Use of anti-family with sequence similarity 19, member a5 antibodies for the treatment of neuropathic pain

Abstract

The present disclosure provides a method for the treatment of a neuropathic pain including a central neuropathic pain or a peripheral neuropathic pain in a subject comprising the administration of antibodies that specifically bind to human FAM19A5 and compositions comprising such antibodies. The present disclosure also provides methods for treating a neuropathic pain including a symptom of neuropathic pain, and/or an underlining cause of a neuropathic pain, by administering an antibody that specifically binds to human FAM19A5. In a specific aspect, the method comprises administering antibodies specifically bind to human FAM19A5, e.g., binds to soluble human FAM19A5 with a K D of 10 nM or less, or binds to membrane bound human FAM19A5 with a K D of 10 nM or less, or both, as measured by a method known in the art, e.g., ELISA.

1 - 7 . (canceled) 
     
     
         8 . A method of increasing a threshold or latency to an external stimulus in a subject in need thereof comprising administering to the subject an antagonist against a family with sequence similarity 19, member A5 (FAM19A5) protein (FAM19A5 antagonist). 
     
     
         9 . The FAM19A5 antagonist for use of  claim 8 , wherein the external stimulus is a mechanical stimulus, a thermal stimulus or both. 
     
     
         10 . (canceled) 
     
     
         11 . A method of increasing a sensory nerve conduction velocity in a subject in need thereof comprising administering to the subject an antagonist against a family with sequence similarity 19, member A5 (FAM19A5) protein (FAM19A5 antagonist). 
     
     
         12 . The method of  claim 8 , wherein the FAM19A5 antagonist comprises (i) an antisense oligonucleotide, siRNA, shRNA, miRNA, dsRNA, aptamer, PNA that specifically targets FAM19A5, or a vector including the same, (ii) an antibody, or an antigen-binding portion thereof, that specifically binds to the FAM19A5 protein (anti-FAM19A5 antibody), (iii) a polynucleotide encoding the anti-FAM19A5 antibody, (iv) a vector comprising the polynucleotide, (v) a cell comprising the polynucleotide, or (vi) combinations thereof. 
     
     
         13 - 21 . 
     
     
         22 . The method of  claim 12 , wherein the anti-FAM19A5 antibody comprises a heavy chain CDR1, CDR2, and CDR3 and a light chain CDR1, CDR2, and CDR3, wherein:
 (i) the heavy chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 17, SEQ ID NO: 14, SEQ ID NO: 11, SEQ ID NO: 20, SEQ ID NO: 89, SEQ ID NO: 95, SEQ ID NO: 101, SEQ ID NO: 107, SEQ ID NO: 113, SEQ ID NO: 119, SEQ ID NO: 125, SEQ ID NO: 131, SEQ ID NO: 137, SEQ ID NO: 143, SEQ ID NO: 149, SEQ ID NO: 207, SEQ ID NO: 209, SEQ ID NO: 211, or SEQ ID NO: 212;   (ii) the heavy chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 18, SEQ ID NO: 15, SEQ ID NO: 12, SEQ ID NO: 21, SEQ ID NO: 90, SEQ ID NO: 96, SEQ ID NO: 102, SEQ ID NO: 108, SEQ ID NO: 114, SEQ ID NO: 120, SEQ ID NO: 126, SEQ ID NO: 132, SEQ ID NO: 138, SEQ ID NO: 144, SEQ ID NO: 150, SEQ ID NO: 208, SEQ ID NO: 210, SEQ ID NO: 263, or SEQ ID NO: 264;   (iii) the heavy chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 19, SEQ ID NO: 16, SEQ ID NO: 13, SEQ ID NO: 22, SEQ ID NO: 91, SEQ ID NO: 97, SEQ ID NO: 103, SEQ ID NO: 109, SEQ ID NO: 115, SEQ ID NO: 121, SEQ ID NO: 127, SEQ ID NO: 133, SEQ ID NO: 139, SEQ ID NO: 145, SEQ ID NO: 151, SEQ ID NO: 260, or SEQ ID NO: 261;   (iv) the light chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 29, SEQ ID NO: 26, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 92, SEQ ID NO: 98, SEQ ID NO: 104, SEQ ID NO: 110, SEQ ID NO: 116, SEQ ID NO: 122, SEQ ID NO: 128, SEQ ID NO: 134, SEQ ID NO: 140, SEQ ID NO: 146, SEQ ID NO: 152, SEQ ID NO: 201, SEQ ID NO: 214, or SEQ ID NO: 253;   (v) the light chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 30, SEQ ID NO: 27, SEQ ID NO: 24, SEQ ID NO: 33, SEQ ID NO: 93, SEQ ID NO: 99, SEQ ID NO: 105, SEQ ID NO: 111, SEQ ID NO: 117, SEQ ID NO: 123, SEQ ID NO: 129, SEQ ID NO: 135, SEQ ID NO: 141, SEQ ID NO: 147, SEQ ID NO: 153, SEQ ID NO: 202, SEQ ID NO: 213, SEQ ID NO: 215, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 221, or SEQ ID NO: 270; and/or   (vi) the light chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 31, SEQ ID NO: 28, SEQ ID NO: 25, SEQ ID NO: 34, SEQ ID NO: 94, SEQ ID NO: 100, SEQ ID NO: 106, SEQ ID NO: 112, SEQ ID NO: 118, SEQ ID NO: 124, SEQ ID NO: 130, SEQ ID NO: 136, SEQ ID NO: 142, SEQ ID NO: 148, SEQ ID NO: 154, SEQ ID NO: 216, SEQ ID NO: 220, or SEQ ID NO: 222.   
     
