Anti-vanin-1 antibody or antigen-binding fragment thereof, and use thereof

Abstract

The present invention provides a novel anti-vanin-1 antibody or an antigen-binding fragment thereof, and a use thereof. Disclosed is an anti-vanin-1 antibody, or an antigen-binding fragment thereof, comprising: a heavy chain CDR1 comprising the amino acid sequence represented by SEQ ID NO: 1, or an amino acid sequence in which 1-3 amino acids in this amino acid sequence are mutated; a heavy chain CDR2 comprising the amino acid sequence represented by formula (1-1): ISYDGX1T (where X1 is N, K, or H), or an amino acid sequence in which 1-3 amino acids in this amino acid sequence are mutated; a heavy chain CDR3 comprising the amino acid sequence represented by formula (1-2): X2X3GWLLSLAX4WG (where X2 is T, A, or S; X3 is S or T; and X4 is E, V, or M), or an amino acid sequence in which 1-3 amino acids in said amino acid sequence are mutated; a light chain CDR1 comprising the amino acid sequence represented by formula (1-3): SEHSX5SY (where X5 is S or R), or an amino acid sequence in which 1-3 amino acids in this amino acid sequence are mutated; a light chain CDR2 comprising the amino acid sequence represented by SEQ ID NO: 5, or an amino acid sequence in which 1-3 amino acids in this amino acid sequence are mutated; and a light chain CDR3 comprising the amino acid sequence represented by SEQ ID NO: 6, or an amino acid sequence in which 1-3 amino acids in this amino acid sequence are mutated.

Description

Anti-vanin-1 antibody or its antigen-binding fragment, and its uses

[0001] This disclosure includes anti-vanin-1 antibodies or their antigen-binding fragments, and their uses.

[0002] Vanin-1 protein in urine (hereinafter sometimes simply referred to as "Vanin-1") is a renal function marker that has been reported to increase in cisplatin-induced kidney damage (Non-Patent Literature 1) and in patients with decreased renal function due to hypertension (Non-Patent Literature 2).

[0003] K. Hosohata et al., Toxicology, 2016; 359-360:71-75K. Hosohata et al., J Clin Hypertens. 2021; 23:1316-1321

[0004] Non-patent documents 1 and 2 measure Vanin-1 using a commercially available ELISA kit (Cloud Clone).

[0005] The object of the present invention is to provide novel anti-Vanin-1 antibodies or antigen-binding fragments thereof, and their uses.

[0006] The inventors, through diligent research to achieve the above objectives, discovered a novel anti-Vanin-1 antibody or its antigen-binding fragment. Based on this finding, the inventors further diligently researched and completed the present invention.

[0007] The present invention encompasses embodiments described in the following sections.

[0008] [Item 1] An anti-Vanin-1 antibody or its antigen-binding fragment selected from (1) to (15) below: (1) A heavy chain CDR1 containing the amino acid sequence shown in GFSITTTNYW (SEQ ID NO: 1), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and Formula (1-1): ISYDGX １ T (where X １ A heavy chain CDR2 containing an amino acid sequence represented by (where is N, K, or H), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (1-2): X ２ X３ GWLLSLAX ４ WG (where X ２ is T, A, or S, and X ３ is S or T, and X ４ is E, V, or M), and a heavy-chain CDR3 comprising an amino acid sequence represented thereby, or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and Formula (1-3): SEHSX ５ SY (where X ５ is S or R), and a light-chain CDR1 comprising an amino acid sequence represented thereby, or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and an amino acid sequence represented by LKSDGSH (SEQ ID NO: 5), or a light-chain CDR2 comprising an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and an amino acid sequence represented by GVAYSGGYV (SEQ ID NO: 6), or a light-chain CDR3 comprising an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; an anti-Vanin-1 antibody or an antigen-binding fragment thereof; (2) Formula (2-1): GFTFSX ６ YW (where X ６ is N or K), and a heavy-chain CDR1 comprising an amino acid sequence represented thereby, or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and Formula (2-2): IX ７ X ８ DX ９ X １０ TX １１ (where X ７ is N or S, X ８ is S, G, H, or V, X ９ is S, R, or G, X １０ is S or T, X １１ is M, I, K, or V), and a heavy-chain CDR2 comprising an amino acid sequence represented thereby, or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and Formula (2-3): X １２ TX １３ GGX １４ WG (where X １２ is M, A, I, or V, X １３ is S, E, K, or T, X １４A heavy chain CDR3 containing an amino acid sequence represented by (where is L or V), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and formula (2-4): QSLLYSGNX １５ X １６ NY (in the formula, X １５ is N or T, X １６ A light chain CDR1 comprising an amino acid sequence represented by (where is N or K), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; a light chain CDR2 comprising an amino acid sequence represented by LAS, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence; Formula (2-5): MQTFGX １７ PRT (where X １７ A light chain CDR3 comprising an amino acid sequence represented by (where is I, T, or L), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and an anti-vanin-1 antibody or its antigen-binding fragment comprising; (3) Formula (3-1): GFTFX １８ NX １９ Y (where X １８ is S or N, X １９ A heavy chain CDR1 containing an amino acid sequence represented by (where is W or Y), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (3-2): ISX ２０ DSSDX ２１ (In the formula, X ２０ is A or D, X ２１ A heavy chain CDR2 containing an amino acid sequence represented by (where is I, L, or M), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and formula (3-3): X ２２ DISGX ２３ GX ２４ (In the formula, X ２２ is A or V, and X ２３ is S or Y, and X ２４ A heavy chain CDR3 containing an amino acid sequence represented by (where is I, F, L, or V), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (3-4): QSLLX ２５ SGNNX ２６ NY (in the formula, X ２５is S or Y, and X ２６ A light chain CDR1 comprising an amino acid sequence represented by (where is K or N), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; a light chain CDR2 comprising an amino acid sequence represented by LAS, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence; and formula (3-5): MQX ２７ X ２８ X ２９ X ３０ PX ３１ T (where X ２７ is D or T, X ２８ is Y or F, and X ２９ is S or G, X ３０ is V or I, X ３１ (1) A light chain CDR3 comprising an amino acid sequence represented by (where is L or R), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and an anti-vanin-1 antibody or its antigen-binding fragment comprising; (4) A heavy chain CDR1 comprising an amino acid sequence represented by GFSLTSYS (SEQ ID NO: 47), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and Formula (4-1): IWSX ３２ GX ３３ X ３４ (In the formula, X ３２ is D or G, X ３３ is S or T, X ３４ A heavy chain CDR2 containing an amino acid sequence represented by (where is P, T, or S), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (4-2): ARDWGX ３５ LDX ３６ (In the formula, X ３５ is S or N, X ３６ A heavy chain CDR3 containing an amino acid sequence represented by (where is V or I), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (4-3): QSX ３７ X ３８ X ３９ Y (where X ３７ is I or V, X ３８ is S, T, N, or K, and X ３９a light chain CDR1 comprising an amino acid sequence represented by R, S, or T), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, a light chain CDR2 comprising an amino acid sequence represented by YTN, SAY, NAY, or YAN, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence, and the formula (4-4): QQYX ４０ X ４１ WPYT (wherein X ４０ is H or Y, and X ４１ is S or N) or a light chain CDR3 comprising an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; an anti-Vanin-1 antibody or an antigen-binding fragment thereof; (5) the formula (5-1): GFX ４２ LTSYS (wherein X ４２ is P or S) or a heavy chain CDR1 comprising an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, the formula (5-2): IWSX ４３ GSX ４４ (wherein X ４３ is D or G, and X ４４ is S or T) or a heavy chain CDR2 comprising an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, an amino acid sequence represented by ARDGGYFH (SEQ ID NO: 64) or ARDRGDFDV (SEQ ID NO: 67), or a heavy chain CDR3 comprising an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and the formula (5-3): QSVNX ４５ Y (wherein X ４５ is S or T) or a light chain CDR1 comprising an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, a light chain CDR2 comprising an amino acid sequence represented by NAY or YTN, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence, and the formula (5-4): QQYX ４６ X ４７ WPYX ４８ (wherein X ４６ is H or Q, X ４７ is S or N, and X ４８a light chain CDR3 comprising an amino acid sequence represented by A or T), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and an anti-Vanin-1 antibody or an antigen-binding fragment thereof; (6) a heavy chain CDR1 comprising an amino acid sequence represented by GFSITTTNYW (SEQ ID NO: 1), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, an amino acid sequence represented by INYDGNT (SEQ ID NO: 69), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, a heavy chain CDR2, an amino acid sequence represented by AREGMVAGFYFDV (SEQ ID NO: 70), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, a heavy chain CDR3, an amino acid sequence represented by QGIDNG (SEQ ID NO: 71), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, a light chain CDR1, an amino acid sequence represented by DAT, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence, a light chain CDR2, and an amino acid sequence represented by QQGSSTPYT (SEQ ID NO: 72), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, an anti-Vanin-1 antibody or an antigen-binding fragment thereof; (7) a heavy chain CDR1 comprising an amino acid sequence represented by GFTFSNSW (SEQ ID NO: 73), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, formula (7-1): INGDSSX ４９ I (where X ４９ is N, D, or T), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, a heavy chain CDR2, formula (7-2): AADPGGNX ５０ HPYX ５１ DV (where X ５０ is S or Y, X ５１A heavy chain CDR3 containing an amino acid sequence represented by (where is L or F), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; a light chain CDR1 containing an amino acid sequence represented by NIGRKS (SEQ ID NO: 76), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; a light chain CDR2 containing an amino acid sequence represented by ADY, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence; Formula (7-3): QVWDX ５２ DSAGX ５３ (In the formula, X ５２ is S or T, X ５３ A light chain CDR3 comprising an amino acid sequence represented by (where is V or L), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and an anti-vanin-1 antibody or its antigen-binding fragment comprising; (8) Formula (8-1): GFTFSX ５４ SW (in the formula, X ５４ A heavy chain CDR1 comprising an amino acid sequence represented by (where is N or D), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (8-2): INGDX ５５ SNI (where X ５５An anti-vanin-1 antibody or its antigen-binding fragment comprising: a heavy chain CDR2 containing an amino acid sequence represented by (where is S or R), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR3 containing an amino acid sequence represented by AADPGGSGYFGYFDI (SEQ ID NO: 84) or AADPSGSGWTVDV (SEQ ID NO: 88), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR1 containing an amino acid sequence represented by NIGRKS (SEQ ID NO: 76), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR2 containing an amino acid sequence represented by ADY, or an amino acid sequence in which 1 amino acid is mutated in said amino acid sequence; and a light chain CDR3 containing an amino acid sequence represented by QVWDADSAQYV (SEQ ID NO: 85), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; (9) An anti-vanin-1 antibody or its antigen-binding fragment comprising: a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNDY (SEQ ID NO: 89), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR2 containing the amino acid sequence indicated by ISGDSNYI (SEQ ID NO: 90), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR3 containing the amino acid sequence indicated by ARHIAAYYFNL (SEQ ID NO: 91), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR1 containing the amino acid sequence indicated by SVNNNF (SEQ ID NO: 92), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR2 containing the amino acid sequence indicated by RTS, or an amino acid sequence in which 1 amino acid is mutated in said amino acid sequence; and a light chain CDR3 containing the amino acid sequence indicated by QQSSNDLT (SEQ ID NO: 93), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence;(10) An anti-vanin-1 antibody or its antigen-binding fragment comprising: a heavy chain CDR1 containing the amino acid sequence indicated by GFLFNTFY (SEQ ID NO: 94), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR2 containing the amino acid sequence indicated by ISHTGGST (SEQ ID NO: 95), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR3 containing the amino acid sequence indicated by LRNGRYSWGTYHYFDV (SEQ ID NO: 96), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR1 containing the amino acid sequence indicated by QGISKN (SEQ ID NO: 97), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR2 containing the amino acid sequence indicated by YAT, or an amino acid sequence in which 1 amino acid is mutated in said amino acid sequence; and a light chain CDR3 containing the amino acid sequence indicated by QHTNSWPQYT (SEQ ID NO: 98), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; (11) A heavy chain CDR1 containing the amino acid sequence indicated by GFTFSDYW (SEQ ID NO: 99), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a heavy chain CDR2 containing the amino acid sequence indicated by INYDGDST (SEQ ID NO: 100), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a heavy chain CDR3 containing the amino acid sequence indicated by ARASMGWNEYQYALDI (SEQ ID NO: 101), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a light chain CDR1 containing the amino acid sequence indicated by SAHSSYY (SEQ ID NO: 102), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a light chain CDR2 containing the amino acid sequence indicated by LKSDGSH (SEQ ID NO: 5), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a light chain CDR3 containing the amino acid sequence indicated by GMSYSGGFV (SEQ ID NO: 103), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; (12) Formula (12-1): GFSLX;５６ SYG (in the formula, X ５６ A heavy chain CDR1 containing an amino acid sequence represented by (where is T or S), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (12-2): X ５７ WDGGX ５８ T (where X ５７ is I or V, X ５８ A heavy chain CDR2 containing an amino acid sequence represented by (where is T, S, or N), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (12-3): ARPX ５９ YGX ６０ YSYYTALDX ６１ (In the formula, X ５９ is G or A, X ６０ is R or T, X ６１ A heavy chain CDR3 containing an amino acid sequence represented by (I, S, F, A, or T), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and a light chain CDR1 containing an amino acid sequence represented by SSNVGSYG (SEQ ID NO: 107), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and formula (12-4): GX ６２ T (where X ６２ A light chain CDR2 containing an amino acid sequence represented by (where is T or F), or an amino acid sequence in which one amino acid is mutated, and formula (12-5): SSWDYSQNVYX ６３ (In the formula, X ６３(13) A light chain CDR3 comprising an amino acid sequence represented by (V, L, or I), or an amino acid sequence in which 1 to 3 amino acids are mutated, and an anti-vanin-1 antibody or its antigen-binding fragment comprising: (13) A heavy chain CDR1 comprising an amino acid sequence represented by GFTFSTYY (SEQ ID NO: 122), or an amino acid sequence in which 1 to 3 amino acids are mutated, a heavy chain CDR2 comprising an amino acid sequence represented by ISNDGSST (SEQ ID NO: 123), or an amino acid sequence in which 1 to 3 amino acids are mutated, a heavy chain CDR3 comprising an amino acid sequence represented by ASFYSKYV (SEQ ID NO: 124), or an amino acid sequence in which 1 to 3 amino acids are mutated, a light chain CDR1 comprising an amino acid sequence represented by QSLLSSGNNKNY (SEQ ID NO: 37), or an amino acid sequence in which 1 to 3 amino acids are mutated, a light chain CDR2 comprising an amino acid sequence represented by LAS, or an amino acid sequence in which 1 amino acid is mutated, An anti-vanin-1 antibody or its antigen-binding fragment comprising: a light chain CDR3 containing the amino acid sequence indicated by MQDYSAPYT (SEQ ID NO: 125), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence;(14) A heavy chain CDR1 containing the amino acid sequence shown in GLTLSNSW (SEQ ID NO: 126), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR2 containing the amino acid sequence shown in INGDSRNI (SEQ ID NO: 127), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR3 containing the amino acid sequence shown in AASLDYYGLDI (SEQ ID NO: 128), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR1 containing the amino acid sequence shown in GLGNKY (SEQ ID NO: 129), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR2 containing the amino acid sequence shown in EDS, or an amino acid sequence in which 1 amino acid is mutated in said amino acid sequence; a light chain CDR3 containing the amino acid sequence shown in AIALGSGSGFHV (SEQ ID NO: 130), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; (15) an anti-vanin-1 antibody or its antigen-binding fragment, including: (15) a heavy chain CDR1 comprising the amino acid sequence shown in GFTFSNSW (SEQ ID NO: 73), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a heavy chain CDR2 comprising the amino acid sequence shown in INGDSTNI (SEQ ID NO: 131), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a heavy chain CDR3 comprising the amino acid sequence shown in AAGPEYYSRNSYYMPFQY (SEQ ID NO: 132), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a light chain CDR1 comprising the amino acid sequence shown in SDISVGRKS (SEQ ID NO: 133), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a light chain CDR2 comprising the amino acid sequence shown in YYSDSDK (SEQ ID NO: 134), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; An anti-vanin-1 antibody or its antigen-binding fragment comprising a light chain CDR3 containing the amino acid sequence indicated by TIWHSGTWV (SEQ ID NO: 135), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence;

[0009] [Item 2] The anti-vanin-1 antibody or antigen-binding fragment thereof as described in Item 1, wherein the mutation is a conservative substitution.

