ZA200300759B - Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents. - Google Patents
Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents. Download PDFInfo
- Publication number
- ZA200300759B ZA200300759B ZA200300759A ZA200300759A ZA200300759B ZA 200300759 B ZA200300759 B ZA 200300759B ZA 200300759 A ZA200300759 A ZA 200300759A ZA 200300759 A ZA200300759 A ZA 200300759A ZA 200300759 B ZA200300759 B ZA 200300759B
- Authority
- ZA
- South Africa
- Prior art keywords
- immunocytokine
- substance
- composition
- treatment
- tumor
- Prior art date
Links
- 229940127130 immunocytokine Drugs 0.000 title claims description 183
- 230000002708 enhancing effect Effects 0.000 title claims description 64
- 238000011282 treatment Methods 0.000 title claims description 60
- 108020001507 fusion proteins Proteins 0.000 title claims description 45
- 102000037865 fusion proteins Human genes 0.000 title claims description 44
- 230000028993 immune response Effects 0.000 title claims description 34
- 230000001404 mediated effect Effects 0.000 title description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 162
- 210000004027 cell Anatomy 0.000 claims description 117
- 229930012538 Paclitaxel Natural products 0.000 claims description 77
- 229960001592 paclitaxel Drugs 0.000 claims description 77
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 77
- 239000003795 chemical substances by application Substances 0.000 claims description 73
- 238000000034 method Methods 0.000 claims description 58
- 102000004127 Cytokines Human genes 0.000 claims description 44
- 108090000695 Cytokines Proteins 0.000 claims description 44
- 239000000203 mixture Substances 0.000 claims description 43
- 239000000427 antigen Substances 0.000 claims description 36
- 102000036639 antigens Human genes 0.000 claims description 36
- 108091007433 antigens Proteins 0.000 claims description 36
- 239000000126 substance Substances 0.000 claims description 32
- 201000011510 cancer Diseases 0.000 claims description 29
- 108010032595 Antibody Binding Sites Proteins 0.000 claims description 28
- 108060003951 Immunoglobulin Proteins 0.000 claims description 27
- 229940123237 Taxane Drugs 0.000 claims description 27
- 102000018358 immunoglobulin Human genes 0.000 claims description 27
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 22
- 229960004397 cyclophosphamide Drugs 0.000 claims description 22
- 241000124008 Mammalia Species 0.000 claims description 20
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 18
- 239000002246 antineoplastic agent Substances 0.000 claims description 13
- 229940127089 cytotoxic agent Drugs 0.000 claims description 13
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 12
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 12
- 231100000409 cytocidal Toxicity 0.000 claims description 11
- 230000000445 cytocidal effect Effects 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 230000001939 inductive effect Effects 0.000 claims description 11
- YWLXLRUDGLRYDR-ZHPRIASZSA-N 5beta,20-epoxy-1,7beta,10beta,13alpha-tetrahydroxy-9-oxotax-11-ene-2alpha,4alpha-diyl 4-acetate 2-benzoate Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-ZHPRIASZSA-N 0.000 claims description 8
- 229960004562 carboplatin Drugs 0.000 claims description 8
- 108010071942 Colony-Stimulating Factors Proteins 0.000 claims description 7
- 102000007644 Colony-Stimulating Factors Human genes 0.000 claims description 7
- 102000015696 Interleukins Human genes 0.000 claims description 7
- 108010063738 Interleukins Proteins 0.000 claims description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 7
- 230000002152 alkylating effect Effects 0.000 claims description 7
- 102000003390 tumor necrosis factor Human genes 0.000 claims description 7
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 5
- 101710160107 Outer membrane protein A Proteins 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229960003668 docetaxel Drugs 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 190000008236 carboplatin Chemical compound 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 description 55
- 102100031940 Epithelial cell adhesion molecule Human genes 0.000 description 37
- 230000000694 effects Effects 0.000 description 36
- 241000699670 Mus sp. Species 0.000 description 34
- 108010002350 Interleukin-2 Proteins 0.000 description 31
- 102000000588 Interleukin-2 Human genes 0.000 description 30
- 241001529936 Murinae Species 0.000 description 30
- 238000002648 combination therapy Methods 0.000 description 21
- 108020004414 DNA Proteins 0.000 description 20
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 18
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 18
- 239000012634 fragment Substances 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 17
- 239000002299 complementary DNA Substances 0.000 description 16
- 230000004614 tumor growth Effects 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- 210000004072 lung Anatomy 0.000 description 12
- 230000001965 increasing effect Effects 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 108010065805 Interleukin-12 Proteins 0.000 description 10
