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 ANGPTL3 and neutralizes at least one activity of ANGPTL3, wherein the monoclonal antibody binds to a peptide consisting of the amino acid sequence of SEQ ID NO: 10.
2. The monoclonal antibody of claim 1 , wherein the monoclonal antibody is a mouse monoclonal antibody.
3. The monoclonal antibody of claim 1 , wherein the monoclonal antibody is a humanized monoclonal antibody.
4. The monoclonal antibody of claim 1 , wherein the monoclonal antibody is a human monoclonal antibody.
5. The monoclonal antibody of claim 1 , wherein the monoclonal antibody decreases the level of at least one serum lipid in vivo.
6. The monoclonal antibody of claim 1 , wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 20 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28.
7. The monoclonal antibody of claim 1 , wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 22 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30.
8. The monoclonal antibody of claim 1 , wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 24 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32.
9. The monoclonal antibody of claim 1 , wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 64 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68.
10. The monoclonal antibody of claim 1 , wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 66 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 70.
11. The monoclonal antibody of claim 1 , wherein the monoclonal antibody specifically binds to the same epitope as an antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 20 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28.
12. The monoclonal antibody of claim 1 , wherein the monoclonal antibody specifically binds to the same epitope as an antibody an antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 22 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30.
13. The monoclonal antibody of claim 1 , wherein the monoclonal antibody specifically binds to the same epitope as an antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 24 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32.
14. The monoclonal antibody of claim 1 , wherein the monoclonal antibody specifically binds to the same epitope as an antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 64 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68.
15. A monoclonal antibody that binds to ANGPTL3 and neutralizes at least one activity of ANGPTL3, wherein the monoclonal antibody specifically binds to the same epitope as an antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 66 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 70.
16. The monoclonal antibody of claim 1 , wherein the antibody binds to a peptide consisting of the amino acid sequence of SEQ ID NO: 10 with a K D of less than 50 nM.
17. The monoclonal antibody of claim 16 , wherein the antibody binds to a peptide consisting of the amino acid sequence of SEQ ID NO: 10 with a K D of less than 30 nM.
18. The monoclonal antibody of claim 16 , wherein the antibody binds to a peptide consisting of the amino acid sequence of SEQ ID NO: 10 with a K D of less than 10 nM.
19. The monoclonal antibody of claim 16 , wherein the antibody binds to a peptide consisting of the amino acid sequence of SEQ ID NO: 10 with a K D of less than 5 nM.