CA2062047A1 - Fusion proteins for prodrug activation, the preparation and use thereof - Google Patents
Fusion proteins for prodrug activation, the preparation and use thereofInfo
- 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
Links
- 102000037865 fusion proteins Human genes 0.000 title abstract 3
- 108020001507 fusion proteins Proteins 0.000 title abstract 3
- 229940002612 prodrug Drugs 0.000 title abstract 3
- 239000000651 prodrug Substances 0.000 title abstract 3
- 230000004913 activation Effects 0.000 title abstract 2
- 206010028980 Neoplasm Diseases 0.000 abstract 2
- 230000004927 fusion Effects 0.000 abstract 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 abstract 1
- 241000282412 Homo Species 0.000 abstract 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 230000008030 elimination Effects 0.000 abstract 1
- 238000003379 elimination reaction Methods 0.000 abstract 1
- 239000012634 fragment Substances 0.000 abstract 1
- 238000010353 genetic engineering Methods 0.000 abstract 1
- 229940097043 glucuronic acid Drugs 0.000 abstract 1
- 230000004807 localization Effects 0.000 abstract 1
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)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Nanotechnology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Medical Informatics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (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 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.
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)
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)
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 |
DK0795334T3 (en) * | 1996-03-12 | 2006-06-06 | Sanofi Aventis Deutschland | New prodrugs for the treatment of 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 |
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 |
CR20190309A (en) | 2017-01-03 | 2019-08-21 | Hoffmann La Roche | Bispecific antigen binding molecules comprising anti-4-1bb clone 20h4.9 |
Family Cites Families (9)
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 |
DE68928946T2 (en) * | 1989-12-11 | 1999-10-21 | Immunomedics, Inc. | METHOD FOR DETECTING DIAGNOSTIC OR THERAPEUTIC AGENTS BY ANTIBODIES |
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 |
-
1991
- 1991-02-28 DE DE4106389A patent/DE4106389A1/en not_active Withdrawn
-
1992
- 1992-02-10 PT PT92102197T patent/PT501215E/en unknown
- 1992-02-10 DE DE59209839T patent/DE59209839D1/en not_active Expired - Lifetime
- 1992-02-10 EP EP92102197A patent/EP0501215B1/en not_active Expired - Lifetime
- 1992-02-10 DK DK92102197T patent/DK0501215T3/en active
- 1992-02-10 AT AT92102197T patent/ATE193326T1/en active
- 1992-02-10 ES ES92102197T patent/ES2149159T3/en not_active Expired - Lifetime
- 1992-02-26 KR KR1019920002961A patent/KR100249576B1/en not_active IP Right Cessation
- 1992-02-27 IE IE063092A patent/IE920630A1/en not_active IP Right Cessation
- 1992-02-27 AU AU11251/92A patent/AU660445B2/en not_active Expired
- 1992-02-28 CA CA002062047A patent/CA2062047C/en not_active Expired - Lifetime
- 1992-02-28 JP JP07864492A patent/JP3524933B2/en not_active Expired - Lifetime
-
2000
- 2000-06-16 GR GR20000401398T patent/GR3033708T3/en unknown
Cited By (3)
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 |
---|---|
EP0501215A3 (en) | 1993-08-11 |
ATE193326T1 (en) | 2000-06-15 |
JP3524933B2 (en) | 2004-05-10 |
PT501215E (en) | 2000-10-31 |
KR100249576B1 (en) | 2000-03-15 |
DE59209839D1 (en) | 2000-06-29 |
GR3033708T3 (en) | 2000-10-31 |
EP0501215B1 (en) | 2000-05-24 |
CA2062047C (en) | 2007-12-18 |
JPH07179500A (en) | 1995-07-18 |
DK0501215T3 (en) | 2000-09-18 |
DE4106389A1 (en) | 1992-09-03 |
AU1125192A (en) | 1993-01-28 |
AU660445B2 (en) | 1995-06-29 |
ES2149159T3 (en) | 2000-11-01 |
IE920630A1 (en) | 1992-09-09 |
EP0501215A2 (en) | 1992-09-02 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKEX | Expiry |