- 102000013462 Interleukin-12 Human genes 0.000 description 10
- 206010027476 Metastases Diseases 0.000 description 10
- 108091034117 Oligonucleotide Proteins 0.000 description 10
- 206010035226 Plasma cell myeloma Diseases 0.000 description 10
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 10
- 229940117681 interleukin-12 Drugs 0.000 description 10
- 210000004698 lymphocyte Anatomy 0.000 description 10
- 201000000050 myeloid neoplasm Diseases 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 108700008509 tucotuzumab celmoleukin Proteins 0.000 description 10
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 230000000259 anti-tumor effect Effects 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000003013 cytotoxicity Effects 0.000 description 9
- 231100000135 cytotoxicity Toxicity 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 241000894007 species Species 0.000 description 9
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 8
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 8
- 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 8
- 230000000973 chemotherapeutic effect Effects 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 8
- 210000000987 immune system Anatomy 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- 229960000485 methotrexate Drugs 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 210000004881 tumor cell Anatomy 0.000 description 8
- 230000004580 weight loss Effects 0.000 description 8
- 102100030698 Interleukin-12 subunit alpha Human genes 0.000 description 7
- 230000000692 anti-sense effect Effects 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000001472 cytotoxic effect Effects 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 230000001976 improved effect Effects 0.000 description 7
- 150000007523 nucleic acids Chemical class 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- 206010029098 Neoplasm skin Diseases 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 208000000453 Skin Neoplasms Diseases 0.000 description 6
- 229940100198 alkylating agent Drugs 0.000 description 6
- 239000002168 alkylating agent Substances 0.000 description 6
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 210000002865 immune cell Anatomy 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 239000013615 primer Substances 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 5
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 5
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 239000006285 cell suspension Substances 0.000 description 5
- 229940047120 colony stimulating factors Drugs 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 229940047122 interleukins Drugs 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 210000002540 macrophage Anatomy 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 230000002195 synergetic effect Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- 241000701022 Cytomegalovirus Species 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 4
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- 102000008072 Lymphokines Human genes 0.000 description 4
- 108010074338 Lymphokines Proteins 0.000 description 4
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 4
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 4
- 206010027458 Metastases to lung Diseases 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- 201000008275 breast carcinoma Diseases 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229940047124 interferons Drugs 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 238000003358 metastasis assay Methods 0.000 description 4
- 210000000822 natural killer cell Anatomy 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 238000002823 phage display Methods 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 108090000172 Interleukin-15 Proteins 0.000 description 3
- 102000003812 Interleukin-15 Human genes 0.000 description 3
- 108090000171 Interleukin-18 Proteins 0.000 description 3
- 102000003810 Interleukin-18 Human genes 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 102000004388 Interleukin-4 Human genes 0.000 description 3
- 108010002616 Interleukin-5 Proteins 0.000 description 3
- 102000000743 Interleukin-5 Human genes 0.000 description 3
- 108010002586 Interleukin-7 Proteins 0.000 description 3
- 102000000704 Interleukin-7 Human genes 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 229930182816 L-glutamine Natural products 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000011284 combination treatment Methods 0.000 description 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000006028 immune-suppresssive effect Effects 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 229940028885 interleukin-4 Drugs 0.000 description 3
- 229940100602 interleukin-5 Drugs 0.000 description 3
- 229940100994 interleukin-7 Drugs 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000001338 necrotic effect Effects 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- -1 taxanes Substances 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 2
