CA2256413C - Anti-endoglin monoclonal antibodies and their use in antiangiogenic therapy - Google Patents
Anti-endoglin monoclonal antibodies and their use in antiangiogenic therapy Download PDFInfo
- Publication number
- CA2256413C CA2256413C CA002256413A CA2256413A CA2256413C CA 2256413 C CA2256413 C CA 2256413C CA 002256413 A CA002256413 A CA 002256413A CA 2256413 A CA2256413 A CA 2256413A CA 2256413 C CA2256413 C CA 2256413C
- Authority
- CA
- Canada
- Prior art keywords
- composition
- matter
- endoglin
- therapeutic treatment
- angiogenesis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000011122 anti-angiogenic therapy Methods 0.000 title abstract description 56
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 103
- 230000033115 angiogenesis Effects 0.000 claims abstract description 63
- 241001529936 Murinae Species 0.000 claims abstract description 49
- 102000012085 Endoglin Human genes 0.000 claims abstract description 46
- 108010036395 Endoglin Proteins 0.000 claims abstract description 46
- 201000010099 disease Diseases 0.000 claims abstract description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 41
- 239000000203 mixture Substances 0.000 claims abstract description 37
- 210000002889 endothelial cell Anatomy 0.000 claims abstract description 33
- 239000012634 fragment Substances 0.000 claims abstract description 33
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 26
- 230000002062 proliferating effect Effects 0.000 claims abstract description 25
- 239000004037 angiogenesis inhibitor Substances 0.000 claims abstract description 15
- 229940121369 angiogenesis inhibitor Drugs 0.000 claims abstract description 15
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims abstract description 12
- 210000003556 vascular endothelial cell Anatomy 0.000 claims abstract description 8
- 229940127121 immunoconjugate Drugs 0.000 claims description 82
- 238000011282 treatment Methods 0.000 claims description 39
- 230000001225 therapeutic effect Effects 0.000 claims description 37
- 230000001772 anti-angiogenic effect Effects 0.000 claims description 26
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 101000881679 Homo sapiens Endoglin Proteins 0.000 claims description 18
- 102000048896 human ENG Human genes 0.000 claims description 18
- 108010039491 Ricin Proteins 0.000 claims description 17
- 238000001990 intravenous administration Methods 0.000 claims description 17
- 230000005747 tumor angiogenesis Effects 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 abstract 1
- 238000000034 method Methods 0.000 description 44
- 210000004027 cell Anatomy 0.000 description 38
- 241000699670 Mus sp. Species 0.000 description 36
- 210000005166 vasculature Anatomy 0.000 description 36
- 238000010172 mouse model Methods 0.000 description 25
- 210000001519 tissue Anatomy 0.000 description 22
- 238000011579 SCID mouse model Methods 0.000 description 20
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 206010006187 Breast cancer Diseases 0.000 description 16
- 208000026310 Breast neoplasm Diseases 0.000 description 16
- 201000011510 cancer Diseases 0.000 description 14
- 238000002560 therapeutic procedure Methods 0.000 description 14
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 13
- 230000003053 immunization Effects 0.000 description 13
- 238000002649 immunization Methods 0.000 description 12
- 230000008685 targeting Effects 0.000 description 12
- 241000282412 Homo Species 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000011081 inoculation Methods 0.000 description 10
- 208000032839 leukemia Diseases 0.000 description 10
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 9
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 8
- 230000001472 cytotoxic effect Effects 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 210000004408 hybridoma Anatomy 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 230000004614 tumor growth Effects 0.000 description 6
