ATE114479T1 - Über thioetherbindungen verknüpfte immunokonjugate, mit verminderter toxizität und vermehrter selektivität. - Google Patents
Über thioetherbindungen verknüpfte immunokonjugate, mit verminderter toxizität und vermehrter selektivität.Info
- Publication number
- ATE114479T1 ATE114479T1 AT88114682T AT88114682T ATE114479T1 AT E114479 T1 ATE114479 T1 AT E114479T1 AT 88114682 T AT88114682 T AT 88114682T AT 88114682 T AT88114682 T AT 88114682T AT E114479 T1 ATE114479 T1 AT E114479T1
- Authority
- AT
- Austria
- Prior art keywords
- protein
- toxin
- group
- forming
- derivatized
- Prior art date
Links
- 229940127121 immunoconjugate Drugs 0.000 title abstract 3
- 230000001988 toxicity Effects 0.000 title 1
- 231100000419 toxicity Toxicity 0.000 title 1
- -1 2-chloro-4-nitrophenyl Chemical group 0.000 abstract 8
- 102000004169 proteins and genes Human genes 0.000 abstract 4
- 108090000623 proteins and genes Proteins 0.000 abstract 4
- 239000003053 toxin Substances 0.000 abstract 4
- 231100000765 toxin Toxicity 0.000 abstract 4
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 abstract 2
- 125000003396 thiol group Chemical group [H]S* 0.000 abstract 2
- JQBCKRZQAMELAD-UHFFFAOYSA-N 1-hydroxypyrrolidin-2-one Chemical group ON1CCCC1=O JQBCKRZQAMELAD-UHFFFAOYSA-N 0.000 abstract 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 abstract 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 abstract 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical group C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 abstract 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical group OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 abstract 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 abstract 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 abstract 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 abstract 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical group ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 abstract 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 125000005647 linker group Chemical group 0.000 abstract 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 abstract 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
Classifications
-
- 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
- A61K47/6829—Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin 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
- A61K47/6801—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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Toxicology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Botany (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/095,178 US4981979A (en) | 1987-09-10 | 1987-09-10 | Immunoconjugates joined by thioether bonds having reduced toxicity and improved selectivity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE114479T1 true ATE114479T1 (de) | 1994-12-15 |
Family
ID=22250495
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT88114682T ATE114479T1 (de) | 1987-09-10 | 1988-09-08 | Über thioetherbindungen verknüpfte immunokonjugate, mit verminderter toxizität und vermehrter selektivität. |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US4981979A (de) |
| EP (1) | EP0306943B1 (de) |
| JP (1) | JPH01163132A (de) |
| AT (1) | ATE114479T1 (de) |
| AU (1) | AU622415B2 (de) |
| CA (1) | CA1336496C (de) |
| DE (1) | DE3852250T2 (de) |
Families Citing this family (83)
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| US4965392A (en) * | 1987-03-26 | 1990-10-23 | Neorx Corporation | Chelating compounds for metal-radionuclide labeled proteins |
| US5792458A (en) * | 1987-10-05 | 1998-08-11 | The United States Of America As Represented By The Department Of Health And Human Services | Mutant diphtheria toxin conjugates |
| US5352447A (en) * | 1987-10-05 | 1994-10-04 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Immunotoxins for treatment of intracranial lesions and as adjunct to chemotherapy |
| US5208021A (en) * | 1987-10-05 | 1993-05-04 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of preparing diphtheria immunotoxins |