- 239000011547 Bouin solution Substances 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 101150074155 DHFR gene Proteins 0.000 description 2
- 239000003155 DNA primer Substances 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 208000012766 Growth delay Diseases 0.000 description 2
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 108090000157 Metallothionein Proteins 0.000 description 2
- 206010027457 Metastases to liver Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 108020005038 Terminator Codon Proteins 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000006023 anti-tumor response Effects 0.000 description 2
- 210000000628 antibody-producing cell Anatomy 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000007402 cytotoxic response Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 210000003722 extracellular fluid Anatomy 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 230000003393 splenic effect Effects 0.000 description 2
- 210000004988 splenocyte Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 1
- 229940123471 Angiotensin II agonist Drugs 0.000 description 1
- 102400000345 Angiotensin-2 Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 108091006020 Fc-tagged proteins Proteins 0.000 description 1
- 102000020897 Formins Human genes 0.000 description 1
- 108091022623 Formins Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 1
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 1
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 1
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 1
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 1
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- 102100022949 Immunoglobulin kappa variable 2-29 Human genes 0.000 description 1
- 235000000177 Indigofera tinctoria Nutrition 0.000 description 1
- 206010062049 Lymphocytic infiltration Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 231100000070 MTS assay Toxicity 0.000 description 1
- 238000000719 MTS assay Methods 0.000 description 1
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 101000964724 Mus musculus Zinc finger protein 382 Proteins 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710118538 Protease Proteins 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 101100274179 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CHA4 gene Proteins 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 241001116498 Taxus baccata Species 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012829 chemotherapy agent Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000012215 gene cloning Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- BWKDAMBGCPRVPI-FMWKWGOESA-N idn 5109 Chemical compound O([C@@H]1[C@]23OC(=O)O[C@H]2[C@@H](C(=C([C@@H](OC(C)=O)C(=O)[C@]2(C)[C@@H](O)C[C@H]4OC[C@]4(C21)OC(C)=O)C3(C)C)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)C(=O)C1=CC=CC=C1 BWKDAMBGCPRVPI-FMWKWGOESA-N 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000006054 immunological memory Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229940097275 indigo Drugs 0.000 description 1
- COHYTHOBJLSHDF-UHFFFAOYSA-N indigo powder Natural products N1C2=CC=CC=C2C(=O)C1=C1C(=O)C2=CC=CC=C2N1 COHYTHOBJLSHDF-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000031261 interleukin-10 production Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- VCMGMSHEPQENPE-UHFFFAOYSA-N ketamine hydrochloride Chemical compound [Cl-].C=1C=CC=C(Cl)C=1C1([NH2+]C)CCCCC1=O VCMGMSHEPQENPE-UHFFFAOYSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000000207 lymphocyte subset Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Substances [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000032258 transport 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
- 239000012588 trypsin Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- 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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
- A61K31/282—Platinum compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/191—Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/193—Colony stimulating factors [CSF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/2013—IL-2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/208—IL-12
-
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6813—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin the drug being a peptidic cytokine, e.g. an interleukin or interferon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Microbiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21503800P | 2000-06-29 | 2000-06-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200300759B true ZA200300759B (en) | 2004-04-28 |
Family
ID=22801380
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200300759A ZA200300759B (en) | 2000-06-29 | 2003-01-28 | Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents. |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US7517526B2 (zh) |
| EP (1) | EP1294401B1 (zh) |
| JP (1) | JP5390055B2 (zh) |
| KR (1) | KR20030064275A (zh) |
