JP2010132660A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2010132660A5 JP2010132660A5 JP2009284862A JP2009284862A JP2010132660A5 JP 2010132660 A5 JP2010132660 A5 JP 2010132660A5 JP 2009284862 A JP2009284862 A JP 2009284862A JP 2009284862 A JP2009284862 A JP 2009284862A JP 2010132660 A5 JP2010132660 A5 JP 2010132660A5
- Authority
- JP
- Japan
- Prior art keywords
- subject
- treatment
- interferon
- antibody
- subjects
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000011282 treatment Methods 0.000 claims description 100
- 230000003902 lesion Effects 0.000 claims description 69
- 108090000467 Interferon-beta Proteins 0.000 claims description 60
- 238000000034 method Methods 0.000 claims description 47
- 201000006417 multiple sclerosis Diseases 0.000 claims description 45
- 102000003996 Interferon-beta Human genes 0.000 claims description 41
- 229960001388 interferon-beta Drugs 0.000 claims description 35
- 108010038453 Interleukin-2 Receptors Proteins 0.000 claims description 33
- 102000010789 Interleukin-2 Receptors Human genes 0.000 claims description 33
- 108010005716 Interferon beta-1a Proteins 0.000 claims description 24
- 229960002806 daclizumab Drugs 0.000 claims description 23
- 239000005557 antagonist Substances 0.000 claims description 18
- 108010005714 Interferon beta-1b Proteins 0.000 claims description 17
- 229960004461 interferon beta-1a Drugs 0.000 claims description 10
- 229960003161 interferon beta-1b Drugs 0.000 claims description 10
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- 108010002350 Interleukin-2 Proteins 0.000 claims description 5
- 102000000588 Interleukin-2 Human genes 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 5
- 108020003519 protein disulfide isomerase Proteins 0.000 claims description 5
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 claims description 2
- 239000002464 receptor antagonist Substances 0.000 claims 5
- 229940044551 receptor antagonist Drugs 0.000 claims 5
- 102100036089 Fascin Human genes 0.000 claims 3
- 102000004527 Interleukin-21 Receptors Human genes 0.000 claims 1
- 108010017411 Interleukin-21 Receptors Proteins 0.000 claims 1
- 206010053395 Progressive multiple sclerosis Diseases 0.000 claims 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 45
- 238000012360 testing method Methods 0.000 description 36
- 210000002966 serum Anatomy 0.000 description 29
- 238000004458 analytical method Methods 0.000 description 25
- 210000001744 T-lymphocyte Anatomy 0.000 description 24
- 238000005259 measurement Methods 0.000 description 23
- 238000009097 single-agent therapy Methods 0.000 description 20
- 102100026720 Interferon beta Human genes 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 17
- 238000001802 infusion Methods 0.000 description 16
- 210000004369 blood Anatomy 0.000 description 15
- 239000008280 blood Substances 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 230000001900 immune effect Effects 0.000 description 15
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 14
- 230000008859 change Effects 0.000 description 14
- 229940079593 drug Drugs 0.000 description 13
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 12
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 12
- 102000014150 Interferons Human genes 0.000 description 12
- 108010050904 Interferons Proteins 0.000 description 12
- 210000004556 brain Anatomy 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 229940079322 interferon Drugs 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 229940003504 avonex Drugs 0.000 description 10
- 238000004820 blood count Methods 0.000 description 10
- 238000011284 combination treatment Methods 0.000 description 10
- 210000004698 lymphocyte Anatomy 0.000 description 10
- 238000009597 pregnancy test Methods 0.000 description 10