[0010] [Item 3] The heavy chain CDR3 of the anti-Vanin-1 antibody (1) comprises the amino acid sequence represented by TSGWLLSLAEWG (SEQ ID NO: 3), TSGWLLSLAVWG (SEQ ID NO: 7), ASGWLLSLAMWG (SEQ ID NO: 10), or STGWLLSLAVWG (SEQ ID NO: 12), and the light chain CDR3 of the anti-Vanin-1 antibody (1) comprises the amino acid sequence represented by GVAYSGGYV (SEQ ID NO: 6), The heavy chain CDR3 of the anti-Vanin-1 antibody (2) comprises the amino acid sequence represented by MTSGGLWG (SEQ ID NO: 15), ATEGGLWG (SEQ ID NO: 19), ATEGGVWG (SEQ ID NO: 24), ATKGGLWG (SEQ ID NO: 27), ITSGGLWG (SEQ ID NO: 29), VTTGGLWG (SEQ ID NO: 31), or ATSGGLWG (SEQ ID NO: 33), and the light chain CDR3 of the anti-Vanin-1 antibody (2) comprises the amino acid sequence represented by MQTFGIPRT (SEQ ID NO: 17), MQTFGTPRT (SEQ ID NO: 21), or MQTFGLPRT (SEQ ID NO: 30). The heavy chain CDR3 of the anti-Vanin-1 antibody (3) comprises an amino acid sequence represented by ADISGSGI (SEQ ID NO: 36), ADISGSGF (SEQ ID NO: 40), ADISGSGL (SEQ ID NO: 42), ADISGYGV (SEQ ID NO: 45), or VDISGYGV (SEQ ID NO: 46), the light chain CDR3 of the anti-Vanin-1 antibody (3) comprises an amino acid sequence represented by MQDYSVPLT (SEQ ID NO: 38) or MQTFGIPRT (SEQ ID NO: 17), the heavy chain CDR3 of the anti-Vanin-1 antibody (4) comprises an amino acid sequence represented by ARDWGSLDV (SEQ ID NO: 49), ARDWGNLDI (SEQ ID NO: 56), or ARDWGSLDI (SEQ ID NO: 60), the light chain CDR3 of the anti-Vanin-1 antibody (4) comprises an amino acid sequence represented by QQYHSWPYT (SEQ ID NO: 51), QQYHNWPYT (SEQ ID NO: 54), or QQYYSWPYT (SEQ ID NO: 59), The heavy chain CDR3 of the anti-Vanin-1 antibody (5) comprises the amino acid sequence represented by ARDGGYFH (SEQ ID NO: 64) or ARDRGDFDV (SEQ ID NO: 67), and the light chain CDR3 of the anti-Vanin-1 antibody (5) comprises the amino acid sequence represented by QQYHSWPYA (SEQ ID NO: 66) or QQYQNWPYT (SEQ ID NO: 68).The heavy chain CDR3 of the anti-Vanin-1 antibody (6) comprises the amino acid sequence represented by AREGMVAGFYFDV (SEQ ID NO: 70), the light chain CDR3 of the anti-Vanin-1 antibody (6) comprises the amino acid sequence represented by QQGSSTPYT (SEQ ID NO: 72), the heavy chain CDR3 of the anti-Vanin-1 antibody (7) comprises the amino acid sequence represented by AADPGGNSHPYLDV (SEQ ID NO: 75), AADPGGNYHPYFDV (SEQ ID NO: 79), or AADPGGNSHPYFDV (SEQ ID NO: 82), the light chain CDR3 of the anti-Vanin-1 antibody (7) comprises the amino acid sequence represented by QVWDSDSAGV (SEQ ID NO: 77), QVWDTDSAGV (SEQ ID NO: 80), or QVWDSDSAGL (SEQ ID NO: 83), The heavy chain CDR3 of the anti-Vanin-1 antibody (8) comprises the amino acid sequence represented by AADPGGSGYFGYFDI (SEQ ID NO: 84) or AADPSGSGWTVDV (SEQ ID NO: 88), the light chain CDR3 of the anti-Vanin-1 antibody (8) comprises the amino acid sequence represented by QVWDADSAQYV (SEQ ID NO: 85), the heavy chain CDR3 of the anti-Vanin-1 antibody (9) comprises the amino acid sequence represented by ARHIAAYYFNL (SEQ ID NO: 91), the light chain CDR3 of the anti-Vanin-1 antibody (9) comprises the amino acid sequence represented by QQSSNDLT (SEQ ID NO: 93), the heavy chain CDR3 of the anti-Vanin-1 antibody (10) comprises the amino acid sequence represented by LRNGRYSWGTYHYFDV (SEQ ID NO: 96), the light chain CDR3 of the anti-Vanin-1 antibody (10) comprises the amino acid sequence represented by QHTNSWPQYT (SEQ ID NO: 98), The heavy chain CDR3 of the anti-Vanin-1 antibody (11) comprises the amino acid sequence represented by ARASMGWNEYQYALDI (SEQ ID NO: 101), and the light chain CDR3 of the anti-Vanin-1 antibody (11) comprises the amino acid sequence represented by GMSYSGGFV (SEQ ID NO: 103).The heavy chain CDR3 of the anti-Vanin-1 antibody (12) comprises an amino acid sequence represented by ARPGYGRYSYYTALDI (SEQ ID NO: 106), ARPGYGRYSYYTALDS (SEQ ID NO: 109), ARPGYGTYSYYTALDI (SEQ ID NO: 111), ARPGYGTYSYYTALDF (SEQ ID NO: 114), ARPGYGTYSYYTALDA (SEQ ID NO: 115), ARPGYGTYSYYTALDT (SEQ ID NO: 116), ARPAYGTYSYYTALDI (SEQ ID NO: 118), or ARPAYGTYSYYTALDF (SEQ ID NO: 119), and the light chain CDR3 of the anti-Vanin-1 antibody (12) comprises an amino acid sequence represented by SSWDYSQNVYV (SEQ ID NO: 108), SSWDYSQNVYL (SEQ ID NO: 112), or SSWDYSQNVYI (SEQ ID NO: 121). The anti-vanin-1 antibody or antigen-binding fragment thereof according to item 1 or 2, wherein the heavy chain CDR3 of the anti-vanin-1 antibody (13) comprises the amino acid sequence represented by ASFYSKYV (SEQ ID NO: 124), the light chain CDR3 of the anti-vanin-1 antibody (13) comprises the amino acid sequence represented by MQDYSAPYT (SEQ ID NO: 125), the heavy chain CDR3 of the anti-vanin-1 antibody (14) comprises the amino acid sequence represented by AASLDYYGLDI (SEQ ID NO: 128), the light chain CDR3 of the anti-vanin-1 antibody (14) comprises the amino acid sequence represented by AIALGSGSGFHV (SEQ ID NO: 130), the heavy chain CDR3 of the anti-vanin-1 antibody (15) comprises the amino acid sequence represented by AAGPEYYSRNSYYMPFQY (SEQ ID NO: 132), and the light chain CDR3 of the anti-vanin-1 antibody (15) comprises the amino acid sequence represented by TIWHSGTWV (SEQ ID NO: 135).

[0011] [Item 4] The heavy chain CDR1 of the anti-Vanin-1 antibody (1) comprises the amino acid sequence shown by GFSITTTNYW (SEQ ID NO: 1), the heavy chain CDR2 comprises the amino acid sequence shown by ISYDGNT (SEQ ID NO: 2), the heavy chain CDR3 comprises the amino acid sequence shown by TSGWLLSLAEWG (SEQ ID NO: 3), the light chain CDR1 comprises the amino acid sequence shown by SEHSSSY (SEQ ID NO: 4), the light chain CDR2 comprises the amino acid sequence shown by LKSDGSH (SEQ ID NO: 5), and the light chain CDR3 comprises the amino acid sequence shown by GVAYSGGYV (SEQ ID NO: 6). The heavy chain CDR1 of the anti-Vanin-1 antibody (2) includes the amino acid sequence indicated by GFTFSNYW (SEQ ID NO: 13), the heavy chain CDR2 includes the amino acid sequence indicated by INSDSSTM (SEQ ID NO: 14), the heavy chain CDR3 includes the amino acid sequence indicated by MTSGGLWG (SEQ ID NO: 15), the light chain CDR1 includes the amino acid sequence indicated by QSLLYSGNNNNY (SEQ ID NO: 16), the light chain CDR2 includes the amino acid sequence indicated by LAS, and the light chain CDR3 includes the amino acid sequence indicated by MQTFGIPRT (SEQ ID NO: 17). The heavy chain CDR1 of the anti-Vanin-1 antibody (3) includes the amino acid sequence indicated by GFTFSNWY (SEQ ID NO: 34), the heavy chain CDR2 includes the amino acid sequence indicated by ISADSSDI (SEQ ID NO: 35), the heavy chain CDR3 includes the amino acid sequence indicated by ADISGSGI (SEQ ID NO: 36), the light chain CDR1 includes the amino acid sequence indicated by QSLLSSGNNKNY (SEQ ID NO: 37), the light chain CDR2 includes the amino acid sequence indicated by LAS, and the light chain CDR3 includes the amino acid sequence indicated by MQDYSVPLT (SEQ ID NO: 38). The heavy chain CDR1 of the anti-Vanin-1 antibody (4) includes the amino acid sequence indicated by GFSLTSYS (SEQ ID NO: 47), the heavy chain CDR2 includes the amino acid sequence indicated by IWSDGSP (SEQ ID NO: 48), the heavy chain CDR3 includes the amino acid sequence indicated by ARDWGSLDV (SEQ ID NO: 49), the light chain CDR1 includes the amino acid sequence indicated by QSISRY (SEQ ID NO: 50), the light chain CDR2 includes the amino acid sequence indicated by YTN, and the light chain CDR3 includes the amino acid sequence indicated by QQYHSWPYT (SEQ ID NO: 51).The heavy chain CDR1 of the anti-Vanin-1 antibody (5) includes the amino acid sequence shown by GFPLTSYS (SEQ ID NO: 63), the heavy chain CDR2 includes the amino acid sequence shown by IWSDGSS (SEQ ID NO: 55), the heavy chain CDR3 includes the amino acid sequence shown by ARDGGYFH (SEQ ID NO: 64), the light chain CDR1 includes the amino acid sequence shown by QSVNSY (SEQ ID NO: 65), the light chain CDR2 includes the amino acid sequence shown by NAY, and the light chain CDR3 includes the amino acid sequence shown by QQYHSWPYA (SEQ ID NO: 66). The heavy chain CDR1 of the anti-Vanin-1 antibody (6) includes the amino acid sequence indicated by GFSITTTNYW (SEQ ID NO: 1), the heavy chain CDR2 includes the amino acid sequence indicated by INYDGNT (SEQ ID NO: 69), the heavy chain CDR3 includes the amino acid sequence indicated by AREGMVAGFYFDV (SEQ ID NO: 70), the light chain CDR1 includes the amino acid sequence indicated by QGIDNG (SEQ ID NO: 71), the light chain CDR2 includes the amino acid sequence indicated by DAT, and the light chain CDR3 includes the amino acid sequence indicated by QQGSSTPYT (SEQ ID NO: 72). The heavy chain CDR1 of the anti-Vanin-1 antibody (7) includes the amino acid sequence indicated by GFTFSNSW (SEQ ID NO: 73), the heavy chain CDR2 includes the amino acid sequence indicated by INGDSSNI (SEQ ID NO: 74), the heavy chain CDR3 includes the amino acid sequence indicated by AADPGGNSHPYLDV (SEQ ID NO: 75), the light chain CDR1 includes the amino acid sequence indicated by NIGRKS (SEQ ID NO: 76), the light chain CDR2 includes the amino acid sequence indicated by ADY, and the light chain CDR3 includes the amino acid sequence indicated by QVWDSDSAGV (SEQ ID NO: 77). The heavy chain CDR1 of the anti-Vanin-1 antibody (8) includes the amino acid sequence indicated by GFTFSNSW (SEQ ID NO: 73), the heavy chain CDR2 includes the amino acid sequence indicated by INGDSSNI (SEQ ID NO: 74), the heavy chain CDR3 includes the amino acid sequence indicated by AADPGGSGYFGYFDI (SEQ ID NO: 84), the light chain CDR1 includes the amino acid sequence indicated by NIGRKS (SEQ ID NO: 76), the light chain CDR2 includes the amino acid sequence indicated by ADY, and the light chain CDR3 includes the amino acid sequence indicated by QVWDADSAQYV (SEQ ID NO: 85).The heavy chain CDR1 of the anti-Vanin-1 antibody (9) includes the amino acid sequence indicated by GFTFSNDY (SEQ ID NO: 89), the heavy chain CDR2 includes the amino acid sequence indicated by ISGDSNYI (SEQ ID NO: 90), the heavy chain CDR3 includes the amino acid sequence indicated by ARHIAAYYFNL (SEQ ID NO: 91), the light chain CDR1 includes the amino acid sequence indicated by SVNNNF (SEQ ID NO: 92), the light chain CDR2 includes the amino acid sequence indicated by RTS, and the light chain CDR3 includes the amino acid sequence indicated by QQSSNDLT (SEQ ID NO: 93). The heavy chain CDR1 of the anti-Vanin-1 antibody (10) includes the amino acid sequence indicated by GFLFNTFY (SEQ ID NO: 94), the heavy chain CDR2 includes the amino acid sequence indicated by ISHTGGST (SEQ ID NO: 95), the heavy chain CDR3 includes the amino acid sequence indicated by LRNGRYSWGTYHYFDV (SEQ ID NO: 96), the light chain CDR1 includes the amino acid sequence indicated by QGISKN (SEQ ID NO: 97), the light chain CDR2 includes the amino acid sequence indicated by YAT, and the light chain CDR3 includes the amino acid sequence indicated by QHTNSWPQYT (SEQ ID NO: 98). The heavy chain CDR1 of the anti-Vanin-1 antibody (11) includes the amino acid sequence indicated by GFTFSDYW (SEQ ID NO: 99), the heavy chain CDR2 includes the amino acid sequence indicated by INYDGDST (SEQ ID NO: 100), the heavy chain CDR3 includes the amino acid sequence indicated by ARASMGWNEYQYALDI (SEQ ID NO: 101), the light chain CDR1 includes the amino acid sequence indicated by SAHSSYY (SEQ ID NO: 102), the light chain CDR2 includes the amino acid sequence indicated by LKSDGSH (SEQ ID NO: 5), and the light chain CDR3 includes the amino acid sequence indicated by GMSYSGGFV (SEQ ID NO: 103). The heavy chain CDR1 of the anti-Vanin-1 antibody (12) includes the amino acid sequence indicated by GFSLTSYG (SEQ ID NO: 104), the heavy chain CDR2 includes the amino acid sequence indicated by IWDGGTT (SEQ ID NO: 105), the heavy chain CDR3 includes the amino acid sequence indicated by ARPGYGRYSYYTALDI (SEQ ID NO: 106), the light chain CDR1 includes the amino acid sequence indicated by SSNVGSYG (SEQ ID NO: 107), the light chain CDR2 includes the amino acid sequence indicated by GTT, and the light chain CDR3 includes the amino acid sequence indicated by SSWDYSQNVYV (SEQ ID NO: 108).The heavy chain CDR1 of the anti-Vanin-1 antibody (13) includes the amino acid sequence indicated by GFTFSTYY (SEQ ID NO: 122), the heavy chain CDR2 includes the amino acid sequence indicated by ISNDGSST (SEQ ID NO: 123), the heavy chain CDR3 includes the amino acid sequence indicated by ASFYSKYV (SEQ ID NO: 124), the light chain CDR1 includes the amino acid sequence indicated by QSLLSSGNNKNY (SEQ ID NO: 37), the light chain CDR2 includes the amino acid sequence indicated by LAS, and the light chain CDR3 includes the amino acid sequence indicated by MQDYSAPYT (SEQ ID NO: 125). The heavy chain CDR1 of the anti-Vanin-1 antibody (14) includes the amino acid sequence indicated by GLTLSNSW (SEQ ID NO: 126), the heavy chain CDR2 includes the amino acid sequence indicated by INGDSRNI (SEQ ID NO: 127), the heavy chain CDR3 includes the amino acid sequence indicated by AASLDYYGLDI (SEQ ID NO: 128), the light chain CDR1 includes the amino acid sequence indicated by GLGNKY (SEQ ID NO: 129), the light chain CDR2 includes the amino acid sequence indicated by EDS, and the light chain CDR3 includes the amino acid sequence indicated by AIALGSGSGFHV (SEQ ID NO: 130). The anti-Vanin-1 antibody (15) according to any one of items 1 to 3, wherein the heavy chain CDR1 comprises the amino acid sequence shown by GFTFSNSW (SEQ ID NO: 73), the heavy chain CDR2 comprises the amino acid sequence shown by INGDSTNI (SEQ ID NO: 131), the heavy chain CDR3 comprises the amino acid sequence shown by AAGPEYYSRNSYYMPFQY (SEQ ID NO: 132), the light chain CDR1 comprises the amino acid sequence shown by SDISVGRKS (SEQ ID NO: 133), the light chain CDR2 comprises the amino acid sequence shown by YYSDSDK (SEQ ID NO: 134), and the light chain CDR3 comprises the amino acid sequence shown by TIWHSGTWV (SEQ ID NO: 135).