| CN (1) | CN1270775C (zh) |
| AT (1) | ATE368475T1 (zh) |
| AU (2) | AU2001271729B2 (zh) |
| BR (1) | BR0112111A (zh) |
| CA (1) | CA2412845C (zh) |
| CZ (1) | CZ2003214A3 (zh) |
| DE (1) | DE60129695T2 (zh) |
| DK (1) | DK1294401T3 (zh) |
| ES (1) | ES2288967T3 (zh) |
| HU (1) | HUP0300868A3 (zh) |
| MX (1) | MXPA02012734A (zh) |
| NO (1) | NO20026245L (zh) |
| PL (1) | PL358582A1 (zh) |
| PT (1) | PT1294401E (zh) |
| RU (1) | RU2272644C2 (zh) |
| SK (1) | SK982003A3 (zh) |
| WO (1) | WO2002002143A2 (zh) |
| ZA (1) | ZA200300759B (zh) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69824039T2 (de) | 1997-12-08 | 2005-08-18 | Lexigen Pharmaceuticals Corp., Lexington | Heterodimäre fusionsproteine zur verwendung für gezielte immuntherapie und allgemeine immunerregung |
| US20030105294A1 (en) * | 1998-02-25 | 2003-06-05 | Stephen Gillies | Enhancing the circulating half life of antibody-based fusion proteins |
| CN1318092C (zh) * | 1998-04-15 | 2007-05-30 | 利思进药品公司 | 含有抗体－细胞因子融合蛋白和血管生成抑制剂的免疫治疗用组合物 |
| MXPA01011845A (es) * | 1999-05-19 | 2002-06-21 | Lexigen Pharm Corp | Expresion y exportacion de proteinas de interferon-alfa como proteinas de fusion fc. |
| US7067110B1 (en) | 1999-07-21 | 2006-06-27 | Emd Lexigen Research Center Corp. | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
| SK782002A3 (en) * | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
| DK1200479T3 (da) * | 1999-08-09 | 2006-05-15 | Emd Lexigen Res Ct Corp | Multiple cytokin-antistof-komplekser |
| US20050202538A1 (en) * | 1999-11-12 | 2005-09-15 | Merck Patent Gmbh | Fc-erythropoietin fusion protein with improved pharmacokinetics |
| CN1406249B (zh) | 2000-02-11 | 2010-06-16 | 默克专利股份有限公司 | 增加基于抗体的融合蛋白的循环半衰期 |
| ATE368475T1 (de) * | 2000-06-29 | 2007-08-15 | Emd Lexigen Res Ct Corp | Steigerung von durch antikörper-zytokin- fusionsproteine mediierten immunantworten durch eine kombinierte behandlung mit mitteln zur erhöhung der immunzytokinaufnahme |
| PL206701B1 (pl) | 2001-03-07 | 2010-09-30 | Merck Patent Gmbh | Immunoglobulinowe białko fuzyjne, kodujący je kwas nukleinowy, replikujący wektor ekspresji zawierający taki kwas nukleinowy, eukariotyczna komórka gospodarza zawierająca taki wektor ekspresji oraz sposób zwiększania ekspresji takiego białka fuzyjnego |
| WO2002079415A2 (en) * | 2001-03-30 | 2002-10-10 | Lexigen Pharmaceuticals Corp. | Reducing the immunogenicity of fusion proteins |
| PL205352B1 (pl) * | 2001-05-03 | 2010-04-30 | Merck Patent Gmbh | Rekombinowane przeciwciało specyficzne dla nowotworu |
| US20030190705A1 (en) | 2001-10-29 | 2003-10-09 | Sunol Molecular Corporation | Method of humanizing immune system molecules |
| JP4795640B2 (ja) * | 2001-12-04 | 2011-10-19 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 調節された選択性を有する免疫サイトカイン |
| AU2003298187B2 (en) * | 2002-12-17 | 2010-09-16 | Merck Patent Gmbh | Humanized antibody (H14.18) of the mouse 14.18 antibody binding to GD2 and its fusion with IL-2 |
| US20050069521A1 (en) * | 2003-08-28 | 2005-03-31 | Emd Lexigen Research Center Corp. | Enhancing the circulating half-life of interleukin-2 proteins |
| PL1699822T3 (pl) | 2003-12-30 | 2008-08-29 | Merck Patent Gmbh | Białka fuzyjne IL-7 z częściami przeciwciała, ich otrzymywanie oraz ich zastosowanie |
| CN1902222A (zh) * | 2003-12-31 | 2007-01-24 | 默克专利有限公司 | 具有改善药物代谢动力学的Fc－促红细胞生成素融合蛋白质 |
| CA2552590A1 (en) * | 2004-01-05 | 2005-07-21 | Emd Lexigen Research Center Corp. | Interleukin-12 targeted to oncofoetal fibronectin |
| WO2005070967A2 (en) | 2004-01-22 | 2005-08-04 | Merck Patent Gmbh | Anti-cancer antibodies with reduced complement fixation |
| US7670595B2 (en) * | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
| AU2005313492B2 (en) * | 2004-12-09 | 2011-12-15 | Merck Patent Gmbh | IL-7 variants with reduced immunogenicity |
| US20070104689A1 (en) * | 2005-09-27 | 2007-05-10 | Merck Patent Gmbh | Compositions and methods for treating tumors presenting survivin antigens |
| DE602006021335D1 (de) | 2005-10-21 | 2011-05-26 | Hoffmann La Roche | Methode zur rekombinanten expression eines polyeptids |
| US20090241202A1 (en) * | 2005-12-15 | 2009-09-24 | Micromet Ag | Domain-grafted antibodies |
| KR101397290B1 (ko) | 2005-12-30 | 2014-05-21 | 메르크 파텐트 게엠베하 | 감소한 면역원성을 가지는 항-ｃｄ19 항체 |
| AU2006332138B2 (en) | 2005-12-30 | 2012-03-22 | Merck Patent Gmbh | Interleukin-12p40 variants with improved stability |
| TW200817438A (en) * | 2006-08-17 | 2008-04-16 | Hoffmann La Roche | A conjugate of an antibody against CCR5 and an antifusogenic peptide |
| JP2010531349A (ja) * | 2007-06-28 | 2010-09-24 | フィロジェン エッセ．ピー．アー． | 化学療法剤と組み合わせた癌の治療用免疫サイトカイン |
| AR067584A1 (es) | 2007-07-20 | 2009-10-14 | Hoffmann La Roche | Un conjugado de un anticuerpo contra la cd4 y peptidos antifusogenicos |
| EP2044949A1 (en) * | 2007-10-05 | 2009-04-08 | Immutep | Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response |
| WO2010046097A1 (en) * | 2008-10-21 | 2010-04-29 | Merck Patent Gmbh | Cancer treatments with radiation and immunocytokines |
| CN102405230A (zh) * | 2009-04-22 | 2012-04-04 | 默克专利有限公司 | 具有修饰的FcRn结合位点的抗体融合蛋白 |
