	US 11,878,063 B2
	Engineered ligands and uses thereof
Ross Cheloha, Boston, MA (US); Hidde L. Ploegh, Boston, MA (US); and Thomas J. Gardella, Boston, MA (US)
Assigned to Children's Medical Center Corporation, Boston, MA (US); and The General Hospital Corporation, Boston, MA (US)
Filed by Children's Medical Center Corporation, Boston, MA (US); and The General Hospital Corporation, Boston, MA (US)
Filed on Mar. 5, 2020, as Appl. No. 16/810,783.
Claims priority of provisional application 62/814,096, filed on Mar. 5, 2019.
Prior Publication US 2020/0316217 A1, Oct. 8, 2020
Int. Cl. A61K 47/68 (2017.01); A61K 47/62 (2017.01)

CPC A61K 47/6849 (2017.08) [A61K 47/62 (2017.08)]

14 Claims

1. An engineered ligand that binds to a human parathyroid hormone receptor 1 (PTHR1), the engineered ligand comprising a sub-optimal ligand conjugated to an antibody that binds to PTHR1;

wherein the sub-optimal ligand comprises an N-terminal fragment of parathyroid hormone (PTH) comprising amino acids 1-9 of PTH (SEQ ID NO: 3) and not comprising amino acids 15-34 of PTH (SEQ ID NO: 3);

wherein the antibody is a nanobody;

wherein the sub-optimal ligand comprises a C-terminus and an N-terminus;

wherein the antibody comprises a C-terminus and an N-terminus; and

wherein the C-terminus of the sub-optimal ligand is conjugated to the C-terminus or the N-terminus of the antibody and wherein the antibody binds to an epitope consisting of the amino acid sequence of any one of SEQ ID NO: 53-55.