- 210000002700 urine Anatomy 0.000 description 10
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 238000002648 combination therapy Methods 0.000 description 8
- 210000001616 monocyte Anatomy 0.000 description 8
- 230000035755 proliferation Effects 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 7
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 7
- 102000004388 Interleukin-4 Human genes 0.000 description 7
- 108090000978 Interleukin-4 Proteins 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 229940021459 betaseron Drugs 0.000 description 7
- 230000005713 exacerbation Effects 0.000 description 7
- 230000006872 improvement Effects 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 229910052688 Gadolinium Inorganic materials 0.000 description 6
- 230000009266 disease activity Effects 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 229940090044 injection Drugs 0.000 description 6
- 230000001186 cumulative effect Effects 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 230000000926 neurological effect Effects 0.000 description 5
- 230000003472 neutralizing effect Effects 0.000 description 5
- 238000002203 pretreatment Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 4
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 229940038850 rebif Drugs 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 210000003289 regulatory T cell Anatomy 0.000 description 4
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- VDABVNMGKGUPEY-UHFFFAOYSA-N 6-carboxyfluorescein succinimidyl ester Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=C2)OC(=O)C1=CC=C2C(=O)ON1C(=O)CCC1=O VDABVNMGKGUPEY-UHFFFAOYSA-N 0.000 description 3
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 description 3
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 102000003812 Interleukin-15 Human genes 0.000 description 3
- 108090000172 Interleukin-15 Proteins 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- -1 OX-40 Proteins 0.000 description 3
- 230000037453 T cell priming Effects 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 230000016396 cytokine production Effects 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 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 3
- 230000005021 gait Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000002493 microarray Methods 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 229960000814 tetanus toxoid Drugs 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- 102000007445 2',5'-Oligoadenylate Synthetase Human genes 0.000 description 2
- 108010086241 2',5'-Oligoadenylate Synthetase Proteins 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
- BPVHBBXCESDRKW-UHFFFAOYSA-N 5(6)-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21.C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BPVHBBXCESDRKW-UHFFFAOYSA-N 0.000 description 2
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 2
- 108010082126 Alanine transaminase Proteins 0.000 description 2
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 2
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 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 2
- 102000014250 Fibroblast growth factor 12 Human genes 0.000 description 2
- 108050003239 Fibroblast growth factor 12 Proteins 0.000 description 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 108010002586 Interleukin-7 Proteins 0.000 description 2
- 102000000704 Interleukin-7 Human genes 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 201000005505 Measles Diseases 0.000 description 2
- 102000006386 Myelin Proteins Human genes 0.000 description 2
- 108010083674 Myelin Proteins Proteins 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 230000006052 T cell proliferation Effects 0.000 description 2
- 210000000447 Th1 cell Anatomy 0.000 description 2