| IL89220A (en) * | 1988-02-11 | 1994-02-27 | Bristol Myers Squibb Co | Anthracycline immunoconjugates, their production and pharmaceutical compositions containing them |
| US5112954A (en) * | 1988-02-26 | 1992-05-12 | Neorx Corporation | Method of enhancing the effect of cytotoxic agents |
| US5024834A (en) * | 1988-07-12 | 1991-06-18 | Cetus Corporation | Thioether linked immunotoxin conjugates |
| US5171563A (en) * | 1988-09-30 | 1992-12-15 | Neorx Corporation | Cleavable linkers for the reduction of non-target organ retention of immunoconjugates |
| NL8802458A (nl) * | 1988-10-07 | 1990-05-01 | Philips Nv | Werkwijze voor de vervaardiging van een epitaxiale indiumfosfide-laag op een substraatoppervlak. |
| DE3900649A1 (de) * | 1989-01-11 | 1990-07-12 | Boehringer Mannheim Gmbh | Verfahren zur abloesung eines analyten von seinem bindeprotein |
| US5714149A (en) * | 1989-02-10 | 1998-02-03 | Celltech Therapeutics Limited | Crosslinked antibodies and processes for their preparation |
| US5354554A (en) * | 1989-02-10 | 1994-10-11 | Celltech Limited | Crosslinked antibodies and processes for their preparation |
| ES2099699T3 (es) * | 1989-05-02 | 1997-06-01 | Abbott Lab | Fijacion covalente de los miembros de union especificos a las fases solidas. |
| GB8927365D0 (en) * | 1989-12-04 | 1990-01-31 | Ici Plc | Reagent |
| WO1992001470A1 (en) * | 1990-07-20 | 1992-02-06 | Kabi Pharmacia Ab | Target specific antibody-superantigen conjugates and their preparation |
| SE9002479D0 (sv) * | 1990-07-20 | 1990-07-20 | Pharmacia Ab | Antibody conjugates |
| US5612034A (en) * | 1990-10-03 | 1997-03-18 | Redcell, Inc. | Super-globuling for in vivo extended lifetimes |
| US5725857A (en) * | 1991-02-11 | 1998-03-10 | The United States Of America As Represented By The Department Of Health And Human Services | Immunotoxin with in vivo T cell suppressant activity and methods of use |
| US5167956A (en) * | 1991-02-11 | 1992-12-01 | The United States Of America As Represented By The Department Of Health And Human Services | Immunotoxin with in-vivo t cell suppressant activity |
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| JPH06506688A (ja) * | 1991-04-10 | 1994-07-28 | バイオサイト・ダイアグノスティックス・インコーポレイテッド | クロストークインヒビターおよびその使用 |
| US5622929A (en) * | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
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| US7288254B2 (en) | 1995-10-30 | 2007-10-30 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services, Nih | Use of immunotoxins to induce immune tolerance to pancreatic islet transplantation |
| US7696338B2 (en) | 1995-10-30 | 2010-04-13 | The United States Of America As Represented By The Department Of Health And Human Services | Immunotoxin fusion proteins and means for expression thereof |
| DE69626849T2 (de) * | 1995-12-22 | 2003-12-24 | Bristol-Myers Squibb Co., Princeton | Verzweigte hydrazongruppen enthaltende kuppler |
| DE19636889A1 (de) * | 1996-09-11 | 1998-03-12 | Felix Dr Kratz | Antineoplastisch wirkende Transferrin- und Albuminkonjugate zytostatischer Verbindungen aus der Gruppe der Anthrazykline, Alkylantien, Antimetabolite und Cisplatin-Analoga und diese enthaltende Arzneimittel |
| AU733898B2 (en) | 1997-03-05 | 2001-05-31 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Immunotoxins and methods of inducing immune tolerance |
| US6187564B1 (en) | 1997-07-10 | 2001-02-13 | Beth Israel Deaconess Medical Center | DNA encoding erythropoietin multimers having modified 5′ and 3′ sequences and its use to prepare EPO therapeutics |
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| US7591994B2 (en) | 2002-12-13 | 2009-09-22 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
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| EP1572242B1 (de) | 2002-12-13 | 2014-04-16 | Immunomedics, Inc. | Immun-conjugate mit einem intrazellular spaltbaren linker |
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| US10195175B2 (en) | 2015-06-25 | 2019-02-05 | Immunomedics, Inc. | Synergistic effect of anti-Trop-2 antibody-drug conjugate in combination therapy for triple-negative breast cancer when used with microtubule inhibitors or PARP inhibitors |
