Binder-drug conjugates (ADCs) and use thereof
View Patent ↗The present application relates to new binder-drug conjugates (ADCs) of N,N-dialkylauristatins that are directed against the target C4.4a, to active metabolites of these ADCs, to processes for preparing these ADCs, to the use of these ADCs for treating and/or preventing illnesses, and also to the use of these ADCs for producing medicaments for treating and/or preventing illnesses, more particularly hyperproliferative and/or angiogenic diseases such as, for example, cancer diseases. Such treatments may be practiced as a monotherapy or else in combination with other medicaments or further therapeutic measures.
1. A binder-drug conjugate having the structure:
or a salt thereof, in which
n is a number from 1 to 20,
and
AK 1 is a human or humanized antibody or an antigen-binding antibody fragment which binds to C4.4a and is bonded via a cysteine residue to the toxophor-linker unit.
2. The binder-drug conjugate of claim 1 , wherein n is a number from 1 to 10.
3. The binder-drug conjugate of claim 1 , wherein n is a number from 2 to 8.
4. The binder-drug conjugate of claim 1 , wherein the antibody or antigen-binding antibody fragment comprises three heavy chain CDR regions comprising the amino acid sequences of SEQ ID NOs: 45-47 and three light chain CDR regions comprising the amino acid sequences of SEQ ID NOs: 48-50.
5. The binder-drug conjugate of claim 1 , wherein the antibody or antigen-binding antibody fragment comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 51 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 52.
6. The binder-drug conjugate of claim 1 , wherein AK 1 is an antibody comprising a heavy chain and a light chain, the heavy chain comprising the amino acid sequence of SEQ ID NO: 353 and the light chain comprising the amino acid sequence of SEQ ID NO: 352.
7. The binder-drug conjugate of claim 3 , wherein the antibody or antigen-binding antibody fragment comprises three heavy chain CDR regions comprising the amino acid sequences of SEQ ID NOs: 45-47 and three light chain CDR regions comprising the amino acid sequences of SEQ ID NOs: 48-50.
8. The binder-drug conjugate of claim 3 , wherein the antibody or antigen-binding antibody fragment comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 51 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 52.
9. The binder-drug conjugate of claim 3 , wherein AK 1 is an antibody comprising a heavy chain and a light chain, the heavy chain comprising the amino acid sequence of SEQ ID NO: 353 and the light chain comprising the amino acid sequence of SEQ ID NO: 352.
10. A medicament comprising the binder-drug conjugate of claim 1 in combination with a pharmaceutically acceptable excipient.
11. A medicament comprising the binder-drug conjugate of claim 4 in combination with a pharmaceutically acceptable excipient.
12. The medicament of claim 11 , wherein n is a number from 2 to 8.