- 210000004241 Th2 cell Anatomy 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 229960002170 azathioprine Drugs 0.000 description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 238000009534 blood test Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 239000003433 contraceptive agent Substances 0.000 description 2
- 230000002254 contraceptive effect Effects 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 210000004405 cytokine-induced killer cell Anatomy 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 229940017105 interferon beta-1a injection Drugs 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000006651 lactation Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 238000009593 lumbar puncture Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 210000005012 myelin Anatomy 0.000 description 2
- AEMBWNDIEFEPTH-UHFFFAOYSA-N n-tert-butyl-n-ethylnitrous amide Chemical compound CCN(N=O)C(C)(C)C AEMBWNDIEFEPTH-UHFFFAOYSA-N 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 238000011056 performance test Methods 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 208000006961 tropical spastic paraparesis Diseases 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- JMTCEFUSRHYJBF-DDJPMISGSA-N 149635-73-4 Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CCCCN)C(O)=O)C1=CC=C(O)C=C1 JMTCEFUSRHYJBF-DDJPMISGSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 206010005186 Blindness unilateral Diseases 0.000 description 1
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 206010051290 Central nervous system lesion Diseases 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- ZHLKXBJTJHRTTE-UHFFFAOYSA-N Chlorobenside Chemical compound C1=CC(Cl)=CC=C1CSC1=CC=C(Cl)C=C1 ZHLKXBJTJHRTTE-UHFFFAOYSA-N 0.000 description 1
- 208000002691 Choroiditis Diseases 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 108010072051 Glatiramer Acetate Proteins 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101000652224 Homo sapiens Suppressor of cytokine signaling 5 Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 101000835093 Homo sapiens Transferrin receptor protein 1 Proteins 0.000 description 1
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 1
- 208000004044 Hypesthesia Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 102100026238 Lymphotoxin-alpha Human genes 0.000 description 1
- 238000012307 MRI technique Methods 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 208000003971 Posterior uveitis Diseases 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010040021 Sensory abnormalities Diseases 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010041415 Spastic paralysis Diseases 0.000 description 1
- 102100030523 Suppressor of cytokine signaling 5 Human genes 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 102000008233 Toll-Like Receptor 4 Human genes 0.000 description 1
- 108010060804 Toll-Like Receptor 4 Proteins 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- BMQYVXCPAOLZOK-UHFFFAOYSA-N Trihydroxypropylpterisin Natural products OCC(O)C(O)C1=CN=C2NC(N)=NC(=O)C2=N1 BMQYVXCPAOLZOK-UHFFFAOYSA-N 0.000 description 1
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000011976 chest X-ray Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- 229960000258 corticotropin Drugs 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 229950007102 daclizumab beta Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000028327 extreme fatigue Diseases 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000005308 flint glass Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 229960003776 glatiramer acetate Drugs 0.000 description 1
- 230000007387 gliosis Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000034783 hypoesthesia Diseases 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 description 1
