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HK1005330A1 - Further improvements relating to drug delivery systems - Google Patents

Further improvements relating to drug delivery systems Download PDF

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Publication number
HK1005330A1
HK1005330A1 HK98104472A HK98104472A HK1005330A1 HK 1005330 A1 HK1005330 A1 HK 1005330A1 HK 98104472 A HK98104472 A HK 98104472A HK 98104472 A HK98104472 A HK 98104472A HK 1005330 A1 HK1005330 A1 HK 1005330A1
Authority
HK
Hong Kong
Prior art keywords
antibody
conjugate
enzyme
carboxypeptidase
hours
Prior art date
Application number
HK98104472A
Other languages
English (en)
French (fr)
Chinese (zh)
Other versions
HK1005330B (en
Inventor
D. Bagshawe Kenneth
T. Rogers Gordon
Sharma Surinder
Original Assignee
Cancer Research Technology Limited
Zeneca Limited
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 Cancer Research Technology Limited, Zeneca Limited filed Critical Cancer Research Technology Limited
Publication of HK1005330A1 publication Critical patent/HK1005330A1/en
Publication of HK1005330B publication Critical patent/HK1005330B/en

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • A61K47/6893—Pre-targeting systems involving an antibody for targeting specific cells clearing therapy or enhanced clearance, i.e. using an antibody clearing agents in addition to T-A and D-M
    • 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
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • A61K47/6897—Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies
    • A61K47/6898—Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies using avidin- or biotin-conjugated antibodies
    • 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
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • A61K47/6899—Antibody-Directed Enzyme Prodrug Therapy [ADEPT]
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3007—Carcino-embryonic Antigens
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Cell Biology (AREA)
  • Nanotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Engineering & Computer Science (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Endocrinology (AREA)
  • Medical Informatics (AREA)
  • Oncology (AREA)
  • Biotechnology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Peptides Or Proteins (AREA)

Claims (13)

  1. Konjugat, umfassend:
    (a) einen Antikörper, ausgewählt aus dem Antikörper A5B7 und dem Antikörper SB10; gebunden an
    (b) ein Enzym, ausgewählt aus Carboxypeptidase G2 (CPG2) und Nitroreduktase.
  2. Konjugat nach Anspruch 1, umfassend den A5B7-Antikörper, gebunden an das Carboxypeptidase-G2-Enzym.
  3. Konjugat nach Anspruch 1 oder Anspruch 2, dadurch gekennzeichnet, daß dem Antikörper ein Fc-Teil fehlt.
  4. Konjugat nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, daß der Antikörper eine F(ab')2-Struktur hat.
  5. Konjugat nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, daß der Antikörper an das Enzym über eine ununterbrochene Peptidbindung gebunden ist.
  6. Konjugat nach einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, daß der Antikörper humanisiert ist.
  7. Konjugat nach Anspruch 4, erhältlich durch Mischen eines Maleimidderivats des Enzyms mit thioliertem Antikörper A5B7-F(ab')2.
  8. Konjugat nach Anspruch 4, erhältlich durch:
    (i) Thiolierung des Antikörpers A5B7-F(ab')2 mit S-Acetylthioglykolsäure-N-hydroxysuccinimidester (SATA);
    (ii) Derivatisierung der Carboxypeptidase G2 mit Succinimidyl-4-(p-maleimidophenyl)butyrat (SMPB);
    (iii) Zusammenmischen der Produkte von (i) und (ii), um ein Konjugat zu bilden; und
    (iv) gegebenenfalls Reinigen des Konjugats.
  9. Zweikomponentensystem, umfassend:
    i) ein Konjugat, wie in einem der Ansprüche 1 bis 8 definiert; und
    ii) ein Prodrug, das unter dem Einfluß des Konjugats in ein cytotoxisches Medikament umwandelbar ist.
  10. Zweikomponentensystem, umfassend:
    i) ein Konjugat, wie in einem der Ansprüche 1 bis 8 definiert; und
    ii) ein N-Lost-Prodrug, welches unter dem Einfluß des Konjugats in ein cytotoxisches Medikament umwandelbar ist.
  11. Konjugat, wie in einem der Ansprüche 1 bis 8 definiert, zur Verwendung in einem Verfahren zur Behandlung des menschlichen oder tierischen Körpers mittels Therapie.
  12. Konjugat wie in Anspruch 11 definiert, zur Verwendung in einem Verfahren zur Behandlung einer malignen Erkrankung.
  13. Pharmazeutisches Mittel, umfassend ein wie in einem der Ansprüche 1 bis 8 definiertes Konjugat.
HK98104472.2A 1988-04-22 1998-05-23 Further improvements relating to drug delivery systems HK1005330B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB888809616A GB8809616D0 (en) 1988-04-22 1988-04-22 Further improvements relating to drug delivery systems
GB8809616 1988-04-22

Publications (2)

Publication Number Publication Date
HK1005330A1 true HK1005330A1 (en) 1998-12-31
HK1005330B HK1005330B (en) 1998-12-31

Family

ID=

Also Published As

Publication number Publication date
EP0633029B1 (de) 1997-11-26
EP0414741B1 (de) 1995-03-15
EP0633029A3 (de) 1995-02-01
JP2733353B2 (ja) 1998-03-30
EP0633029A2 (de) 1995-01-11
CA1336166C (en) 1995-07-04
JPH07324041A (ja) 1995-12-12
DE68921749T2 (de) 1995-07-13
EP0414741A1 (de) 1991-03-06
DE68928466T2 (de) 1998-03-19
ATE160506T1 (de) 1997-12-15
JP2726635B2 (ja) 1998-03-11
ATE119782T1 (de) 1995-04-15
DE68928466D1 (de) 1998-01-08
GB8809616D0 (en) 1988-05-25
JPH03503898A (ja) 1991-08-29
WO1989010140A1 (en) 1989-11-02
DE68921749D1 (de) 1995-04-20

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Legal Events

Date Code Title Description
PC Patent ceased (i.e. patent has lapsed due to the failure to pay the renewal fee)

Effective date: 20040421

PC Patent ceased (i.e. patent has lapsed due to the failure to pay the renewal fee)