- 201000004624 Dermatitis Diseases 0.000 description 5
- 206010025323 Lymphomas Diseases 0.000 description 5
- 206010029113 Neovascularisation Diseases 0.000 description 5
- 201000004681 Psoriasis Diseases 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 238000011717 athymic nude mouse Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000003013 cytotoxicity Effects 0.000 description 5
- 231100000135 cytotoxicity Toxicity 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000003127 radioimmunoassay Methods 0.000 description 5
- 230000009257 reactivity Effects 0.000 description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 description 5
- 230000002792 vascular Effects 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 238000011725 BALB/c mouse Methods 0.000 description 4
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 3
- 201000003076 Angiosarcoma Diseases 0.000 description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 description 3
- 208000001258 Hemangiosarcoma Diseases 0.000 description 3
- 208000017604 Hodgkin disease Diseases 0.000 description 3
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 3
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 230000005875 antibody response Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 201000008275 breast carcinoma Diseases 0.000 description 3
- 208000025188 carcinoma of pharynx Diseases 0.000 description 3
- 201000003959 cecum carcinoma Diseases 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 3
- 230000009260 cross reactivity Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 201000005296 lung carcinoma Diseases 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 201000008968 osteosarcoma Diseases 0.000 description 3
- 208000024011 parotid gland neoplasm Diseases 0.000 description 3
- 208000028165 rectosigmoid carcinoma Diseases 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 description 3
- 210000003606 umbilical vein Anatomy 0.000 description 3
- DWNIXHARVTYMBF-UHFFFAOYSA-N 7-methylbenzo[b]quinolizin-5-ium-8,9-diol;bromide Chemical compound [Br-].C1=CC=[N+]2C=C3C(C)=C(O)C(O)=CC3=CC2=C1 DWNIXHARVTYMBF-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 241000588832 Bordetella pertussis Species 0.000 description 2
- 102100030497 Cytochrome c Human genes 0.000 description 2
- 108010075031 Cytochromes c Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 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
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 206010024305 Leukaemia monocytic Diseases 0.000 description 2
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 2
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 210000004712 air sac Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 210000003989 endothelium vascular Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005917 in vivo anti-tumor Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 201000006894 monocytic leukemia Diseases 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 150000004032 porphyrins Chemical class 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- PVYJZLYGTZKPJE-UHFFFAOYSA-N streptonigrin Chemical compound C=1C=C2C(=O)C(OC)=C(N)C(=O)C2=NC=1C(C=1N)=NC(C(O)=O)=C(C)C=1C1=CC=C(OC)C(OC)=C1O PVYJZLYGTZKPJE-UHFFFAOYSA-N 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- GKSPIZSKQWTXQG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[1-(pyridin-2-yldisulfanyl)ethyl]benzoate Chemical compound C=1C=C(C(=O)ON2C(CCC2=O)=O)C=CC=1C(C)SSC1=CC=CC=N1 GKSPIZSKQWTXQG-UHFFFAOYSA-N 0.000 description 1
- WCGUUGGRBIKTOS-GPOJBZKASA-N (3beta)-3-hydroxyurs-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C WCGUUGGRBIKTOS-GPOJBZKASA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 description 1
- ATCGGEJZONJOCL-UHFFFAOYSA-N 6-(2,5-dichlorophenyl)-1,3,5-triazine-2,4-diamine Chemical compound NC1=NC(N)=NC(C=2C(=CC=C(Cl)C=2)Cl)=N1 ATCGGEJZONJOCL-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 102400000068 Angiostatin Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000006579 Chemokine CXCL10 Human genes 0.000 description 1