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000021267 infertility disease Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003933 intellectual function Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 108040006852 interleukin-4 receptor activity proteins Proteins 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 208000018883 loss of balance Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000025020 negative regulation of T cell proliferation Effects 0.000 description 1
- BMQYVXCPAOLZOK-XINAWCOVSA-N neopterin Chemical compound OC[C@@H](O)[C@@H](O)C1=CN=C2NC(N)=NC(=O)C2=N1 BMQYVXCPAOLZOK-XINAWCOVSA-N 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 238000013515 script 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
- 229940115586 simulect Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 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
- 238000002255 vaccination Methods 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39302102P | 2002-06-28 | 2002-06-28 | |
| PCT/US2002/038290 WO2004002500A1 (en) | 2002-06-28 | 2002-11-27 | Method of treating autoimmune diseases with interferon-beta and il-2r antagonist |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004518039A Division JP2006508039A (ja) | 2002-06-28 | 2003-06-27 | 多発性硬化症を治療する方法 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012217520A Division JP2013032372A (ja) | 2002-06-28 | 2012-09-28 | 多発性硬化症を治療する方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010132660A JP2010132660A (ja) | 2010-06-17 |
| JP2010132660A5 true JP2010132660A5 (enExample) | 2012-11-15 |
Family
ID=30000962
Family Applications (8)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004517494A Withdrawn JP2005535636A (ja) | 2002-06-28 | 2002-11-27 | インターフェロンβおよびＩＬ−２Ｒアンタゴニストを用いて自己免疫疾患を治療する方法 |
| JP2004518039A Withdrawn JP2006508039A (ja) | 2002-06-28 | 2003-06-27 | 多発性硬化症を治療する方法 |
| JP2009284862A Withdrawn JP2010132660A (ja) | 2002-06-28 | 2009-12-16 | 多発性硬化症を治療する方法 |
| JP2011082497A Withdrawn JP2011157378A (ja) | 2002-06-28 | 2011-04-04 | インターフェロンβおよびＩＬ−２Ｒアンタゴニストを用いて自己免疫疾患を治療する方法 |
| JP2012217520A Withdrawn JP2013032372A (ja) | 2002-06-28 | 2012-09-28 | 多発性硬化症を治療する方法 |
| JP2013086246A Pending JP2013139478A (ja) | 2002-06-28 | 2013-04-17 | インターフェロンβおよびＩＬ−２Ｒアンタゴニストを用いて自己免疫疾患を治療する方法 |
| JP2014147314A Expired - Lifetime JP5905534B2 (ja) | 2002-06-28 | 2014-07-18 | 多発性硬化症を治療する方法 |
| JP2016030540A Withdrawn JP2016145220A (ja) | 2002-06-28 | 2016-02-22 | 多発性硬化症を治療する方法 |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004517494A Withdrawn JP2005535636A (ja) | 2002-06-28 | 2002-11-27 | インターフェロンβおよびＩＬ−２Ｒアンタゴニストを用いて自己免疫疾患を治療する方法 |
| JP2004518039A Withdrawn JP2006508039A (ja) | 2002-06-28 | 2003-06-27 | 多発性硬化症を治療する方法 |
Family Applications After (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011082497A Withdrawn JP2011157378A (ja) | 2002-06-28 | 2011-04-04 | インターフェロンβおよびＩＬ−２Ｒアンタゴニストを用いて自己免疫疾患を治療する方法 |
| JP2012217520A Withdrawn JP2013032372A (ja) | 2002-06-28 | 2012-09-28 | 多発性硬化症を治療する方法 |
| JP2013086246A Pending JP2013139478A (ja) | 2002-06-28 | 2013-04-17 | インターフェロンβおよびＩＬ−２Ｒアンタゴニストを用いて自己免疫疾患を治療する方法 |
| JP2014147314A Expired - Lifetime JP5905534B2 (ja) | 2002-06-28 | 2014-07-18 | 多発性硬化症を治療する方法 |
| JP2016030540A Withdrawn JP2016145220A (ja) | 2002-06-28 | 2016-02-22 | 多発性硬化症を治療する方法 |
Country Status (15)
| Country | Link |
|---|---|
| US (11) | US7575742B2 (enExample) |
| EP (3) | EP3269377A1 (enExample) |
| JP (8) | JP2005535636A (enExample) |
| AU (3) | AU2002368055B2 (enExample) |
| CA (3) | CA2490804C (enExample) |
| CY (2) | CY2016043I1 (enExample) |
| DK (2) | DK2314627T3 (enExample) |
| ES (2) | ES2637011T3 (enExample) |
| HK (1) | HK1249850A1 (enExample) |
| HU (2) | HUE036677T2 (enExample) |
| IL (2) | IL165973A (enExample) |
| LU (1) | LU93315I2 (enExample) |
| PT (2) | PT2314627T (enExample) |