[0012] [Item 5] The anti-Vanin-1 antibody or antigen-binding fragment thereof according to any one of items 1 to 4, wherein the anti-Vanin-1 antibody is a monoclonal antibody.

[0013] [Item 6] A polynucleotide comprising the coding sequence of an anti-Vanin-1 antibody or its antigen-binding fragment as described in any of Items 1 to 5.

[0014] [Item 7] A cell containing the polynucleotide described in Item 6.

[0015] [Item 8] A reagent or pharmaceutical product comprising an anti-Vanin-1 antibody or its antigen-binding fragment as described in any of Items 1 to 5, a polynucleotide as described in Item 6, or cells as described in Item 7.

[0016] [Item 9] A kit for detecting the Vanin-1 protein, comprising an anti-Vanin-1 antibody or its antigen-binding fragment as described in any of Items 1 to 5.

[0017] [Item 10] A kit for detecting the Vanin-1 protein, comprising two or more anti-Vanin-1 antibodies or antigen-binding fragments thereof as described in any of Items 1 to 5, wherein at least two of the anti-Vanin-1 antibodies or antigen-binding fragments thereof bind to different regions of the Vanin-1 protein.

[0018] The present invention provides a novel anti-Vanin-1 antibody or its antigen-binding fragment, and its applications. This anti-Vanin-1 antibody or its antigen-binding fragment can detect the Vanin-1 protein with higher sensitivity than existing ones. Furthermore, by using two or more of these anti-Vanin-1 antibodies or their fragments that recognize different regions (epitopes) in the Vanin-1 protein, the Vanin-1 protein can be detected with even higher sensitivity.

[0019] 1. Definitions, etc. In this specification, Vanin-1 means Vascular noninflammatory molecule-1.

[0020] In this specification, amino acids may be natural or unnatural amino acids. Examples of unnatural amino acids include, but are not limited to, citrulline, ornithine, ε-acetyl-lysine, β-alanine, aminobenzoic acid, 6-aminocaproic acid, aminobutyric acid, hydroxyproline, mercaptopropionic acid, 3-nitrotyrosine, norleucine, and pyroglutamic acid. Furthermore, amino acids may be, for example, L-amino acids, D-amino acids, or DL-amino acids.

[0021] In this specification, amino acid sequence identity refers to the degree of amino acid agreement when two or more amino acid sequences being compared are optimally aligned. Amino acid sequence identity can be calculated using commercially available analysis tools or tools available via telecommunication lines (the Internet). For example, it can be calculated using the commercially available software GENETYX (Genetics Co., Ltd.) or using the default parameters of the National Center for Biotechnology Information (NCBI) homology algorithm BLAST (Basic local alignment search tool) (http: / / www.ncbi.nlm.nih.gov / BLAST / ).

[0022] The amino acid sequences disclosed herein may have one or more amino acids (e.g., 1, 2, or 3) deleted, substituted, or modified, or one or more amino acids (e.g., 1, 2, or 3) inserted or added to the sequence, as long as this does not inhibit binding to the Vanin-1 protein.

[0023] Amino acid substitutions are preferably conserved substitutions, which are substitutions with other amino acids that have similar structure and / or properties. Examples of conservative substitutions include substitutions within the groups shown in Table 1.

[0024]

[0025] Examples of amino acid modifications include the modification of functional groups such as amino groups, carboxyl groups, hydroxyl groups, and sulfhydryl (SH) groups. These functional group modifications may include, for example, glycosylation; methylation; esterification; amidation; PEGylation; phosphorylation; hydroxylation; binding with protecting groups such as t-butoxycarbonyl (Boc) groups and 9-fluorenylmethyloxycarbonyl (Fmoc) groups; biotinylation; binding with fluorescent dyes such as fluorescein isothiocyanate (FITC); and binding with enzymes such as peroxidase (HRP) and alkaline phosphatase (ALP).

[0026] In this specification, the antibody may be a monoclonal antibody or a polyclonal antibody, but it is preferably a monoclonal antibody. The antibody can be any isotype, such as IgG, IgA, IgD, IgE, IgM, etc. The antibody may be a human antibody or a non-human antibody. Examples of non-human antibodies include, but are not limited to, mouse antibodies, rat antibodies, guinea pig antibodies, rabbit antibodies, etc. The antibody may be a chimeric antibody. The antibody may be a partially or fully humanized antibody.

[0027] In this specification, the antigen-binding fragment of the antibody is not particularly limited as long as it includes heavy chain CDR1-3 and light chain CDR1-3, for example, Fv, Fab, Fab', (Fab') ２ Examples include scFv, scFv-Fc, diabody, triabody, tetrabody, and minibody.

[0028] In this specification, heavy chain CDR1-3 and light chain CDR1-3 are defined based on the IMGT method.

[0029] In this specification, nucleotides such as DNA and RNA may be subjected to known chemical modifications as exemplified below. To prevent degradation by hydrolytic enzymes such as nucleases, the phosphate residue of each nucleotide can be replaced with a chemically modified phosphate residue such as phosphorothioate (PS), methylphosphonate, or phosphorodithionate. The hydroxyl group at position 2 of the sugar (ribose) of each ribonucleotide may also be replaced with -OR (where R represents, for example, -CH3, -CH2CH2OCH3, -CH2CH2NHC(NH)NH2, -CH2CONHCH3, -CH2CH2CN, etc.). Furthermore, the base portion (pyrimidine, purine) may be chemically modified, for example, by introducing a methyl group or cationic functional group at position 5 of the pyrimidine base, or by substituting the carbonyl group at position 2 with a thiocarbonyl group. Furthermore, the phosphate portion or hydroxyl portion may be modified with, for example, biotin, an amino group, a lower alkylamine group, or an acetyl group, but is not limited to these.

[0030] In this specification, the Vanin-1 protein (antigen) is a protein registered in humans as National Center for Biotechnology Information (NCBI) Reference Sequence: NP_004657.2 and has the amino acid sequence shown in SEQ ID NO: 136: MTTQLPAYVAILLFYVSRASCQDTFTAAVYEHAAILPNATLTPVSREEALALMNRNLDILEGAITSAADQGAHIIVTPEDAIYGWNFNRDSLYPYLEDIPDPEVNWIPCNNRNRFGQTPVQERLSCLAKNNSIYVVANIGDKKPCDTSDPQCPPDGRYQYNTDVVFDSQGKLVARYHKQNLFMGENQFNVPKEPEIVTFNTTFGSFGIFTCFDILFHDPAVTLVKDFHVDTIVFPTAWMNVLPHLSAVEFHSAWAM GMRVNFLASNIHYPSKKMTGSGIYAPNSSRAFHYDMKTEEGKLLLSQLDSHPHSAVVNWTSYASSIEALSSGNKEFKGTVFFDEFTFVKLTGVAGNYTVCQKDLCCHLSYKMSENIPNEVYALGAFD GLHTVEGRYYLQICTLLKCKTTNLNTCGDSAETASTRFEMFSLSGTFGTQYVFPEVLLSENQLAPGEFQVSTDGRLFSLKPTSGPVLTVTLFGRLYEKDWASNASSGLTAQARIIMLIVIAPIVCSLSW

[0031] All patent and non-patent document disclosures cited herein are incorporated in their entirety by reference.

[0032] 2. Anti-Vanin-1 antibody or antigen-binding fragment thereof In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or antigen-binding fragment (1) preferably includes or consists of an amino acid sequence shown in GFSITTTNYW (SEQ ID NO: 1), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 3rd to 10th positions with the N-terminus as the 1st position.

[0033] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (1) is of formula (1-1): ISYDGX １ T (where X １ It is preferable to include or consist of an amino acid sequence represented by (where is N, K, or H), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferable to select from the 2nd and 6th positions, with the N-terminus being the 1st. The mutated sequence may include, for example, X in formula (1-1). １ It includes amino acid sequences where R, Q, or P is present, and INYDGNT (SEQ ID NO: 69).

[0034] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (1) is of formula (1-2): X ２ X ３ GWLLSLAX ４ WG (in the formula, X ２ is T, A, or S, X ３ is S or T, X ４It is preferable to include or consist of an amino acid sequence represented by (where is E, V, or M), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (1-2) is preferably selected from TSGWLLSLAEWG (SEQ ID NO: 3), TSGWLLSLAVWG (SEQ ID NO: 7), ASGWLLSLAMWG (SEQ ID NO: 10), and STGWLLSLAVWG (SEQ ID NO: 12). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 1st, 2nd, and 10th positions with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (1-2). ２ G is and / or X ４ The amino acid sequence contains D, L, I, or C.

[0035] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (1) is of formula (1-3): SEHSX ５ SY (where X ５ It is preferable to include or consist of an amino acid sequence represented by (where is S or R), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferably the 5th position with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (1-3). ５ It contains an amino acid sequence in which is T, K, N, Q, or P.

[0036] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (1) preferably includes or consists of an amino acid sequence represented by LKSDGSH (SEQ ID NO: 5), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, the 1st, 2nd, and 5th to 7th positions with the N-terminus as the 1st position.

[0037] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (1) preferably includes or consists of an amino acid sequence represented by GVAYSGGYV (SEQ ID NO: 6), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited.

[0038] In an anti-vanin-1 antibody or its antigen-binding fragment (1), it is preferable that the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 3, 7, 10, or 12, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 6.

[0039] In an anti-vanin-1 antibody or its antigen-binding fragment (1), it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 1, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 2, 9, or 11, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 3, 7, 10, or 12, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 4 or 8, the light chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 5, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 6.

[0040] In an anti-vanin-1 antibody or its antigen-binding fragment (1), (1-1) heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 1, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 2, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 3, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 4, light chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 5, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 6, or (1-2) heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 1, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 2, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 7, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 8, light chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 5, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 6, or (1-3) It is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 1, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 9, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 10, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 4, the light chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 5, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 6, or (1-4) It is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 1, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 11, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 12, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 4, the light chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 5, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 6.

[0041] The anti-Vanin-1 antibody or its antigen-binding fragment (1) is preferably the anti-Vanin-1 antibody or its antigen-binding fragment (1-1).

[0042] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (2) is of formula (2-1): GFTFSX ６ YW (in the formula, X ６ It is preferable to include or consist of an amino acid sequence represented by (where is N or K), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferable to select from the 2nd and 4th to 8th positions, with the N-terminus being the 1st. The mutated sequence may include, for example, X in formula (2-1). ６ This includes amino acid sequences where is R, Q, or P, amino acid sequences represented by formula (3-1), amino acid sequences represented by formula (8-1), GFTFSNDY (SEQ ID NO: 89), and GLTLSNSW (SEQ ID NO: 126).

[0043] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (2) is formula (2-2): IX ７ X ８ DX ９ X １０ TX １１ (In the formula, X ７ is N or S, X ８ is S, G, H, or V, and X ９ is S, R, or G, and X １０ is S or T, X １１It is preferable to include or consist of an amino acid sequence represented by (where is M, I, K, or V), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (2-2) is preferably selected from INSDSSTM (SEQ ID NO: 14), ISGDRTTI (SEQ ID NO: 18), INHDSSTK (SEQ ID NO: 23), INVDSSTV (SEQ ID NO: 26), ISGDSSTI (SEQ ID NO: 28), and INGDGSTI (SEQ ID NO: 32). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd, 3rd, and 5th to 8th positions, with the N-terminus being the 1st. The mutated sequence may include, for example, X in formula (2-2). ７ is K, R, Q, P, or T, and / or X ８ is T, A, F, W, Y, L, I, or D, and / or X ９ is T, K, N, Q, P, or A and / or X １１ An amino acid sequence in which is A, L, P, F, W, R, N, or Q, an amino acid sequence represented by formula (3-2), or in formula (7-1) where X ４９ This includes amino acid sequences where is N or D, amino acid sequences represented by formula (8-2), ISGDSNYI (SEQ ID NO: 90), and INGDSRNI (SEQ ID NO: 127).

[0044] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (2) is of formula (2-3): X １２ TX １３ GGX １４ WG (in the formula, X １２ is M, A, I, or V, X １３ is S, E, K, or T, X １４It is preferable to include or consist of an amino acid sequence represented by (where is L or V), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (2-3) is preferably selected from MTSGGLWG (SEQ ID NO: 15), ATEGGLWG (SEQ ID NO: 19), ATEGGVWG (SEQ ID NO: 24), ATKGGLWG (SEQ ID NO: 27), ITSGGLWG (SEQ ID NO: 29), VTTGGLWG (SEQ ID NO: 31), and ATSGGLWG (SEQ ID NO: 33). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 1st, 3rd, and 6th positions with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (2-3). １２ is C, G, L, P, F, or W, and / or X １３ is D, R, N, Q, or P, and / or X １４ It contains an amino acid sequence where is I.