| MX2012002014A (es) * | 2009-08-17 | 2012-06-13 | Roche Glycart Ag | Inmunoconjugados dirigidos. |
| US20120244145A1 (en) * | 2009-11-16 | 2012-09-27 | Duke University | Enhanced immunological responses |
| EP2723380B1 (en) | 2011-06-24 | 2019-08-21 | Stephen D. Gillies | Light chain immunoglobulin fusion proteins and methods of use thereof |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| GB201419184D0 (en) | 2014-10-28 | 2014-12-10 | Adc Biotechnology Ltd | Method of synthesising biomolecule-effector/reporter-conjugates using affinity resins |
| US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
| WO2018083248A1 (en) | 2016-11-03 | 2018-05-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| JP2020530280A (ja) * | 2017-07-03 | 2020-10-22 | トルク セラピューティクス， インコーポレイテッド | 免疫刺激性融合分子およびその使用 |
| KR20200100098A (ko) | 2017-12-19 | 2020-08-25 | 젠코어 인코포레이티드 | 조작된 il-2 fc 융합 단백질 |
| MX2021003765A (es) | 2018-10-03 | 2021-07-15 | Xencor Inc | Proteínas il-12 de fusión a fc heterodimérico. |
| CA3141459A1 (en) | 2019-05-17 | 2020-11-26 | Xencor, Inc. | Il-7-fc-fusion proteins |
| EP4037700A2 (en) | 2019-10-03 | 2022-08-10 | Xencor, Inc. | Targeted il-12 heterodimeric fc-fusion proteins |
| AU2021206449A1 (en) | 2020-01-10 | 2022-07-21 | Bright Peak Therapeutics Ag | Modified IL-2 polypeptides and uses thereof |
| US11365233B2 (en) | 2020-04-10 | 2022-06-21 | Cytomx Therapeutics, Inc. | Activatable cytokine constructs and related compositions and methods |
| EP4308594A2 (en) | 2021-03-16 | 2024-01-24 | CytomX Therapeutics, Inc. | Masked activatable cytokine constructs and related compositions and methods |
| US20240158537A1 (en) * | 2021-07-09 | 2024-05-16 | Bright Peak Therapeutics Ag | Synthetic il-7 and il-7 immunocytokines |
| KR20240040134A (ko) * | 2021-07-09 | 2024-03-27 | 브라이트 피크 테라퓨틱스 아게 | 항체 접합체 및 이의 제조 |
Family Cites Families (119)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4196265A (en) | 1977-06-15 | 1980-04-01 | The Wistar Institute | Method of producing antibodies |
| DE2952486A1 (de) * | 1978-12-26 | 1980-07-17 | Canon Kk | Elektrophotographisches verfahren und einrichtung zu dessen durchfuehrung |
| US4469797A (en) | 1982-09-23 | 1984-09-04 | Miles Laboratories, Inc. | Digoxigenin immunogens, antibodies, labeled conjugates, and related derivatives |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| NZ210501A (en) | 1983-12-13 | 1991-08-27 | Kirin Amgen Inc | Erythropoietin produced by procaryotic or eucaryotic expression of an exogenous dna sequence |
| US4703008A (en) | 1983-12-13 | 1987-10-27 | Kiren-Amgen, Inc. | DNA sequences encoding erythropoietin |
| KR850004274A (ko) | 1983-12-13 | 1985-07-11 | 원본미기재 | 에리트로포이에틴의 제조방법 |
| US5082658A (en) | 1984-01-16 | 1992-01-21 | Genentech, Inc. | Gamma interferon-interleukin-2 synergism |
| 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 |
| US5679543A (en) | 1985-08-29 | 1997-10-21 | Genencor International, Inc. | DNA sequences, vectors and fusion polypeptides to increase secretion of desired polypeptides from filamentous fungi |
| US5643565A (en) | 1985-09-20 | 1997-07-01 | Chiron Corporation | Human IL-2 as a vaccine adjuvant |
| US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
| US4935233A (en) | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
| US5359035A (en) | 1985-12-21 | 1994-10-25 | Hoechst Aktiengesellschaft | Bifunctional proteins including interleukin-2 (IL-2) and granuloctyte macrophage colony stimulating factor (GM-CSF) |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| DK173067B1 (da) | 1986-06-27 | 1999-12-13 | Univ Washington | Humant erythropoietin-gen, fremgangsmåde til ekspression deraf i transficerede cellelinier, de transficerede cellelinier sa |
| US4894227A (en) * | 1986-08-01 | 1990-01-16 | Cetus Corporation | Composition of immunotoxins with interleukin-2 |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5508031A (en) | 1986-11-21 | 1996-04-16 | Cetus Oncology Corporation | Method for treating biological damage using a free-radial scavenger and interleukin-2 |
| US5019368A (en) | 1989-02-23 | 1991-05-28 | Cancer Biologics, Inc. | Detection of necrotic malignant tissue and associated therapy |
| JP3101690B2 (ja) | 1987-03-18 | 2000-10-23 | エス・ビィ・２・インコーポレイテッド | 変性抗体の、または変性抗体に関する改良 |
| US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
| US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| JP3040121B2 (ja) | 1988-01-12 | 2000-05-08 | ジェネンテク，インコーポレイテッド | 増殖因子レセプターの機能を阻害することにより腫瘍細胞を処置する方法 |
| US5120525A (en) | 1988-03-29 | 1992-06-09 | Immunomedics, Inc. | Radiolabeled antibody cytotoxic therapy of cancer |
| US4975369A (en) | 1988-04-21 | 1990-12-04 | Eli Lilly And Company | Recombinant and chimeric KS1/4 antibodies directed against a human adenocarcinoma antigen |
| US5601819A (en) | 1988-08-11 | 1997-02-11 | The General Hospital Corporation | Bispecific antibodies for selective immune regulation and for selective immune cell binding |
| US5457038A (en) | 1988-11-10 | 1995-10-10 | Genetics Institute, Inc. | Natural killer stimulatory factor |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5116964A (en) | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
