CA2010164A1 - Anthracycline immunoconjugates having a novel linker and methods for their production - Google Patents
Anthracycline immunoconjugates having a novel linker and methods for their productionInfo
- Publication number
- CA2010164A1 CA2010164A1 CA2010164A CA2010164A CA2010164A1 CA 2010164 A1 CA2010164 A1 CA 2010164A1 CA 2010164 A CA2010164 A CA 2010164A CA 2010164 A CA2010164 A CA 2010164A CA 2010164 A1 CA2010164 A1 CA 2010164A1
- Authority
- CA
- Canada
- Prior art keywords
- immunoconjugates
- anthracycline
- methods
- antibody
- keto
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to novel immuno-conjugates, methods for their production, pharmaceutical compositions and methods for delivering cytotoxic anthracyclines to a selected population of cells desired to be eliminated. More particularly, the invention relates to immunoconjugates comprised of an antibody reactive with a selected cell population, having a number of anthracycline molecules linked to its structure. Each anthracycline molecule, having a keto group at the C-13 position, is conjugated to the antibody via a linker arm and is bound to that linker arm via an acid-sensitive acylhydrazone bond at the 13-keto position of the anthracycline. A preferred embodiment of the invention relates to an adriamycin immunoconjugate wherein a 13-keto acylhydrazone bond is the site of the adriamycin attachment to the linker arm, the linker additionally containing a disulfide or thioether linkage as part of the antibody attachment to the immunoconjugate. In addition, novel anthracycline acylhydrazone derivatives are disclosed that are useful in the preparation of the immunoconjugates of this invention.
The acid-sensitive hydrazone bond of the immunoconjugates of this invention allows the release of free anthracycline from the immunoconjugates in the acidic external or internal environment of the target cell. The immunoconjugates and methods of the invention are therefore useful in antibody-mediated drug delivery systems for the preferential killing of a selected cell population in the treatment of diseases such as cancers and other tumors, non-cytocidal viral or other pathogenic infections, and autoimmune disorders.
The acid-sensitive hydrazone bond of the immunoconjugates of this invention allows the release of free anthracycline from the immunoconjugates in the acidic external or internal environment of the target cell. The immunoconjugates and methods of the invention are therefore useful in antibody-mediated drug delivery systems for the preferential killing of a selected cell population in the treatment of diseases such as cancers and other tumors, non-cytocidal viral or other pathogenic infections, and autoimmune disorders.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15518188A | 1988-02-11 | 1988-02-11 |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2010164A1 true CA2010164A1 (en) | 1991-08-15 |
CA2010164C CA2010164C (en) | 2000-08-29 |
Family
ID=22554403
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002010164A Expired - Lifetime CA2010164C (en) | 1988-02-11 | 1990-02-15 | Anthracycline immunoconjugates having a novel linker and methods for their production |
Country Status (2)
Country | Link |
---|---|
CA (1) | CA2010164C (en) |
ZA (1) | ZA89938B (en) |
-
1989
- 1989-02-07 ZA ZA89938A patent/ZA89938B/en unknown
-
1990
- 1990-02-15 CA CA002010164A patent/CA2010164C/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
ZA89938B (en) | 1989-11-29 |
CA2010164C (en) | 2000-08-29 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKEX | Expiry |