Methods of treating cardiovascular disease with an anti-ASGR antibody or binding fragments thereof
Antigen binding proteins that interact with ASGR, ASGR-1 and/or ASGR-2 are described as well as methods of making and using such antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of ASGR, ASGR-1 and/or ASGR-2 antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of interfering RNA compositions that reduce expression of ASGR, ASGR-1 and/or ASGR-2 are described.
1. A method of treating or preventing a cardiovascular disease comprising administering to a patient in need thereof a therapeutically effective dose of an isolated antigen binding protein that binds to ASGR-1 (asialoglycoprotein receptor 1), wherein the isolated antigen binding protein is a neutralizing antibody or a neutralizing antigen binding fragment thereof.
2. The method of claim 1 , wherein said cardiovascular disease is coronary artery disease or myocardial infarction.
3. The method of claim 1 , wherein the cardiovascular disease is thereby treated.
4. The method of claim 1 , wherein the cardiovascular disease is thereby prevented.
5. A method of reducing LDL (low density lipoprotein) cholesterol levels in a patient comprising administering to a patient in need thereof a therapeutically effective dose of an isolated antigen binding protein that binds to ASGR-1 (asialoglycoprotein receptor 1), wherein the isolated antigen binding protein is a neutralizing antibody or a neutralizing antigen binding fragment thereof.
6. The method of claim 5 , wherein LDL is reduced by at least 20%.
7. The method of claim 5 , wherein the patient has coronary artery disease or myocardial infarction.
8. A method of reducing non-HDL (non-high density lipoprotein) cholesterol levels in a patient comprising administering to a patient in need thereof a therapeutically effective dose of an isolated antigen binding protein that binds to ASGR-1 (asialoglycoprotein receptor 1), wherein the isolated antigen binding protein is a neutralizing antibody or a neutralizing antigen binding fragment thereof.
9. The method of claim 8 , wherein non-HDL is reduced by at least 20%.
10. The method of claim 8 , wherein the patient has coronary artery disease or myocardial infarction.
11. A method of increasing ALP (alkaline phosphatase) levels in a patient comprising administering to a patient in need thereof a therapeutically effective dose of an isolated antigen binding protein that binds to ASGR-1 (asialoglycoprotein receptor 1), wherein the isolated antigen binding protein is a neutralizing antibody or a neutralizing antigen binding fragment thereof.
12. The method of claim 11 , wherein ALP is increased by at least 40%.
13. The method of claim 11 , wherein the patient has coronary artery disease or myocardial infarction.
14. The method of claim 1 , wherein the isolated antigen binding protein is administered sequentially with at least one agent that lowers cholesterol.
15. The method of claim 14 , wherein the at least one agent is a statin, an anti-PCSK9 inhibitor or a combination thereof.
16. The method of claim 5 , wherein the isolated antigen binding protein is administered sequentially with at least one agent that lowers cholesterol.
17. The method of claim 16 , wherein the at least one agent is a statin, an anti-PCSK9 inhibitor or a combination thereof.
18. The method of claim 8 , wherein the isolated antigen binding protein is administered sequentially with at least one agent that lowers cholesterol.
19. The method of claim 18 , wherein the at least one agent is a statin, an anti-PCSK9 inhibitor or a combination thereof.
20. The method of claim 11 , wherein the isolated antigen binding protein is administered sequentially with at least one agent that lowers cholesterol.
21. The method of claim 20 , wherein the at least one agent is a statin, an anti-PCSK9 inhibitor or a combination thereof.
22. The method of claim 1 , wherein the ASGR-1 (asialoglycoprotein receptor 1) is a human ASGR-1 having the sequence in SEQ ID NO: 32699.
23. The method of claim 5 , wherein the ASGR-1 (asialoglycoprotein receptor 1) is a human ASGR-1 having the sequence in SEQ ID NO: 32699.
24. The method of claim 8 , wherein the ASGR-1 (asialoglycoprotein receptor 1) is a human ASGR-1 having the sequence in SEQ ID NO: 32699.
25. The method of claim 11 , wherein the ASGR-1 (asialoglycoprotein receptor 1) is a human ASGR-1 having the sequence in SEQ ID NO: 32699.