[0045] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (2) is of formula (2-4): QSLLYSGNX １５ X １６ NY (in the formula, X １５ is N or T, X １６ It is preferable to include or consist of an amino acid sequence represented by (where is N or K), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (2-4) is preferably selected from QSLLYSGNNNNY (SEQ ID NO: 16), QSLLYSGNNKNY (SEQ ID NO: 20), and QSLLYSGNTKNY (SEQ ID NO: 25). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 5th, 9th, and 10th positions, with the N-terminus being the 1st. The mutated sequence may include, for example, X in formula (2-4). １５ is S, K, R, Q, or P, and / or X １６ An amino acid sequence in which is R, Q, or P, and in formula (3-4) X ２５It contains an amino acid sequence where S is present.

[0046] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (2) preferably includes or consists of an amino acid sequence represented by LAS, or an amino acid sequence in which one amino acid in said amino acid sequence is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited.

[0047] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (2) is of formula (2-5): MQTFGX １７ PRT (where X １７ It is preferable to include or consist of an amino acid sequence represented by (where is I, T, or L), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferably the 6th position with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (2-5). １７ It contains an amino acid sequence where V or S is present.

[0048] In the anti-Vanin-1 antibody or its antigen-binding fragment (2), it is preferable that the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NOs: 12, 15, 19, 24, 27, 29, 31, or 33, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NOs: 17, 21, or 30.

[0049] In the anti-Vanin-1 antibody or its antigen-binding fragment (2), it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 13 or 22, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 18, 23, 26, 28, or 32, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 15, 19, 24, 27, 29, 31, or 33, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 16, 20, or 25, the light chain CDR2 comprises or consists of the amino acid sequence shown in LAS, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 17, 21, or 30.

[0050] In an anti-vanin-1 antibody or its antigen-binding fragment (2), (2-1) heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 13, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 14, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 15, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 16, light chain CDR2 contains or consists of the amino acid sequence shown in LAS, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 17, or (2-2) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 13, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 18, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 19, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 20, light chain CDR2 contains or consists of the amino acid sequence shown in LAS, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 21, or (2-3) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 22, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 23, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 24, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 25, light chain CDR2 contains or consists of the amino acid sequence shown in LAS, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 21, or (2-4) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 13, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 26, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 27, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 16, light chain CDR2 contains or consists of the amino acid sequence shown in LAS, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 17, or(2-5) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 13, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 28, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 29, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 20, light chain CDR2 contains or consists of the amino acid sequence shown in LAS, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 30, or (2-6) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 13, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 26, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 31, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 20, light chain CDR2 contains or consists of the amino acid sequence shown in LAS, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 17, or (2-7) It is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 13, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 32, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 33, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 20, the light chain CDR2 contains or consists of the amino acid sequence shown in LAS, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 17.

[0051] The anti-Vanin-1 antibody or its antigen-binding fragment (2) is preferably the anti-Vanin-1 antibody or its antigen-binding fragment (2-1).

[0052] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (3) is of formula (3-1): GFTFX １８ NX １９ Y (where X １８ is S or N, X １９It is preferable to include or consist of an amino acid sequence represented by (where is W or Y), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (3-1) is preferably selected from GFTFSNWY (SEQ ID NO: 34) and GFTFNNYY (SEQ ID NO: 43). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd and 4th to 8th positions, with the N-terminus being the 1st. Examples of mutated sequences include the amino acid sequence represented by formula (2-1), and in formula (3-1) X １８ is T, K, R, Q, or P, and / or X １９ This includes amino acid sequences where is F or H, amino acid sequences shown in formula (8-1), and GFTFSNDY (SEQ ID NO: 89).

[0053] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (3) is of formula (3-2): ISX ２０ DSSDX ２１ (In the formula, X ２０ is A or D, X ２１ It is preferable to include or consist of an amino acid sequence represented by formula (I, L, or M), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (3-2) is preferably selected from ISADSSDI (SEQ ID NO: 35), ISDDSSDL (SEQ ID NO: 39), ISDDSSDM (SEQ ID NO: 41), and ISDDSSDI (SEQ ID NO: 44). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd, 3rd, and 5th to 8th positions, with the N-terminus being the 1st. Examples of mutated sequences include the amino acid sequence represented by formula (2-2), and X in formula (3-2). ２０ is G or E, and / or X ２１ This includes amino acid sequences where is V or C, amino acid sequences represented by formula (7-1), amino acid sequences represented by formula (8-2), ISGDSNYI (SEQ ID NO: 90), and INGDSRNI (SEQ ID NO: 127).

[0054] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (3) is of formula (3-3): X ２２ DISGX ２３ GX ２４ (In the formula, X ２２ is A or V, and X ２３ is S or Y, and X ２４ It is preferable to include or consist of an amino acid sequence represented by (where is I, F, L, or V), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (3-3) is preferably selected from ADISGSGI (SEQ ID NO: 36), ADISGSGF (SEQ ID NO: 40), ADISGSGL (SEQ ID NO: 42), ADISGYGV (SEQ ID NO: 45), and VDISGYGV (SEQ ID NO: 46). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 1st, 6th, and 8th positions with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (3-3). ２２ is G, L, or I, and / or X ２３ is T, L, or I, and / or X ２４ The amino acid sequence contains W, H, or Y.

[0055] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (3) is of formula (3-4): QSLLX ２５ SGNNX ２６ NY (in the formula, X ２５ is S or Y, and X ２６It is preferable to include or consist of an amino acid sequence represented by (where is K or N), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (3-4) is preferably selected from QSLLYSGNNNNY (SEQ ID NO: 16) and QSLLSSGNNKNY (SEQ ID NO: 37). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 5th, 9th, and 10th positions, with the N-terminus being the 1st. The mutated sequence may include, for example, X in formula (2-4). １５ The amino acid sequence in which is T, and in formula (3-4) X ２５ is T, F, W, or H, and / or X ２６ The amino acid sequence contains R, Q, or P.

[0056] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (3) preferably includes or consists of an amino acid sequence represented by LAS, or an amino acid sequence in which one amino acid in said amino acid sequence is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited.

[0057] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (3) is of formula (3-5): MQX ２７ X ２８ X ２９ X ３０ PX ３１ T (where X ２７ is D or T, X ２８ is Y or F, and X ２９ is S or G, X ３０ is V or I, X ３１It is preferable to include or consist of an amino acid sequence represented by (where is L or R), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (3-5) is preferably selected from MQTFGIPRT (SEQ ID NO: 17) and MQDYSVPLT (SEQ ID NO: 38). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 3rd to 6th and 8th positions, with the N-terminus being the 1st position. The mutated sequence may include, for example, X in formula (3-5). ２７ is E or S, and / or X ２８ is W or H, and / or X ２９ is T or A, and / or X ３０ L is and / or X ３１ This includes amino acid sequences where is V, I, K, N, Q, or P, as well as MQDYSAPYT (SEQ ID NO: 125).

[0058] In the anti-Vanin-1 antibody or its antigen-binding fragment (3), it is preferable that the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 36, 40, 42, 45, or 46, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 17 or 38.

[0059] In an anti-Vanin-1 antibody or its antigen-binding fragment (3), it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 34 or 43, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 35, 39, 41, or 44, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 36, 40, 42, 45, or 46, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 16 or 37, the light chain CDR2 comprises or consists of the amino acid sequence shown in LAS, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 17 or 38.

[0060] In an anti-vanin-1 antibody or its antigen-binding fragment (3), (3-1) heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 34, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 35, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 36, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 37, light chain CDR2 contains or consists of the amino acid sequence shown in LAS, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 38, or (3-2) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 34, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 39, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 40, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 37, light chain CDR2 contains or consists of the amino acid sequence shown in LAS, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 38, or (3-3) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 34, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 41, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 42, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 16, light chain CDR2 contains or consists of the amino acid sequence shown in LAS, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 17, or (3-4) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 43, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 44, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 45, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 37, light chain CDR2 contains or consists of the amino acid sequence shown in LAS, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 38, or(3-5) It is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 43, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 44, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 46, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 37, the light chain CDR2 contains or consists of the amino acid sequence shown in LAS, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 38.

[0061] The anti-Vanin-1 antibody or its antigen-binding fragment (3) is preferably the anti-Vanin-1 antibody or its antigen-binding fragment (3-1).

[0062] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (4) preferably includes or consists of an amino acid sequence represented by GFSLTSYS (SEQ ID NO: 47), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 3rd to 8th positions (e.g., the 3rd position) with the N-terminus as the 1st position. The mutated sequence includes, for example, the amino acid sequence represented by GFPLTSYS (SEQ ID NO: 63).

[0063] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (4) is of formula (4-1): IWSX ３２ GX ３３ X ３４ (In the formula, X ３２ is D or G, X ３３ is S or T, X ３４It is preferable to include or consist of an amino acid sequence represented by (where is P, T, or S), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (4-1) is preferably selected from IWSDGSP (SEQ ID NO: 48), IWSGGST (SEQ ID NO: 52), IWSDGSS (SEQ ID NO: 55), and IWSGGTT (SEQ ID NO: 58). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 4th, 6th, and 7th positions, with the N-terminus being the 1st. The mutated sequence may include, for example, X in formula (4-1). ３２ is E or A, and / or X ３４ The amino acid sequence contains K, R, N, or Q.

[0064] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (4) is of formula (4-2): ARDWGX ３５ LDX ３６ (In the formula, X ３５ is S or N, X ３６ It is preferable to include or consist of an amino acid sequence represented by (where is V or I), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (4-2) is preferably selected from ARDWGSLDV (SEQ ID NO: 49), ARDWGNLDI (SEQ ID NO: 56), and ARDWGSLDI (SEQ ID NO: 60). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 6th and 9th positions with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (4-2). ３５ is T, K, R, Q, or P, and / or X ３６ It contains an amino acid sequence where L is present.

[0065] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (4) is of formula (4-3): QSX ３７ X ３８ X ３９ Y (where X ３７is I or V, X ３８ is S, T, N, or K, and X ３９ It is preferable to include or consist of an amino acid sequence represented by (where is R, S, or T), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (4-3) is preferably selected from QSISRY (SEQ ID NO: 50), QSVTSY (SEQ ID NO: 53), QSVNTY (SEQ ID NO: 57), QSVKSY (SEQ ID NO: 61), and QSVNSY (SEQ ID NO: 65). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 3rd to 5th positions with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (4-3). ３７ L is and / or X ３８ is R, Q, or P, and / or X ３９ It contains an amino acid sequence in which is K, N, Q, or P.

[0066] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (4) preferably includes or consists of an amino acid sequence represented by YTN, SAY, NAY, or YAN, or an amino acid sequence in which one amino acid is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the first and second positions, with the N-terminus being the first. Examples of mutated sequences include YSN, YGN, TAY, KAY, RAY, QAY, and PAY.

[0067] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (4) is of formula (4-4): QQYX ４０ X ４１ WPYT (where X ４０ is H or Y, and X ４１It is preferable to include or consist of an amino acid sequence represented by (where is S or N), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (4-4) is preferably selected from QQYHSWPYT (SEQ ID NO: 51), QQYHNWPYT (SEQ ID NO: 54), and QQYYSWPYT (SEQ ID NO: 59). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 4th and 5th positions with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (4-4). ４０ is F or W, and / or X ４１ The amino acid sequence contains T, K, R, Q, or P.

[0068] In the anti-Vanin-1 antibody or its antigen-binding fragment (4), it is preferable that the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 49, 56, or 60, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 51, 54, or 59.

[0069] In an anti-Vanin-1 antibody or its antigen-binding fragment (4), it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 47, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 48, 52, 55, or 58, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 49, 56, or 60, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 50, 53, 57, 61, or 62, the light chain CDR2 comprises or consists of the amino acid sequence shown in YTN, SAY, NAY, or YAN, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 51, 54, or 59.

[0070] In an anti-vanin-1 antibody or its antigen-binding fragment (4), (4-1) heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 47, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 48, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 49, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 50, light chain CDR2 contains or consists of the amino acid sequence shown in YTN, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 51, or (4-2) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 47, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 52, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 49, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 53, light chain CDR2 contains or consists of the amino acid sequence shown in SAY, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 54, or (4-3) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 47, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 55, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 56, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 57, light chain CDR2 contains or consists of the amino acid sequence shown in YTN, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 51, or (4-4) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 47, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 58, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 49, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 53, light chain CDR2 contains or consists of the amino acid sequence shown in NAY, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 59, or(4-5) It is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 47, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 55, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 60, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 61, the light chain CDR2 contains or consists of the amino acid sequence shown in YAN, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 51, or (4-6) it is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 43, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 44, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 46, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 37, the light chain CDR2 contains or consists of the amino acid sequence shown in LAS, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 38.

[0071] The anti-Vanin-1 antibody or its antigen-binding fragment (4) is preferably the anti-Vanin-1 antibody or its antigen-binding fragment (4-1).

[0072] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (5) is of formula (5-1): GFX ４２ LTSYS (where X ４２ It is preferable to include or consist of an amino acid sequence represented by (where is P or S), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferably the 3rd position with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (5-1). ４２ The amino acid sequence contains T, K, R, N, or Q.

[0073] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (5) is of formula (5-2): IWSX ４３ GSX ４４ (In the formula, X ４３is D or G, X ４４ It is preferable to include or consist of an amino acid sequence represented by (where is S or T), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (5-2) is preferably selected from IWSGGST (SEQ ID NO: 52) and IWSDGSS (SEQ ID NO: 55). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 4th, 6th, and 7th positions, with the N-terminus being the 1st. The mutated sequence may include, for example, X in formula (4-1). ３３ is T and / or X ３４ The amino acid sequence in which is P, and in formula (5-2) X ４３ is E or A, and / or X ４４ The amino acid sequence contains K, R, N, or Q.

[0074] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (5) preferably includes or consists of an amino acid sequence represented by ARDGGYFH (SEQ ID NO: 64) or ARDRGDFDV (SEQ ID NO: 67), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 4th position onward, with the N-terminus being the 1st position.

[0075] In one embodiment, the light chain CDR1 of the anti-vanin-1 antibody or its antigen-binding fragment (5) is of formula (5-3): QSVNX ４５ Y (where X ４５ It is preferable to include or consist of an amino acid sequence represented by (where is S or T), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferable to select from the 3rd to 5th positions, with the N-terminus being the 1st. The mutated sequence may include, for example, X in formula (4-3). ３７I is and / or X ３８ is S, T, or K, and / or X ３９ It contains an amino acid sequence where R is present.

[0076] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (5) preferably includes or consists of an amino acid sequence represented by NAY or YTN, or an amino acid sequence in which one amino acid is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the first and second positions, with the N-terminus being the first. Examples of mutated sequences include SAY and YAN.

[0077] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (5) is of formula (5-4): QQYX ４６ X ４７ WPYX ４８ (In the formula, X ４６ is H or Q, and X ４７ is S or N, X ４８ It is preferable to include or consist of an amino acid sequence represented by (where is A or T), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (5-4) is preferably selected from QQYHSWPYA (SEQ ID NO: 66) and QQYQNWPYT (SEQ ID NO: 68). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 4th, 5th, and 9th positions, with the N-terminus being the 1st. Examples of mutated sequences include the amino acid sequence represented by formula (4-4), and in formula (5-4), X ４６ is F, W, Y, K, R, N, or P, and / or X ４７ is T, K, R, Q, or P, and / or X ４８ It contains an amino acid sequence where the first amino acid is G or S.

[0078] In the anti-Vanin-1 antibody or its antigen-binding fragment (5), it is preferable that the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 64 or 67, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 66 or 68.

