WO1987003205A1 - Anticorps couples a une enzyme - Google Patents

Anticorps couples a une enzyme Download PDF

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Publication number
WO1987003205A1
WO1987003205A1 PCT/GB1986/000711 GB8600711W WO8703205A1 WO 1987003205 A1 WO1987003205 A1 WO 1987003205A1 GB 8600711 W GB8600711 W GB 8600711W WO 8703205 A1 WO8703205 A1 WO 8703205A1
Authority
WO
WIPO (PCT)
Prior art keywords
enzyme
antibody
coupled
antigen
cell
Prior art date
Application number
PCT/GB1986/000711
Other languages
English (en)
Inventor
Selby John Starkie
Original Assignee
Coral Sociedade Brasileira De Pesquisas E Desenvol
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Coral Sociedade Brasileira De Pesquisas E Desenvol filed Critical Coral Sociedade Brasileira De Pesquisas E Desenvol
Publication of WO1987003205A1 publication Critical patent/WO1987003205A1/fr

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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
    • A61K47/6815—Enzymes

Definitions

  • ENZYME-COUPLED ANTIBODIES This invention relates to antibodies and their use in killing specific organisms or tissue cells which carry appropriate antigens. The invention is thus of potential value in therapy.
  • Antibodies bind specifically with appropriate antigens. However, the presence of specific antibodies in body fluids, in vivo, and their binding with antigens of organisms or tissue cells, are not necessarily sufficient to kill the organisms or tissue cell. The primary causes of killing are phagocytosis, macrophages, and lysis by complement. Antibodies bound to antigens on the organism or tissue cell often mediate opsonisation or the activation of complement. The role of antibodies in this respect is incompletely understood, but may be related to the class or subclass of the antibody, the nature and distribution of the antigen, the availability and activation of various kinds of phagocytic and accessory cells and the concentration and nature of the components and inhibitors of complement.
  • WO-A-8303679 discloses "polydomas", i.e. the product of the fusion of a hybrido a with a B-lymphocyte or another hybridoma.
  • the polydomas produce a hybrid monoclonal antibody having dual specificity, e.g. one specificity directed against a target antigen and the other against a moiety which permits a diagnosis to be made or which delivers an agent lethal to the target antigen or associated tissue.
  • enzymes such as alkaline phosphatase and horseradish peroxidase have been coupled to antibodies, and the properties of the enzyme used in order to detect antibody-antigen binding.
  • the substrate of the enzyme should undergo a readily-detectable (e.g. colour) change in the presence of the enzyme.
  • Toxins such as ricin, gelonin or diphtheria toxin may be bound to antibodies.
  • Such toxins are enzymes and result in the death of cells by degradation of components of the protein synthetic mechanisms within the cell. To achieve this effect, the complex of antibody and enzyme requires introduction into the cytoplasm of the cell, usually by a mechanism of the cell itself characteristic of a fluid cell membrane. In general, organisms with non-fluid cell walls do not internalise complex molecules of this kind, so that toxin-conjugated antibodies would not kill some organisms.
  • the enzyme has the ability to catalyse degradative or synthetic reactions which result in the death of the cell.
  • the present invention is based on the concept that an enzyme attached to an antibody is brought into close proximity with the cell when the antibody binds with the antigen on the cell.
  • the substrate of the enzyme is a substance close to, or part of, the cell or the antigen, or the fluid around the cell or the antigen.
  • the antibody need not have been produced from a polydoma, but can retain a single specificity.
  • Suitable enzymes are lipases, phospholipases, proteases and glycases, substrates for which might be lipids, phospholipids, proteins, sugars and glycoproteins in the cell walls.
  • Glucose oxidase is an example of an enzyme which has a natural plasma substrate, glucose; one of the products of glucose oxidation is hydrogen peroxide which can kill cells by oxidation of components of the cell wall.
  • complement Many of the components of complement are enzymes. When some forms of antibody bind with some forms of antigen, the enzymatic components of complement are activated in a cascade, i.e. each activated component catalyses the activation of the next component.
  • the classical pathway of complement activation is initiated by the activation of the first components by antibody bound to an antigen, but not by a free antibody.
  • the concept of the present invention is that the enzyme is irreversibly bound to the antibody.
  • an enzyme- coupled antibody according to the invention can be used therapeutically.
  • an enzyme selected to kill the cell can be coupled to an antibody, e.g. a monoclonal antibody, specific to an antigen of the organism or cell, and the coupled product administered to the subject.
  • Coupling can be by any convenient, conventional method, e.g. the glutaraldehyde or the SPDP method.
  • Administration may also be by any suitable conventional method, e.g. inoculation; for inoculation, a conventional composition may be formulated which comprises the product and a physiologically- acceptable excipient.
  • a monoclonal antibody against Shigella as described in Example 1 of WO-A-8600646 is coupled, not with alkaline phosphatase as described in section G therein, but with glucose oxidase.
  • Administration of the enzyme-coupled antibody into plasma containing the antigen leads to (i) antibody-antigen reaction and thus the proximity of enzyme and antigen-bearing cell, and (ii) the local production of cell-toxic hydrogen peroxide by enzymatic oxidation of glucose in the plasma.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Un anticorps couplé à une enzyme comprend une enzyme, par exemple couplée à un anticorps monoclonal, pouvant catalyser les réactions se traduisant par la mort de cellules portant des sites antigéniques sur lesquels l'anticorps peut se fixer. De tels produits présentent un intérêt thérapeutique.
PCT/GB1986/000711 1985-11-22 1986-11-21 Anticorps couples a une enzyme WO1987003205A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB8528761 1985-11-22
GB858528761A GB8528761D0 (en) 1985-11-22 1985-11-22 Enzyme-coupled antibodies

