Specific antibody drug conjugates (ADCs) having KSP inhibitors

Patent metadata

Field	Value
Publication number	US-11433140-B2
Application number	US-201716472682-A
Country	US
Kind code	B2
Filing date	Dec 18, 2017
Priority date	Dec 21, 2016
Publication date	Sep 6, 2022
Grant date	Sep 6, 2022

Abstract

Specific binder-drug conjugates (ADCs) of kinesin spindle protein inhibitors, effective metabolites of these ADCs, processes for preparing these ADCs, the use of these ADCs for the treatment and/or prevention of diseases and to the use of these ADCs for preparing medicaments for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases, are described.

First claim

The invention claimed is:

1. An antibody-drug conjugate (ADC) of formula (I):

or a salt, a solvate, or a salt of the solvate thereof;
wherein:
n is 1 to 8;
AK is an anti-CD123 antibody comprising a variable region of the heavy chain (VH) comprising the variable CDR1 sequence of the heavy chain (H-CDR1), as shown by SEQ ID NO: 12, the variable CDR2 sequence of the heavy chain (H CDR2), as shown by SEQ ID NO: 13 and the variable CDR3 sequence of the heavy chain (H-CDR3), as shown by SEQ ID NO: 14, and a variable region of the light chain (VL) comprising the variable CDR1 sequence of the light chain (L CDR1), as shown by SEQ ID NO: 16, the variable CDR2 sequence of the light chain (L-CDR2), as shown by SEQ ID NO: 17 and the variable CDR3 sequence of the light chain (L-CDR3), as shown by SEQ ID NO: 18, or is an antigen-binding fragment thereof, wherein the antibody or the antigen-binding fragment thereof is attached via a sulfur atom of a cysteine side group.

2. The antibody-drug conjugate according to claim 1 , or a salt, a solvate, or a salt of the solvate thereof, wherein n is 2 to 8.

3. The antibody-drug conjugate according to claim 1 , or a salt, a solvate or a salt of the solvate thereof wherein n is 4 to 8.

4. The antibody-drug conjugate according to claim 1 , or a salt, a solvate, or a salt of the solvate thereof, wherein AK is an anti-CD123 antibody comprising a variable region of the heavy chain (VH) as shown in SEQ ID NO: 11 and a variable region of the light chain (VL) as shown in SEQ ID NO: 15, or is an antigen-binding fragment thereof.

5. The antibody-drug conjugate according to claim 1 , or a salt, a solvate, or a salt of the solvate thereof, wherein AK is an anti-CD123 antibody comprising a region of the heavy chain as shown in SEQ ID NO: 19 and a region of the light chain as shown in SEQ ID NO: 20, or is an antigen-binding fragment thereof.

6. A pharmaceutical composition comprising at least one antibody-drug conjugate (ADC) according to claim 1 , or a salt, a solvate, or a salt of the solvate thereof, in combination with an inert, non-toxic, pharmaceutically suitable auxiliary.

7. A method for treatment of hyperproliferative and/or angiogenic disorders which overexpress CD123 or CXCR5, comprising administering to a patient in need thereof an effective amount of an antibody-drug conjugate according to claim 1 , or a salt, a solvate, or a salt of the solvate thereof.

8. A method for treatment of cancer and tumours which overexpress CD123 or CXCR5, comprising administering to a human in need thereof an effective amount of an antibody-drug conjugate according to claim 1 , or a salt, a solvate, or a salt of the solvate thereof.

9. A method for treatment of cancer and tumours which overexpress CD123 or CXCR5, comprising administering to a human in need thereof an effective amount of an antibody-drug conjugate according to claim 1 , or a salt, a solvate, or a salt of the solvate thereof, in combination with one or more therapeutic approaches for cancer immunotherapy or with one or more active compounds directed against a molecular target of cancer immunotherapy.

Assignees

• Bayer Pharma AG

Inventors

• Lerchen Hans-Georg
• Rebstock Anne-Sophie
• Stelte-Ludwig Beatrix
• Kirchhoff Dennis
• Berndt Sandra
• Dietz Lisa
• Märsch Stephan
• Hammer Stefanie

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6889

  Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment · CPC title