| SI (2) | SI2314627T1 (enExample) |
| WO (2) | WO2004002500A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2676065C (en) * | 2001-04-26 | 2011-02-01 | Motion Technologies, Llc | Continuously variable transmission |
| CA2490804C (en) * | 2002-06-28 | 2016-12-06 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating autoimmune diseases with interferon-beta and il-2r antagonist |
| US20060134750A1 (en) * | 2004-03-10 | 2006-06-22 | Pepgen Corporation | Method of treatment using interferon-tau |
| EP1845925B1 (en) | 2005-01-12 | 2016-08-24 | Biogen MA Inc. | Method for delivering interferon-beta |
| US20080279819A1 (en) * | 2005-02-15 | 2008-11-13 | Adamas Pharmaceuticals, Inc. | Combinations Therapy for Treatment of Demyelinating Conditions |
| CN101675071B (zh) | 2007-05-02 | 2014-06-18 | Ambrx公司 | 经修饰干扰素β多肽和其用途 |
| BRPI0918842A2 (pt) * | 2008-08-28 | 2015-12-08 | Abbott Biotherapeutics Corp | método para tratar pacientes com esclerose múltipla com anticorpos anti-il2r |
| EP2355660A4 (en) * | 2008-10-13 | 2012-05-02 | Biovista Inc | COMPOSITIONS AND METHODS FOR THE TREATMENT OF MULTIPLE SCLEROSIS |
| WO2010068923A2 (en) * | 2008-12-12 | 2010-06-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Agents that selectively inhibit cd25 on dendritic cells or t cells and their use |
| AU2010286427A1 (en) * | 2009-08-31 | 2012-03-08 | Abbott Biotherapeutics Corp. | Use of an immunoregulatory NK cell population for monitoring the efficacy of anti-IL-2R antibodies in multiple sclerosis patients |
| EP2560994B1 (en) | 2010-04-08 | 2016-10-12 | JN Biosciences LLC | Antibodies to cd122 |
| CA2824515C (en) | 2011-01-18 | 2022-09-13 | Bioniz, Llc | Compositions and methods for modulating gamma-c-cytokine activity |
| EP2741773A1 (en) | 2011-08-08 | 2014-06-18 | AbbVie Biotherapeutics Inc. | Methods of treating progressive forms of multiple sclerosis |
| US9959384B2 (en) | 2013-12-10 | 2018-05-01 | Bioniz, Llc | Methods of developing selective peptide antagonists |
| EP3978512A1 (en) | 2015-10-09 | 2022-04-06 | Bioniz, LLC | Modulating gamma-c-cytokine activity |
| WO2018027195A1 (en) | 2016-08-05 | 2018-02-08 | Abbvie Biotherapeutics Inc. | Compositions containing reduced amounts of daclizumab acidic isoforms and methods for preparing the same |
| DE102017104088A1 (de) * | 2017-02-28 | 2018-08-30 | L&O Hunting Group GmbH | Integralschalldämpfer für einen Gewehrlauf |
| KR102707650B1 (ko) | 2017-04-07 | 2024-09-19 | 바이오니즈 테라퓨틱스, 아이엔씨. | 감마-c-사이토카인 활성의 안정한 조절자 |
| BR112021021878A2 (pt) | 2019-05-03 | 2022-01-18 | Bioniz Llc | Modulação dos efeitos de sinalização da gama-c-citocina para tratamento da alopecia e distúrbios associados |
| WO2021026362A1 (en) * | 2019-08-07 | 2021-02-11 | Edifice Health, Inc. | Treatment of prevention of cardiovascular disease |
| US20240043499A1 (en) | 2022-08-07 | 2024-02-08 | Protean Bio, Inc. | Peptides for beta-cell survival and insulin production |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| US4819150A (en) | 1985-04-05 | 1989-04-04 | Unisys Corporation | Array for simulating computer functions for large computer systems |
| US5336489A (en) | 1985-09-05 | 1994-08-09 | The Beth Israel Hospital Association | Treatment of allograft rejection with IL-2 receptor-specific cytotoxins |
| US5011684A (en) | 1985-09-05 | 1991-04-30 | Beth Israel Hospital Association | Lysing or blocking unwanted cells with IL-2 receptor-specific binding substance |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| GB2188941B (en) * | 1986-04-14 | 1990-06-06 | Bayer Ag | Monoclonal antibodies recognizing human interleukin-2-receptor |
| US6051405A (en) * | 1986-09-24 | 2000-04-18 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Constructs encoding recombinant antibody-toxin fusion proteins |
