CA2010164A1 - Anthracycline immunoconjugates having a novel linker and methods for their production - Google Patents

Anthracycline immunoconjugates having a novel linker and methods for their production

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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
Application number
CA2010164A
Other languages
French (fr)
Other versions
CA2010164C (en
Inventor
Robert S. Greenfield
Gary R. Braslawsky
Lee J. Olech
Takushi Kaneko
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.)
Bristol Myers Squibb Co
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of CA2010164A1 publication Critical patent/CA2010164A1/en
Application granted granted Critical
Publication of CA2010164C publication Critical patent/CA2010164C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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  • 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.
CA002010164A 1988-02-11 1990-02-15 Anthracycline immunoconjugates having a novel linker and methods for their production Expired - Lifetime CA2010164C (en)

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)

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