US 2026/0306648 A1 · DELIVERY OF DUAL PAYLOAD OF MMAF OR MMAE AND TLR7 AGONISTS

Abstract

Disclosed herein are antibody-drug-conjugates (ADC) of Formula (A) containing both a toll-like receptor (TLR) agonist (immune stimulant) and MMAF or MMAE: The antibody-drug-conjugates are useful as therapeutic agents for treating various cancers. Pharmaceutical compositions which include the ADCs are also disclosed. Also disclosed are methods of treating a tumor or abnormal cell proliferation by administering a therapeutically effective amount of an antibody-drug-conjugate disclosed herein under conditions effective to treat a tumor or abnormal cell proliferation. Also disclosed are methods for stimulating an immune response and/or inducing an anti-tumor immune response in a subject by administering a therapeutically effective amount of an antibody-drug-conjugate disclosed herein.

Claims25

Dependent claims

An antibody-drug conjugate of Formula (A):

wherein:
P1 comprises a TLR7 agonist, MMAE, or MMAF;
LP1 comprises a cleavable or noncleavable linker;
J1 comprises a first conjugation handle;
SQ is —S(C1-C6)alkylNH—, wherein the NH is attached to the carbonyl of a Q295 residue of Ab;
Ab comprises an antibody;
J2 comprises a second conjugation handle attached at a sulfur atom of a cysteine residue of Ab;
LP2 comprises a cleavable or noncleavable linker;
and
P2 comprises a TLR7 agonist, MMAE or MMAF;
wherein:
d1 is between 1 and about 2;
d2 is between about 2 and about 10;
LP1 and LP2 may be the same or different;
J1 and J2 may be the same or different;
and
when P1 is a TLR7 agonist, P2 is selected from MMAE or MMAF;
and when P1 is MMAE or MMAF, P2 is a TLR7 agonist.

15 more elements

Dependencies are inferred from the claim text.

Delivery of dual payload of mmaf or mmae and tlr7 agonists

Life of this patent

Delivery of dual payload of mmaf or mmae and tlr7 agonists

Life of this patent

Abstract

Claims25