     
         23 - 28 . (canceled) 
     
     
         29 . The method of  claim 22 , wherein:
 (i) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 17, 18, and 19, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 29, 30, and 31, respectively;   (ii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 14, 15, and 16, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 26, 27, and 28, respectively;   (iii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 11, 12, and 13, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 23, 24, and 25, respectively;   (iv) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 20, 21, and 22, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 32, 33, and 34, respectively;   (v) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 89, 90, and 91, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 92, 93, and 94, respectively;   (vi) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 95, 96, and 97, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 98, 99, and 100, respectively;   (vii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 101, 102, and 103, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 104, 105, and 106, respectively;   (viii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 107, 108, and 109, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 110, 111, and 112, respectively;   (ix) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 113, 114, and 115, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 116, 117, and 118, respectively;   (x) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 119, 120, and 121, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 122, 123, and 124, respectively;   (xi) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 125, 126, and 127, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 128, 129, and 130, respectively;   (xii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 131, 132, and 133, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 134, 135, and 136, respectively;   (xiii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 137, 138, and 139, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 140, 141, and 142, respectively;   (xiv) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 143, 144, and 145, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 146, 147, and 148, respectively;   (xv) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 149, 150, and 151, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 152, 153, and 154, respectively;   (xvi) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 17, 18, and 19, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 201, 270, and 31, respectively;   (xvii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 17, 263, and 19, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 201, 202, and 31, respectively;   (xviii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 17, 264, and 19, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 201, 202, and 31, respectively;   (xix) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 207, 208, and 16, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 26, 213, and 28, respectively;   (xx) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 209, 210, and 16, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 214, 215, and 216, respectively;   (xxi) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 209, 210, and 16, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 214, 217, and 216, respectively;   (xxii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 209, 210, and 16, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 26, 218, and 216, respectively;   (xxiii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 209, 210, and 16, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 26, 217, and 216, respectively;   (xxiv) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 209, 210, and 16, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 26, 219, and 220, respectively;   (xxv) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 209, 210, and 16, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 26, 221, and 222, respectively;   (xxvi) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 211, 12, and 13, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 253, 24, and 25, respectively;   (xxvii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 212, 12, and 13, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 253, 24, and 25, respectively;   (xxviii) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 212, 12, and 260, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 253, 24, and 25, respectively; or   (xxiv) the heavy chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 212, 12, and 261, respectively, and the light chain CDR1, CDR2, and CDR3 comprises SEQ ID NOs: 253, 24, and 25, respectively.   
     