Publications (1)

Publication Number Publication Date
WO1987003205A1 true WO1987003205A1 (fr) 1987-06-04

Family

ID=10588603

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1986/000711 WO1987003205A1 (fr) 1985-11-22 1986-11-21 Anticorps couples a une enzyme

Country Status (3)

Country Link
EP (1) EP0250477A1 (fr)
GB (1) GB8528761D0 (fr)
WO (1) WO1987003205A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0302473A2 (fr) * 1987-08-04 1989-02-08 Bristol-Myers Squibb Company Conjugues anticorps-enzyme associés à des prodrogues pour la libération d'agents cytotoxyques dans les cellules tumorales
EP0361908A2 (fr) * 1988-09-28 1990-04-04 Ideon Corporation Immunothérapie à base d'une combinaison d'enzymes
FR2643267A1 (fr) * 1989-02-23 1990-08-24 Centre Nat Rech Scient Compositions a proprietes cytolytiques specifiques vis-a-vis de cellules cibles appropriees et leurs applications
US4975278A (en) * 1988-02-26 1990-12-04 Bristol-Myers Company Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells
WO1991000108A1 (fr) * 1989-06-30 1991-01-10 Brunswick Corporation Conjugues d'anticorps-oxydase a substrats non systemiques
WO1991009134A1 (fr) * 1989-12-15 1991-06-27 Takeda Chemical Industries, Ltd. Anticorps biospecifique des cellules cancereuses et enzyme presentant des caracteristiques d'activation promedicamenteuse
WO1991011201A2 (fr) * 1990-01-24 1991-08-08 Imperial Cancer Research Technology Limited Composes
WO1996025952A1 (fr) * 1995-02-22 1996-08-29 The Secretary Of State For Defence Compositions pharmaceutiques et dosages utilisant des sous-unites enzymatiques
US5632990A (en) * 1988-04-22 1997-05-27 Cancer Research Campaign Tech. Ltd. Treatment for tumors comprising conjugated antibody A5B7 and a prodrug
US5716990A (en) * 1987-03-09 1998-02-10 Cancer Research Campaign Technology Limited Drug delivery systems
US5759774A (en) * 1988-05-18 1998-06-02 Cobe Laboratories, Inc. Method of detecting circulating antibody types using dried or lyophilized cells
WO1999018999A1 (fr) * 1997-10-16 1999-04-22 Pharmacal Biotechnologies, Inc. Compositions permettant de reguler la colonisation bacterienne
NL1009834C2 (nl) * 1998-08-10 2000-02-11 Stanislaus Laurens Johan Woute Antistoffen voor toepassing in de gerichte en tijdelijke behandeling van mens en dier.
WO2000076453A2 (fr) * 1999-06-16 2000-12-21 Ks Biomedix Ltd. Mort cellulaire assistee par emzymes

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1168150A (fr) * 1981-12-18 1984-05-29 The Governors Of The University Of Alberta Conjugats d'albumine et d'agents therapeutiques
FR2543969A1 (fr) * 1983-04-08 1984-10-12 Kureha Chemical Ind Co Ltd Anticorps dirige contre les champignons du genre candida, hybridome et procede pour la preparation de cet anticorps, procede d'identification et/ou de classification des champignons du genre candida utilisant cet anticorps ou un de ses derives ou produits de restriction et medicament contre les candidoses contenant cet anticorps ou ses derives
WO1986000646A1 (fr) * 1984-07-03 1986-01-30 Technology Licence Company Limited Anticorps monoclonaux et leur utilisation

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1168150A (fr) * 1981-12-18 1984-05-29 The Governors Of The University Of Alberta Conjugats d'albumine et d'agents therapeutiques
FR2543969A1 (fr) * 1983-04-08 1984-10-12 Kureha Chemical Ind Co Ltd Anticorps dirige contre les champignons du genre candida, hybridome et procede pour la preparation de cet anticorps, procede d'identification et/ou de classification des champignons du genre candida utilisant cet anticorps ou un de ses derives ou produits de restriction et medicament contre les candidoses contenant cet anticorps ou ses derives
WO1986000646A1 (fr) * 1984-07-03 1986-01-30 Technology Licence Company Limited Anticorps monoclonaux et leur utilisation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Biological Abstracts, Volume 80, No. 6, 1985, R.B. LAL et al.: "Selective Elimination of Lymphocyte Subpopulations by Monoclonal Antibody-Enzyme Conjugates" see page 438, Abstract 49774, & J. Immunol. Methods 79(2): 307-318, May 1985 *
CHEMICAL ABSTRACTS, Volume 79, No. 21, 26 November 1973, (Columbus, Ohio, US), T.J. SULLIVAN et al.: "Specific Killing of Parasites by Antibody-Enzyme Conjugates", see Abstract No. 124533b, & Res. Commun. Chem. Pathol. Pharmacol. 1973, 6(2), 709-17 *