- 108010008978 Chemokine CXCL10 Proteins 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010008177 Fd immunoglobulins Proteins 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- CEVCTNCUIVEQOY-UHFFFAOYSA-N Fumagillol Natural products O1C(CC=C(C)C)C1(C)C1C(OC)C(O)CCC21CO2 CEVCTNCUIVEQOY-UHFFFAOYSA-N 0.000 description 1
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 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 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 101000881680 Mus musculus Endoglin Proteins 0.000 description 1
- 101100293261 Mus musculus Naa15 gene Proteins 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 101150082943 NAT1 gene Proteins 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- MSHZHSPISPJWHW-PVDLLORBSA-N O-(chloroacetylcarbamoyl)fumagillol Chemical compound C([C@H]([C@H]([C@@H]1[C@]2(C)[C@H](O2)CC=C(C)C)OC)OC(=O)NC(=O)CCl)C[C@@]21CO2 MSHZHSPISPJWHW-PVDLLORBSA-N 0.000 description 1
- MSHZHSPISPJWHW-UHFFFAOYSA-N O-(chloroacetylcarbamoyl)fumagillol Chemical compound O1C(CC=C(C)C)C1(C)C1C(OC)C(OC(=O)NC(=O)CCl)CCC21CO2 MSHZHSPISPJWHW-UHFFFAOYSA-N 0.000 description 1
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000007452 Plasmacytoma Diseases 0.000 description 1
- 102000004211 Platelet factor 4 Human genes 0.000 description 1
- 108090000778 Platelet factor 4 Proteins 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000007135 Retinal Neovascularization Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 108010084592 Saporins Proteins 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 208000021388 Sezary disease Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 241000473945 Theria <moth genus> Species 0.000 description 1
- 108010046722 Thrombospondin 1 Proteins 0.000 description 1
- 102100036034 Thrombospondin-1 Human genes 0.000 description 1
- 102100029529 Thrombospondin-2 Human genes 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 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 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 230000006427 angiogenic response Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000003822 cell turnover Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 229960003983 diphtheria toxoid Drugs 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- ZOOODBUHSVUZEM-UHFFFAOYSA-N ethoxymethanedithioic acid Chemical compound CCOC(S)=S ZOOODBUHSVUZEM-UHFFFAOYSA-N 0.000 description 1
- 231100000776 exotoxin Toxicity 0.000 description 1
- 239000002095 exotoxin Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- CEVCTNCUIVEQOY-STXHBLNNSA-N fumagillol Chemical compound C([C@@H](O)[C@H](C1[C@]2(C)[C@H](O2)CC=C(C)C)OC)C[C@@]21CO2 CEVCTNCUIVEQOY-STXHBLNNSA-N 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 229940045109 genistein Drugs 0.000 description 1
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 1
- 235000006539 genistein Nutrition 0.000 description 1
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- MCAHMSDENAOJFZ-BVXDHVRPSA-N herbimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](OC)[C@@H](OC)C[C@H](C)[C@@H](OC)C2=CC(=O)C=C1C2=O MCAHMSDENAOJFZ-BVXDHVRPSA-N 0.000 description 1
- 229930193320 herbimycin Natural products 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229950010984 irsogladine Drugs 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 208000025036 lymphosarcoma Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- FRQMUZJSZHZSGN-HBNHAYAOSA-N medroxyprogesterone Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FRQMUZJSZHZSGN-HBNHAYAOSA-N 0.000 description 1