     
         30 . (canceled) 
     
     
         31 . The method of  claim 22 , wherein the anti-FAM19A5 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:
 (i) the VH comprises the amino acid sequence set forth in SEQ ID NO: 37 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 41;   (ii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 36 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 40;   (iii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 35 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 39;   (iv) the VH comprises the amino acid sequence set forth in SEQ ID NO: 38 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 42;   (v) the VH comprises the amino acid sequence set forth in SEQ ID NO: 155 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 166;   (vi) the VH comprises the amino acid sequence set forth in SEQ ID NO: 156 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 167;   (vii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 157 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 168;   (viii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 158 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 169;   (ix) the VH comprises the amino acid sequence set forth in SEQ ID NO: 159 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 170;   (x) the VH comprises the amino acid sequence set forth in SEQ ID NO: 160 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 171;   (xi) the VH comprises the amino acid sequence set forth in SEQ ID NO: 161 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 172;   (xii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 162 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 173;   (xiii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 163 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 174;   (xiv) the VH comprises the amino acid sequence set forth in SEQ ID NO: 164 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 175;   (xv) the VH comprises the amino acid sequence set forth in SEQ ID NO: 165 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 176;   (x) the VH comprises the amino acid sequence set forth in SEQ ID NO: 271 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 272;   (xvii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 203 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 204;   (xviii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 254 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 204;   (xix) the VH comprises the amino acid sequence set forth in SEQ ID NO: 223 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 227;   (xx) the VH comprises the amino acid sequence set forth in SEQ ID NO: 224 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 228;   (xxi) the VH comprises the amino acid sequence set forth in SEQ ID NO: 224 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 229;   (xxii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 224 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 230;   (xxiii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 224 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 231;   (xxiv) the VH comprises the amino acid sequence set forth in SEQ ID NO: 224 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 232;   (xxv) the VH comprises the amino acid sequence set forth in SEQ ID NO: 224 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 233;   (xxvi) the VH comprises the amino acid sequence set forth in SEQ ID NO: 225 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 234;   (xxvii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 275 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 234;   (xxviii) the VH comprises the amino acid sequence set forth in SEQ ID NO: 226 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 234; or   (xxix) the VH comprises the amino acid sequence set forth in SEQ ID NO: 257 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 234.   
     
     
         32 - 36 . (canceled) 
     
     
         37 . The method of  claim 22 , wherein the anti-FAM19A5 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence which has at least about 85% sequence identity to the amino acid sequence set forth in SEQ ID NO: 37, 36, 35, 38, 155-165, 203, 223-226, 254, 257, 271, or 275; and wherein the VL comprises an amino acid sequence which has at least about 85% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41, 40, 39, 42, 166-176, 204, 227-234, or 272. 
     
     
         38 . The method of  claim 22 , wherein the antibody antigen-binding portion thereof comprises an Fab, an Fab′, an F(ab′)2, an Fv, or a single chain Fv (scFv). 
     
     
         39 - 42 . (canceled) 
     
     
         43 . The method of  claim 22 , wherein the anti-FAM19A5 antibody is a chimeric antibody, a human antibody, or a humanized antibody. 
     
     
         44 - 45 . (canceled) 
     
     
         46 . The method of  claim 8 , wherein the FAM19A5 antagonist is administered intravenously, orally, parenterally, intrathecally, intra-cerebroventricularly, pulmonarily, intramuscularly, subcutaneously, intraperitoneally, intravitreally, or intraventricularly. 
     
     
         47 . (canceled) 
     
     
         48 . The method of  claim 11 , wherein the FAM19A5 antagonist comprises (i) an antisense oligonucleotide, siRNA, shRNA, miRNA, dsRNA, aptamer, PNA that specifically targets FAM19A5, or a vector including the same, (ii) an antibody, or an antigen-binding portion thereof, that specifically binds to the FAM19A5 protein (anti-FAM19A5 antibody), (iii) a polynucleotide encoding the anti-FAM19A5 antibody, (iv) a vector comprising the polynucleotide, (v) a cell comprising the polynucleotide, or (vi) combinations thereof. 
     
