description 1
- 235000010746 mayonnaise Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000005298 paramagnetic effect Effects 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 239000012521 purified sample Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method 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
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000008733 trauma 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
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000001262 western blot Methods 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
- C07K16/2839—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 integrin superfamily
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- C07K16/2839—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 integrin superfamily
- C07K16/2842—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 integrin superfamily against integrin beta1-subunit-containing molecules, e.g. CD29, CD49
-
- 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
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Pain & Pain Management (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18626994A | 1994-01-25 | 1994-01-25 | |
| PCT/US1995/001219 WO1995019790A1 (en) | 1994-01-25 | 1995-01-25 | Humanized antibodies against leukocyte adhesion molecule vla-4 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO963097D0 NO963097D0 (no) | 1996-07-24 |
| NO963097L NO963097L (no) | 1996-09-24 |
| NO319867B1 true NO319867B1 (no) | 2005-09-26 |
Family
ID=22684288
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19963097A NO319867B1 (no) | 1994-01-25 | 1996-07-24 | Humaniserte antistoffer mot leukocytt-adhesjonsmolekyl VLA-4, bindingsfragment derav, farmasoytisk preparat omfattende det humaniserte antistoffet eller et bindingsfragment derav, samt anvendelser av det humaniserte antistoff. |
| NO2006008C NO2006008I2 (no) | 1994-01-25 | 2006-08-07 | Natalizumab, anti alfa-4 integrin humanized monoclonal antibody |
| NO2017040C NO2017040I2 (no) | 1994-01-25 | 2017-08-01 | Natalizumab, anti alfa-4 integrin humanisert monoklonalt antistoff - forlenget SPC |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO2006008C NO2006008I2 (no) | 1994-01-25 | 2006-08-07 | Natalizumab, anti alfa-4 integrin humanized monoclonal antibody |
| NO2017040C NO2017040I2 (no) | 1994-01-25 | 2017-08-01 | Natalizumab, anti alfa-4 integrin humanisert monoklonalt antistoff - forlenget SPC |
Country Status (21)
| Country | Link |
|---|---|
| EP (2) | EP1759709B1 (ja) |
| JP (5) | JP4115517B2 (ja) |
| KR (1) | KR100367948B1 (ja) |
| CN (1) | CN1211123C (ja) |
| AT (1) | ATE333895T1 (ja) |
| AU (1) | AU703152B2 (ja) |
| CA (1) | CA2182013C (ja) |
| DE (2) | DE122006000043I1 (ja) |
| DK (2) | DK1759709T3 (ja) |
| ES (2) | ES2270425T3 (ja) |
| FI (1) | FI117509B (ja) |
| FR (1) | FR06C0024I2 (ja) |
| HU (1) | HU220799B1 (ja) |
| LU (1) | LU91271I2 (ja) |
| MX (1) | MX9602971A (ja) |
| NL (1) | NL300238I2 (ja) |
| NO (3) | NO319867B1 (ja) |
| NZ (1) | NZ279730A (ja) |
| PL (1) | PL181827B1 (ja) |
| PT (1) | PT804237E (ja) |
| WO (1) | WO1995019790A1 (ja) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6307025B1 (en) | 1989-04-28 | 2001-10-23 | Biogen, Inc. | VCAM fusion proteins and DNA coding therefor |
| US5871734A (en) * | 1992-01-13 | 1999-02-16 | Biogen, Inc. | Treatment for asthma with VLA-4 blocking agents |
| US5932214A (en) | 1994-08-11 | 1999-08-03 | Biogen, Inc. | Treatment for inflammatory bowel disease with VLA-4 blockers |
| DK0678122T3 (da) | 1993-01-12 | 2000-03-06 | Biogen Inc | Rekombinante anti-VLA4 antistofmolekyler |
| AU687790B2 (en) * | 1993-02-09 | 1998-03-05 | Biogen Idec Ma Inc. | Treatment for insulin dependent diabetes |
| US5840299A (en) * | 1994-01-25 | 1998-11-24 | Athena Neurosciences, Inc. | Humanized antibodies against leukocyte adhesion molecule VLA-4 |
