| 主权项 |
1. An isolated multivalent antibody or antigen-binding fragment thereof having at least two receptor binding domains for two different binding sites of a low density lipoprotein-related protein 6 (LRP6) target receptor, wherein the first receptor binding domain binds to a first binding site on the target receptor and the second receptor binding domain binds to a second binding site on the same LRP6 target receptor, wherein the first and second receptor binding domains are linked together such that the binding of the first and second receptor binding domains to the first and second binding sites of the LRP6 target receptor inhibits a canonical Wnt signal transduction pathway, and wherein the antibody or antigen binding fragment displays no significant potentiation of a Wnt signal;
wherein the first receptor binding domain is an IgG antibody and the second receptor binding domain is an scFv fragment, wherein the IgG antibody and scFv fragment are linked together by a linker with a spatial distribution that permits the IgG antibody and scFv fragment to bind to the first and second epitopes of LRP6, respectively; andwherein the heavy chain of the IgG antibody is selected from the group consisting of SEQ ID NO: 18, 66, and 86, and the light chain is selected from the group consisting of SEQ ID NO: 17, and 85. |
