CA1062156A - Immunological materials - Google Patents
Immunological materialsInfo
- Publication number
- CA1062156A CA1062156A CA245,033A CA245033A CA1062156A CA 1062156 A CA1062156 A CA 1062156A CA 245033 A CA245033 A CA 245033A CA 1062156 A CA1062156 A CA 1062156A
- Authority
- CA
- Canada
- Prior art keywords
- amino
- bis
- chloroethyl
- free
- group
- 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
Links
- 239000000463 material Substances 0.000 title description 8
- 230000001900 immune effect Effects 0.000 title 1
- 229920000642 polymer Polymers 0.000 claims abstract description 90
- 108060003951 Immunoglobulin Proteins 0.000 claims abstract description 61
- 102000018358 immunoglobulin Human genes 0.000 claims abstract description 61
- 229940127089 cytotoxic agent Drugs 0.000 claims abstract description 58
- 239000002254 cytotoxic agent Substances 0.000 claims abstract description 58
- 231100000599 cytotoxic agent Toxicity 0.000 claims abstract description 32
- 239000000427 antigen Substances 0.000 claims abstract description 13
- 102000036639 antigens Human genes 0.000 claims abstract description 13
- 108091007433 antigens Proteins 0.000 claims abstract description 13
- 125000003277 amino group Chemical group 0.000 claims description 61
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 60
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 44
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 38
- 229920002307 Dextran Polymers 0.000 claims description 36
- 229920002643 polyglutamic acid Polymers 0.000 claims description 28
- 238000002360 preparation method Methods 0.000 claims description 28
- 108010020346 Polyglutamic Acid Proteins 0.000 claims description 27
- 229920000656 polylysine Polymers 0.000 claims description 26
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 25
- 108010039918 Polylysine Proteins 0.000 claims description 24
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 18
- 150000004986 phenylenediamines Chemical class 0.000 claims description 17
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 15
- 229920002873 Polyethylenimine Polymers 0.000 claims description 14
- 229960002989 glutamic acid Drugs 0.000 claims description 14
- -1 2,4-diamino-6-pteridinyl Chemical group 0.000 claims description 13
- AYKYXWQEBUNJCN-UHFFFAOYSA-N 3-methylfuran-2,5-dione Chemical compound CC1=CC(=O)OC1=O AYKYXWQEBUNJCN-UHFFFAOYSA-N 0.000 claims description 13
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 13
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin 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(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 12
- 150000001718 carbodiimides Chemical class 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 12
- 210000002966 serum Anatomy 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 229960005190 phenylalanine Drugs 0.000 claims description 11
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 9
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 8
- 239000000969 carrier Substances 0.000 claims description 8
- 239000002244 precipitate Substances 0.000 claims description 8
- 229940080818 propionamide Drugs 0.000 claims description 8
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 7
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 7
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 6
- 229920001577 copolymer Polymers 0.000 claims description 6
- 229960004679 doxorubicin Drugs 0.000 claims description 6
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 6
- 235000008729 phenylalanine Nutrition 0.000 claims description 6
- 229920000724 poly(L-arginine) polymer Polymers 0.000 claims description 6
- 108010011110 polyarginine Proteins 0.000 claims description 6
- KKZUMAMOMRDVKA-UHFFFAOYSA-N 2-chloropropane Chemical group [CH2]C(C)Cl KKZUMAMOMRDVKA-UHFFFAOYSA-N 0.000 claims description 5
- 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 claims description 5
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 claims description 5
- 102000016607 Diphtheria Toxin Human genes 0.000 claims description 5
- 108010053187 Diphtheria Toxin Proteins 0.000 claims description 5
- 102000008946 Fibrinogen Human genes 0.000 claims description 5
- 108010049003 Fibrinogen Proteins 0.000 claims description 5
- 229920000805 Polyaspartic acid Polymers 0.000 claims description 5
- 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 claims description 5
- 229940012952 fibrinogen Drugs 0.000 claims description 5
- 229940072221 immunoglobulins Drugs 0.000 claims description 5
- 108010064470 polyaspartate Proteins 0.000 claims description 5