- 229960004616 medroxyprogesterone Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229940100243 oleanolic acid Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 108700028325 pokeweed antiviral Proteins 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 201000006845 reticulosarcoma Diseases 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- 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 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 108010060887 thrombospondin 2 Proteins 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 229940096998 ursolic acid Drugs 0.000 description 1
- PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000012991 xanthate Substances 0.000 description 1
- 238000012447 xenograft mouse model Methods 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- 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
- A61K47/6817—Toxins
- A61K47/6819—Plant toxins
- A61K47/6825—Ribosomal inhibitory proteins, i.e. RIP-I or RIP-II, e.g. Pap, gelonin or dianthin
- A61K47/6827—Ricin A
-
- 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
- A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Toxicology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cell Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Botany (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US655,953 | 1984-09-28 | ||
| US65595396A | 1996-05-31 | 1996-05-31 | |
| PCT/US1997/009610 WO1997045450A1 (en) | 1996-05-31 | 1997-05-30 | Anti-endoglin monoclonal antibodies and their use in antiangiogenic therapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2256413A1 CA2256413A1 (en) | 1997-12-04 |
| CA2256413C true CA2256413C (en) | 2007-07-03 |
Family
ID=24631047
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002256413A Expired - Lifetime CA2256413C (en) | 1996-05-31 | 1997-05-30 | Anti-endoglin monoclonal antibodies and their use in antiangiogenic therapy |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US5928641A (enExample) |
| EP (1) | EP0938505B1 (enExample) |
| JP (1) | JP4318752B2 (enExample) |
| AT (1) | ATE214075T1 (enExample) |
| CA (1) | CA2256413C (enExample) |
| DE (1) | DE69710911T2 (enExample) |
| ES (1) | ES2169864T3 (enExample) |
| WO (1) | WO1997045450A1 (enExample) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5965132A (en) | 1992-03-05 | 1999-10-12 | Board Of Regents, The University Of Texas System | Methods and compositions for targeting the vasculature of solid tumors |
| US6749853B1 (en) | 1992-03-05 | 2004-06-15 | Board Of Regents, The University Of Texas System | Combined methods and compositions for coagulation and tumor treatment |
| DE19845798A1 (de) * | 1998-09-29 | 2000-04-13 | Schering Ag | Verwendung von Neoangiogenese-Markern für Diagnose und Therapie von Tumoren, diese enthaltende Mittel, sowie Verfahren zu deren Herstellung |
| EP1150701A4 (en) * | 1999-01-22 | 2003-03-26 | Burnham Inst | TARGETING PRO-APOPTOTIC CONJUGATES AND METHODS FOR USE THEREOF |
| DE60135633D1 (de) * | 2000-02-10 | 2008-10-16 | Massachusetts Eye & Ear Infirm | Photodynamische therapie zur behandlung von augenerkrankungen |
| AU2006203034B2 (en) * | 2000-02-10 | 2006-09-07 | Massachusetts Eye And Ear Infirmary | Methods and compositions for treating conditions of the eye |
| DE10043481A1 (de) * | 2000-09-04 | 2002-04-11 | Vectron Therapeutics Ag Imt | Humaner Antikörper gegen Endoglin (CD105) und seine Verwendung |
| JP2003021631A (ja) * | 2001-05-10 | 2003-01-24 | Chugai Pharmaceut Co Ltd | 骨転移抑制剤のスクリーニング方法 |
| CA2461905A1 (en) * | 2001-09-27 | 2003-04-10 | Board Of Regents, The University Of Texas System | Combined compositions and methods for tumor vasculature coagulation and treatment |
| US20050106667A1 (en) * | 2003-08-01 | 2005-05-19 | Genentech, Inc | Binding polypeptides with restricted diversity sequences |
| US7758859B2 (en) | 2003-08-01 | 2010-07-20 | Genentech, Inc. | Anti-VEGF antibodies |
| WO2005044853A2 (en) * | 2003-11-01 | 2005-05-19 | Genentech, Inc. | Anti-vegf antibodies |
| AP2012006644A0 (en) * | 2003-08-01 | 2012-12-31 | Genentech Inc | Anti-VEGF antibodies |
