DK0501215T3 - Fusion proteins containing monoclonal antibody, linker and beta-glucuronidase for pro-drug activation, their preparation - Google Patents

Fusion proteins containing monoclonal antibody, linker and beta-glucuronidase for pro-drug activation, their preparation

Info

Publication number
DK0501215T3
DK0501215T3 DK92102197T DK92102197T DK0501215T3 DK 0501215 T3 DK0501215 T3 DK 0501215T3 DK 92102197 T DK92102197 T DK 92102197T DK 92102197 T DK92102197 T DK 92102197T DK 0501215 T3 DK0501215 T3 DK 0501215T3
Authority
DK
Denmark
Prior art keywords
beta
hutumab
gluc
fusion proteins
glucuronidase
Prior art date
Application number
DK92102197T
Other languages
Danish (da)
Inventor
Gerhard Seemann
Klaus Bosslet
Joerg Czech
Cenek Kolar
Dieter Hoffmann
Hans-Harald Sedlacek
Original Assignee
Hoechst Ag
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 Hoechst Ag filed Critical Hoechst Ag
Application granted granted Critical
Publication of DK0501215T3 publication Critical patent/DK0501215T3/en

Links

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
    • A61K47/6835—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
    • A61K47/6851—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 determinant of a tumour cell
    • 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
    • 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
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2405—Glucanases
    • C12N9/2434—Glucanases acting on beta-1,4-glucosidic bonds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01031—Beta-glucuronidase (3.2.1.31)
    • 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
    • C07K2319/00—Fusion polypeptide

Landscapes

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

Abstract

The invention relates to fusion proteins for prodrug activation of the general formula huTuMAb-L- beta -gluc, where huTuMAb is a humanised or human tumour-specific monoclonal antibody or a fragment thereof, L is a linker and beta -gluc comprises human beta -glucuronidase. These fusion proteins are prepared by genetic manipulation. huTuMAb ensures specific location of tumours, L connects huTuMAb to beta -gluc in a way which does not hinder the specific properties of the two fusion partners, and beta -gluc activates a suitable prodrug compound by elimination of glucuronic acid, and owing to the humanised or human fusion partner a virtually autologous system is available for use in humans.
DK92102197T 1991-02-28 1992-02-10 Fusion proteins containing monoclonal antibody, linker and beta-glucuronidase for pro-drug activation, their preparation DK0501215T3 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE4106389A DE4106389A1 (en) 1991-02-28 1991-02-28 FUSION PROTEINS FOR PRODRUG ACTIVATION, THEIR PRODUCTION AND USE

Publications (1)

Publication Number Publication Date
DK0501215T3 true DK0501215T3 (en) 2000-09-18

Family

ID=6426148

Family Applications (1)

Application Number Title Priority Date Filing Date
DK92102197T DK0501215T3 (en) 1991-02-28 1992-02-10 Fusion proteins containing monoclonal antibody, linker and beta-glucuronidase for pro-drug activation, their preparation

Country Status (12)