- IERHLVCPSMICTF-UHFFFAOYSA-N Cytosine arabinoside monophosphate Chemical compound O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(O)=O)O1 IERHLVCPSMICTF-UHFFFAOYSA-N 0.000 claims description 4
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 150000004712 monophosphates Chemical class 0.000 claims description 3
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 8
- 229960000587 glutaral Drugs 0.000 claims 4
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims 2
- JJGIDUGGQLLVSW-LBPRGKRZSA-N (2s)-2-[2,2-bis(2-chloroethyl)hydrazinyl]-3-phenylpropanoic acid Chemical compound ClCCN(CCCl)N[C@H](C(=O)O)CC1=CC=CC=C1 JJGIDUGGQLLVSW-LBPRGKRZSA-N 0.000 claims 1
- KVLZELYWWJRKHH-JTQLQIEISA-N (2s)-2-[4-[bis(2-chloroethyl)amino]anilino]propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=C(N(CCCl)CCCl)C=C1 KVLZELYWWJRKHH-JTQLQIEISA-N 0.000 claims 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims 1
- 229940104302 cytosine Drugs 0.000 claims 1
- 229920000136 polysorbate Polymers 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000000243 solution Substances 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 229960002086 dextran Drugs 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 229940079593 drug Drugs 0.000 description 20
- 239000003814 drug Substances 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 14
- 241000283973 Oryctolagus cuniculus Species 0.000 description 13
- 206010028980 Neoplasm Diseases 0.000 description 11
- 241000283707 Capra Species 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 230000002152 alkylating effect Effects 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 231100000433 cytotoxic Toxicity 0.000 description 7
- 230000001472 cytotoxic effect Effects 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 102000006395 Globulins Human genes 0.000 description 6
- 108010044091 Globulins Proteins 0.000 description 6
- 206010025323 Lymphomas Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 5
- 201000001441 melanoma Diseases 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000004611 spectroscopical analysis Methods 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 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 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 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 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229920005654 Sephadex Polymers 0.000 description 3
- 239000012507 Sephadex™ Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 3
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 3
- 235000011130 ammonium sulphate Nutrition 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- FZQZRBQKXXGAMZ-UHFFFAOYSA-N 2-benzyl-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1CC1=CC=CC=C1 FZQZRBQKXXGAMZ-UHFFFAOYSA-N 0.000 description 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
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- 230000001154 acute effect Effects 0.000 description 2
- ZRPDXDBGEYHEBJ-UHFFFAOYSA-N alpha-(hydroxymethyl)serine Chemical compound OCC(N)(CO)C(O)=O ZRPDXDBGEYHEBJ-UHFFFAOYSA-N 0.000 description 2
- 230000002494 anti-cea effect Effects 0.000 description 2
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- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
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- 230000001085 cytostatic effect Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 2
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 2
- 235000019797 dipotassium phosphate Nutrition 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
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- WZCQRUWWHSTZEM-UHFFFAOYSA-N 1,3-phenylenediamine Chemical compound NC1=CC=CC(N)=C1 WZCQRUWWHSTZEM-UHFFFAOYSA-N 0.000 description 1
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- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- WTCZXLWFWRKOPE-UHFFFAOYSA-N 2-[amino(hydroxy)methyl]-2-(hydroxymethyl)-3-oxo-3-phenylmethoxypropanoic acid Chemical compound C(=O)(OCC1=CC=CC=C1)C(C(=O)O)(C(O)N)CO WTCZXLWFWRKOPE-UHFFFAOYSA-N 0.000 description 1
- 238000010600 3H thymidine incorporation assay Methods 0.000 description 1
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- 102100024133 Coiled-coil domain-containing protein 50 Human genes 0.000 description 1
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- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
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- 101000910772 Homo sapiens Coiled-coil domain-containing protein 50 Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 101000913968 Ipomoea purpurea Chalcone synthase C Proteins 0.000 description 1
