CA2062047A1 - Fusion proteins for prodrug activation, the preparation and use thereof - Google Patents

Fusion proteins for prodrug activation, the preparation and use thereof

Info

Publication number
CA2062047A1
CA2062047A1 CA002062047A CA2062047A CA2062047A1 CA 2062047 A1 CA2062047 A1 CA 2062047A1 CA 002062047 A CA002062047 A CA 002062047A CA 2062047 A CA2062047 A CA 2062047A CA 2062047 A1 CA2062047 A1 CA 2062047A1
Authority
CA
Canada
Prior art keywords
beta
hutumab
gluc
fusion proteins
human
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.)
Granted
Application number
CA002062047A
Other languages
French (fr)
Other versions
CA2062047C (en
Inventor
Gerhard Seemann
Klaus Bosslet
Joerg Czech
Cenek Kolar
Dieter Hoffman
Hans-Harald Sedlacek
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Siemens Healthcare Diagnostics GmbH Germany
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of CA2062047A1 publication Critical patent/CA2062047A1/en
Application granted granted Critical
Publication of CA2062047C publication Critical patent/CA2062047C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], 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)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Public Health (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biotechnology (AREA)
  • Epidemiology (AREA)
  • Nanotechnology (AREA)
  • Cell Biology (AREA)
  • Biophysics (AREA)
  • Medical Informatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • General Chemical & Material Sciences (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 humanized or human tumor-specific monoclonal antibody or a fragment thereof, L is linker, and .beta.-Gluc comprises human .beta.-glucuronidase. These fusion proteins are prepared by genetic manipulation. huTuMAb ensures the specific localization of tumors, L connects huTuMAb to .beta.-Gluc in such a way that the specific properties of the two fusion partners are not imparied, and .beta.-Gluc activates a suitable prodrug compound by elimination of glucuronic acid, where a virtually autologous system for use in humans is provided by the humanized or human fusion partners.
CA002062047A 1991-02-28 1992-02-28 Fusion proteins for prodrug activation, the preparation and use thereof Expired - Lifetime CA2062047C (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP4106389.9 1991-02-28
DE4106389A DE4106389A1 (en) 1991-02-28 1991-02-28 FUSION PROTEINS FOR PRODRUG ACTIVATION, THEIR PRODUCTION AND USE

Publications (2)

Publication Number Publication Date
CA2062047A1 true CA2062047A1 (en) 1992-08-29
CA2062047C CA2062047C (en) 2007-12-18

Family

ID=6426148

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002062047A Expired - Lifetime CA2062047C (en) 1991-02-28 1992-02-28 Fusion proteins for prodrug activation, the preparation and use thereof

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)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7060495B2 (en) 1992-10-02 2006-06-13 Behrinwerke Aktienegesellschaft Fusion proteins for prodrug activation
US8552159B2 (en) * 1993-05-04 2013-10-08 Behringwerke Aktiengesellschaft Bifunctional glycoproteins having a modified carbohydrate complement and their use in tumor-selective therapy

Families Citing this family (11)

* 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
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
EP0795334B1 (en) * 1996-03-12 2006-02-01 Sanofi-Aventis Deutschland GmbH Prodrugs for the treatment tumors and inflammatory diseases
GB9709421D0 (en) * 1997-05-10 1997-07-02 Zeneca Ltd Chemical compounds
ATE499115T1 (en) * 1998-09-18 2011-03-15 Immunomedics Inc ANTIBODIES REFERRED ENZYME PRODRUG THERAPY WITH GLUCURONIDASE
US6361774B1 (en) 1999-09-17 2002-03-26 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
WO2005000902A1 (en) * 2003-06-30 2005-01-06 Mu-Hyeon Choe The dimer of chimeric recombinant binding domain-functional group fusion formed via disulfide-bond-bridge and the processes for producing the same
WO2018127473A1 (en) 2017-01-03 2018-07-12 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
JP3273608B2 (en) * 1989-01-23 2002-04-08 アクゾ・エヌ・ヴエー Site-specific in vivo activation of therapeutic agents
DE3909799A1 (en) * 1989-03-24 1990-09-27 Behringwerke Ag MONOCLONAL ANTIBODIES (MAK) AGAINST TUMOR ASSOCIATED ANTIGENS, THEIR PRODUCTION AND USE
WO1991008770A1 (en) * 1989-12-11 1991-06-27 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

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7060495B2 (en) 1992-10-02 2006-06-13 Behrinwerke Aktienegesellschaft Fusion proteins for prodrug activation
US7273727B2 (en) 1992-10-02 2007-09-25 Behrinwerke Aktiengesellschaft Fusion proteins for prodrug activation
US8552159B2 (en) * 1993-05-04 2013-10-08 Behringwerke Aktiengesellschaft Bifunctional glycoproteins having a modified carbohydrate complement and their use in tumor-selective therapy

Also Published As

Publication number Publication date
AU1125192A (en) 1993-01-28
PT501215E (en) 2000-10-31
CA2062047C (en) 2007-12-18
DE4106389A1 (en) 1992-09-03
EP0501215B1 (en) 2000-05-24
GR3033708T3 (en) 2000-10-31
EP0501215A2 (en) 1992-09-02
AU660445B2 (en) 1995-06-29
ES2149159T3 (en) 2000-11-01
KR100249576B1 (en) 2000-03-15
ATE193326T1 (en) 2000-06-15
DE59209839D1 (en) 2000-06-29
IE920630A1 (en) 1992-09-09
DK0501215T3 (en) 2000-09-18
JPH07179500A (en) 1995-07-18
JP3524933B2 (en) 2004-05-10
EP0501215A3 (en) 1993-08-11

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