Monoclonal antibodies against ANGPTL3
View Patent ↗Monoclonal antibodies that specifically bind to ANGPTL3 are provided. Monoclonal antibodies that neutralize at least one activity of ANGPTL3 are provided. Methods of treating a disorder of lipid metabolism using neutralizing monoclonal antibodies are provided.
1. A monoclonal antibody that binds to angiopoietin-like protein 3 (ANGPTL3) and neutralizes at least one activity of ANGPTL3, wherein the antibody binds to a peptide consisting of the amino acid sequence of SEQ ID NO: 9 with at least 3-fold greater affinity than the antibody binds to a peptide consisting of the amino acid sequence of SEQ ID NO: 86, 87, or 88.
2. The antibody of claim 1 , wherein the antibody decreases the level of at least one serum lipid in vivo.
3. The antibody of claim 2 , wherein the at least one serum lipid is selected from serum triglycerides, total cholesterol, and free fatty acids.
4. The antibody of claim 3 , wherein the antibody decreases the level of at least two serum lipids in vivo.
5. The antibody of claim 1 , wherein the antibody binds to mouse ANGPTL3 and human ANGPTL3.
6. The antibody of claim 1 , wherein the antibody is selected from a mouse monoclonal antibody, a humanized monoclonal antibody, and a human monoclonal antibody.
7. The antibody of claim 1 , wherein the antibody is an antibody fragment.
8. The antibody of claim 7 , wherein the antibody fragment is selected from a scFv, a Fab, a Fab′, and a F(ab′) 2 .
9. The monoclonal antibody of claim 1 , wherein the heavy chain comprises a CDR1 as set forth in SEQ ID NO: 35, a CDR2 as set forth in SEQ ID NO: 36, and a CDR3 as set forth in SEQ ID NO: 37; and the light chain comprises a CDR1 as set forth in SEQ ID NO: 44, a CDR2 as set forth in SEQ ID NO: 45, and a CDR3 as set forth in SEQ ID NO: 46.
10. The monoclonal antibody of claim 1 , wherein the heavy chain comprises a CDR1 as set forth in SEQ ID NO: 38, a CDR2 as set forth in SEQ ID NO: 39, and a CDR3 as set forth in SEQ ID NO: 40; and the light chain comprises a CDR1 as set forth in SEQ ID NO: 47, a CDR2 as set forth in SEQ ID NO: 48, and a CDR3 as set forth in SEQ ID NO: 49.
11. The monoclonal antibody of claim 1 , wherein the heavy chain comprises a CDR1 as set forth in SEQ ID NO: 41, a CDR2 as set forth in SEQ ID NO: 42, and a CDR3 as set forth in SEQ ID NO: 43; and the light chain comprises a CDR1 as set forth in SEQ ID NO: 50, a CDR2 as set forth in SEQ ID NO: 51, and a CDR3 as set forth in SEQ ID NO: 52.
12. The monoclonal antibody of claim 1 , wherein the heavy chain comprises a CDR1 as set forth in SEQ ID NO: 53, a CDR2 as set forth in SEQ ID NO: 54, and a CDR3 as set forth in SEQ ID NO: 55; and the light chain comprises a CDR1 as set forth in SEQ ID NO: 56, a CDR2 as set forth in SEQ ID NO: 57, and a CDR3 as set forth in SEQ ID NO: 58.
13. The monoclonal antibody of claim 1 , wherein the heavy chain comprises a CDR1 as set forth in SEQ ID NO: 71, a CDR2 as set forth in SEQ ID NO: 72, and a CDR3 as set forth in SEQ ID NO: 73; and the light chain comprises a CDR1 as set forth in SEQ ID NO: 77, a CDR2 as set forth in SEQ ID NO: 78, and a CDR3 as set forth in SEQ ID NO: 79.
14. The monoclonal antibody of claim 1 , wherein the heavy chain comprises a CDR1 as set forth in SEQ ID NO: 74, a CDR2 as set forth in SEQ ID NO: 75, and a CDR3 as set forth in SEQ ID NO: 76; and the light chain comprises a CDR1 as set forth in SEQ ID NO: 80, a CDR2 as set forth in SEQ ID NO: 81, and a CDR3 as set forth in SEQ ID NO: 82.
15. A pharmaceutical composition comprising the antibody of claim 1 .
16. A method of treating a disorder of lipid metabolism comprising administering to a patient an effective amount of the pharmaceutical composition of claim 15 , wherein the disorder of lipid metabolism is selected from hypertriglyceridemia and hypercholesterolemia.
17. A method of decreasing the level of one or more serum lipids comprising administering to a patient an effective amount of the pharmaceutical composition of claim 15 .