| EP1533617A1 (en) * | 2003-11-19 | 2005-05-25 | RMF Dictagene S.A. | Angiogenesis inhibiting molecules, their selection, production and their use in the treatment and diagnosis of cancer |
| US20060052286A1 (en) * | 2004-08-13 | 2006-03-09 | Yale University | Factor VII conjugates for selectively treating neovascularization disorders |
| US7740849B2 (en) * | 2004-09-24 | 2010-06-22 | Beth Israel Deaconess Medical Center | Use of compounds that bind soluble endoglin and SFLT-1 for the treatment of pregnancy related hypertensive disorders |
| US20060067937A1 (en) * | 2004-09-24 | 2006-03-30 | Karumanchi S A | Methods of diagnosing and treating complications of pregnancy |
| BRPI0519096A2 (pt) * | 2004-12-15 | 2008-12-23 | Beth Israel Hospital | Ácidos nuclÉicos e polipeptÍdeos éteis para o diagnàstico e tratamento de complicaÇÕes na gravidez |
| US20090286271A1 (en) * | 2006-05-31 | 2009-11-19 | Karumanchi Ananth S | Methods of Diagnosing and Treating Complications of Pregnancy |
| US8642031B2 (en) | 2006-11-02 | 2014-02-04 | Acceleron Pharma, Inc. | Antagonists of BMP9, BMP10, ALK1 and other ALK1 ligands, and uses thereof |
| KR101581961B1 (ko) | 2006-11-02 | 2016-01-04 | 악셀레론 파마 인코포레이티드 | Ａｌｋ１ 수용체 및 리간드 길항제 및 그의 용도 |
| US10059756B2 (en) | 2006-11-02 | 2018-08-28 | Acceleron Pharma Inc. | Compositions comprising ALK1-ECD protein |
| AR069501A1 (es) | 2007-11-30 | 2010-01-27 | Genentech Inc | Anticuerpos anti- vegf (factor de crecimiento endotelial vascular) |
| KR20180029111A (ko) | 2008-05-02 | 2018-03-19 | 악셀레론 파마 인코포레이티드 | 혈관신생 및 혈관주위세포 적용범위의 조정을 위한 ａｌｋ１ 길항제 기재의 방법 및 조성물 |
| US20100082438A1 (en) * | 2008-10-01 | 2010-04-01 | Ronnie Jack Garmon | Methods and systems for customer performance scoring |
| EP3281637A1 (en) * | 2009-08-17 | 2018-02-14 | Tracon Pharmaceuticals, Inc. | Combination therapy of cancer with anti-endoglin antibodies and anti-vegf agents |
| US8221753B2 (en) | 2009-09-30 | 2012-07-17 | Tracon Pharmaceuticals, Inc. | Endoglin antibodies |
| TWI488642B (zh) * | 2009-12-09 | 2015-06-21 | Bayer Schering Pharma Ag | 抗－Ｃ４．４ａ抗體及其用途 |
| CA2827952A1 (en) | 2011-02-23 | 2012-11-01 | Health Research, Inc. | Anti-endoglin antibodies and knockin mice expressing novel human/mouse chimeric endoglin |
| US9255595B2 (en) * | 2011-04-29 | 2016-02-09 | Bae Systems Information And Electronic Systems Integration Inc. | Optical dome bezel |
| UA115789C2 (uk) | 2012-09-05 | 2017-12-26 | Трейкон Фармасутікалз, Інк. | Композиція антитіла до cd105 та її застосування |
| ES2710203T3 (es) | 2013-06-14 | 2019-04-23 | Agilent Technologies Inc | Sistema y método para facilitar la clasificación manual de objetos |
| GB201402006D0 (en) | 2014-02-06 | 2014-03-26 | Oncomatryx Biopharma S L | Antibody-drug conjugates and immunotoxins |
| US10155820B2 (en) | 2014-11-12 | 2018-12-18 | Tracon Pharmaceuticals, Inc. | Anti-endoglin antibodies and uses thereof |
| US9926375B2 (en) | 2014-11-12 | 2018-03-27 | Tracon Pharmaceuticals, Inc. | Anti-endoglin antibodies and uses thereof |
| US10072075B2 (en) | 2015-09-23 | 2018-09-11 | Genentech, Inc. | Optimized variants of anti-VEGF antibodies and methods of treatment thereof by reducing or inhibiting angiogenesis |
| RU2607029C1 (ru) * | 2015-10-20 | 2017-01-10 | ФЕДЕРАЛЬНОЕ ГОСУДАРСТВЕННОЕ БЮДЖЕТНОЕ УЧРЕЖДЕНИЕ "РОССИЙСКИЙ НАУЧНЫЙ ЦЕНТР РАДИОЛОГИИ И ХИРУРГИЧЕСКИХ ТЕХНОЛОГИЙ" МИНИСТЕРСТВА ЗДРАВООХРАНЕНИЯ РОССИЙСКОЙ ФЕДЕРАЦИИ / ФГБУ "РНЦРХТ" Минздрава России | ШТАММ ГИБРИДНЫХ КУЛЬТИВИРУЕМЫХ КЛЕТОК ЖИВОТНЫХ Mus musculus L. - EN-4C9 - ПРОДУЦЕНТ МОНОКЛОНАЛЬНЫХ АНТИТЕЛ ПРОТИВ ЭНДОГЛИНА (CD105) ЧЕЛОВЕКА |
| CN106928359B (zh) * | 2015-12-30 | 2020-10-13 | 广西医科大学 | 一种CD105纳米抗体Nb59 |
| CN106928355B (zh) * | 2015-12-30 | 2020-09-29 | 广西医科大学 | 一种CD105纳米抗体Nb184 |
| GB2566221B (en) | 2016-06-24 | 2021-08-04 | Univ South Carolina | Inhibin as targetable regulators of angiogenesis |
| EP3900733A1 (en) | 2020-04-24 | 2021-10-27 | Derma Innovate S.L. | Src kinase activators and eng function inhibitors as enhancers of skin homeostasis/regeneration and hair growth |