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- 101000907988 Petunia hybrida Chalcone-flavanone isomerase C Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
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- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
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- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/44—Antibodies bound to carriers
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- 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
- A61K47/56—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
- A61K47/56—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
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- A—HUMAN NECESSITIES
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- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
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- 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
- A61K47/6883—Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy
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- 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
- A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/806—Antigenic peptides or proteins
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA314,487A CA1079268A (en) | 1975-02-04 | 1978-10-27 | Immunological materials |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB4696/75A GB1541435A (en) | 1975-02-04 | 1975-02-04 | Immunological materials |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1062156A true CA1062156A (en) | 1979-09-11 |
Family
ID=9782084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA245,033A Expired CA1062156A (en) | 1975-02-04 | 1976-02-04 | Immunological materials |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US4046722A (OSRAM) |
| CA (1) | CA1062156A (OSRAM) |
| DE (1) | DE2603120A1 (OSRAM) |
| FR (2) | FR2299872A1 (OSRAM) |
| GB (1) | GB1541435A (OSRAM) |
| SE (1) | SE7901858L (OSRAM) |
Families Citing this family (160)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2708018A1 (de) * | 1977-02-24 | 1978-09-07 | Boehringer Mannheim Gmbh | An polyamid fixiertes biologisch aktives protein und verfahren zu seiner herstellung |
| WO1979000515A1 (en) * | 1978-01-16 | 1979-08-09 | Univ Boston | Method of effecting cellular uptake of molecules |
| US4701521A (en) * | 1978-07-17 | 1987-10-20 | The Trustees Of Boston University | Method of effecting cellular uptake of molecules |
| US4235969A (en) * | 1978-05-08 | 1980-11-25 | Syva Company | Procainamide antigen conjugates and antibodies |
| FR2437213A1 (fr) * | 1978-09-28 | 1980-04-25 | Cm Ind | Produits cytotoxiques formes par liaison covalente de la chaine a de la ricine avec un anticorps et leur procede de preparation |
| US4315851A (en) * | 1978-12-29 | 1982-02-16 | Kureha Kagaku Kogyo Kabushiki Kaisha | Pharmaceutical composition having antitumor activity |
| AT388707B (de) * | 1979-02-22 | 1989-08-25 | Gao Ges Automation Org | Verfahren zur herstellung einer mehrschichtigen ausweiskarte, kreditkarte, scheckkarte od.dgl. |
| JPS55124719A (en) * | 1979-03-22 | 1980-09-26 | Kowa Co | Preparation of immune globulin administrable by intravenous injection |
| SE445013B (sv) * | 1979-06-21 | 1986-05-26 | Landstingens Inkopscentral | Medel for att forebygga eller behandla infektioner hos menniskor och djur |
| JPS5639022A (en) * | 1979-09-05 | 1981-04-14 | Hayashibara Biochem Lab Inc | Preparation of vaccine |
| DE3175151D1 (en) * | 1980-05-21 | 1986-09-25 | Teijin Ltd | Reactive polymer and process for the preparation thereof |
| JPS57106625A (en) * | 1980-12-22 | 1982-07-02 | Teijin Ltd | Cytotoxic protein complex and its preparation |
| JPS57106626A (en) * | 1980-12-22 | 1982-07-02 | Teijin Ltd | Cytotoxic protein complex and its preparation |
| US5144011A (en) * | 1981-06-26 | 1992-09-01 | Boston University | Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers |
| US4631190A (en) * | 1981-06-26 | 1986-12-23 | Shen Wei C | Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers |
| US4749570A (en) * | 1981-12-31 | 1988-06-07 | The Governors Of The University Of Alberta | Targeting conjugates of albumin and therapeutic agents |
| US5108987A (en) * | 1982-02-25 | 1992-04-28 | Faulk Ward P | Conjugates of proteins with anti-tumor agents |
| GB2116979B (en) * | 1982-02-25 | 1985-05-15 | Ward Page Faulk | Conjugates of proteins with anti-tumour agents |
| US4880911A (en) * | 1982-03-19 | 1989-11-14 | G. D. Searle & Co. | Fused polypeptides and methods for their detection |
| US4460560A (en) * | 1982-06-18 | 1984-07-17 | University Of Southern California | Drug delivery by polymeric carriers |
| US4485093A (en) * | 1982-08-13 | 1984-11-27 | Runge Richard G | Immunotoxin conjugate which comprises arsanilic acid, useful for treating malignant tumors, particularly pancreatic cancer |