[0079] In an anti-vanin-1 antibody or its antigen-binding fragment (5), it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 47 or 63, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 52 or 55, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 64 or 67, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 57 or 65, the light chain CDR2 comprises or consists of the amino acid sequence shown in NAY or YTN, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 66 or 68.

[0080] In an anti-vanin-1 antibody or its antigen-binding fragment (5), (5-1) heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 63, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 55, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 64, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 65, light chain CDR2 contains or consists of the amino acid sequence shown in NAY, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 66, or (5-2) It is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 47, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 52, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 67, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 57, the light chain CDR2 contains or consists of the amino acid sequence shown in YTN, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 68.

[0081] The anti-Vanin-1 antibody or its antigen-binding fragment (5) is preferably the anti-Vanin-1 antibody or its antigen-binding fragment (5-1).

[0082] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (6) preferably includes or consists of an amino acid sequence represented by GFSITTTNYW (SEQ ID NO: 1), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 3rd to 10th positions with the N-terminus as the 1st position.

[0083] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (6) preferably includes or consists of an amino acid sequence represented by INYDGNT (SEQ ID NO: 69), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd and 6th positions, with the N-terminus being the 1st. The mutated sequence includes, for example, the amino acid sequence represented by formula (1-1).

[0084] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (6) preferably includes or consists of an amino acid sequence represented by AREGMVAGFYFDV (SEQ ID NO: 70), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 3rd to 13th positions with the N-terminus as the 1st position.

[0085] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (6) preferably includes or consists of an amino acid sequence represented by QGIDNG (SEQ ID NO: 71), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 2nd to 6th positions with the N-terminus as the 1st position.

[0086] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (6) preferably includes or consists of an amino acid sequence represented by DAT, or an amino acid sequence in which one amino acid in said amino acid sequence is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited.

[0087] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (6) preferably includes or consists of an amino acid sequence represented by QQGSSTPYT (SEQ ID NO: 72), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 3rd to 6th and 9th positions with the N-terminus as the 1st position.

[0088] In an anti-vanin-1 antibody or its antigen-binding fragment (6), it is preferable that the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 70, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 72.

[0089] In an anti-vanin-1 antibody or its antigen-binding fragment (6), (6-1) it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 1, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 69, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 70, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 71, the light chain CDR2 comprises or consists of the amino acid sequence shown in DAT, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 72.

[0090] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (7) preferably includes or consists of an amino acid sequence represented by GFTFSNSW (SEQ ID NO: 73), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd and 4th to 8th positions, with the N-terminus being the 1st. Examples of mutated sequences include the amino acid sequence represented by formula (2-1), the amino acid sequence represented by formula (3-1), GFTFSDSW (SEQ ID NO: 86), GFTFSNDY (SEQ ID NO: 89), and GLTLSNSW (SEQ ID NO: 126).

[0091] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (7) is of formula (7-1):INGDSSX ４９ I (where X ４９ It is preferable to include or consist of an amino acid sequence represented by (where is N, D, or T), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferable to select from the 2nd, 3rd, and 5th to 8th positions, with the N-terminus being the 1st. The mutated sequence may include, for example, X in formula (2-2). ７ S is and / or X ８ is S, H, or V, and / or X ９is R or G, and / or X １０ is T and / or X １１ An amino acid sequence in which is M, K, or V, an amino acid sequence represented by formula (3-2), or in formula (7-1) where X ４９ An amino acid sequence in formula (8-2) where X is K, R, Q, P, E, or S. ５５ This includes amino acid sequences where R is present, as well as ISGDSNYI (SEQ ID NO: 90).

[0092] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (7) is of formula (7-2): AADPGGNX ５０ HPYX ５１ DV (in the formula, X ５０ is S or Y, and X ５１ It is preferable to include or consist of an amino acid sequence represented by (where is L or F), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (7-2) is preferably selected from AADPGGNSHPYLDV (SEQ ID NO: 75), AADPGGNYHPYFDV (SEQ ID NO: 79), and AADPGGNSHPYFDV (SEQ ID NO: 82). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 8th and 12th positions with the N-terminus as the 1st position. The mutated sequence may include, for example, X in formula (7-2). ５０ is T, L, or I, and / or X ５１ The amino acid sequence contains V, I, W, H, or Y.

[0093] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (7) preferably includes or consists of an amino acid sequence represented by NIGRKS (SEQ ID NO: 76), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited.

[0094] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (7) preferably includes or consists of an amino acid sequence represented by ADY, or an amino acid sequence in which one amino acid is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited.

[0095] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (7) is of formula (7-3): QVWDX ５２ DSAGX ５３ (In the formula, X ５２ is S or T, X ５３ It is preferable to include or consist of an amino acid sequence represented by (where is V or L), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (7-3) is preferably selected from QVWDSDSAGV (SEQ ID NO: 77), QVWDTDSAGV (SEQ ID NO: 80), and QVWDSDSAGL (SEQ ID NO: 83). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 5th and 10th positions with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (7-3). ５３ It contains an amino acid sequence where is I.

[0096] In the anti-Vanin-1 antibody or its antigen-binding fragment (7), it is preferable that the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 75, 79, or 82, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 77, 80, or 83.

[0097] In an anti-vanin-1 antibody or its antigen-binding fragment (7), it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 73, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 74, 78, or 81, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 75, 79, or 82, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 76, the light chain CDR2 comprises or consists of the amino acid sequence shown in ADY, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 77, 80, or 83.

[0098] In an anti-vanin-1 antibody or its antigen-binding fragment (7), (7-1) heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 73, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 74, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 75, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 76, light chain CDR2 contains or consists of the amino acid sequence shown in ADY, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 77, or (7-2) It is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 73, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 78, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 79, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 76, the light chain CDR2 contains or consists of the amino acid sequence shown in ADY, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 80, or (7-3) it is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 73, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 81, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 82, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 76, the light chain CDR2 contains or consists of the amino acid sequence shown in ADY, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 83.

[0099] The anti-Vanin-1 antibody or its antigen-binding fragment (7) is preferably the anti-Vanin-1 antibody or its antigen-binding fragment (7-1).

[0100] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (8) is of formula (8-1): GFTFSX ５４ SW (in the formula, X ５４It is preferable to include or consist of an amino acid sequence represented by (where is N or D), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferable to select from the 2nd and 4th to 8th positions, with the N-terminus being the 1st. Examples of mutated sequences include the amino acid sequence represented by formula (2-1), the amino acid sequence represented by formula (3-1), and the X in formula (8-1). ５４ The amino acid sequences include GFTFSNDY (SEQ ID NO: 89) and GLTLSNSW (SEQ ID NO: 126), where is K, R, Q, P, or E.

[0101] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (8) is of formula (8-2): INGDX ５５ SNI (where X ５５ It is preferable to include or consist of an amino acid sequence represented by (where is S or R), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferable to select from the 2nd, 3rd, and 5th to 8th positions, with the N-terminus being the 1st. Examples of mutated sequences include the amino acid sequence represented by formula (2-2), the amino acid sequence represented by formula (3-2), and the X in formula (7-1). ４９ An amino acid sequence in which is D or T, in formula (8-2) X ５５ The amino acid sequence includes T, K, N, Q, or P, and ISGDSNYI (SEQ ID NO: 90).

[0102] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (8) preferably includes or consists of an amino acid sequence represented by AADPGGSGYFGYFDI (SEQ ID NO: 84) or AADPSGSGWTVDV (SEQ ID NO: 88), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conserved substitutions). The location of the amino acid mutation is not particularly limited, but may be, for example, selected from the 5th and 9th positions onward, with the N-terminus being the 1st position.

[0103] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (8) preferably includes or consists of an amino acid sequence represented by NIGRKS (SEQ ID NO: 76), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited.

[0104] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (8) preferably includes or consists of an amino acid sequence represented by ADY, or an amino acid sequence in which one amino acid is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited.

[0105] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (8) preferably includes or consists of an amino acid sequence represented by QVWDADSAQYV (SEQ ID NO: 85), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 5th and 9th to 11th positions with the N-terminus as the 1st position.

[0106] In the anti-Vanin-1 antibody or its antigen-binding fragment (8), it is preferable that the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 84 or 88, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 85.

[0107] In an anti-vanin-1 antibody or its antigen-binding fragment (8), it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 73 or 86, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 74 or 87, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 84 or 88, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 76, the light chain CDR2 comprises or consists of the amino acid sequence shown in ADY, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 85.

[0108] In an anti-vanin-1 antibody or its antigen-binding fragment (8), (8-1) heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 73, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 74, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 84, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 76, light chain CDR2 contains or consists of the amino acid sequence shown in ADY, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 85, or (8-2) It is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 86, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 87, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 88, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 76, the light chain CDR2 contains or consists of the amino acid sequence shown in ADY, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 85.

[0109] The anti-Vanin-1 antibody or its antigen-binding fragment (8) is preferably the anti-Vanin-1 antibody or its antigen-binding fragment (8-1).

[0110] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (9) preferably includes or consists of an amino acid sequence represented by GFTFSNDY (SEQ ID NO: 89), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd and 4th to 8th positions, with the N-terminus being the 1st. Mutant sequences include, for example, the amino acid sequence represented by formula (2-1), the amino acid sequence represented by formula (3-1), and the amino acid sequence represented by formula (8-1).

[0111] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (9) preferably includes or consists of an amino acid sequence represented by ISGDSNYI (SEQ ID NO: 90), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd, 3rd, and 5th to 8th positions, with the N-terminus being the 1st. Examples of mutated sequences include the amino acid sequence represented by formula (2-2), the amino acid sequence represented by formula (3-2), the amino acid sequence represented by formula (7-1), the amino acid sequence represented by formula (8-2), and INGDSRNI (SEQ ID NO: 127).

[0112] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (9) preferably includes or consists of an amino acid sequence represented by ARHIAAYYFNL (SEQ ID NO: 91), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 3rd to 11th positions with the N-terminus as the 1st position.

[0113] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (9) preferably includes or consists of an amino acid sequence represented by SVNNNF (SEQ ID NO: 92), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited.

[0114] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (9) preferably includes or consists of an amino acid sequence shown in RTS, or an amino acid sequence in which one amino acid in said amino acid sequence is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited.

[0115] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (9) preferably includes or consists of an amino acid sequence represented by QQSSNDLT (SEQ ID NO: 93), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 2nd to 8th or 3rd to 8th positions with the N-terminus as the 1st position.

[0116] In the anti-Vanin-1 antibody or its antigen-binding fragment (9), it is preferable that the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 91, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 93.

[0117] In an anti-vanin-1 antibody or its antigen-binding fragment (9), (9-1) it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 89, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 90, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 91, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 92, the light chain CDR2 comprises or consists of the amino acid sequence shown in RTS, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 93.

[0118] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (10) preferably includes or consists of an amino acid sequence represented by GLFNTFY (SEQ ID NO: 94), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 3rd, 5th, and 7th positions, with the N-terminus being the 1st. Examples of mutated sequences include GFTFSTYY (SEQ ID NO: 122).

[0119] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (10) preferably includes or consists of an amino acid sequence represented by ISHTGGST (SEQ ID NO: 95), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 3rd, 4th, and 6th positions, with the N-terminus being the 1st. Examples of mutated sequences include ISNDGSST (SEQ ID NO: 123).

[0120] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (10) preferably includes or consists of an amino acid sequence represented by LRNGRYSWGTYHYFDV (SEQ ID NO: 96), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited.

[0121] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (10) preferably includes or consists of an amino acid sequence represented by QGISKN (SEQ ID NO: 97), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 4th to 6th positions with the N-terminus as the 1st position.

[0122] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (10) preferably includes or consists of an amino acid sequence represented by YAT, or an amino acid sequence in which one amino acid is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited.

[0123] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (10) preferably includes or consists of an amino acid sequence represented by QHTNSWPQYT (SEQ ID NO: 98), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 2nd to 10th positions with the N-terminus as the 1st position.

[0124] In the anti-Vanin-1 antibody or its antigen-binding fragment (10), it is preferable that the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 96, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 98.

[0125] In an anti-Vanin-1 antibody or its antigen-binding fragment (10), it is preferable that (10-1) heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 94, heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 95, heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 96, light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 97, light chain CDR2 comprises or consists of the amino acid sequence shown in YAT, and light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 98.

[0126] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (11) preferably includes or consists of an amino acid sequence represented by GFTFSDYW (SEQ ID NO: 99), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be selected from positions 3 to 8 (e.g., 6 to 8) with the N-terminus as the 1st position.

[0127] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (11) preferably includes or consists of an amino acid sequence represented by INYDGDST (SEQ ID NO: 100), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 3rd to 6th positions with the N-terminus as the 1st position.

[0128] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (11) preferably includes or consists of an amino acid sequence represented by ARASMGWNEYQYALDI (SEQ ID NO: 101), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 3rd to 16th positions with the N-terminus as the 1st position.

[0129] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (11) preferably includes or consists of an amino acid sequence represented by SAHSSYY (SEQ ID NO: 102), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 2nd to 7th positions with the N-terminus as the 1st position (e.g., the 2nd position).

[0130] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (11) preferably includes or consists of an amino acid sequence represented by LKSDGSH (SEQ ID NO: 5), or an amino acid sequence in which one amino acid is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 1st, 2nd, and 5th to 7th positions with the N-terminus as the 1st position.

[0131] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (11) preferably includes or consists of an amino acid sequence represented by GMSYSGGFV (SEQ ID NO: 103), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 2nd to 9th positions with the N-terminus as the 1st position.

[0132] In an anti-vanin-1 antibody or its antigen-binding fragment (11), it is preferable that the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 101, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 103.

[0133] In an anti-vanin-1 antibody or its antigen-binding fragment (11), (11-1) it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 99, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 100, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 101, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 102, the light chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 5, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 103.

[0134] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (12) is of formula (12-1): GFSLX ５６ SYG (in the formula, X ５６ It is preferable to include or consist of an amino acid sequence represented by (where is T or S), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferably the 5th position with the N-terminus as the 1st.

[0135] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (12) is of formula (12-2): X ５７ WDGGX ５８ T (where X ５７ is I or V, X ５８It is preferable to include or consist of an amino acid sequence represented by (where is T, S, or N), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The amino acid sequence represented by formula (12-2) is preferably selected from IWDGGTT (SEQ ID NO: 105), IWDGGST (SEQ ID NO: 110), IWDGGNT (SEQ ID NO: 113), and VWDGGST (SEQ ID NO: 120). The position of the amino acid mutation is not particularly limited, but it is preferably selected from the 1st and 6th positions with the N-terminus as the 1st. The mutated sequence may include, for example, X in formula (12-2). ５７ L is and / or X ５８ The amino acid sequence contains K, R, Q, or P.

[0136] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (12) is of formula (12-3): ARPX ５９ YGX ６０ YSYYTALDX ６１ (In the formula, X ５９ is G or A, X ６０ is R or T, X ６１ It is preferable to include or consist of an amino acid sequence represented by (where is I, S, F, A, or T), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The position of the amino acid mutation is not particularly limited, but it is preferable to select from the 4th, 7th, and 16th positions, with the N-terminus being the 1st. The mutated sequence may include, for example, X in formula (12-3). ６０ is K, N, Q, P, or S, and / or X ６１ It contains an amino acid sequence in which is L, V, W, H, Y, or G.

[0137] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (12) preferably includes or consists of an amino acid sequence represented by SSNVGSYG (SEQ ID NO: 107), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 2nd to 8th positions with the N-terminus as the 1st position.

