![]() (ii) the VH comprises a CDR1 (VH-CDR1) comprising the amino acid sequence of SEQ ID NO:1, a VH-CDR2 comprising the amino acid sequence selected from SEQ ID NO:6, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:13 and the VL comprises a CDR1 (VL-CDR1) comprising the amino acid sequence of SEQ ID NO:18, a VL-CDR2 comprising the amino acid sequence selected from any one of SEQ ID NO:23, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:33.(i) the VH comprises a CDR1 (VH-CDR1) comprising the amino acid sequence of SEQ ID NO:1, a VH-CDR2 comprising the amino acid sequence selected from SEQ ID NO:8, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:13 and the VL comprises a CDR1 (VL-CDR1) comprising the amino acid sequence of SEQ ID NO:18, a VL-CDR2 comprising the amino acid sequence selected from any one of SEQ ID NO:23, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:33.In some embodiments, the antibody construct comprises an Fc domain wherein the antibody construct or the antigen binding domain specific for ASGR1 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein: In various aspects, a TGFβR1 inhibitor conjugate comprises:Ī) an antibody construct comprising an antigen binding domain that specifically binds to a first antigen on a liver cell, wherein the first antigen is ASGR1 (such as human ASGR1) ī) a TGFβR1 inhibitor, e.g., a compound of Formula (A-I) or Formula (B-I) andĬ) a linker covalently attached to the TGFβR1 inhibitor and to the antibody construct. Thus, there remains a considerable need for alternative or improved treatments for fibrotic diseases. However, current therapeutics for treating fibrotic diseases are lacking or have drawbacks. Every year, millions of people are hospitalized due to the damaging effects of fibrosis. Scar tissue blocks arteries, immobilizes joints and damages internal organs, wreaking havoc on the body's ability to maintain vital functions. Fibrosis can occur in many tissues within the body, typically as a result of inflammation or damage, which include the lungs, liver, heart, and brain. BACKGROUNDįibrosis is the formation of excess fibrous connective tissue or scar tissue in an organ or tissue in a reparative or reactive process. ![]() 6, 2020, and is being submitted electronically via EFS-Web. ![]() The text file is 367 KB, was created on Oct. The name of the text file containing the Sequence Listing is 860234_407_SEQUENCE_LISTING.txt. The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. ![]()
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