| US4666697A (en) * | 1982-12-08 | 1987-05-19 | Nihon Medi-Physics Co., Ltd. | Radioactive diagnostic agent |
| JPS59116232A (ja) * | 1982-12-24 | 1984-07-05 | Teijin Ltd | 細胞毒性複合体及びその製造法 |
| JPS59116229A (ja) * | 1982-12-24 | 1984-07-05 | Teijin Ltd | 細胞毒性複合体を活性成分とする癌治療用剤およびその製造法 |
| JPH0651643B2 (ja) * | 1983-01-19 | 1994-07-06 | 帝人株式会社 | 殺細胞性修飾免疫グロブリン及びその製造方法 |
| ATE57187T1 (de) * | 1983-03-30 | 1990-10-15 | Lilly Industries Ltd | Vincaleukoblastin-derivate. |
| JPS59186924A (ja) * | 1983-04-08 | 1984-10-23 | Kureha Chem Ind Co Ltd | ヒト免疫グロブリン結合抗腫瘍剤 |
| US4863729A (en) * | 1984-06-20 | 1989-09-05 | Linus Pauling Institute Of Science And Medicine | Method for preparing a macromolecular monoclonal antibody composition |
| IL73883A (en) * | 1984-12-20 | 1990-12-23 | Yeda Res & Dev | Monoclonal antibodies against tnf-alpha,hybridomas producing them and method for the purification of tnf-alpha |
| AT384549B (de) * | 1985-01-08 | 1987-11-25 | Strasser Engelbert | Verfahren zur herstellung einer vaccine |
| US4667030A (en) * | 1985-06-17 | 1987-05-19 | Eli Lilly And Company | Hydrazide succinimide derivatives of antineoplastic indole-dihydroindole alkaloids |
| US4675400A (en) * | 1985-06-17 | 1987-06-23 | Eli Lilly And Company | Bifunctional derivatives of 4-desacetyl indole-dihydroindole alkaloids |
| US5223242A (en) * | 1985-11-05 | 1993-06-29 | The General Hospital Corporation | Negatively charged specific affinity reagents |
| EP0268707A3 (en) * | 1985-11-05 | 1989-03-08 | The General Hospital Corporation | Negatively charged specific affinity reagents |
| CH667874A5 (fr) * | 1985-12-19 | 1988-11-15 | Battelle Memorial Institute | Polypeptide synthetique biodegradable et son utilisation pour la preparation de medicaments. |
| EP0250486A4 (en) * | 1986-01-03 | 1988-05-25 | Univ Melbourne | MELPHALAN DERIVATIVES. |
| US4699784A (en) * | 1986-02-25 | 1987-10-13 | Center For Molecular Medicine & Immunology | Tumoricidal methotrexate-antibody conjugate |
| ZA877535B (en) * | 1986-10-09 | 1988-04-11 | F. Hoffmann-La Roche & Co. Aktiengesellschaft | Factor ix-peptides |
| GB8628398D0 (en) * | 1986-11-27 | 1986-12-31 | Central Blood Lab Authority | Pharmaceutically-active conjugates |
| CA1329119C (en) * | 1988-03-29 | 1994-05-03 | Milton David Goldenberg | Cytotoxic therapy |
| US5120525A (en) * | 1988-03-29 | 1992-06-09 | Immunomedics, Inc. | Radiolabeled antibody cytotoxic therapy of cancer |
| US20030232010A2 (en) * | 1988-03-29 | 2003-12-18 | Immunomedics, Inc. | Improved cytotoxic therapy |
| US5135736A (en) * | 1988-08-15 | 1992-08-04 | Neorx Corporation | Covalently-linked complexes and methods for enhanced cytotoxicity and imaging |
| US5252713A (en) * | 1988-09-23 | 1993-10-12 | Neorx Corporation | Polymeric carriers for non-covalent drug conjugation |
| US5116944A (en) * | 1989-12-29 | 1992-05-26 | Neorx Corporation | Conjugates having improved characteristics for in vivo administration |
| US5272253A (en) * | 1991-07-01 | 1993-12-21 | Eli Lilly And Company | Cluster conjugates of drugs with antibodies |
| CA2114934A1 (en) * | 1991-08-05 | 1993-02-18 | Mark T. Martin | Prodrugs activated by targeted catalytic proteins |
| ES2049656B1 (es) * | 1992-10-08 | 1994-11-16 | Lilly Co Eli | Grupos de conjugados de farmacos con anticuerpos. |
| US6090925A (en) * | 1993-03-09 | 2000-07-18 | Epic Therapeutics, Inc. | Macromolecular microparticles and methods of production and use |
| US5981719A (en) * | 1993-03-09 | 1999-11-09 | Epic Therapeutics, Inc. | Macromolecular microparticles and methods of production and use |
| US5670347A (en) | 1994-05-11 | 1997-09-23 | Amba Biosciences Llc | Peptide-mediated gene transfer |
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-
1975
- 1975-02-04 GB GB4696/75A patent/GB1541435A/en not_active Expired
-
1976
- 1976-01-14 US US05/648,841 patent/US4046722A/en not_active Expired - Lifetime
- 1976-01-28 DE DE19762603120 patent/DE2603120A1/de not_active Withdrawn
- 1976-02-04 FR FR7603102A patent/FR2299872A1/fr active Granted
- 1976-02-04 CA CA245,033A patent/CA1062156A/en not_active Expired
- 1976-08-27 FR FR7626045A patent/FR2362119A1/fr active Granted
-
1979
- 1979-03-01 SE SE7901858A patent/SE7901858L/xx not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| GB1541435A (en) | 1979-02-28 |
| FR2362119A1 (fr) | 1978-03-17 |
| FR2362119B1 (OSRAM) | 1978-12-22 |
| SE7901858L (sv) | 1979-03-01 |
| FR2299872B1 (OSRAM) | 1979-09-28 |
| FR2299872A1 (fr) | 1976-09-03 |
| US4046722A (en) | 1977-09-06 |
| DE2603120A1 (de) | 1976-08-05 |
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