| US5013548A (en) | 1987-09-08 | 1991-05-07 | Duke University | Production of antibodies to HIV |
| US5695927A (en) | 1988-03-31 | 1997-12-09 | The University Of Arizona, Department Of Internal Medicine, Section Of Hematology And Oncology | Monoclonal antibodies specific for HIV and the hybridomas for production thereof |
| KR900700134A (ko) | 1988-04-15 | 1990-08-11 | 원본미기재 | Il-2 수용체-특이적 키메릭 항체 |
| DE3815472A1 (de) * | 1988-05-06 | 1989-11-16 | Centre Regional De Transfusion | Monoklonaler antikoerper und seine verwendung |
| US5152980A (en) | 1988-05-19 | 1992-10-06 | The Beth Israel Hospital Association | Induction of tolerance to a foreign antigen IL-2 receptor-binding substances |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| IL162181A (en) * | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| EP1690935A3 (en) | 1990-01-12 | 2008-07-30 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| ES2139598T3 (es) | 1990-07-10 | 2000-02-16 | Medical Res Council | Procedimientos para la produccion de miembros de parejas de union especifica. |
| US5620686A (en) | 1990-09-28 | 1997-04-15 | British Technology Group Limited | Antigen-antibody conjugates |
| US5747444A (en) * | 1990-10-09 | 1998-05-05 | Chiron Corporation | Method of treating graft-versus-host disease |
| FR2672291A1 (fr) | 1991-01-31 | 1992-08-07 | Inst Nat Sante Rech Med | Composition d'anticorps diriges contre le recepteur de l'interleukine-2 humaine ou animale. |
| GB9115010D0 (en) | 1991-07-11 | 1991-08-28 | Wellcome Found | Antibody |
| JPH05244982A (ja) * | 1991-12-06 | 1993-09-24 | Sumitomo Chem Co Ltd | 擬人化ｂ−ｂ１０ |
| JPH07503132A (ja) | 1991-12-17 | 1995-04-06 | ジェンファーム インターナショナル，インコーポレイティド | 異種抗体を産生することができるトランスジェニック非ヒト動物 |
| US5571507A (en) | 1992-02-25 | 1996-11-05 | Seragen, Inc. | Methods of treating diabetes |
| US5643756A (en) | 1992-08-28 | 1997-07-01 | The Public Health Research Institute Of The City Of New York, Inc. | Fusion glycoproteins |
| DK0699077T3 (da) | 1993-05-07 | 2002-01-21 | Bio Merieux Inc | Immunogele HIV-komplekser |
| WO1995005734A1 (en) | 1993-08-27 | 1995-03-02 | The Pillsbury Company | Mechanical gas flushing system |
| US5635597A (en) | 1994-05-27 | 1997-06-03 | Affymax Technologies, N.V. | Peptides that bind IL-2 receptors |
| AU713040B2 (en) | 1994-07-15 | 1999-11-18 | University Of Iowa Research Foundation, The | Immunomodulatory oligonucleotides |
| US6096728A (en) * | 1996-02-09 | 2000-08-01 | Amgen Inc. | Composition and method for treating inflammatory diseases |
| US6013256A (en) | 1996-09-24 | 2000-01-11 | Protein Design Labs, Inc. | Method of preventing acute rejection following solid organ transplantation |
| AU3710597A (en) * | 1997-08-06 | 1999-03-01 | Laboratorio Medinfar-Produtos Farmaceuticos, Lda | Dna integration into "mycobacterium spp." genome by trans-complementation using a site-specific integration system |
| WO2000025816A1 (en) | 1998-10-30 | 2000-05-11 | The University Of Miami | Treatment of hepatitis c by administration of anti-il-2 receptor monoclonal antibody and an antiviral compound |
| US6346247B1 (en) | 1999-10-28 | 2002-02-12 | Promega Corporation | Prevention and treatment of autoimmune disease with luminally administered polyclonal antibodies |
| WO2001080891A1 (en) * | 2000-04-25 | 2001-11-01 | Nippon Organon K. K. | Remedies for interstitial pneumonia, method of constructing animal model of this disease and screening method with the use of the same |
| WO2002081508A2 (en) * | 2001-04-06 | 2002-10-17 | University Of Bristol | Use of cd25 binding molecules in steroid-resistant patients |
| CA2490804C (en) * | 2002-06-28 | 2016-12-06 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating autoimmune diseases with interferon-beta and il-2r antagonist |
| WO2004003156A2 (en) | 2002-07-01 | 2004-01-08 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Il-21 as a regulator of immunoglobin production |
