Anti-ASGR1 antibody TLR8 agonist comprising conjugates and uses thereof
Inventors
Baum, Peter R. • DuBose, Robert • Odegard, Valerie • Tan, Philip • Thompson, Peter A. • Smith, Sean W. • STEVENS, Brenda
Assignees
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Publication Number
US-11541126-B1
Publication Date
2023-01-03
Expiration Date
Abstract
The disclosure provides conjugates of anti-ASGR1 antibodies or antigen binding fragments thereof to a myeloid cell agonist, compositions comprising the conjugates, and methods of treating liver viral infections with the conjugates. The disclosure also provides for anti-ASGR1 antibodies or antigen binding fragments thereof and methods for using the antibodies or antigen binding fragments thereof in treating liver viral infections.
Core Innovation
The invention relates to a myeloid cell agonist conjugate, or a salt thereof, represented by Formula (I). The conjugate includes an anti-ASGR1 antibody or antigen-binding fragment thereof comprising a heavy chain variable region (VH) and a light chain variable region (VL) defined by specified CDR amino acid sequences using SEQ ID NOs, and a linker (L) connects the antibody to a TLR8 agonist-containing portion.
The anti-ASGR1 antibody is defined by VH-CDR1 of SEQ ID NO:1, VH-CDR2 of SEQ ID NO:6 or SEQ ID NO:8, VH-CDR3 of SEQ ID NO:13, VL-CDR1 of SEQ ID NO:18, VL-CDR2 of SEQ ID NO:23 or SEQ ID NO:24, and VL-CDR3 of SEQ ID NO:33. The attachment concept uses RX* as a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to an antibody residue, and the linker is further described with peptide C-terminal and linker segment definitions.
The disclosure further describes cleavable and non-cleavable embodiments, lysosome-cleavable peptide motifs, polymer and peptide linker segments, and representative structural formulae. The documented structural framework supports covalent attachment of the TLR8 agonist to the anti-ASGR1 antibody through the defined linker families.
Claims Coverage
The independent claim covers one myeloid cell agonist conjugate defined by Formula (I), combining an anti-ASGR1 antibody with specified VH and VL CDR amino acid sequences, a linker L, and a TLR8 agonist-containing portion, with n and z each selected from 1 to 20. Three inventive features recur most consistently: antibody CDR definition, linker attachment chemistry, and defined linker architecture.
Myeloid cell agonist conjugate with anti-ASGR1 antibody linked to TLR8 agonist via linker
A myeloid cell agonist conjugate or salt represented by Formula (I), wherein A is an anti-ASGR1 antibody or antigen-binding fragment defined by VH-CDR1 of SEQ ID NO:1, VH-CDR2 of SEQ ID NO:6 or SEQ ID NO:8, VH-CDR3 of SEQ ID NO:13, VL-CDR1 of SEQ ID NO:18, VL-CDR2 of SEQ ID NO:23 or SEQ ID NO:24, and VL-CDR3 of SEQ ID NO:33; L is a linker; and D_x comprises a TLR8 agonist.
Linker attachment via RX* to antibody residue
The linker attachment chemistry uses RX* selected as a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to an antibody residue as the point of attachment.
Defined linker architecture with peptide C-terminal and linker segment
The linker is further defined by peptide C-terminal and linker segment features, including peptide-based and polymer-based linker embodiments.
The claim coverage centers on a Formula (I) conjugate that links an anti-ASGR1 antibody, defined by specified VH and VL CDR sequences, to a TLR8 agonist through a linker, with n and z constrained to 1 to 20. Dependent claims further specify linker architecture, RX* attachment chemistry, and permitted TLR8 agonist selection.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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