[0138] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (12) is of formula (12-4): GX ６２ T (where X ６２ It is preferable that the amino acid sequence is represented by (where is T or F), or that the amino acid sequence includes or consists of an amino acid sequence in which one amino acid is mutated (preferably a conservative substitution). The position of the amino acid mutation is not particularly limited, but it is preferably the second position with the N-terminus as the first. The mutated sequence may include, for example, X in formula (12-4). ６２ It contains an amino acid sequence in which is S, W, H, or Y.

[0139] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (12) is of formula (12-5): SSWDYSQNVYX ６３ (In the formula, X ６３ It is preferable to include or consist of an amino acid sequence represented by (where is V, L, or I), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The position of the amino acid mutation is not particularly limited, but it is preferably the 11th position with the N-terminus as the 1st.

[0140] In an anti-Vanin-1 antibody or its antigen-binding fragment (12), it is preferable that the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NOs. 106, 109, 111, 114, 115, 116, 118, or 119, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NOs. 108, 112, or 121.

[0141] In an anti-Vanin-1 antibody or its antigen-binding fragment (12), it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 104 or 117, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 105, 110, 113, or 120, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 106, 109, 111, 114, 115, 116, 118, or 119, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 107, the light chain CDR2 comprises or consists of the amino acid sequence shown in GTT or GFT, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 108, 112, or 121.

[0142] In an anti-vanin-1 antibody or its antigen-binding fragment (12), (12-1) heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 104, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 105, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 106, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 107, light chain CDR2 contains or consists of the amino acid sequence shown in GTT, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 108, or (12-2) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 104, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 105, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 109, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 107, light chain CDR2 contains or consists of the amino acid sequence shown in GTT, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 108, or (12-3) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 104, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 110, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 111, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 107, light chain CDR2 contains or consists of the amino acid sequence shown in GTT, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 112, or (12-4) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 104, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 113, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 114, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 107, light chain CDR2 contains or consists of the amino acid sequence shown in GTT, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 108, or(12-5) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 104, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 110, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 115, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 107, light chain CDR2 contains or consists of the amino acid sequence shown in GTT, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 108, or (12-6) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 104, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 113, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 116, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 107, light chain CDR2 contains or consists of the amino acid sequence shown in GTT, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 108, or (12-7) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 117, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 110, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 118, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 107, light chain CDR2 contains or consists of the amino acid sequence shown in GTT, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 108, or (12-8) Heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 104, heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 110, heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 118, light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 107, light chain CDR2 contains or consists of the amino acid sequence shown in GTT, light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 108, or(12-9) It is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 104, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 113, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 119, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 107, the light chain CDR2 contains or consists of the amino acid sequence shown in GFT, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 108, or (12-10) it is preferable that the heavy chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 104, the heavy chain CDR2 contains or consists of the amino acid sequence shown in SEQ ID NO: 120, the heavy chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 119, the light chain CDR1 contains or consists of the amino acid sequence shown in SEQ ID NO: 107, the light chain CDR2 contains or consists of the amino acid sequence shown in GFT, and the light chain CDR3 contains or consists of the amino acid sequence shown in SEQ ID NO: 121.

[0143] The anti-Vanin-1 antibody or its antigen-binding fragment (12) is preferably the anti-Vanin-1 antibody or its antigen-binding fragment (12-1).

[0144] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (13) preferably includes or consists of an amino acid sequence represented by GFTFSTYY (SEQ ID NO: 122), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 3rd, 5th, and 7th positions, with the N-terminus being the 1st. Examples of mutated sequences include GFLFNTFY (SEQ ID NO: 94).

[0145] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (13) preferably includes or consists of an amino acid sequence represented by ISNDGSST (SEQ ID NO: 123), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 3rd, 4th, and 6th positions, with the N-terminus being the 1st. Examples of mutated sequences include ISHTGGST (SEQ ID NO: 95).

[0146] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (13) preferably includes or consists of an amino acid sequence represented by ASFYSKYV (SEQ ID NO: 124), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 2nd to 8th positions with the N-terminus as the 1st position.

[0147] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (13) preferably includes or consists of an amino acid sequence represented by QSLLSSGNNKNY (SEQ ID NO: 37), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 5th, 9th, and 10th positions, with the N-terminus being the 1st. Examples of the mutated sequences include the amino acid sequence represented by formula (2-4), and the X in formula (3-4). ２５ Y is and / or X ２６ It contains an amino acid sequence where N is present.

[0148] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (13) preferably includes or consists of an amino acid sequence represented by LAS, or an amino acid sequence in which one amino acid in said amino acid sequence is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited.

[0149] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (13) preferably includes or consists of an amino acid sequence represented by MQDYSAPYT (SEQ ID NO: 125), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from positions 6 to 8, with the N-terminus being the 1st position. An example of a mutated sequence is MQDYSVPLT (SEQ ID NO: 38).

[0150] In an anti-vanin-1 antibody or its antigen-binding fragment (13), (13-1) it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 122, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 123, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 124, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 37, the light chain CDR2 comprises or consists of the amino acid sequence shown in LAS, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 125.

[0151] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (14) preferably includes or consists of an amino acid sequence represented by GLTLSNSW (SEQ ID NO: 126), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd and 4th to 8th positions, with the N-terminus being the 1st. Mutant sequences include, for example, the amino acid sequence represented by formula (2-1), the amino acid sequence represented by formula (3-1), and the amino acid sequence represented by formula (8-1).

[0152] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (14) preferably includes or consists of an amino acid sequence represented by INGDSRNI (SEQ ID NO: 127), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd, 3rd, and 5th to 8th positions, with the N-terminus being the 1st. Examples of mutated sequences include the amino acid sequence represented by formula (2-2), the amino acid sequence represented by formula (7-1), the amino acid sequence represented by formula (8-2), and ISGDSNYI (SEQ ID NO: 90).

[0153] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (14) preferably includes or consists of an amino acid sequence represented by AASLDYYGLDI (SEQ ID NO: 128), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 2nd to 11th positions with the N-terminus as the 1st position.

[0154] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (14) preferably includes or consists of an amino acid sequence represented by GLGNKY (SEQ ID NO: 129), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited.

[0155] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (14) preferably includes or consists of an amino acid sequence shown in EDS, or an amino acid sequence in which one amino acid in said amino acid sequence is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited.

[0156] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (14) preferably includes or consists of an amino acid sequence represented by AIALGSGSGFHV (SEQ ID NO: 130), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited.

[0157] In an anti-vanin-1 antibody or its antigen-binding fragment (14), (14-1) it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 126, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 127, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 128, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 129, the light chain CDR2 comprises or consists of the amino acid sequence shown in EDS, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 130.

[0158] In one embodiment, the heavy chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (15) preferably includes or consists of an amino acid sequence represented by GFTFSNSW (SEQ ID NO: 73), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd and 4th to 8th positions, with the N-terminus being the 1st. Examples of mutated sequences include the amino acid sequence represented by formula (2-1), the amino acid sequence represented by formula (3-1), GFTFSDSW (SEQ ID NO: 86), GFTFSNDY (SEQ ID NO: 89), and GLTLSNSW (SEQ ID NO: 126).

[0159] In one embodiment, the heavy chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (15) preferably includes or consists of an amino acid sequence represented by INGDSTNI (SEQ ID NO: 131), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but it is preferably selected from the 2nd, 3rd, and 5th to 8th positions, with the N-terminus being the 1st. Examples of mutated sequences include the amino acid sequence represented by formula (2-2), the amino acid sequence represented by formula (7-1), the amino acid sequence represented by formula (8-2), ISGDSNYI (SEQ ID NO: 90), and INGDSRNI (SEQ ID NO: 127).

[0160] In one embodiment, the heavy chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (15) preferably includes or consists of an amino acid sequence represented by AAGPEYYSRNSYYMPFQY (SEQ ID NO: 132), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservative substitutions). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 3rd to 18th positions with the N-terminus as the 1st position.

[0161] In one embodiment, the light chain CDR1 of the anti-Vanin-1 antibody or its antigen-binding fragment (15) preferably includes or consists of an amino acid sequence represented by SDISVGRKS (SEQ ID NO: 133), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited.

[0162] In one embodiment, the light chain CDR2 of the anti-Vanin-1 antibody or its antigen-binding fragment (15) preferably includes or consists of an amino acid sequence represented by YYSDSDK (SEQ ID NO: 134), or an amino acid sequence in which one amino acid is mutated (preferably a conservative substitution). The location of the amino acid mutation is not particularly limited, but may be, for example, a position selected from the 1st, 2nd, and 5th to 7th positions with the N-terminus as the 1st position.

[0163] In one embodiment, the light chain CDR3 of the anti-Vanin-1 antibody or its antigen-binding fragment (15) preferably includes or consists of an amino acid sequence represented by TIWHSGTWV (SEQ ID NO: 135), or an amino acid sequence in which 1 to 3 (preferably 1 or 2, more preferably 1) amino acids are mutated (preferably conservatively substituted). The location of the amino acid mutation is not particularly limited.

[0164] In an anti-vanin-1 antibody or its antigen-binding fragment (15), (15-1) it is preferable that the heavy chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 73, the heavy chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 131, the heavy chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 132, the light chain CDR1 comprises or consists of the amino acid sequence shown in SEQ ID NO: 133, the light chain CDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 134, and the light chain CDR3 comprises or consists of the amino acid sequence shown in SEQ ID NO: 135.

[0165] Anti-Vanin-1 antibodies or their antigen-binding fragments can be produced by combining known methods, for example, by a method comprising the following steps (P1) to (P6): (P1) obtaining cells that produce antibodies that bind to the Vanin-1 protein from antibody-producing cells of animals (e.g., guinea pigs, rats, rabbits) immunized with an antigen (full-length Vanin-1 protein) and optionally an adjuvant; (P2) obtaining an antibody variable region gene fragment from the cells obtained in step (P1); (P3) obtaining a gene expression unit from the antibody variable region gene fragment obtained in step (P2); (P4) introducing the gene expression unit obtained in step (P3) into cells to express antibodies that bind to the Vanin-1 protein; (P5) recovering the antibodies expressed in step (P4); and (P6) obtaining antibodies that bind to the Vanin-1 protein from the antibodies recovered in step (P5).

[0166] Step (P1) can be carried out in accordance with, for example, the method described in U.S. Patent Application Publication No. 2013 / 0029325 (ERIAA method) or the method described in the literature (Novel method for the high-throughput production of phosphorylation site-specific monoclonal antibodies, Scientific Reports, 2016, 6:25174) (FIXAA method).

[0167] Step (P2) can be carried out according to the method described in the literature (A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood, Nature Medicine 2009, 15(9), 1088-92) (ISAAC method) or the method described in the literature (Rapid production of antigen-specific monoclonal antibodies from a variety of animals, BMC Biology 2012, 10:80) (MAGrahd method).

[0168] Step (P3) can be carried out, for example, in accordance with the method described in U.S. Patent Application Publication No. 2013 / 0023009 (TS-jPCR method).

[0169] Step (P4) can be carried out by known gene transfer methods, such as calcium phosphate method, lipofection method, DEAE dextran method, electroporation method, microinjection method, etc. The cells into which the gene expression unit is introduced are not particularly limited as long as they can transiently express the antibody, and examples of mammalian cells include CHO cells, HEK293 cells, Expi293 cells, 293F cells, 293T cells, and 293FT cells.

[0170] Step (P6) can be carried out by selecting antibodies that specifically bind to the antigen using known screening methods, such as enzyme immunosorbent assay (ELISA), Western blotting, or immunohistochemical staining.

[0171] Furthermore, the antibodies may be purified as needed by known methods, such as salting-out methods using ammonium sulfate, sodium sulfate, etc.; affinity chromatography using protein A, etc.; ion exchange chromatography using DEAE cellulose, etc.; gel filtration; or purification methods using His-tag, FLAG-tag, etc.

[0172] A method comprising steps (P1) to (P6) can be used to obtain various antibodies or antigen-binding fragments thereof that bind to the Vanin-1 protein (where each antibody or antigen-binding fragment has a different amino acid sequence in at least one of the heavy chain CDR1-3 and light chain CDR1-3).

[0173] 3. Polynucleotides The polynucleotides of the present invention preferably contain a coding sequence for an antibody or its antigen-binding fragment that binds to the Vanin-1 protein. Examples of such coding sequences include, but are not limited to, base sequences encoding an antibody or its antigen-binding fragment that includes the heavy chain CDR1-3 and light chain CDR1-3 described in 2 above.

[0174] In one embodiment, the polynucleotide of the present invention preferably comprises an expression cassette of an antibody or antigen-binding fragment thereof that binds to the Vanin-1 protein. The expression cassette is not particularly limited as long as it enables expression in a host cell, and may include, for example, a promoter and a coding sequence positioned under the control of the promoter.

[0175] The promoter is not particularly limited and can be appropriately selected depending on the type of host cell. For example, various pol II system promoters can be used. There are no particular limitations on pol II system promoters, but examples include the CMV promoter, EF1 promoter, SV40 promoter, MSCV promoter, etc. Other examples of promoters include tryptophan promoters such as trc and tac; lac promoter; T7 promoter; T5 promoter; T3 promoter; SP6 promoter; arabinose-inducible promoter; cold shock promoter; tetracycline-inducible promoter, etc.

[0176] The expression cassette may contain other elements as needed. Examples of other elements include multiple cloning sites (MCS), drug resistance genes, origins of replication, enhancer sequences, repressor sequences, insulator sequences, reporter protein coding sequences, and drug resistance gene coding sequences. These may be present individually or in combination of two or more.

[0177] The polynucleotides of the present invention can be in the form of vectors, for example. An appropriate vector is selected depending on the intended use, the type of host cell, etc. Examples of vectors that use E. coli as a host include M13 phage or its variants, λ phage or its variants, pBR322 or its variants (e.g., pB325, pAT153, pUC8), etc. Examples of vectors that use yeast as a host include pYepSec1, pMFa, pYES2, pPIC3.5K, etc. Examples of vectors that use insect cells as a host include pAc, pVL, etc. Examples of vectors that use mammalian cells as a host include pcDNA, pCDM8, pMT2PC, etc.

[0178] 4. Cells The cells of the present invention preferably contain the polynucleotides described in 3 above. Examples of cells include Escherichia coli K12 and other Escherichia coli, Bacillus bacteria such as Bacillus subtilis MI114, yeast such as Saccharomyces cerevisiae AH22, Sf cell lineage derived from Spodoptera frugiperda or HighFive cell lineage derived from Trichoplusia ni, insect cells such as olfactory nerve cells, and animal cells. Examples of animal cells include cultured cells derived from mammals, specifically COS7 cells, CHO cells, HEK293 cells, Expi293 cells, 293F cells, 293T cells, 293FT cells, Hela cells, PC12 cells, N1E-115 cells, SH-SY5Y cells, and the like.

[0179] In one embodiment, it is preferable that the cells of the present invention express an antibody or an antigen-binding fragment thereof that binds to the Vanin-1 protein.

[0180] In one embodiment, it is preferable that the cells of the present invention secrete or have on their cell surface an antibody that binds to the Vanin-1 protein or an antigen-binding fragment thereof.

[0181] 5. Reagents or Pharmaceuticals The reagents or pharmaceuticals of the present invention preferably contain the antibody or antigen-binding fragment thereof described in 2 above, the polynucleotide described in 3 above, or the cells described in 4 above. The reagents or pharmaceuticals of the present invention preferably further contain pharmaceutically acceptable excipients or carriers and / or additives.

[0182] Examples of the excipients or carriers include starch, lactose, crystalline cellulose, sorbitol, calcium hydrogen phosphate, water, ethanol, (poly)ethylene glycol, (poly)propylene glycol, glycerol, and vegetable oil. These can be used individually or in combination of two or more.