Country Link
EP (1) EP0501215B1 (en)
JP (1) JP3524933B2 (en)
KR (1) KR100249576B1 (en)
AT (1) ATE193326T1 (en)
AU (1) AU660445B2 (en)
CA (1) CA2062047C (en)
DE (2) DE4106389A1 (en)
DK (1) DK0501215T3 (en)
ES (1) ES2149159T3 (en)
GR (1) GR3033708T3 (en)
IE (1) IE920630A1 (en)
PT (1) PT501215E (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4225853A1 (en) * 1992-08-05 1994-02-10 Behringwerke Ag Granulocyte-binding antibody fragments, their production and use
DE4233152A1 (en) 1992-10-02 1994-04-07 Behringwerke Ag Antibody-enzyme conjugates for prodrug activation
DE4314556A1 (en) 1993-05-04 1994-11-10 Behringwerke Ag Modified antibody-enzyme conjugates and fusion proteins and their use in tumor-selective therapy
EP0647450A1 (en) * 1993-09-09 1995-04-12 BEHRINGWERKE Aktiengesellschaft Improved prodrugs for enzyme mediated activation
GB9324807D0 (en) * 1993-12-03 1994-01-19 Cancer Res Campaign Tech Tumour antibody
DE19513676A1 (en) 1995-04-11 1996-10-17 Behringwerke Ag Cytoplasmic expression of antibodies, antibody fragments and antibody fragment fusion molecules in E. coli
ATE316799T1 (en) * 1996-03-12 2006-02-15 Sanofi Aventis Deutschland NOVEL PRODRUGS FOR THE THERAPY OF TUMORS AND INFLAMMATORY DISEASES
GB9709421D0 (en) * 1997-05-10 1997-07-02 Zeneca Ltd Chemical compounds
US6361774B1 (en) 1999-09-17 2002-03-26 Immunomedics, Inc. Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug
AU763628B2 (en) * 1998-09-18 2003-07-31 Immunomedics Inc. Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug
US7232888B2 (en) 2002-07-01 2007-06-19 Massachusetts Institute Of Technology Antibodies against tumor surface antigens
US7834258B2 (en) * 2003-06-30 2010-11-16 Mu-Hyeon Choe Dimer of chimeric recombinant binding domain-functional group fusion formed via disulfide-bond-bridge and the processes for producing the same
AU2018206138A1 (en) 2017-01-03 2019-07-11 F. Hoffmann-La Roche Ag Bispecific antigen binding molecules comprising anti-4-1BB clone 20H4.9

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT80662B (en) * 1984-06-20 1986-12-09 Sanofi Sa Process to obtain anti-tumoral glycoprotein modified on its glycidic portions
FR2591895B1 (en) * 1985-12-20 1988-08-26 Sanofi Sa LONG-LASTING IN VIVO IMMUNOTOXINS HAVING MODIFIED RICIN A CHAIN ON ITS POLYSACCHARIDE PATTERNS
GB8705477D0 (en) * 1987-03-09 1987-04-15 Carlton Med Prod Drug delivery systems
NZ225599A (en) * 1987-08-04 1991-09-25 Bristol Myers Co Antibody-enzyme conjugates and combinations with prodrugs for the treatment of tumour cells
DE3825615A1 (en) * 1988-07-28 1990-02-01 Behringwerke Ag ANTIGENT CONSTRUCTS OF "MAJOR HISTOCOMPATIBILITY COMPLEX" CLASS I ANTIGENS WITH SPECIFIC CARRIER MOLECULES, THEIR PRODUCTION AND USE
EP0454783B1 (en) * 1989-01-23 1995-06-07 Akzo Nobel N.V. Site specific in-vivo activation of therapeutic drugs
DE3909799A1 (en) * 1989-03-24 1990-09-27 Behringwerke Ag MONOCLONAL ANTIBODIES (MAK) AGAINST TUMOR ASSOCIATED ANTIGENS, THEIR PRODUCTION AND USE
AU649952B2 (en) * 1989-12-11 1994-06-09 Immunomedics Inc. Method for antibody targeting of diagnostic or therapeutic agents
DE4002888A1 (en) * 1990-02-01 1991-08-08 Behringwerke Ag ANTHRACYCLIN-GLYCOSYL PRODRUGS, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE IN COMBINATION WITH FUNCTIONALIZED TUMOR-SPECIFIC ENZYME CONJUGATES

Also Published As

Publication number Publication date
ATE193326T1 (en) 2000-06-15
JPH07179500A (en) 1995-07-18
AU1125192A (en) 1993-01-28
ES2149159T3 (en) 2000-11-01
JP3524933B2 (en) 2004-05-10
EP0501215A2 (en) 1992-09-02
AU660445B2 (en) 1995-06-29
GR3033708T3 (en) 2000-10-31
CA2062047C (en) 2007-12-18
EP0501215B1 (en) 2000-05-24
EP0501215A3 (en) 1993-08-11
DE59209839D1 (en) 2000-06-29
PT501215E (en) 2000-10-31
DE4106389A1 (en) 1992-09-03
KR100249576B1 (en) 2000-03-15
IE920630A1 (en) 1992-09-09
CA2062047A1 (en) 1992-08-29

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