| US7435802B2 (en) | 1994-01-25 | 2008-10-14 | Elan Pharaceuticals, Inc. | Humanized anti-VLA4 immunoglobulins |
| US7803904B2 (en) | 1995-09-01 | 2010-09-28 | Millennium Pharmaceuticals, Inc. | Mucosal vascular addressing and uses thereof |
| US6551593B1 (en) | 1995-02-10 | 2003-04-22 | Millennium Pharmaceuticals, Inc. | Treatment of Inflammatory bowel disease by inhibiting binding and/or signalling through α 4 β 7 and its ligands and madcam |
| US7750137B2 (en) | 1995-09-01 | 2010-07-06 | Millennium Pharmaceuticals, Inc. | Mucosal vascular addressins |
| US7147851B1 (en) * | 1996-08-15 | 2006-12-12 | Millennium Pharmaceuticals, Inc. | Humanized immunoglobulin reactive with α4β7 integrin |
| AU7348798A (en) * | 1997-05-09 | 1998-12-08 | John P. Robarts Research Institute, The | Method for dislodging infiltrated leukocytes from a tissue |
| DE19741235A1 (de) | 1997-09-18 | 1999-03-25 | Hoechst Marion Roussel De Gmbh | Neue Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| DE19741873A1 (de) * | 1997-09-23 | 1999-03-25 | Hoechst Marion Roussel De Gmbh | Neue 5-Ring-Heterocyclen, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| DE19751251A1 (de) | 1997-11-19 | 1999-05-20 | Hoechst Marion Roussel De Gmbh | Substituierte Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmezeutische Präparate |
| DE19821483A1 (de) | 1998-05-14 | 1999-11-18 | Hoechst Marion Roussel De Gmbh | Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| US7618630B2 (en) | 1998-09-14 | 2009-11-17 | Board Of Regents, The University Of Texas System | Methods of treating multiple myeloma and myeloma-induced bone resorption using integrin antagonists |
| WO2000015247A2 (en) * | 1998-09-14 | 2000-03-23 | Board Of Regents, The University Of Texas System | Methods of treating multiple myeloma and myeloma-induced bone resorption using integrin antagonists |
| KR100837715B1 (ko) * | 1999-04-22 | 2008-06-13 | 바이오겐 아이덱 엠에이 인코포레이티드 | 인테그린 알파-4 서브유닛의 길항 물질을 사용하는섬유증의 치료 방법 |
| DE19922462A1 (de) | 1999-05-17 | 2000-11-23 | Aventis Pharma Gmbh | Spiro-imidazolidinderivate, ihre Herstellung ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| CA2375827C (en) | 1999-06-01 | 2017-01-10 | Biogen, Inc. | A blocking monoclonal antibody to vla-1 and its use for the treatment of inflammatory disorders |
| DE60043308D1 (de) * | 1999-12-16 | 2009-12-24 | Biogen Idec Inc | Verfahren zur behandlung der schädigung des zentralnervensystems durch ischämie oder durch hämorrhagie mit antagonisten von alpha4 integrin |
| DE10111877A1 (de) | 2001-03-10 | 2002-09-12 | Aventis Pharma Gmbh | Neue Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| US7358054B2 (en) | 2001-04-13 | 2008-04-15 | Biogen Idec Ma Inc. | Antibodies to VLA-1 |
| DE10137595A1 (de) | 2001-08-01 | 2003-02-13 | Aventis Pharma Gmbh | Neue Imidazolidinderivate, ihre Herstellung und ihre Verwendung |
| IL163725A0 (en) | 2002-02-25 | 2005-12-18 | Elan Pharm Inc | Administration of agents for the treatment of inflammation |
| JP2005535572A (ja) * | 2002-04-12 | 2005-11-24 | メディミューン，インコーポレーテッド | 組換え抗インターロイキン−９抗体 |
| GB0210121D0 (en) * | 2002-05-02 | 2002-06-12 | Celltech R&D Ltd | Biological products |
| AR040778A1 (es) * | 2002-08-06 | 2005-04-20 | Glaxo Group Ltd | Anticuerpos alterados o fragmentos funcionales que se unen a mag (glicoproteina asociada a mielina). |
| PL211180B1 (pl) * | 2002-12-17 | 2012-04-30 | Merck Patent Gmbh | Białko fuzyjne typu przeciwciało-IL2, wektor zawierający sekwencję kwasów nukleinowych kodujących takie białko, kompozycja farmaceutyczna zawierająca takie białko fuzyjne oraz jego zastosowania do wytwarzania leków |
| CU23403A1 (es) * | 2003-04-23 | 2009-08-04 | Centro Inmunologia Molecular | Anticuerpos recombinantes y fragmentos que reconocen el gangliósido n-glicolil gm3 y su uso para diagnóstico y tratamiento de tumores |