| US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
| US6750329B1 (en) | 1989-05-05 | 2004-06-15 | Research Development Foundation | Antibody delivery system for biological response modifiers |
| US6291158B1 (en) | 1989-05-16 | 2001-09-18 | Scripps Research Institute | Method for tapping the immunological repertoire |
| US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
| EP0406857B1 (en) | 1989-07-07 | 1995-05-24 | Takeda Chemical Industries, Ltd. | Proteins and production thereof |
| US5073627A (en) | 1989-08-22 | 1991-12-17 | Immunex Corporation | Fusion proteins comprising GM-CSF and IL-3 |
| US5856298A (en) | 1989-10-13 | 1999-01-05 | Amgen Inc. | Erythropoietin isoforms |
| US5314995A (en) | 1990-01-22 | 1994-05-24 | Oncogen | Therapeutic interleukin-2-antibody based fusion proteins |
| US5349053A (en) | 1990-06-01 | 1994-09-20 | Protein Design Labs, Inc. | Chimeric ligand/immunoglobulin molecules and their uses |
| US5650150A (en) * | 1990-11-09 | 1997-07-22 | Gillies; Stephen D. | Recombinant antibody cytokine fusion proteins |
| US5709859A (en) | 1991-01-24 | 1998-01-20 | Bristol-Myers Squibb Company | Mixed specificity fusion proteins |
| US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
| US20020037558A1 (en) * | 1991-10-23 | 2002-03-28 | Kin-Ming Lo | E.coli produced immunoglobulin constructs |
| US6627615B1 (en) | 1991-12-17 | 2003-09-30 | The Regents Of The University Of California | Methods and compositions for in vivo gene therapy |
| DE69333433T2 (de) | 1992-04-01 | 2004-12-02 | The Rockefeller University | Verfahren zur in vitro kultivierung dendritischer vorläuferzellen und deren verwendung zur immunogen herstellung |
| DK0615451T3 (da) | 1992-05-26 | 2006-04-24 | Immunex Corp | Hidtil ukendt cytokin der binder til CD30 |
| EP0646178A1 (en) | 1992-06-04 | 1995-04-05 | The Regents Of The University Of California | expression cassette with regularoty regions functional in the mammmlian host |
| US5614184A (en) | 1992-07-28 | 1997-03-25 | New England Deaconess Hospital | Recombinant human erythropoietin mutants and therapeutic methods employing them |
| DE69332485T2 (de) | 1992-08-11 | 2003-11-13 | Harvard College | Immunmodulierende peptide |
| DE4228839A1 (de) | 1992-08-29 | 1994-03-03 | Behringwerke Ag | Verfahren zum Nachweis und zur Bestimmung von Mediatoren |
| CA2126967A1 (en) | 1992-11-04 | 1994-05-11 | Anna M. Wu | Novel antibody construct |
| WO1994009820A1 (en) | 1992-11-05 | 1994-05-11 | Sloan-Kettering Institute For Cancer Research | Prostate-specific membrane antigen |
| US5738849A (en) | 1992-11-24 | 1998-04-14 | G. D. Searle & Co. | Interleukin-3 (IL-3) variant fusion proteins, their recombinant production, and therapeutic compositions comprising them |
| US5543297A (en) | 1992-12-22 | 1996-08-06 | Merck Frosst Canada, Inc. | Human cyclooxygenase-2 cDNA and assays for evaluating cyclooxygenase-2 activity |
| US6096331A (en) * | 1993-02-22 | 2000-08-01 | Vivorx Pharmaceuticals, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
| US5759551A (en) | 1993-04-27 | 1998-06-02 | United Biomedical, Inc. | Immunogenic LHRH peptide constructs and synthetic universal immune stimulators for vaccines |
| HUT73876A (en) | 1993-04-29 | 1996-10-28 | Abbott Lab | Erythropoietin analog compositions and methods |
| US5554512A (en) | 1993-05-24 | 1996-09-10 | Immunex Corporation | Ligands for flt3 receptors |
| CA2125763C (en) | 1993-07-02 | 2007-08-28 | Maurice Kent Gately | P40 homodimer of interleukin-12 |
| WO1995029242A1 (en) | 1994-04-26 | 1995-11-02 | The Children's Medical Center Corporation | Angiostatin and method of use for inhibition of angiogenesis |
| US5639725A (en) | 1994-04-26 | 1997-06-17 | Children's Hospital Medical Center Corp. | Angiostatin protein |
| US5837682A (en) | 1996-03-08 | 1998-11-17 | The Children's Medical Center Corporation | Angiostatin fragments and method of use |
| CU22615A1 (es) | 1994-06-30 | 2000-02-10 | Centro Inmunologia Molecular | Procedimiento de obtención de anticuerpos monoclonales murinos menos inmunogénicos. anticuerpos monoclonales obtenidos |
| US5888773A (en) | 1994-08-17 | 1999-03-30 | The United States Of America As Represented By The Department Of Health And Human Services | Method of producing single-chain Fv molecules |
| US5541087A (en) | 1994-09-14 | 1996-07-30 | Fuji Immunopharmaceuticals Corporation | Expression and export technology of proteins as immunofusins |
| US6086875A (en) | 1995-01-17 | 2000-07-11 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of immunogens |
| US6485726B1 (en) | 1995-01-17 | 2002-11-26 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of therapeutics |
| US5691309A (en) | 1995-01-31 | 1997-11-25 | Eli Lilly And Company | Anti-obesity proteins |
| US5552524A (en) | 1995-01-31 | 1996-09-03 | Eli Lilly And Company | Anti-obesity proteins |
| US5891680A (en) | 1995-02-08 | 1999-04-06 | Whitehead Institute For Biomedical Research | Bioactive fusion proteins comprising the p35 and p40 subunits of IL-12 |