[0183] Examples of the aforementioned additives include buffering agents, isotonic agents, thickeners, chelating agents, emulsifiers, colorants, and preservatives. These can be used individually or in combination of two or more.

[0184] The reagent or pharmaceutical of the present invention may be an antibody that binds to the Vanin-1 protein or an antigen-binding fragment thereof dissolved or dispersed in a solvent, or it may be lyophilized.

[0185] 6. Kit for detecting Vanin-1 protein The kit for detecting Vanin-1 protein of the present invention preferably includes the antibody described in item 1 above or its antigen-binding fragment. The antibody or its antigen-binding fragment may be in the form of the reagent described in item 5 above, for example.

[0186] The kit preferably contains two or more (for example, two, three, or four) antibodies or antigen-binding fragments thereof that bind to the Vanin-1 protein. It is preferable that at least one of the antibodies or antigen-binding fragments thereof is the antibody or antigen-binding fragment described in item 1 above. Furthermore, it is preferable that at least two of the antibodies or antigen-binding fragments thereof bind to different regions (epitopes) of the Vanin-1 protein, and that the amino acid sequences of at least one CDR among the heavy chain CDR1-3 and light chain CDR1-3 are different. Here, "epitope" refers to the antibody recognition site on the antigen.

[0187] In the kit, it is preferable that two or more of the aforementioned antibodies or their antigen-binding fragments (hereinafter referred to as "the first antibody or its antigen-binding fragment") are immobilized, and the remainder (hereinafter referred to as "the second antibody or its antigen-binding fragment") is labeled. Examples of the immobilized phase on which the first antibody or its antigen-binding fragment is immobilized include, but are not limited to, beads, wells, tips, strips, etc. There are no particular limitations on the method for immobilizing the first antibody or its antigen-binding fragment, but examples include contacting a biotinylated first antibody or its antigen-binding fragment with a solid phase surface containing avidin. There are no particular limitations on the labeling substance for labeling the second antibody or its antigen-binding fragment, but examples include enzymes such as peroxidase (HRP) and alkaline phosphatase (ALP).

[0188] The combination of the first antibody or its antigen-binding fragment and the second antibody or its antigen-binding fragment may be two types selected from anti-Vanin-1 antibodies or their antigen-binding fragments (1) to (15), and it is preferable that the combination be two types selected from anti-Vanin-1 antibodies or their antigen-binding fragments (1-1), (2-1), (3-1), (4-1), (5-1), (6-1), (7-1), (8-1), (9-1), (10-1), (11-1), (12-1), (13-1), (14-1), and (15-1).

[0189] In one embodiment, the combination of the first antibody or its antigen-binding fragment and the second antibody or its antigen-binding fragment is preferably a combination of anti-Vanin-1 antibody or its antigen-binding fragment (1), (4), (5), or (14) and anti-Vanin-1 antibody or its antigen-binding fragment (9) or (15), and the following combinations are even more preferred: • Combination of anti-Vanin-1 antibody or its antigen-binding fragment (14) and (15) • Combination of anti-Vanin-1 antibody or its antigen-binding fragment (4) and (15) • Combination of anti-Vanin-1 antibody or its antigen-binding fragment (5) and (15) • Combination of anti-Vanin-1 antibody or its antigen-binding fragment (1) and (15) • Combination of anti-Vanin-1 antibody or its antigen-binding fragment (4) and (9)

[0190] In one embodiment, the combination of the first antibody or its antigen-binding fragment and the second antibody or its antigen-binding fragment is preferably a combination of an anti-Vanin-1 antibody or its antigen-binding fragment (1-1), (4-1), (5-1), or (14-1) and an anti-Vanin-1 antibody or its antigen-binding fragment (9-1) or (15-1), and the following combinations are even more preferred: • Combination of anti-Vanin-1 antibody or its antigen-binding fragment (14-1) and (15-1) • Combination of anti-Vanin-1 antibody or its antigen-binding fragment (4-1) and (15-1) • Combination of anti-Vanin-1 antibody or its antigen-binding fragment (5-1) and (15-1) • Combination of anti-Vanin-1 antibody or its antigen-binding fragment (1-1) and (15-1) • Combination of anti-Vanin-1 antibody or its antigen-binding fragment (4-1) and (9-1)

[0191] The kit is preferably a kit for detecting Vanin-1 protein in a sample. In this specification, detection includes qualitative measurements to determine whether or not Vanin-1 is present in the sample, semi-quantitative measurements to determine the Vanin-1 concentration in the sample as "absent," "low," "moderate," or "high," and quantitative measurements to measure the Vanin-1 concentration in the sample.

[0192] The sample is not particularly limited as long as it may contain Vanin-1. The sample may be a non-biological sample, but a biological sample is preferred. The sample includes not only the sample as it was collected, but also the sample after pretreatment such as removal of impurities.

[0193] Examples of biological samples include, but are not limited to, urine, blood, serum, plasma, interstitial fluid, and ascites. Urine may be spontaneous urine, collected urine, catheterized urine, or urine obtained by puncture of the bladder or kidney.

[0194] In one embodiment, the sample is derived from a subject, who may have a kidney disease such as impaired renal function or kidney damage. The kit can also be used to determine whether or not a subject has a kidney disease.

[0195] There are no particular limitations on the method for detecting Vanin-1 protein using the kit, but examples include immunochromatography, enzyme immunoassay, chemiluminescence immunoassay, chemiluminescence enzyme immunoassay, radioimmunoassay, electrochemiluminescence immunoassay, and immunoturbidimetry.

[0196] Depending on the method of preparing the test sample, the method of detecting the Vanin-1 protein, etc., the kit may also contain other reagents (e.g., buffer solution, enzyme solution, diluent, secondary antibody, etc.). Two or more reagents may be sealed in the same container or in separate containers. In addition to reagents, the kit may also include equipment for use, instructions for use, etc.

[0197] 7. Method for detecting Vanin-1 protein A method for detecting Vanin-1 protein in a sample preferably includes the following steps (1) to (3): (1) immobilizing a first antibody or its antigen-binding fragment that binds to Vanin-1 protein onto a solid phase; (2) applying the sample and a second antibody or its antigen-binding fragment that binds thereto (wherein the second antibody or its antigen-binding fragment recognizes a different epitope from the first antibody or its antigen-binding fragment and is labeled with a labeling substance); and (3) detecting a label derived from the labeling substance of the second antibody or its antigen-binding fragment bound to the solid phase.

[0198] The first antibody or its antigen-binding fragment, and the second antibody or its antigen-binding fragment, can each be selected from the anti-Vanin-1 antibody or its antigen-binding fragment described in item 2 above.

[0199] Examples of solid phases include, but are not limited to, beads, wells, tips, and strips. There are no particular limitations on the method for immobilizing the first antibody or its antigen-binding fragment onto the solid phase, but examples include contacting a biotinylated first antibody or its antigen-binding fragment with a solid phase surface containing avidin. There are no particular limitations on the labeling substance used to label the second antibody or its antigen-binding fragment, but examples include enzymes such as peroxidase (HRP) and alkaline phosphatase (ALP).

[0200] The present invention will be described more specifically below based on examples, but the present invention is not limited to these examples.

[0201] (Example 1) Production of anti-Vanin-1 monoclonal antibody (Acquisition of antibody-producing cells by animal immunization) As the first immunization, 100 μg of recombinant Vanin-1 protein (SEQ ID NO: 136) suspended in PBS was mixed with the adjuvant TiterMAX Gold (Funakoshi Co., Ltd.) and administered intramuscularly to the left and right gluteal muscles of guinea pigs. 21 days after the first immunization, 100 μg of recombinant Vanin-1 protein suspended in PBS was mixed with TiterMAX Gold and administered as an additional immunization subcutaneously to the dorsal base of the guinea pigs' limbs. Furthermore, 21 days after the additional immunization, 100 μg of recombinant Vanin-1 protein suspended in PBS was administered again as an additional immunization intramuscularly to the left and right gluteal muscles of the guinea pigs. 7 days after the second additional immunization, the two guinea pigs were anesthetized, had their blood totaled and euthanized, and their lumbar lymph nodes were removed.

[0202] (Sorting of plasma cells producing anti-Vanin-1 antibody) This was carried out in accordance with the method (ERIAA method) described in "Fluorescent probe for plasma cell identification and isolation and method for identifying or isolating plasma cells using the probe" (U.S. Patent Application Publication 2013 / 0029325).

[0203] Cells obtained from excised lumbar lymph nodes were fixed in formaldehyde PBS solution on ice for 10 minutes. The fixed cells were stained with Dylight488-labeled Vanin-1 protein, Dylight650-labeled anti-guinea pig IgG antibody, and DAPI (4',6-diamidino-2-phenylindole). Plasma cells showing strong positivity for both Vanin-1 protein and anti-guinea pig IgG antibody were sorted by flow cytometry.

[0204] (Synthesis of antibody variable region gene fragments) For each cell obtained by sorting, mRNA extraction, cDNA synthesis, and amplification of antibody variable region gene fragments were performed according to the method of Kurosawa et al. (MAGrahd method) (Rapid production of antigen-specific monoclonal antibodies from a variety of animals, BMC Biology 2012, 10:80).

[0205] (Preparation of antibody gene expression units) Antibody gene expression units were prepared from amplified antibody variable region gene fragments according to the method (TS-jPCR method) described in "Specific method for producing linked DNA fragments containing target gene-derived sequences" (U.S. Patent Application Publication No. 2013 / 0023009).

[0206] (Transient antibody expression in 293FT cells) The prepared antibody gene expression unit, FuGENE HD Transfection Reagent (trademark), and OptiPRO (trademark) were mixed in a 1:1:100 liquid-volume ratio and allowed to stand at room temperature for 20 minutes. The antibody gene expression unit was then introduced into 293FT cells suspended in DMEM medium containing 10% (w / v) FBS. The 293FT cells into which the antibody gene expression unit had been introduced were seeded in a 24-well plate and incubated at 37°C in 5% (v / v) CO2. ２ After incubation in the environment for 3 days, the culture supernatant was collected. Subsequent screening was performed using antibodies released in the culture supernatant.

[0207] (Antibody screening by ELISA) Screening was performed by evaluating the binding activity of each antibody to the Vanin-1 protein by ELISA. For the ELISA, Vanin-1 protein was immobilized on the bottom of a 96-well plate at a concentration of 10 ng / well, blocked with 1% (w / v) BSA-TBS-T, and then 100 μL of the culture supernatant of 293FT cells transiently expressing the antibody was added. The antigen-antibody reaction was carried out at room temperature for 1 hour. Guinea pig antibodies bound to the antigen were detected using alkaline phosphatase-labeled goat anti-guinea pig antibodies, and the absorbance at 405 nm was measured using a microplate reader.

[0208] (Preparation of antibody expression plasmids) Based on the results of ELISA evaluation, DNA encoding the sequence containing the CDR of the antibody was obtained from antibody clones that showed good reactivity. Antibody expression plasmids containing guinea pig-derived heavy chain and light chain constant regions were prepared using the Mammalian PowerExpress System (trademark) (MPH-102 and MPL-202, Toyobo Co., Ltd.) in accordance with the accompanying instructions.

[0209] (Transient Expression and Purification of Antibodies in ExpiCHO-S® Cells) Antibodies were produced by introducing the prepared antibody expression plasmids into ExpiCHO-S® cells. For gene transfer, ExpiCHO-S® Expression Medium (Thermo Fisher Scientific) and ExpiFectamine® CHO Transfection Kit (Thermo Fisher Scientific) were used. Gene transfer was performed by mixing 20 μg of each prepared antibody expression plasmid with 920 μL of OptiPRO® SFM and 80 μL of ExpiFectamine® CHO Reagent, allowing it to stand for 5 minutes, and then adding it to 25 mL of culture medium containing ExpiCHO-S® cells. 37°C, 5% (v / v) CO2 ２After 5 days of shaking culture at 110 rpm, the culture supernatant was collected. Next, the culture supernatant was passed through a HiTrap Protein A HP column (Cytiva) using the NGC™ Chromatography System (Bio-Rad) to adsorb the antibody. The column was washed with washing buffer (20 mM phosphate buffer, pH 7.4), and then eluted with elution buffer (0.1 M citrate-NaOH, pH 3.0) to obtain purified antibody. The obtained purified antibody was evaluated using a PD-10 column (Cytiva) with Tris-buffered saline (pH 7.4) instead of Tris buffer.

[0210] Table 2 shows the amino acid sequences (based on IMTG method) of the heavy chain CDR1-3 and light chain CDR1-3 for 48 antibody clones that specifically bound to the Vanin-1 protein from among the acquired antibody clones.

[0211]

[0212]

[0213] (Example 2) ELISA using recombinant Vanin-1 antigen Anti-His Tag antibody (Jackson) was immobilized on the bottom of a 96-well plate at a concentration of 0.25 μg / well. Blocking was performed with 1% (w / v) BSA-TBS-T, and recombinant Vanin-1 protein was added at a concentration of 1 ng / well. The mixture was then reacted at room temperature for 1 hour. Next, after washing with TBS-T, the anti-Vanin-1 protein antibody prepared in Example 1, or an existing commercially available anti-Vanin-1 monoclonal antibody A (CLOUD-CLONE), labeled with horseradish peroxidase, was added at a concentration of 0.1 μg / well and reacted at room temperature for 1 hour. After washing with TBS-T, TMB was added and a color reaction was performed, followed by the addition of 1N HCl to stop the reaction. The absorbance at 450 nm was then measured using a microplate reader. The results are shown in Table 3.

[0214]

[0215] Compared to using the commercially available anti-vanin-1 monoclonal antibody A (CLOUD-CLONE), the antibody prepared in Example 1 showed improved detection sensitivity.

[0216] (Example 3) Sandwich ELISA using clinical samples Antibody evaluation was performed by sandwich ELISA using urine samples (Proteogenex) from patients with chronic kidney disease (CKD) whose Vanin-1 content was confirmed using a commercially available Vanin-1 ELISA kit (Biomedica). The antibody prepared in Example 1 was immobilized on the bottom of a 96-well plate at a concentration of 0.25 μg / well, and after blocking with 1% (w / v) BSA-TBS-T, 100 μL / well of CKD patient urine sample (Proteogenex) was added and the mixture was reacted at room temperature for 1 hour. Next, after washing with TBS-T, 0.1 μg / well of the anti-Vanin-1 protein antibody prepared in Example 1 or an existing commercially available anti-Vanin-1 monoclonal antibody A (CLOUD-CLONE), labeled with horseradish peroxidase, was added and the mixture was reacted at room temperature for 1 hour. After washing with TBS-T, TMB was added to initiate the color reaction, and then 1N HCl was added to stop the reaction. Next, the absorbance at 450 nm was measured using a microplate reader. The results are shown in Table 4.

[0217]

[0218] Compared to sandwich ELISA using an existing commercially available anti-Vanin-1 monoclonal antibody A (CLOUD-CLONE), the sandwich ELISA using the antibody prepared in Example 1 showed improved detection sensitivity.