-
2002
- 2002-11-27 CA CA2490804A patent/CA2490804C/en not_active Expired - Lifetime
- 2002-11-27 US US10/519,311 patent/US7575742B2/en not_active Expired - Fee Related
- 2002-11-27 AU AU2002368055A patent/AU2002368055B2/en not_active Ceased
- 2002-11-27 JP JP2004517494A patent/JP2005535636A/ja not_active Withdrawn
- 2002-11-27 WO PCT/US2002/038290 patent/WO2004002500A1/en not_active Ceased
-
2003
- 2003-06-27 EP EP17175522.6A patent/EP3269377A1/en not_active Withdrawn
- 2003-06-27 DK DK10182563.6T patent/DK2314627T3/en active
- 2003-06-27 US US10/607,598 patent/US7258859B2/en not_active Expired - Lifetime
- 2003-06-27 PT PT101825636T patent/PT2314627T/pt unknown
- 2003-06-27 SI SI200332543T patent/SI2314627T1/sl unknown
- 2003-06-27 EP EP10182563.6A patent/EP2314627B1/en not_active Expired - Lifetime
- 2003-06-27 PT PT37621810T patent/PT1539200E/pt unknown
- 2003-06-27 EP EP03762181.0A patent/EP1539200B1/en not_active Expired - Lifetime
- 2003-06-27 ES ES10182563.6T patent/ES2637011T3/es not_active Expired - Lifetime
- 2003-06-27 JP JP2004518039A patent/JP2006508039A/ja not_active Withdrawn
- 2003-06-27 WO PCT/US2003/020428 patent/WO2004002421A2/en not_active Ceased
- 2003-06-27 ES ES03762181.0T patent/ES2474718T3/es not_active Expired - Lifetime
- 2003-06-27 CA CA2844639A patent/CA2844639A1/en not_active Abandoned
- 2003-06-27 SI SI200332375T patent/SI1539200T1/sl unknown
- 2003-06-27 DK DK03762181.0T patent/DK1539200T3/da active
- 2003-06-27 HU HUE10182563A patent/HUE036677T2/hu unknown
- 2003-06-27 CA CA2490186A patent/CA2490186C/en not_active Expired - Fee Related
- 2003-06-27 AU AU2003247813A patent/AU2003247813C1/en not_active Ceased
-
2004
- 2004-12-23 IL IL165973A patent/IL165973A/en active IP Right Grant
-
2007
- 2007-07-13 US US11/827,876 patent/US8454965B2/en not_active Expired - Fee Related
-
2008
- 2008-09-04 AU AU2008212004A patent/AU2008212004B2/en not_active Ceased
-
2009
- 2009-03-10 US US12/401,543 patent/US8298525B2/en not_active Expired - Fee Related
- 2009-12-16 JP JP2009284862A patent/JP2010132660A/ja not_active Withdrawn
-
2011
- 2011-04-04 JP JP2011082497A patent/JP2011157378A/ja not_active Withdrawn
-
2012
- 2012-05-18 US US13/475,688 patent/US20130017152A1/en not_active Abandoned
- 2012-09-12 US US13/612,763 patent/US8636997B2/en not_active Expired - Fee Related
- 2012-09-28 JP JP2012217520A patent/JP2013032372A/ja not_active Withdrawn
-
2013
- 2013-04-17 JP JP2013086246A patent/JP2013139478A/ja active Pending
-
2014
- 2014-07-18 JP JP2014147314A patent/JP5905534B2/ja not_active Expired - Lifetime
- 2014-09-15 US US14/487,012 patent/US20150010477A1/en not_active Abandoned
-
2015
- 2015-07-06 US US14/792,432 patent/US20150337044A1/en not_active Abandoned
- 2015-10-06 IL IL241920A patent/IL241920A0/en unknown
-
2016
- 2016-02-22 JP JP2016030540A patent/JP2016145220A/ja not_active Withdrawn
- 2016-08-11 US US15/234,575 patent/US20170190779A1/en not_active Abandoned
- 2016-11-17 LU LU93315C patent/LU93315I2/fr unknown
- 2016-12-07 HU HUS1600050C patent/HUS1600050I1/hu unknown
- 2016-12-09 CY CY2016043C patent/CY2016043I1/el unknown
-
2017
- 2017-09-21 CY CY20171100999T patent/CY1119389T1/el unknown
-
2018
- 2018-04-18 US US15/956,458 patent/US20180237532A1/en not_active Abandoned
- 2018-07-17 HK HK18109281.9A patent/HK1249850A1/en unknown
- 2018-09-17 US US16/132,852 patent/US20190002575A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5905534B2 (ja) | 多発性硬化症を治療する方法 | |
| US20170143824A1 (en) | Rituximab induction therapy followed by glatiramer acetate therapy | |
| HK1157192A (en) | Method for the treatment of multiple sclerosis | |
| HK1157192B (en) | Method for the treatment of multiple sclerosis | |
| HK1074769B (en) | Method for the treatment of multiple sclerosis |