Antibody drug conjugates comprising sting agonists
Inventors
DUVALL, Jeremy R. • Bentley, Keith W. • BUKHALID, Raghida A. • CETINBAS, Naniye • DAMELIN, Marc I. • Kelleher, Eugene W. • Lowinger, Timothy B. • Thomas, Joshua D. • Toader, Dorin • Xu, Ling • Yang, Liping
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12156870-B2
Publication Date
2024-12-03
Expiration Date
Abstract
The present disclosure provides scaffolds and antibody-drug conjugates (ADCs) comprising a stimulator of interferon genes (STING). The present disclosure also provides uses of the ADCs in treatment, e.g., treatment of cancer.
Core Innovation
The invention provides a scaffold of Formula (II), or a pharmaceutically acceptable salt, isomer, or solvate thereof, in which a peptide moiety M_A is connected to a divalent linker moiety L_D and further to a compound D of Formula (A). The peptide moiety M_A contains from two to ten amino acids selected from glycine, serine, glutamic acid, lysine, aspartic acid, cysteine and stereoisomers and combinations thereof. A monovalent linker moiety A1′ comprises a functional group capable of forming a covalent bond with a functional group of a protein-based recognition-molecule (PBRM).
The scaffold includes attachment relationships denoted by attachment to A1′ and to D, and the monovalent linker A1′ is connected to L_C. The divalent linker moiety L_D connects D to M_A, and the scaffold further includes a hydrophilic group T1. The formula is represented as A1′-(L_C)0-D-(L_D)0-M_A, consistent with the structural depiction of Formula (II).
Compound D is defined by Formula (A) with atom-type choices and substituent options for Y1, Y2, Z1, Z2, X1, X2, W1, W2, X3, X4, X5, X6, and X7, together with definitions for R3, R5, R_c, R_A2, R_A1, R_d, R_e, R_f, R14, R15, R16, R17, R18, and R19. The scaffold further specifies connectivity constraints stating that at least one of R_A2 and R_A1, or at least one of R_C2 and R_C1, is directly or indirectly connected to L_C via at least one functional group, and D is selected from defined variants.
Claims Coverage
The provided material includes one independent claim, clm-00001. Its inventive coverage centers on a Formula (II) scaffold that combines a peptide moiety M_A, a hydrophilic group T1, a divalent linker moiety L_D connecting D to M_A, and a monovalent linker moiety A1′ capable of covalently bonding to a protein-based recognition-molecule (PBRM), together with a highly variable compound D defined by Formula (A).
Formula (II) scaffold with peptide moiety and divalent linker
A scaffold of Formula (II), or a pharmaceutically acceptable salt, isomer, or solvate thereof, wherein M_A is a peptide moiety containing from two to ten amino acids selected from glycine, serine, glutamic acid, lysine, aspartic acid, cysteine and stereoisomers and combinations thereof, and L_D is a divalent linker moiety connecting D to M_A.
Monovalent linker A1′ capable of covalent bonding to PBRM
A1′ is a monovalent linker moiety comprising a functional group capable of forming a covalent bond with a functional group of a PBRM, where PBRM denotes a protein-based recognition-molecule.
Hydrophilic group T1
T1 is a hydrophilic group within the scaffold.
Defined D by Formula (A) with substituent and connectivity constraints
D is a compound of Formula (A), or a solvate, pharmaceutically acceptable salt, or tautomer thereof, with specified atom-type choices for Y1, Y2, Z1, Z2, X1, X2, W1, W2, X3, X4, X5, X6, and X7, and with defined substituent options for R3, R5, R_c, R_A2, R_A1, R_d, R_e, R_f, R14, R15, R16, R17, R18, and R19, together with connectivity requirements to L_C via functional groups.
Overall, the claim coverage is directed to a Formula (II) scaffold that integrates a peptide moiety M_A, a hydrophilic group T1, a divalent linker L_D to D, and a monovalent covalent-bond-forming linker A1′ for attachment to a PBRM, while D is defined through Formula (A) with extensive atom-type, substituent, and attachment constraints.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Preparation and characterization of STING-agonist antibody conjugates with different mAbs/linker variants, including reporting STING agonist to mAb ratio metrics and DAR values for example conjugates 32d and 32e.
Interested in licensing this patent?