| US20170224837A1 (en) | 2016-02-10 | 2017-08-10 | Immunomedics, Inc. | Combination of abcg2 inhibitors with sacituzumab govitecan (immu-132) overcomes resistance to sn-38 in trop-2 expressing cancers |
| RU2725292C2 (ru) | 2016-04-27 | 2020-06-30 | Иммьюномедикс, Инк. | Эффективность конъюгатов антитела против trop-2 с лекарственным средством sn-38 для терапии рецидивирующих/рефрактерных к ингибиторам контрольной точки опухолей |
| WO2018158716A1 (en) | 2017-03-02 | 2018-09-07 | Cadila Healthcare Limited | Novel protein drug conjugate formulation |
| RU2758234C2 (ru) | 2017-03-27 | 2021-10-26 | Иммьюномедикс, Инк. | ЛЕЧЕНИЕ ТРИЖДЫ НЕГАТИВНОГО РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ, ХАРАКТЕРИЗУЮЩЕГОСЯ ЭКСПРЕССИЕЙ Trop-2, С ПОМОЩЬЮ САЦИТУЗУМАБА ГОВИТЕКАНА И ИНГИБИТОРА Rad51 |
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| US4429008B1 (en) * | 1981-12-10 | 1995-05-16 | Univ California | Thiol reactive liposomes |
| CA1203164A (en) * | 1982-03-09 | 1986-04-15 | Thomas J. Mckearn | Antibody conjugates |
| US4520226A (en) * | 1982-07-19 | 1985-05-28 | The United States Of America As Represented By The Department Of Health And Human Services | Treatment of graft versus host disease using a mixture of T-lymphocyte specific monoclonal antibody: ricin conjugates |
| US4434236A (en) * | 1982-10-20 | 1984-02-28 | E. I. Du Pont De Nemours & Co. | Immunoassay wherein labeled antibody is displaced from immobilized analyte-analogue |
| 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 |
| US4545985A (en) * | 1984-01-26 | 1985-10-08 | The United States Of America As Represented By The Secretary, Dept. Of Health And Human Services | Pseudomonas exotoxin conjugate immunotoxins |
| EP0158291A3 (de) * | 1984-04-10 | 1988-07-27 | Takeda Chemical Industries, Ltd. | Verfahren zur Reinigung von karzinoembryonischem Antigen und Verfahren zur Herstellung eines monoklonalen Antikörpers, der mit karzinoembryonischem Antigen reagiert |
| CA1283661C (en) * | 1984-06-20 | 1991-04-30 | Franz Jansen | Imidazolides, process for their preparation and application as intermediates for the synthesis of cytotoxic conjugates |
| US4542225A (en) * | 1984-08-29 | 1985-09-17 | Dana-Farber Cancer Institute, Inc. | Acid-cleavable compound |
| US4657853A (en) * | 1984-09-14 | 1987-04-14 | E. I. Du Pont De Nemours And Company | Immunoassays utilizing covalent conjugates of polymerized enzyme and antibody |
| US4659839A (en) * | 1984-10-10 | 1987-04-21 | Mallinckrodt, Inc. | Coupling agents for radiolabeled antibody fragments |
| FR2577135B1 (fr) * | 1985-02-13 | 1989-12-15 | Sanofi Sa | Immunotoxines a longue duree d'action comportant un constituant glycopeptidique inactivant les ribosomes modifie sur ses motifs polysaccharidiques |
| US4678667A (en) * | 1985-07-02 | 1987-07-07 | 501 Regents of the University of California | Macrocyclic bifunctional chelating agents |
| US4680338A (en) * | 1985-10-17 | 1987-07-14 | Immunomedics, Inc. | Bifunctional linker |
| IL80972A (en) * | 1985-12-20 | 1992-08-18 | Sanofi Sa | Modified ribosome-inactivating glycoproteins,their preparation,immunotoxins containing them and pharmaceutical compositions containing such immunotoxins |
-
1987
- 1987-09-10 US US07/095,178 patent/US4981979A/en not_active Expired - Lifetime
-
1988
- 1988-09-08 AT AT88114682T patent/ATE114479T1/de active
- 1988-09-08 DE DE3852250T patent/DE3852250T2/de not_active Expired - Fee Related
- 1988-09-08 EP EP88114682A patent/EP0306943B1/de not_active Expired - Lifetime
- 1988-09-09 AU AU22095/88A patent/AU622415B2/en not_active Ceased
- 1988-09-09 CA CA000576911A patent/CA1336496C/en not_active Expired - Fee Related
- 1988-09-10 JP JP63225564A patent/JPH01163132A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE3852250T2 (de) | 1995-06-29 |
| DE3852250D1 (de) | 1995-01-12 |
| EP0306943B1 (de) | 1994-11-30 |
| US4981979A (en) | 1991-01-01 |
| EP0306943A3 (en) | 1989-11-15 |
| CA1336496C (en) | 1995-08-01 |
| JPH01163132A (ja) | 1989-06-27 |
| EP0306943A2 (de) | 1989-03-15 |
| AU622415B2 (en) | 1992-04-09 |
| AU2209588A (en) | 1989-03-16 |
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