| JP3342873B2 (ja) | 1995-03-10 | 2002-11-11 | ジェネンテク・インコーポレイテッド | ｇａｓ６による受容体活性化 |
| US5719266A (en) | 1995-03-17 | 1998-02-17 | Eli Lilly And Company | Anti-obesity proteins |
| US6281010B1 (en) | 1995-06-05 | 2001-08-28 | The Trustees Of The University Of Pennsylvania | Adenovirus gene therapy vehicle and cell line |
| KR19990028388A (ko) | 1995-06-30 | 1999-04-15 | 피터 지. 스트링거 | 당뇨병 치료 방법 |
| US6406689B1 (en) | 1995-10-03 | 2002-06-18 | Frank W. Falkenberg | Compositions and methods for treatment of tumors and metastatic diseases |
| US5854205A (en) | 1995-10-23 | 1998-12-29 | The Children's Medical Center Corporation | Therapeutic antiangiogenic compositions and methods |
| US5678543A (en) * | 1995-11-16 | 1997-10-21 | Portable Hyperbarics, Inc. | Hyperbaric chamber |
| US5723125A (en) | 1995-12-28 | 1998-03-03 | Tanox Biosystems, Inc. | Hybrid with interferon-alpha and an immunoglobulin Fc linked through a non-immunogenic peptide |
| US6080409A (en) | 1995-12-28 | 2000-06-27 | Dendreon Corporation | Immunostimulatory method |
| US6750334B1 (en) | 1996-02-02 | 2004-06-15 | Repligen Corporation | CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor |
| CN1136197C (zh) | 1996-05-30 | 2004-01-28 | 霍夫曼-拉罗奇有限公司 | 新的哒嗪酮衍生物 |
| US5922685A (en) | 1996-06-05 | 1999-07-13 | Powderject Vaccines, Inc. | IL-12 gene therapy of tumors |
| EP0826696B1 (de) | 1996-09-03 | 2002-05-29 | GSF-Forschungszentrum für Umwelt und Gesundheit GmbH | Verwendung bi-und trispezifischer Antikörper zur Induktion einer Tumorimmunität |
| WO1998016246A1 (en) * | 1996-10-16 | 1998-04-23 | Johns Hopkins University | Cytokine enhanced immunotherapy for brain tumors |
| US5994104A (en) | 1996-11-08 | 1999-11-30 | Royal Free Hospital School Of Medicine | Interleukin-12 fusion protein |
| US6100387A (en) | 1997-02-28 | 2000-08-08 | Genetics Institute, Inc. | Chimeric polypeptides containing chemokine domains |
| US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| CA2284726A1 (en) | 1997-04-11 | 1998-10-22 | G.D. Searle & Co. | Antagonistic anti-avb3 integrin antibodies |
| DE69824039T2 (de) * | 1997-12-08 | 2005-08-18 | Lexigen Pharmaceuticals Corp., Lexington | Heterodimäre fusionsproteine zur verwendung für gezielte immuntherapie und allgemeine immunerregung |
| US20030105294A1 (en) * | 1998-02-25 | 2003-06-05 | Stephen Gillies | Enhancing the circulating half life of antibody-based fusion proteins |
| CN1318092C (zh) * | 1998-04-15 | 2007-05-30 | 利思进药品公司 | 含有抗体－细胞因子融合蛋白和血管生成抑制剂的免疫治疗用组合物 |
| EP1071469A2 (en) * | 1998-04-17 | 2001-01-31 | Lexigen Pharmaceuticals Corp. | Enhancement of antibody-cytokine fusion protein mediated immune responses by co-administration with prostaglandin inhibitor |
| AU3655899A (en) | 1998-04-20 | 1999-11-08 | Regents Of The University Of California, The | Modified immunoglobulin molecules and methods for use thereof |
| US6620382B1 (en) * | 1998-05-22 | 2003-09-16 | Biopheresis Technologies, Llc. | Method and compositions for treatment of cancers |
| JP2002522063A (ja) * | 1998-08-17 | 2002-07-23 | アブジェニックス インコーポレイテッド | 増加した血清半減期を有する改変された分子の生成 |
| HUP0103329A3 (en) * | 1998-08-25 | 2003-09-29 | Lexigen Pharmaceuticals Corp L | Expression and export of angiostatin and endostatin as immunofusis |
| US6646113B1 (en) | 1998-09-17 | 2003-11-11 | The Trustees Of The University Of Pennsylvania | Nucleic acid molecule encoding human survival of motor neuron-interacting protein 1 (SIP1) deletion mutants |
| US6335176B1 (en) | 1998-10-16 | 2002-01-01 | Pharmacopeia, Inc. | Incorporation of phosphorylation sites |
| KR20020007287A (ko) * | 1999-01-07 | 2002-01-26 | 추후보정 | Ｆｃ 융합 단백질로서 항-비만 단백질의 발현 및 이출 |
| MXPA01011250A (es) | 1999-05-06 | 2002-08-12 | Univ Wake Forest | Composiciones y metodos para identificar antigenos que producen una respuesta inmune. |
| US6348192B1 (en) | 1999-05-11 | 2002-02-19 | Bayer Corporation | Interleukin-2 mutein expressed from mammalian cells |
| MXPA01011845A (es) * | 1999-05-19 | 2002-06-21 | Lexigen Pharm Corp | Expresion y exportacion de proteinas de interferon-alfa como proteinas de fusion fc. |
| CZ299516B6 (cs) | 1999-07-02 | 2008-08-20 | F. Hoffmann-La Roche Ag | Konjugát erythropoetinového glykoproteinu, zpusobjeho výroby a použití a farmaceutická kompozice sjeho obsahem |
| PE20010288A1 (es) | 1999-07-02 | 2001-03-07 | Hoffmann La Roche | Derivados de eritropoyetina |
| DK1200479T3 (da) | 1999-08-09 | 2006-05-15 | Emd Lexigen Res Ct Corp | Multiple cytokin-antistof-komplekser |
| CN1406249B (zh) * | 2000-02-11 | 2010-06-16 | 默克专利股份有限公司 | 增加基于抗体的融合蛋白的循环半衰期 |
| PT1257297E (pt) * | 2000-02-24 | 2006-12-29 | Philogen Spa | Composições e método para tratamento da angiogénese em lesões patológicas |
| US6586398B1 (en) | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
| MXPA02011016A (es) * | 2000-05-12 | 2004-03-16 | Neose Technologies Inc | Glicopeptidos recombinantes de glucolisacion in vitro. |
| ATE368475T1 (de) * | 2000-06-29 | 2007-08-15 | Emd Lexigen Res Ct Corp | Steigerung von durch antikörper-zytokin- fusionsproteine mediierten immunantworten durch eine kombinierte behandlung mit mitteln zur erhöhung der immunzytokinaufnahme |