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5716990A (en) * 1987-03-09 1998-02-10 Cancer Research Campaign Technology Limited Drug delivery systems
EP0302473A3 (en) * 1987-08-04 1990-01-17 Bristol-Myers Company Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells
EP0302473A2 (fr) * 1987-08-04 1989-02-08 Bristol-Myers Squibb Company Conjugues anticorps-enzyme associés à des prodrogues pour la libération d'agents cytotoxyques dans les cellules tumorales
AU614532B2 (en) * 1987-08-04 1991-09-05 Bristol-Myers Squibb Company Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells
US4975278A (en) * 1988-02-26 1990-12-04 Bristol-Myers Company Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells
US5683694A (en) * 1988-04-22 1997-11-04 Cancer Research Campaign Tech. Ltd. & Zeneca Ltd. Method for the treatment of tumors with conjugated antibody A5B7 and a prodrug
US5632990A (en) * 1988-04-22 1997-05-27 Cancer Research Campaign Tech. Ltd. Treatment for tumors comprising conjugated antibody A5B7 and a prodrug
US5759774A (en) * 1988-05-18 1998-06-02 Cobe Laboratories, Inc. Method of detecting circulating antibody types using dried or lyophilized cells
EP0361908A2 (fr) * 1988-09-28 1990-04-04 Ideon Corporation Immunothérapie à base d'une combinaison d'enzymes
EP0361908A3 (fr) * 1988-09-28 1990-09-05 Ideon Corporation Immunothérapie à base d'une combinaison d'enzymes
EP0396434A1 (fr) * 1989-02-23 1990-11-07 Ideon Corporation Compositions à propriétés cytolytiques specifiques vis-à-vis de cellules cibles appropriées et leurs applications
WO1990009803A1 (fr) * 1989-02-23 1990-09-07 Ideon Corporation Compositions a proprietes cytolytiques specifiques vis-a-vis de cellules cibles appropriees et leurs applications
FR2643267A1 (fr) * 1989-02-23 1990-08-24 Centre Nat Rech Scient Compositions a proprietes cytolytiques specifiques vis-a-vis de cellules cibles appropriees et leurs applications
WO1991000108A1 (fr) * 1989-06-30 1991-01-10 Brunswick Corporation Conjugues d'anticorps-oxydase a substrats non systemiques
WO1991009134A1 (fr) * 1989-12-15 1991-06-27 Takeda Chemical Industries, Ltd. Anticorps biospecifique des cellules cancereuses et enzyme presentant des caracteristiques d'activation promedicamenteuse
GB2256198B (en) * 1990-01-24 1994-01-12 Imp Cancer Res Tech Enzymatically-active compound having a portion able to target a cell
GB2256198A (en) * 1990-01-24 1992-12-02 Imp Cancer Res Tech Compounds
WO1991011201A3 (fr) * 1990-01-24 1991-09-05 Imp Cancer Res Tech Composes
WO1991011201A2 (fr) * 1990-01-24 1991-08-08 Imperial Cancer Research Technology Limited Composes
WO1996025952A1 (fr) * 1995-02-22 1996-08-29 The Secretary Of State For Defence Compositions pharmaceutiques et dosages utilisant des sous-unites enzymatiques
US6472365B1 (en) 1995-02-22 2002-10-29 Biovation Limited Pharmaceuticals and assays using enzyme subunits
US6974699B2 (en) 1995-02-22 2005-12-13 Biovation Limited Pharmaceuticals and assays using enzyme subunits
WO1999018999A1 (fr) * 1997-10-16 1999-04-22 Pharmacal Biotechnologies, Inc. Compositions permettant de reguler la colonisation bacterienne
NL1009834C2 (nl) * 1998-08-10 2000-02-11 Stanislaus Laurens Johan Woute Antistoffen voor toepassing in de gerichte en tijdelijke behandeling van mens en dier.
WO2000009164A1 (fr) * 1998-08-10 2000-02-24 Wouters Stanislaus Laurens Joh Anticorps utilises dans des traitements cibles et temporaires de sujets humains et animaux
US7288247B2 (en) 1998-08-10 2007-10-30 Wouters Stanislaus Laurens Joh Antibodies for use in targeted and temporary treatment of humans and animals
WO2000076453A2 (fr) * 1999-06-16 2000-12-21 Ks Biomedix Ltd. Mort cellulaire assistee par emzymes
WO2000076453A3 (fr) * 1999-06-16 2001-08-02 Ks Biomedix Ltd Mort cellulaire assistee par emzymes

Also Published As

Publication number Publication date
EP0250477A1 (fr) 1988-01-07
GB8528761D0 (en) 1985-12-24

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