     
         49 . The method of  claim 48 , wherein the anti-FAM19A5 antibody comprises a heavy chain CDR1, CDR2, and CDR3 and a light chain CDR1, CDR2, and CDR3, wherein:
 (i) the heavy chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 17, SEQ ID NO: 14, SEQ ID NO: 11, SEQ ID NO: 20, SEQ ID NO: 89, SEQ ID NO: 95, SEQ ID NO: 101, SEQ ID NO: 107, SEQ ID NO: 113, SEQ ID NO: 119, SEQ ID NO: 125, SEQ ID NO: 131, SEQ ID NO: 137, SEQ ID NO: 143, SEQ ID NO: 149, SEQ ID NO: 207, SEQ ID NO: 209, SEQ ID NO: 211, or SEQ ID NO: 212;   (ii) the heavy chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 18, SEQ ID NO: 15, SEQ ID NO: 12, SEQ ID NO: 21, SEQ ID NO: 90, SEQ ID NO: 96, SEQ ID NO: 102, SEQ ID NO: 108, SEQ ID NO: 114, SEQ ID NO: 120, SEQ ID NO: 126, SEQ ID NO: 132, SEQ ID NO: 138, SEQ ID NO: 144, SEQ ID NO: 150, SEQ ID NO: 208, SEQ ID NO: 210, SEQ ID NO: 263, or SEQ ID NO: 264;   (iii) the heavy chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 19, SEQ ID NO: 16, SEQ ID NO: 13, SEQ ID NO: 22, SEQ ID NO: 91, SEQ ID NO: 97, SEQ ID NO: 103, SEQ ID NO: 109, SEQ ID NO: 115, SEQ ID NO: 121, SEQ ID NO: 127, SEQ ID NO: 133, SEQ ID NO: 139, SEQ ID NO: 145, SEQ ID NO: 151, SEQ ID NO: 260, or SEQ ID NO: 261;   (iv) the light chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 29, SEQ ID NO: 26, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 92, SEQ ID NO: 98, SEQ ID NO: 104, SEQ ID NO: 110, SEQ ID NO: 116, SEQ ID NO: 122, SEQ ID NO: 128, SEQ ID NO: 134, SEQ ID NO: 140, SEQ ID NO: 146, SEQ ID NO: 152, SEQ ID NO: 201, SEQ ID NO: 214, or SEQ ID NO: 253;   (v) the light chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 30, SEQ ID NO: 27, SEQ ID NO: 24, SEQ ID NO: 33, SEQ ID NO: 93, SEQ ID NO: 99, SEQ ID NO: 105, SEQ ID NO: 111, SEQ ID NO: 117, SEQ ID NO: 123, SEQ ID NO: 129, SEQ ID NO: 135, SEQ ID NO: 141, SEQ ID NO: 147, SEQ ID NO: 153, SEQ ID NO: 202, SEQ ID NO: 213, SEQ ID NO: 215, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 221, or SEQ ID NO: 270; and/or   (vi) the light chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 31, SEQ ID NO: 28, SEQ ID NO: 25, SEQ ID NO: 34, SEQ ID NO: 94, SEQ ID NO: 100, SEQ ID NO: 106, SEQ ID NO: 112, SEQ ID NO: 118, SEQ ID NO: 124, SEQ ID NO: 130, SEQ ID NO: 136, SEQ ID NO: 142, SEQ ID NO: 148, SEQ ID NO: 154, SEQ ID NO: 216, SEQ ID NO: 220, or SEQ ID NO: 222.   
     
     
         50 . The method of  claim 48 , wherein the anti-FAM19A5 antibody is capable of specifically binding to (a) the FAM19A5 epitope sequence TLDRDSSQPRRTIARQTARC (SEQ ID NO: 6) or a fragment thereof, (b) CDMLPCLEGEGCDLLINRSG (SEQ ID NO: 9) or a fragment thereof, or (c) both (a) and (b). 
     
     
         51 . A method of increasing a motor function in a subject in need thereof comprising administering to the subject an antagonist against a family with sequence similarity 19, member A5 (FAM19A5) protein (FAM19A5 antagonist). 
     
     
         52 . The method of  claim 51 , wherein the FAM19A5 antagonist comprises (i) an antisense oligonucleotide, siRNA, shRNA, miRNA, dsRNA, aptamer, PNA that specifically targets FAM19A5, or a vector including the same, (ii) an antibody, or an antigen-binding portion thereof, that specifically binds to the FAM19A5 protein (anti-FAM19A5 antibody), (iii) a polynucleotide encoding the anti-FAM19A5 antibody, (iv) a vector comprising the polynucleotide, (v) a cell comprising the polynucleotide, or (vi) combinations thereof. 
     