| WO2002057435A2 (en) * | 2001-01-18 | 2002-07-25 | Merck Patent Gmbh | Bifunctional fusion proteins with glucocerebrosidase activity |
| CA2438652A1 (en) * | 2001-02-19 | 2002-09-06 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Method for identification of t-cell epitopes and use for preparing molecules with reeduced immunogenicity |
| AU2002233340B2 (en) * | 2001-02-19 | 2008-05-22 | Merck Patent Gmbh | Artificial fusion proteins with reduced immunogenicity |
| PL206701B1 (pl) * | 2001-03-07 | 2010-09-30 | Merck Patent Gmbh | Immunoglobulinowe białko fuzyjne, kodujący je kwas nukleinowy, replikujący wektor ekspresji zawierający taki kwas nukleinowy, eukariotyczna komórka gospodarza zawierająca taki wektor ekspresji oraz sposób zwiększania ekspresji takiego białka fuzyjnego |
| WO2002079415A2 (en) * | 2001-03-30 | 2002-10-10 | Lexigen Pharmaceuticals Corp. | Reducing the immunogenicity of fusion proteins |
| PL205352B1 (pl) * | 2001-05-03 | 2010-04-30 | Merck Patent Gmbh | Rekombinowane przeciwciało specyficzne dla nowotworu |
| JP4795640B2 (ja) * | 2001-12-04 | 2011-10-19 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 調節された選択性を有する免疫サイトカイン |
| US6996009B2 (en) * | 2002-06-21 | 2006-02-07 | Micron Technology, Inc. | NOR flash memory cell with high storage density |
| AU2003298187B2 (en) * | 2002-12-17 | 2010-09-16 | Merck Patent Gmbh | Humanized antibody (H14.18) of the mouse 14.18 antibody binding to GD2 and its fusion with IL-2 |
-
2001
- 2001-06-29 AT AT01950766T patent/ATE368475T1/de active
- 2001-06-29 PL PL01358582A patent/PL358582A1/xx unknown
- 2001-06-29 KR KR1020027017778A patent/KR20030064275A/ko not_active Application Discontinuation
- 2001-06-29 US US09/896,909 patent/US7517526B2/en not_active Expired - Fee Related
- 2001-06-29 CN CNB018119247A patent/CN1270775C/zh not_active Expired - Fee Related
- 2001-06-29 AU AU2001271729A patent/AU2001271729B2/en not_active Ceased
- 2001-06-29 CZ CZ2003214A patent/CZ2003214A3/cs unknown
- 2001-06-29 MX MXPA02012734A patent/MXPA02012734A/es active IP Right Grant
- 2001-06-29 AU AU7172901A patent/AU7172901A/xx active Pending
- 2001-06-29 DK DK01950766T patent/DK1294401T3/da active
- 2001-06-29 PT PT01950766T patent/PT1294401E/pt unknown
- 2001-06-29 BR BR0112111-1A patent/BR0112111A/pt not_active IP Right Cessation
- 2001-06-29 WO PCT/US2001/020958 patent/WO2002002143A2/en active IP Right Grant
- 2001-06-29 RU RU2003100873/15A patent/RU2272644C2/ru not_active IP Right Cessation
- 2001-06-29 SK SK98-2003A patent/SK982003A3/sk unknown
- 2001-06-29 ES ES01950766T patent/ES2288967T3/es not_active Expired - Lifetime
- 2001-06-29 EP EP01950766A patent/EP1294401B1/en not_active Expired - Lifetime
- 2001-06-29 CA CA2412845A patent/CA2412845C/en not_active Expired - Lifetime
- 2001-06-29 DE DE60129695T patent/DE60129695T2/de not_active Expired - Lifetime
- 2001-06-29 JP JP2002506764A patent/JP5390055B2/ja not_active Expired - Fee Related
- 2001-06-29 HU HU0300868A patent/HUP0300868A3/hu unknown
-
2002
- 2002-12-27 NO NO20026245A patent/NO20026245L/no not_active Application Discontinuation
-
2003
- 2003-01-28 ZA ZA200300759A patent/ZA200300759B/en unknown
-
2009
- 2009-02-27 US US12/395,159 patent/US20100297060A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| PL358582A1 (en) | 2004-08-09 |
| HUP0300868A3 (en) | 2005-11-28 |
| EP1294401A2 (en) | 2003-03-26 |
| PT1294401E (pt) | 2007-11-09 |
| CN1529619A (zh) | 2004-09-15 |
| JP2004501981A (ja) | 2004-01-22 |
| MXPA02012734A (es) | 2003-04-25 |
| CN1270775C (zh) | 2006-08-23 |
| HUP0300868A2 (hu) | 2003-07-28 |
| BR0112111A (pt) | 2003-05-06 |
| DK1294401T3 (da) | 2007-10-08 |
| US7517526B2 (en) | 2009-04-14 |
| KR20030064275A (ko) | 2003-07-31 |
| US20030049227A1 (en) | 2003-03-13 |
| JP5390055B2 (ja) | 2014-01-15 |
| NO20026245D0 (no) | 2002-12-27 |
| DE60129695T2 (de) | 2008-06-05 |
| DE60129695D1 (de) | 2007-09-13 |
| CA2412845A1 (en) | 2002-01-10 |
| EP1294401B1 (en) | 2007-08-01 |
| CZ2003214A3 (cs) | 2003-08-13 |
| ATE368475T1 (de) | 2007-08-15 |
| CA2412845C (en) | 2014-07-22 |
| NO20026245L (no) | 2003-02-26 |
| WO2002002143A2 (en) | 2002-01-10 |
| SK982003A3 (en) | 2004-05-04 |
| AU2001271729B2 (en) | 2007-01-04 |
| ES2288967T3 (es) | 2008-02-01 |
| US20100297060A1 (en) | 2010-11-25 |
| RU2272644C2 (ru) | 2006-03-27 |
| WO2002002143A3 (en) | 2002-07-18 |
| AU7172901A (en) | 2002-01-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2001271729B2 (en) | Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents | |
| AU2001271729A1 (en) | Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents | |
| EP1071468B1 (en) | Enhancement of antibody-cytokine fusion protein mediated immune responses by co-administration with angiogenesis inhibitor | |
| AU758851B2 (en) | Enhancement of antibody-cytokine fusion protein mediated immune responses by co-administration with prostaglandin inhibitor | |
| SK156294A3 (en) | Immunoconjugates | |
| JP2012506394A (ja) | 放射線および免疫サイトカインによる癌治療 |