Antibodies to oxidized phospholipids
The disclosure provides for single chain variable fragments to oxidized phospholipid epitopes and methods of use thereof, including the production of transgenic animal models and the use of the fragments as therapeutic agents for treating CAS.
1. A method of treating non-alcoholic steatohepatitis (NASH) in a subject in need thereof, the method comprising administering to the subject an antibody or a fragment thereof that specifically binds to a phosphocholine (PC) headgroup of an oxidized phospholipid, the antibody comprising: a VH comprising the complementarity determining regions (CDRs) of the VH amino acid sequence set forth in SEQ ID NO: 2; and a VL comprising the CDRs of the VL amino acid sequence set forth in SEQ ID NO: 2, wherein the VH comprises the VH amino acid sequence set forth in SEQ ID NO: 2.
2. The method of claim 1 , wherein the VH comprises the CDR amino acid sequences set forth in SEQ ID NOs: 6, 7, and 8.
3. The method of claim 1 , wherein the VL comprises the CDR amino acid sequences set forth in SEQ ID NOs: 9, 10, and 11.
4. The method of claim 1 , wherein the VH comprises the CDR amino acid sequences set forth in SEQ ID NOs: 6, 7, and 8, and the VL comprises the CDR amino acid sequences set forth in SEQ ID NOs: 9, 10, and 11.
5. The method of claim 1 , wherein the VH comprises the VH amino acid sequence set forth in SEQ ID NO: 2, and the VL comprises the VL amino acid sequence set forth in SEQ ID NO: 2.
6. The method of claim 1 , wherein the antibody or fragment comprises the amino acid sequence of SEQ ID NO: 2.
7. The method of claim 1 , wherein the antibody or fragment is a chimeric antibody or humanized antibody.
8. The method of claim 1 , wherein the antibody or fragment further comprises an Fc region, optionally wherein:
the Fc region is from an IgG, IgM, IgA, IgD, IgE antibody, or any subclass thereof;
the Fc region is a native Fc region; and/or
the Fc region is a variant Fc region.
9. The method of claim 8 , wherein the antibody or fragment comprises the amino acid sequence of SEQ ID NO: 14.
10. A method of treating non-alcoholic steatohepatitis (NASH) in a subject in need thereof, the method comprising administering to the subject an antibody or a fragment thereof that specifically binds to a phosphocholine (PC) headgroup of an oxidized phospholipid, the antibody comprising: a VH comprising the complementarity determining regions (CDRs) of the VH amino acid sequence set forth in SEQ ID NO: 2; and a VL comprising the CDRs of the VL amino acid sequence set forth in SEQ ID NO: 2, wherein the VL comprises the VL amino acid sequence set forth in SEQ ID NO: 2.
11. The method of claim 10 , wherein the VH comprises the CDR amino acid sequences set forth in SEQ ID NOs: 6, 7, and 8, and the VL comprises the CDR amino acid sequences set forth in SEQ ID NOs: 9, 10, and 11.
12. The method of claim 10 , wherein the VH comprises the VH amino acid sequence set forth in SEQ ID NO: 2, and the VL comprises the VL amino acid sequence set forth in SEQ ID NO: 2.
13. The method of claim 10 , wherein the antibody or fragment comprises the amino acid sequence of SEQ ID NO: 2.
14. The method of claim 10 , wherein the antibody or fragment is a chimeric antibody or humanized antibody.
15. The method of claim 10 , wherein the antibody or fragment further comprises an Fc region, optionally wherein:
the Fc region is from an IgG, IgM, IgA, IgD, IgE antibody, or any subclass thereof;
the Fc region is a native Fc region; and/or
the Fc region is a variant Fc region.
16. The method of claim 15 , wherein the antibody or fragment comprises the amino acid sequence of SEQ ID NO: 14.
17. The method of claim 10 , wherein the VH comprises the CDR amino acid sequences set forth in SEQ ID NOs: 6, 7, and 8.
18. The method of claim 10 , wherein the VL comprises the CDR amino acid sequences set forth in SEQ ID NOs: 9, 10, and 11.