| CN115991773B (zh) * | 2022-08-15 | 2023-11-17 | 营龄(武汉)生物科技有限公司 | 一种含有人血白蛋白的药物组合物 |
| CN116063496B (zh) * | 2022-08-15 | 2023-10-24 | 营龄(武汉)生物科技有限公司 | 载药的人血白蛋白联合单克隆抗体在制备药物组合物中的用途 |
| WO2026017807A1 (en) | 2024-07-18 | 2026-01-22 | Beech Biotech Sa | Compositions and uses thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL94389A0 (en) * | 1989-06-01 | 1991-03-10 | Health Research Inc | Monoclonal antibody reactive to a unique antigen widely present on various human leukemia and lymphoma cells and method of using same for diagnosis and treatment |
| US5776427A (en) * | 1992-03-05 | 1998-07-07 | Board Of Regents, The University Of Texas System | Methods for targeting the vasculature of solid tumors |
-
1997
- 1997-05-30 JP JP54307197A patent/JP4318752B2/ja not_active Expired - Lifetime
- 1997-05-30 EP EP97926889A patent/EP0938505B1/en not_active Expired - Lifetime
- 1997-05-30 DE DE69710911T patent/DE69710911T2/de not_active Expired - Lifetime
- 1997-05-30 AT AT97926889T patent/ATE214075T1/de active
- 1997-05-30 ES ES97926889T patent/ES2169864T3/es not_active Expired - Lifetime
- 1997-05-30 WO PCT/US1997/009610 patent/WO1997045450A1/en not_active Ceased
- 1997-05-30 CA CA002256413A patent/CA2256413C/en not_active Expired - Lifetime
- 1997-08-29 US US08/920,537 patent/US5928641A/en not_active Expired - Lifetime
-
1999
- 1999-05-14 US US09/312,382 patent/US6200566B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US6200566B1 (en) | 2001-03-13 |
| WO1997045450A1 (en) | 1997-12-04 |
| EP0938505A1 (en) | 1999-09-01 |
| CA2256413A1 (en) | 1997-12-04 |
| DE69710911T2 (de) | 2002-09-19 |
| EP0938505B1 (en) | 2002-03-06 |
| US5928641A (en) | 1999-07-27 |
| JP4318752B2 (ja) | 2009-08-26 |
| EP0938505A4 (en) | 2000-07-19 |
| JP2000511425A (ja) | 2000-09-05 |
| ES2169864T3 (es) | 2002-07-16 |
| DE69710911D1 (de) | 2002-04-11 |
| ATE214075T1 (de) | 2002-03-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2256413C (en) | Anti-endoglin monoclonal antibodies and their use in antiangiogenic therapy | |
| US6190660B1 (en) | Anti-endoglin monoclonal antibodies and their use in antiangiogenic therapy | |
| DE69605181T3 (de) | Antikörper gegen cd30, die proteolytische spaltung und abgabe des membrangebundenen cd30 antigens verhindern | |
| US5686072A (en) | Epitope-specific monoclonal antibodies and immunotoxins and uses thereof | |
| RU2571923C2 (ru) | Моноклональные антитела против клаудина-18 для лечения рака | |
| RU2561041C2 (ru) | Применения иммуноконъюгатов, мишенью которых является cd138 | |
| US8734799B2 (en) | Unconjugated anti-TfR antibodies and compositions thereof for the treatment of cancer | |
| US7090844B2 (en) | Use of antibodies against the MUC18 antigen | |
| JP3213314B2 (ja) | 幹細胞因子レセプターに対するモノクローナル抗体 | |
| EP1896507B1 (en) | Anti-cd71 monoclonal antibodies and uses thereof for treating malignant tumour cells | |
| JP6326137B2 (ja) | 抗ｈｅｒ２抗体及びその結合体 | |
| AU640863B2 (en) | Methods and substances for recruiting therapeutic agents to solid tissues | |
| CA2447139A1 (en) | Specific binding proteins and uses thereof | |
| JP2005526044A (ja) | 抗ｃｄ２２抗体を使用した治療方法 | |
| Zangemeister-Wittke | Antibodies for targeted cancer therapy–technical aspects and clinical perspectives | |
| MXPA06009759A (es) | Codocito para trastornos por linfocitos b. | |
| US9315582B2 (en) | Anti-endoglin antibodies and knockin mice expressing novel human/mouse chimeric endoglin | |
| Reisfeld | Monoclonal antibodies in cancer immunotherapy | |
| US20200165350A1 (en) | Strong potentiation of immune checkpoint blockade therapy of cancer by combination with endoglin-targeting therapy | |
| US6685930B1 (en) | Methods and substances for recruiting therapeutic agents to solid tumors | |
| US20030133938A1 (en) | Antibody-avidin fusion proteins as cytotoxic drugs | |
| WO1996022310A1 (en) | Antibodies for use in cancer therapy and diagnosis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20170530 |