Method of treating or ameliorating metabolic disorders using binding proteins for gastric inhibitory peptide receptor (GIPR) in combination with GLP-1 agonists
Methods of treating metabolic diseases and disorders using an antigen binding protein specific for the GIPR polypeptide are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the antigen binding protein is administered in combination with a GLP-1 receptor agonist.
1. An isolated antigen binding protein that specifically binds to a human gastric inhibitory peptide receptor (GIPR) polypeptide, wherein said antigen binding protein is an antibody or a fragment thereof, and wherein said antibody comprises a CDRL1, a CDRL2, a CDRL3, a CDRH1, a CDRH2, and a CDRH3 wherein said. CDRL1 comprises SEQ ID NO: 702 ; said CDRL2 comprises SEQ ID NO: 859; said CDRL3 comprises SEQ ID NO: 1016; said CDRH1 comprises SEQ ID NO: 1173; said CDRH2 comprises SEQ ID NO: 1330; and said CDRH3 comprises SEQ ID NO: 1487.
2. The isolated antigen binding protein of claim 1 , wherein said human GIPR has a sequence comprising a sequence selected from the group consisting of SEQ ID NO: 3141, SEQ ID NO: 3143, and SEQ ID NO: 3145.
3. The isolated antigen binding protein of claim 1 or 2 , wherein said antigen binding protein is a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a human antibody, a humanized antibody, a chimeric antibody, a multispecific antibody, or an antibody fragment thereof.
4. The isolated antigen binding protein of claim 3 wherein, said antibody fragment is a Fab fragment, a Fab′ fragment, or a F(ab′)2 fragment.
5. The isolated antigen binding protein of claim 3 , wherein said antigen binding protein is a human antibody.
6. The isolated antigen binding protein of claim 3 , wherein said antigen binding protein is a monoclonal antibody.
7. The isolated antigen binding protein of claim 3 , wherein said antigen binding protein is of the IgG1-, IgG2- IgG3- or IgG4-type.
8. The isolated antigen binding protein of claim 7 , wherein said antigen binding protein is of the IgG1- or the IgG2-type.
9. The isolated antigen binding protein of any of claim 3 , wherein said antigen binding protein is coupled to a labeling group.
10. The isolated antigen binding protein of one of claim 3 , wherein said antigen binding protein inhibits binding of GIP to the extracellular portion of human GIPR.
11. The isolated antigen binding protein of claim 3 . wherein said antigen binding protein is an antibody or a fragment thereof, and wherein said antibody or fragment thereof comprises a light chain variable region comprising SEQ ID NO: 74 and a heavy chain variable region comprising SEQ ID NO: 231.
12. The isolated antigen binding protein of claim 3 , wherein said antigen binding protein is an antibody, and wherein said antibody comprises a light chain comprising SEQ ID NO: 388 and a heavy chain comprising SEQ ID NO: 545.
13. The isolated antigen binding protein of claim 1 , wherein said antibody comprises a CDRL1, a CDRL2, a CDRL3, a CDRH1, a CDRH2, and a CDRH3, wherein said CDRL1 consists of SEQ ID NO: 702 ; said CDRL2 consists of SEQ ID NO: 859; said CDRL3consists of SEQ ID NO: 1016; said CDRH1 consists of SEQ ID NO: 1173; said CDRH2 consists of SEQ ID NO: 1330; and said CDRH3 consists of SEQ ID NO: 1487.
14. A pharmaceutical composition comprising at least one antibody or fragment thereof according to any one of claims 1 , 11 , 12 , and 13 , and pharmaceutically acceptable excipient.