| KR101194176B1 (ko) | 2003-12-22 | 2012-10-24 | 아지노모토 가부시키가이샤 | 신규한 페닐알라닌 유도체 |
| CN103169965A (zh) * | 2004-11-19 | 2013-06-26 | 比奥根艾迪克Ma公司 | 治疗多发性硬化 |
| AU2006316629A1 (en) * | 2005-11-17 | 2007-05-31 | Millennium Pharmaceuticals, Inc. | Humanized immunoglobulin reactive with alpha 4 beta 7 integrin |
| WO2007140249A1 (en) | 2006-05-25 | 2007-12-06 | Biogen Idec Ma Inc. | Methods of treating stroke |
| AU2008219007A1 (en) | 2007-02-20 | 2008-08-28 | Merrimack Pharmaceuticals, Inc. | Methods of treating multiple sclerosis by administration of alpha-fetoprotein in combination with an integrin antagonist |
| PL2170390T3 (pl) * | 2007-06-14 | 2019-05-31 | Biogen Ma Inc | Preparaty przeciwciała natalizumab |
| CN101889036B (zh) | 2007-12-13 | 2013-01-02 | 株式会社德山 | 光致变色固化性组合物 |
| PL2288715T3 (pl) | 2008-04-11 | 2015-03-31 | Merrimack Pharmaceuticals Inc | Łączniki będące albuminą surowicy ludzkiej i ich koniugaty |
| TWI466681B (zh) | 2009-03-20 | 2015-01-01 | Amgen Inc | α４β７雜二聚體專一性拮抗抗體 |
| WO2011020874A1 (en) | 2009-08-20 | 2011-02-24 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Vla-4 as a biomarker for prognosis and target for therapy in duchenne muscular dystrophy |
| US20140161794A1 (en) | 2010-04-16 | 2014-06-12 | Biogen Idec Ma Inc. | Anti-vla-4 antibodies |
| TWI723339B (zh) | 2011-05-02 | 2021-04-01 | 美商千禧製藥公司 | 抗-α4β7抗體之調配物 |
| UA116189C2 (uk) | 2011-05-02 | 2018-02-26 | Мілленніум Фармасьютікалз, Інк. | КОМПОЗИЦІЯ АНТИ-α4β7 АНТИТІЛА |
| US10160808B2 (en) | 2012-02-16 | 2018-12-25 | Santarus, Inc. | Anti-VLA1 (CD49A) antibody pharmaceutical compositions |
| WO2018002036A1 (en) | 2016-06-28 | 2018-01-04 | Zaklady Farmaceutyczne Polpharma Sa | Recombinant production of monoclonal antibodies |
| US20190374639A1 (en) | 2016-11-21 | 2019-12-12 | Polpharma Biologics S.A. | Aqueous pharmaceutical formulations |
| EP3583126A1 (en) * | 2017-02-17 | 2019-12-25 | Sanofi | Multispecific binding molecules having specificity to dystroglycan and laminin-2 |
| WO2018224673A1 (en) | 2017-06-08 | 2018-12-13 | Zaklady Farmaceutyczne Polpharma S.A. | Improved methods of cell culture |
| CN112867394B (zh) | 2018-06-04 | 2024-09-13 | 马萨诸塞州渤健公司 | 具有降低的效应功能的抗vla-4抗体 |
| EP4284947A1 (en) | 2021-01-29 | 2023-12-06 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods of assessing the risk of developing progressive multifocal leukoencephalopathy in patients treated with vla-4 antagonists |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| IL162181A (en) * | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| IL95501A (en) * | 1989-09-01 | 1997-04-15 | Hutchinson Fred Cancer Res | Inhibition by antibodies of lymphocyte adherence to vascular endothelium utilizing an extracellular matrix receptor-ligand interaction, and pharmaceutical compositions containing said antibodies |
| WO1993015764A1 (en) * | 1992-02-12 | 1993-08-19 | Biogen, Inc. | Treatment for inflammatory bowel disease |
| DK0678122T3 (da) * | 1993-01-12 | 2000-03-06 | Biogen Inc | Rekombinante anti-VLA4 antistofmolekyler |
| AUPP647298A0 (en) | 1998-10-13 | 1998-11-05 | Keystone Retaining Wall Systems, Inc. | Retaining wall block |
-
1995
- 1995-01-25 CN CNB951913549A patent/CN1211123C/zh not_active Expired - Lifetime
- 1995-01-25 DK DK06013916.9T patent/DK1759709T3/da active
- 1995-01-25 PT PT95908741T patent/PT804237E/pt unknown
- 1995-01-25 DE DE1995635133 patent/DE122006000043I1/de active Pending
- 1995-01-25 ES ES95908741T patent/ES2270425T3/es not_active Expired - Lifetime
- 1995-01-25 JP JP51977095A patent/JP4115517B2/ja not_active Expired - Lifetime
- 1995-01-25 KR KR1019960703987A patent/KR100367948B1/ko not_active IP Right Cessation
- 1995-01-25 CA CA002182013A patent/CA2182013C/en not_active Expired - Lifetime
- 1995-01-25 AT AT95908741T patent/ATE333895T1/de active
- 1995-01-25 EP EP06013916A patent/EP1759709B1/en not_active Expired - Lifetime
