Treatment of disease responsive to modulation of cannabanoid 1(CB1) receptor signaling
The present invention relates to novel antibodies and fragments thereof that binds cannabinoid 1 (CB1) receptor. The antibodies and fragments thereof as disclosed herein include humanized antibodies that bind CB1 receptor. The invention also includes uses of the antibodies for treating a disease or disorder responsive to antagonism or agonism of the CB1 receptor.
1. A method for reducing CB1 receptor signaling in a subject, the method comprising administering to the subject an antibody or antigen binding fragment thereof, comprising
a heavy chain comprising a CDR1 amino acid sequence of SEQ ID NO: 352, a CDR2 amino acid sequence of SEQ ID NO: 353, and a CDR3 amino acid sequence of SEQ ID NO: 354; and
a light chain comprising a CDR1 amino acid sequence of SEQ ID NO: 355, a CDR2 amino acid sequence of SEQ ID NO: 356, and a CDR3 amino acid sequence of SEQ ID NO: 357, and
wherein the subject is suffering from a disease or disorder selected from the group consisting of obesity, type 2 diabetes, fibrosis, and non-alcoholic steatohepatitis (NASH).
2. The method of claim 1 , wherein the disease or disorder is fibrosis.
3. The method of claim 1 , wherein the antibody is humanized.
4. The method of claim 3 , wherein the antibody is an IgG2 isotype.
5. The method of claim 3 , wherein the antibody is an IgG4 isotype.
6. The method of claim 1 , wherein the disease or disorder is obesity.
7. The method of claim 1 , wherein the disease or disorder is liver fibrosis.
8. The method of claim 1 , wherein the disease or disorder is NASH.
9. The method of claim 1 , wherein the disease or disorder is kidney fibrosis.
10. The method of claim 1 , wherein the antibody or antigen binding fragment thereof is a negative allosteric modulator of CB1 receptor signaling.
11. The method of claim 1 , wherein:
the heavy chain variable region comprises SEQ ID NO: 339, and
the light chain variable region comprises SEQ ID NO: 337.
12. The method of claim 1 , wherein:
the heavy chain variable region comprises SEQ ID NO: 340, and
the light chain variable region comprises SEQ ID NO: 337.
13. The method of claim 1 , wherein:
the heavy chain variable region comprises SEQ ID NO: 341, and
the light chain variable region comprises SEQ ID NO: 337.
14. The method of claim 1 , wherein:
the heavy chain constant region comprises SEQ ID NO: 342, 433, 434, or 435.
15. The method of claim 1 , wherein:
the heavy chain amino comprises one of SEQ ID NOs: 343-351, and
the light chain comprises SEQ ID NO: 338.
16. The method of claim 1 , wherein:
the heavy chain comprises SEQ ID NOs: 436-441, and
the light chain comprises SEQ ID NO: 338.
17. The method of claim 1 , wherein:
the heavy chain comprises SEQ ID NO: 437; and
the light chain comprises SEQ ID NO: 338.