Anti-family with sequence similarity 19, member A5 antibodies and method of use thereof
The present disclosure provides antibodies that specifically bind to human FAM19A5 and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human FAM19A5 and modulate FAM19A5 activity, e.g., inhibit, suppress, reduce, or reverse the onset of reactive gliosis and/or excessive proliferation of reactive astrocytes, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as central nervous system damage, a degenerative brain disorder, or a neuropathic pain, by administering an antibody that specifically binds to human FAM19A5.
1. An isolated antibody, or antigen-binding portion thereof, which specifically binds to human family with sequence similarity 19, member A5 (“FAM19A5”) protein (“anti-FAM19A5 antibody”) comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 5 and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 6.
2. An isolated antibody, or antigen-binding portion thereof, which specifically binds to human family with sequence similarity 19, member A5 (“FAM19A5”) protein (“anti-FAM19A5 antibody”) comprising a heavy chain CDR1, CDR2, and CDR3 and a light chain CDR1, CDR2, and CDR3,
(i) wherein the heavy chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 9;
(ii) wherein the heavy chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 7;
(iii) wherein the heavy chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 8;
(iv) wherein the light chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 10;
(v) wherein the light chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 11; and
(vi) wherein the light chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 12.
3. The anti-FAM19A5 antibody of claim 2 , which comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence which is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 5 and/or wherein the VL comprises an amino acid sequence which is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 6.
4. The anti-FAM19A5 antibody of claim 2 , which is a chimeric antibody or a humanized antibody.
5. The anti-FAM19A5 antibody of claim 2 , which comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises the amino acid sequence set forth in SEQ ID NO: 27, and/or wherein the LC comprises the amino acid sequence set forth in SEQ ID NO: 28.
6. The anti-FAM19A5 antibody of claim 2 , which exhibits one or more of the following properties:
(a) binds to soluble human FAM19A5 with a K D of 10 nM or less as measured by enzyme-linked immunosorbent assay (ELISA);
(b) binds to membrane bound human FAM19A5 with a K D of 10 nM or less as measured by ELISA;
(c) reduces, reverses, delays, and/or prevents an onset of reactive gliosis;
(d) suppresses an excessive proliferation of reactive astrocytes;
(e) decreases expression of chondroitin sulfate proteoglycans including neurocan and neuron-glial antigen 2 (NG2);
(f) increases expression of c-fos and pERK in the nucleus of neurons;
(g) promotes survival of neurons;
(h) increases expression of GAP43 in neurons; and
(i) promotes regrowth of an axon.
7. A composition comprising the anti-FAM19A5 antibody of claim 2 and a carrier.
8. A method of treating a traumatic brain injury, spinal cord injury, or both in a subject in need thereof comprising administering to the subject the anti-FAM19A5 antibody of claim 2 .
9. A method of treating a traumatic brain injury, spinal cord injury, or both in a subject in need thereof comprising administering to the subject the anti-FAM19A5 antibody of claim 1 .
10. A composition comprising the anti-FAM19A5 antibody of claim 1 and a carrier.
11. The anti-FAM19A5 antibody of claim 2 , which comprises a heavy chain constant region selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, and a variant thereof.
12. The anti-FAM19A5 antibody of claim 1 , which comprises a heavy chain constant region selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, and a variant thereof.
13. The anti-FAM19A5 antibody of claim 1 , which is a chimeric antibody or a humanized antibody.
14. The anti-FAM19A5 antibody of claim 1 , which comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises the amino acid sequence set forth in SEQ ID NO: 27, and/or wherein the LC comprises the amino acid sequence set forth in SEQ ID NO: 28.
15. A bispecific molecule comprising the anti-FAM19A5 antibody of claim 1 .
16. A bispecific molecule comprising the anti-FAM19A5 antibody of claim 2 .
17. The anti-FAM19A5 antibody of claim 1 , wherein the antigen-binding portion thereof comprises a Fab, Fab′, F(ab′)2, Fv fragment, single chain Fv (scFv), single domain antibody (sdAb), or combinations thereof.
18. The anti-FAM19A5 antibody of claim 2 , wherein the antigen-binding portion thereof comprises a Fab, Fab′, F(ab′)2, Fv fragment, single chain Fv (scFv), single domain antibody (sdAb), or combinations thereof.
19. An immunoconjugate comprising the anti-FAM19A5 antibody of claim 1 linked to an agent.
20. An immunoconjugate comprising the anti-FAM19A5 antibody of claim 2 linked to an agent.