- 1995-01-25 PL PL95315634A patent/PL181827B1/pl unknown
- 1995-01-25 HU HU9602019A patent/HU220799B1/hu active Protection Beyond IP Right Term
- 1995-01-25 AU AU16960/95A patent/AU703152B2/en not_active Expired
- 1995-01-25 DK DK95908741T patent/DK0804237T3/da active
- 1995-01-25 EP EP95908741A patent/EP0804237B8/en not_active Expired - Lifetime
- 1995-01-25 ES ES06013916T patent/ES2424292T3/es not_active Expired - Lifetime
- 1995-01-25 NZ NZ279730A patent/NZ279730A/en not_active IP Right Cessation
- 1995-01-25 WO PCT/US1995/001219 patent/WO1995019790A1/en active IP Right Grant
- 1995-01-25 DE DE69535133T patent/DE69535133T2/de not_active Expired - Lifetime
-
1996
- 1996-07-24 FI FI962958A patent/FI117509B/fi active Protection Beyond IP Right Term
- 1996-07-24 NO NO19963097A patent/NO319867B1/no not_active IP Right Cessation
- 1996-07-24 MX MX9602971A patent/MX9602971A/es unknown
-
2005
- 2005-08-05 JP JP2005228930A patent/JP2006045237A/ja not_active Withdrawn
-
2006
- 2006-07-27 FR FR06C0024C patent/FR06C0024I2/fr active Active
- 2006-08-02 NL NL300238C patent/NL300238I2/nl unknown
- 2006-08-02 LU LU91271C patent/LU91271I2/fr unknown
- 2006-08-07 NO NO2006008C patent/NO2006008I2/no unknown
-
2009
- 2009-05-18 JP JP2009120421A patent/JP2009235078A/ja not_active Withdrawn
-
2013
- 2013-02-18 JP JP2013028635A patent/JP5487382B2/ja not_active Expired - Lifetime
- 2013-03-18 JP JP2013054628A patent/JP2013165718A/ja not_active Withdrawn
-
2017
- 2017-08-01 NO NO2017040C patent/NO2017040I2/no unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO319867B1 (no) | Humaniserte antistoffer mot leukocytt-adhesjonsmolekyl VLA-4, bindingsfragment derav, farmasoytisk preparat omfattende det humaniserte antistoffet eller et bindingsfragment derav, samt anvendelser av det humaniserte antistoff. | |
| US5840299A (en) | Humanized antibodies against leukocyte adhesion molecule VLA-4 | |
| US8246958B2 (en) | Methods of inhibiting alpha-4-dependent interactions with VCAM-1 with anti-VLA-4 antibodies | |
| DK0918797T4 (en) | A humanized immunoglobulin reactive with alpha4beta7 integrin | |
| KR100240308B1 (ko) | 인간화된단클론성항체및혼성단클론성항체 | |
| AU747898B2 (en) | Monoclonal antibodies to human CD6 | |
| JP3276369B2 (ja) | 改良ヒト化免疫グロブリン | |
| EP2070948B1 (en) | Humanized Anti-CD4 antibody with immunosuppressive properties | |
| PL180157B1 (en) | Humanised antibodies and their application | |
| CA2544365A1 (en) | Modified anti-cd52 antibody | |
| CN114269788B (zh) | 一种能够与人4-1bb结合的分子及其应用 | |
| CN115947855B (zh) | 抗cd24抗体的制备及其用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| SPCF | Filing of supplementary protection certificate |
Free format text: PRODUCT NAME: TYSABRI - NATALIZUMAB; NAT. REG. NO/DATE: EU106346001NO 20060713 Spc suppl protection certif: 2006008 Filing date: 20060807 Extension date: 20200125 |
|
| SPCG | Granted supplementary protection certificate |
Free format text: PRODUCT NAME: TYSABRI - NATALIZUMAB; NAT. REG. NO/DATE: EU106346001NO 20060713 Spc suppl protection certif: 2006008 Filing date: 20060807 Extension date: 20200125 |
|
| MK1K | Patent expired | ||
| SPCE | Application to extend a supplementary protection certificate (spc) |
Free format text: PRODUCT NAME: NATALIZUMAB, ANTI ALFA-4 INTEGRIN HUMANISERT MONOKLONALT ANTISTOFF; NAT. REG. NO/DATE: EU/1/06/346/001 20060627; FIRST REG. NO/DATE: EU , EU/1/06/346/001 20060627 Spc suppl protection certif: 2017040 Filing date: 20170801 |
|
| SPCH | Extension of a supplementary protection certificate (spc) granted |
Free format text: PRODUCT NAME: NATALIZUMAB, ANTI ALFA-4 INTEGRIN HUMANISERT MONOKLONALT ANTISTOFF; NAT. REG. NO/DATE: EU/1/06/346/001 20060627; FIRST REG. NO/DATE: EU , EU/1/06/346/001 20060627 Spc suppl protection certif: 2017040 Filing date: 20170801 |
|
| SPCX | Expiry of an spc |
Spc suppl protection certif: 2006008 |