     
         53 . The method of  claim 52 , wherein the anti-FAM19A5 antibody comprises a heavy chain CDR1, CDR2, and CDR3 and a light chain CDR1, CDR2, and CDR3, wherein:
 (i) the heavy chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 17, SEQ ID NO: 14, SEQ ID NO: 11, SEQ ID NO: 20, SEQ ID NO: 89, SEQ ID NO: 95, SEQ ID NO: 101, SEQ ID NO: 107, SEQ ID NO: 113, SEQ ID NO: 119, SEQ ID NO: 125, SEQ ID NO: 131, SEQ ID NO: 137, SEQ ID NO: 143, SEQ ID NO: 149, SEQ ID NO: 207, SEQ ID NO: 209, SEQ ID NO: 211, or SEQ ID NO: 212;   (ii) the heavy chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 18, SEQ ID NO: 15, SEQ ID NO: 12, SEQ ID NO: 21, SEQ ID NO: 90, SEQ ID NO: 96, SEQ ID NO: 102, SEQ ID NO: 108, SEQ ID NO: 114, SEQ ID NO: 120, SEQ ID NO: 126, SEQ ID NO: 132, SEQ ID NO: 138, SEQ ID NO: 144, SEQ ID NO: 150, SEQ ID NO: 208, SEQ ID NO: 210, SEQ ID NO: 263, or SEQ ID NO: 264;   (iii) the heavy chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 19, SEQ ID NO: 16, SEQ ID NO: 13, SEQ ID NO: 22, SEQ ID NO: 91, SEQ ID NO: 97, SEQ ID NO: 103, SEQ ID NO: 109, SEQ ID NO: 115, SEQ ID NO: 121, SEQ ID NO: 127, SEQ ID NO: 133, SEQ ID NO: 139, SEQ ID NO: 145, SEQ ID NO: 151, SEQ ID NO: 260, or SEQ ID NO: 261;   (iv) the light chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 29, SEQ ID NO: 26, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 92, SEQ ID NO: 98, SEQ ID NO: 104, SEQ ID NO: 110, SEQ ID NO: 116, SEQ ID NO: 122, SEQ ID NO: 128, SEQ ID NO: 134, SEQ ID NO: 140, SEQ ID NO: 146, SEQ ID NO: 152, SEQ ID NO: 201, SEQ ID NO: 214, or SEQ ID NO: 253;   (v) the light chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 30, SEQ ID NO: 27, SEQ ID NO: 24, SEQ ID NO: 33, SEQ ID NO: 93, SEQ ID NO: 99, SEQ ID NO: 105, SEQ ID NO: 111, SEQ ID NO: 117, SEQ ID NO: 123, SEQ ID NO: 129, SEQ ID NO: 135, SEQ ID NO: 141, SEQ ID NO: 147, SEQ ID NO: 153, SEQ ID NO: 202, SEQ ID NO: 213, SEQ ID NO: 215, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 221, or SEQ ID NO: 270; and/or   (vi) the light chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 31, SEQ ID NO: 28, SEQ ID NO: 25, SEQ ID NO: 34, SEQ ID NO: 94, SEQ ID NO: 100, SEQ ID NO: 106, SEQ ID NO: 112, SEQ ID NO: 118, SEQ ID NO: 124, SEQ ID NO: 130, SEQ ID NO: 136, SEQ ID NO: 142, SEQ ID NO: 148, SEQ ID NO: 154, SEQ ID NO: 216, SEQ ID NO: 220, or SEQ ID NO: 222.   
     
     
         54 . The method of  claim 52 , wherein the anti-FAM19A5 antibody comprise a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence which has at least about 85% sequence identity to the amino acid sequence set forth in SEQ ID NO: 37, 36, 35, 38, 155-165, 203, 223-226, 254, 257, 271, or 275; and wherein the VL comprises an amino acid sequence which has at least about 85% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41, 40, 39, 42, 166-176, 204, 227-234, or 272. 
     
     
         55 . The method of  claim 52 , wherein the anti-FAM19A5 antibody is capable of specifically binding to (a) the FAM19A5 epitope sequence TLDRDSSQPRRTIARQTARC (SEQ ID NO: 6) or a fragment thereof, (b) CDMLPCLEGEGCDLLINRSG (SEQ ID NO: 9) or a fragment thereof, or (c) both (a) and (b).