26. The method of claim 1 , wherein the isolated antigen binding protein is administered parenterally.
27. The method of claim 5 , wherein the isolated antigen binding protein is administered parenterally.
28. The method of claim 8 , wherein the isolated antigen binding protein is administered parenterally.
29. The method of claim 11 , wherein the isolated antigen binding protein is administered parenterally.
30. The method of claim 1 , wherein the isolated antigen binding protein is the neutralizing antibody.
31. The method of claim 5 , wherein the isolated antigen binding protein is the neutralizing antibody.
32. The method of claim 8 , wherein the isolated antigen binding protein is the neutralizing antibody.
33. The method of claim 11 , wherein the isolated antigen binding protein is the neutralizing antibody.
34. The method of claim 1 , wherein the isolated antigen binding protein is a neutralizing human antibody.
35. The method of claim 5 , wherein the isolated antigen binding protein is a neutralizing human antibody.
36. The method of claim 8 , wherein the isolated antigen binding protein is a neutralizing human antibody.
37. The method of claim 11 , wherein the isolated antigen binding protein is a neutralizing human antibody.
38. The method of claim 1 , wherein the isolated antigen binding protein is the neutralizing antigen binding fragment of the antibody.
39. The method of claim 5 , wherein the isolated antigen binding protein is the neutralizing antigen binding fragment of the antibody.
40. The method of claim 8 , wherein the isolated antigen binding protein is the neutralizing antigen binding fragment of the antibody.
41. The method of claim 11 , wherein the isolated antigen binding protein is the neutralizing antigen binding fragment of the antibody.
42. The method of claim 1 , wherein the isolated antigen binding protein competes with an antibody having a heavy chain CDR1 sequence of SEQ ID NO: 4780, a heavy chain CDR2 sequence of SEQ ID NO: 12792, a heavy chain CDR3 sequence of SEQ ID NO: 20804, a light chain CDR1 sequence of SEQ ID NO: 772, a light chain CDR2 sequence of SEQ ID NO: 8784, and a light chain CDR3 sequence of SEQ ID NO: 16796.
43. The method of claim 5 , wherein the isolated antigen binding protein competes with an antibody having a heavy chain CDR1 sequence of SEQ ID NO: 4780, a heavy chain CDR2 sequence of SEQ ID NO: 12792, a heavy chain CDR3 sequence of SEQ ID NO: 20804, a light chain CDR1 sequence of SEQ ID NO: 772, a light chain CDR2 sequence of SEQ ID NO: 8784, and 50213, and a light chain CDR3 sequence of SEQ ID NO: 16796.
44. The method of claim 8 , wherein the isolated antigen binding protein competes with an antibody having a heavy chain CDR1 sequence of SEQ ID NO: 4780, a heavy chain CDR2 sequence of SEQ ID NO: 12792, a heavy chain CDR3 sequence of SEQ ID NO: 20804, a light chain CDR1 sequence of SEQ ID NO: 772, a light chain CDR2 sequence of SEQ ID NO: 8784, and a light chain CDR3 sequence of SEQ ID NO: 16796.
45. The method of claim 11 , wherein the isolated antigen binding protein competes with an antibody having a heavy chain CDR1 sequence of SEQ ID NO: 4780, a heavy chain CDR2 sequence of SEQ ID NO: 12792, a heavy chain CDR3 sequence of SEQ ID NO: 20804, a light chain CDR1 sequence of SEQ ID NO: 772, a light chain CDR2 sequence of SEQ ID NO: 8784, and a light chain CDR3 sequence of SEQ ID NO: 16796.
46. A method of treating a cardiovascular disease, the method comprising administering to a patient in need thereof a therapeutically effective dose of an isolated antigen binding protein that binds to ASGR-1 (asialoglycoprotein receptor 1), wherein said cardiovascular disease is coronary artery disease or myocardial infarction, and wherein the isolated antigen binding protein is a neutralizing antibody or a neutralizing antigen binding fragment thereof.
47. The method of claim 46 , wherein the isolated antigen binding protein competes with an antibody having a heavy chain CDR1 sequence of SEQ ID NO: 4780, a heavy chain CDR2 sequence of SEQ ID NO: 12792, a heavy chain CDR3 sequence of SEQ ID NO: 20804, a light chain CDR1 sequence of SEQ ID NO: 772, a light chain CDR2 sequence of SEQ ID NO: 8784, and a light chain CDR3 sequence of SEQ ID NO: 16796.