Claims

1. An anti-Vanin-1 antibody or an antigen-binding fragment thereof selected from the following (1) to (15): (1) A heavy-chain CDR1 comprising the amino acid sequence represented by GFSITTTNYW (SEQ ID NO: 1), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and the formula (1-1): ISYDGX １ T (where X １ is N, K, or H), or a heavy-chain CDR2 comprising the amino acid sequence represented by this amino acid sequence or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and the formula (1-2): X ２ X ３ GWLLSLAX ４ WG (where X ２ is T, A, or S, X ３ is S or T, X ４ is E, V, or M), or a heavy-chain CDR3 comprising the amino acid sequence represented by this amino acid sequence or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and the formula (1-3): SEHSX ５ SY (where X ５ is S or R), or a light-chain CDR1 comprising the amino acid sequence represented by this amino acid sequence or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, a light-chain CDR2 comprising the amino acid sequence represented by LKSDGSH (SEQ ID NO: 5), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and a light-chain CDR3 comprising the amino acid sequence represented by GVAYSGGYV (SEQ ID NO: 6), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; an anti-Vanin-1 antibody or an antigen-binding fragment thereof; (2) The formula (2-1): GFTFSX ６ YW (where X ６ is N or K), or a heavy-chain CDR1 comprising the amino acid sequence represented by this amino acid sequence or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and the formula (2-2): IX ７ X ８ DX ９ X １０ TX １１ (where X ７ is N or S, X ８ is S, G, H, or V, X ９ is S, R, or G, and X １０ is S or T, X １１ A heavy chain CDR2 containing an amino acid sequence represented by (where is M, I, K, or V), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (2-3): X １２ TX １３ GGX １４ WG (in the formula, X １２ is M, A, I, or V, X １３ is S, E, K, or T, X １４ A heavy chain CDR3 containing an amino acid sequence represented by (where is L or V), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and formula (2-4): QSLLYSGNX １５ X １６ NY (in the formula, X １５ is N or T, and X １６ A light chain CDR1 comprising an amino acid sequence represented by (where is N or K), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; a light chain CDR2 comprising an amino acid sequence represented by LAS, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence; Formula (2-5): MQTFGX １７ PRT (where X １７ A light chain CDR3 comprising an amino acid sequence represented by (where is I, T, or L), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and an anti-vanin-1 antibody or its antigen-binding fragment comprising; (3) Formula (3-1): GFTFX １８ NX １９ Y (where X １８ is S or N, X １９ A heavy chain CDR1 containing an amino acid sequence represented by (where is W or Y), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (3-2): ISX ２０ DSSDX ２１ (In the formula, X ２０ is A or D, and X ２１ A heavy chain CDR2 containing an amino acid sequence represented by (where is I, L, or M), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and formula (3-3): X ２２ DISGX ２３ GX ２４ (In the formula, X ２２ is A or V, and X ２３ is S or Y, and X ２４ A heavy chain CDR3 containing an amino acid sequence represented by (where is I, F, L, or V), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (3-4): QSLLX ２５ SGNNX ２６ NY (in the formula, X ２５ is S or Y, and X ２６ A light chain CDR1 comprising an amino acid sequence represented by (where is K or N), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; a light chain CDR2 comprising an amino acid sequence represented by LAS, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence; and formula (3-5): MQX ２７ X ２８ X ２９ X ３０ PX ３１ T (where X ２７ is D or T, X ２８ is Y or F, and X ２９ is S or G, X ３０ is V or I, X ３１ (1) A light chain CDR3 comprising an amino acid sequence represented by (where is L or R), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and an anti-vanin-1 antibody or its antigen-binding fragment comprising; (4) A heavy chain CDR1 comprising an amino acid sequence represented by GFSLTSYS (SEQ ID NO: 47), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and Formula (4-1): IWSX ３２ GX ３３ X ３４ (In the formula, X ３２ is D or G, X ３３ is S or T, X ３４ A heavy chain CDR2 containing an amino acid sequence represented by (where is P, T, or S), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (4-2): ARDWGX ３５ LDX ３６ (In the formula, X ３５ is S or N, and X ３６ is V or I), and a heavy-chain CDR3 comprising an amino acid sequence represented by the formula (4-3): QSX ３７ X ３８ X ３９ Y (wherein X ３７ is I or V, and X ３８ is S, T, N, or K, and X ３９ is R, S, or T), and a light-chain CDR1 comprising an amino acid sequence represented by the formula (4-4): QSX ４０ X ４１ WPYT (wherein X ４０ is H or Y, and X ４１ is S or N), and a light-chain CDR3 comprising an amino acid sequence represented by the formula (4-5): QQYX ４２ LTSYS (wherein X ４２ is P or S), and a heavy-chain CDR1 comprising an amino acid sequence represented by the formula (5-1): GFX ４３ GSX ４４ (wherein X ４３ is D or G, and X ４４ is S or T), and a heavy-chain CDR2 comprising an amino acid sequence represented by the formula (5-2): IWSX ４５ Y (wherein X ４５ The light chain CDR1 comprising an amino acid sequence represented by (which is S or T), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, the light chain CDR2 comprising an amino acid sequence represented by NAY or YTN, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence, and the formula (5-4): QQYX ４６ X ４７ WPYX ４８ (wherein X ４６ is H or Q, X ４７ is S or N, X ４８ is A or T), or the light chain CDR3 comprising an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and an anti-Vanin-1 antibody or an antigen-binding fragment thereof; (6) The heavy chain CDR1 comprising an amino acid sequence represented by GFSITTTNYW (SEQ ID NO: 1), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, the heavy chain CDR2 comprising an amino acid sequence represented by INYDGNT (SEQ ID NO: 69), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, the heavy chain CDR3 comprising an amino acid sequence represented by AREGMVAGFYFDV (SEQ ID NO: 70), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, the light chain CDR1 comprising an amino acid sequence represented by QGIDNG (SEQ ID NO: 71), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, the light chain CDR2 comprising an amino acid sequence represented by DAT, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence, and the light chain CDR3 comprising an amino acid sequence represented by QQGSSTPYT (SEQ ID NO: 72), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and an anti-Vanin-1 antibody or an antigen-binding fragment thereof; (7) The heavy chain CDR1 comprising an amino acid sequence represented by GFTFSNSW (SEQ ID NO: 73), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence, and the formula (7-1): INGDSSX ４９ I(wherein X ４９ A heavy chain CDR2 containing an amino acid sequence represented by (where is N, D, or T), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (7-2): AADPGGNX ５０ HPYX ５１ DV (in the formula, X ５０ is S or Y, and X ５１ A heavy chain CDR3 containing an amino acid sequence represented by (where is L or F), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; a light chain CDR1 containing an amino acid sequence represented by NIGRKS (SEQ ID NO: 76), or an amino acid sequence in which 1 to 3 amino acids are mutated in the amino acid sequence; a light chain CDR2 containing an amino acid sequence represented by ADY, or an amino acid sequence in which 1 amino acid is mutated in the amino acid sequence; Formula (7-3): QVWDX ５２ DSAGX ５３ (In the formula, X ５２ is S or T, X ５３ A light chain CDR3 comprising an amino acid sequence represented by (where is V or L), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and an anti-vanin-1 antibody or its antigen-binding fragment comprising; (8) Formula (8-1): GFTFSX ５４ SW (in the formula, X ５４ A heavy chain CDR1 comprising an amino acid sequence represented by (where is N or D), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (8-2): INGDX ５５ SNI (where X ５５ An anti-vanin-1 antibody or its antigen-binding fragment comprising: a heavy chain CDR2 containing an amino acid sequence represented by (where is S or R), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR3 containing an amino acid sequence represented by AADPGGSGYFGYFDI (SEQ ID NO: 84) or AADPSGSGWTVDV (SEQ ID NO: 88), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR1 containing an amino acid sequence represented by NIGRKS (SEQ ID NO: 76), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR2 containing an amino acid sequence represented by ADY, or an amino acid sequence in which 1 amino acid is mutated in said amino acid sequence; and a light chain CDR3 containing an amino acid sequence represented by QVWDADSAQYV (SEQ ID NO: 85), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; (9) An anti-vanin-1 antibody or its antigen-binding fragment comprising: a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNDY (SEQ ID NO: 89), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR2 containing the amino acid sequence indicated by ISGDSNYI (SEQ ID NO: 90), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR3 containing the amino acid sequence indicated by ARHIAAYYFNL (SEQ ID NO: 91), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR1 containing the amino acid sequence indicated by SVNNNF (SEQ ID NO: 92), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR2 containing the amino acid sequence indicated by RTS, or an amino acid sequence in which 1 amino acid is mutated in said amino acid sequence; and a light chain CDR3 containing the amino acid sequence indicated by QQSSNDLT (SEQ ID NO: 93), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence;(10) An anti-vanin-1 antibody or its antigen-binding fragment comprising: a heavy chain CDR1 containing the amino acid sequence indicated by GFLFNTFY (SEQ ID NO: 94), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR2 containing the amino acid sequence indicated by ISHTGGST (SEQ ID NO: 95), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR3 containing the amino acid sequence indicated by LRNGRYSWGTYHYFDV (SEQ ID NO: 96), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR1 containing the amino acid sequence indicated by QGISKN (SEQ ID NO: 97), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR2 containing the amino acid sequence indicated by YAT, or an amino acid sequence in which 1 amino acid is mutated in said amino acid sequence; and a light chain CDR3 containing the amino acid sequence indicated by QHTNSWPQYT (SEQ ID NO: 98), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; (11) A heavy chain CDR1 containing the amino acid sequence indicated by GFTFSDYW (SEQ ID NO: 99), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a heavy chain CDR2 containing the amino acid sequence indicated by INYDGDST (SEQ ID NO: 100), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a heavy chain CDR3 containing the amino acid sequence indicated by ARASMGWNEYQYALDI (SEQ ID NO: 101), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a light chain CDR1 containing the amino acid sequence indicated by SAHSSYY (SEQ ID NO: 102), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a light chain CDR2 containing the amino acid sequence indicated by LKSDGSH (SEQ ID NO: 5), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a light chain CDR3 containing the amino acid sequence indicated by GMSYSGGFV (SEQ ID NO: 103), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; (12) Formula (12-1): GFSLX; ５６ SYG (in the formula, X ５６ A heavy chain CDR1 containing an amino acid sequence represented by (where is T or S), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (12-2): X ５７ WDGGX ５８ T (where X ５７ is I or V, X ５８ A heavy chain CDR2 containing an amino acid sequence represented by (where is T, S, or N), or an amino acid sequence in which 1 to 3 amino acids are mutated, and formula (12-3): ARPX ５９ YGX ６０ YSYYTALDX ６１ (In the formula, X ５９ is G or A, X ６０ is R or T, X ６１ A heavy chain CDR3 containing an amino acid sequence represented by (I, S, F, A, or T), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and a light chain CDR1 containing an amino acid sequence represented by SSNVGSYG (SEQ ID NO: 107), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence, and formula (12-4): GX ６２ T (where X ６２ A light chain CDR2 containing an amino acid sequence represented by (where is T or F), or an amino acid sequence in which one amino acid is mutated, and formula (12-5): SSWDYSQNVYX ６３ (In the formula, X ６３ (13) A light chain CDR3 comprising an amino acid sequence represented by (V, L, or I), or an amino acid sequence in which 1 to 3 amino acids are mutated, and an anti-vanin-1 antibody or its antigen-binding fragment comprising: (13) A heavy chain CDR1 comprising an amino acid sequence represented by GFTFSTYY (SEQ ID NO: 122), or an amino acid sequence in which 1 to 3 amino acids are mutated, a heavy chain CDR2 comprising an amino acid sequence represented by ISNDGSST (SEQ ID NO: 123), or an amino acid sequence in which 1 to 3 amino acids are mutated, a heavy chain CDR3 comprising an amino acid sequence represented by ASFYSKYV (SEQ ID NO: 124), or an amino acid sequence in which 1 to 3 amino acids are mutated, a light chain CDR1 comprising an amino acid sequence represented by QSLLSSGNNKNY (SEQ ID NO: 37), or an amino acid sequence in which 1 to 3 amino acids are mutated, a light chain CDR2 comprising an amino acid sequence represented by LAS, or an amino acid sequence in which 1 amino acid is mutated, An anti-vanin-1 antibody or its antigen-binding fragment comprising: a light chain CDR3 containing the amino acid sequence shown in MQDYSAPYT (SEQ ID NO: 125), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence;(14) A heavy chain CDR1 containing the amino acid sequence shown in GLTLSNSW (SEQ ID NO: 126), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR2 containing the amino acid sequence shown in INGDSRNI (SEQ ID NO: 127), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a heavy chain CDR3 containing the amino acid sequence shown in AASLDYYGLDI (SEQ ID NO: 128), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR1 containing the amino acid sequence shown in GLGNKY (SEQ ID NO: 129), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; a light chain CDR2 containing the amino acid sequence shown in EDS, or an amino acid sequence in which 1 amino acid is mutated in said amino acid sequence; a light chain CDR3 containing the amino acid sequence shown in AIALGSGSGFHV (SEQ ID NO: 130), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; (15) an anti-vanin-1 antibody or its antigen-binding fragment, including: (15) a heavy chain CDR1 comprising the amino acid sequence shown in GFTFSNSW (SEQ ID NO: 73), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a heavy chain CDR2 comprising the amino acid sequence shown in INGDSTNI (SEQ ID NO: 131), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a heavy chain CDR3 comprising the amino acid sequence shown in AAGPEYYSRNSYYMPFQY (SEQ ID NO: 132), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a light chain CDR1 comprising the amino acid sequence shown in SDISVGRKS (SEQ ID NO: 133), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; a light chain CDR2 comprising the amino acid sequence shown in YYSDSDK (SEQ ID NO: 134), or an amino acid sequence in which 1 to 3 amino acids are mutated in the said amino acid sequence; An anti-vanin-1 antibody or its antigen-binding fragment comprising a light chain CDR3 containing the amino acid sequence indicated by TIWHSGTWV (SEQ ID NO: 135), or an amino acid sequence in which 1 to 3 amino acids are mutated in said amino acid sequence; 2. The anti-vanin-1 antibody or antigen-binding fragment thereof according to claim 1, wherein the mutation is a conservative substitution.

3. The heavy chain CDR3 of the anti-Vanin-1 antibody (1) contains the amino acid sequence represented by TSGWLLSLAEWG (SEQ ID NO: 3), TSGWLLSLAVWG (SEQ ID NO: 7), ASGWLLSLAMWG (SEQ ID NO: 10), or STGWLLSLAVWG (SEQ ID NO: 12), and the light chain CDR3 of the anti-Vanin-1 antibody (1) contains the amino acid sequence represented by GVAYSGGYV (SEQ ID NO: 6), The heavy chain CDR3 of the anti-Vanin-1 antibody (2) comprises the amino acid sequence represented by MTSGGLWG (SEQ ID NO: 15), ATEGGLWG (SEQ ID NO: 19), ATEGGVWG (SEQ ID NO: 24), ATKGGLWG (SEQ ID NO: 27), ITSGGLWG (SEQ ID NO: 29), VTTGGLWG (SEQ ID NO: 31), or ATSGGLWG (SEQ ID NO: 33), and the light chain CDR3 of the anti-Vanin-1 antibody (2) comprises the amino acid sequence represented by MQTFGIPRT (SEQ ID NO: 17), MQTFGTPRT (SEQ ID NO: 21), or MQTFGLPRT (SEQ ID NO: 30). The heavy chain CDR3 of the anti-Vanin-1 antibody (3) comprises an amino acid sequence represented by ADISGSGI (SEQ ID NO: 36), ADISGSGF (SEQ ID NO: 40), ADISGSGL (SEQ ID NO: 42), ADISGYGV (SEQ ID NO: 45), or VDISGYGV (SEQ ID NO: 46), the light chain CDR3 of the anti-Vanin-1 antibody (3) comprises an amino acid sequence represented by MQDYSVPLT (SEQ ID NO: 38) or MQTFGIPRT (SEQ ID NO: 17), the heavy chain CDR3 of the anti-Vanin-1 antibody (4) comprises an amino acid sequence represented by ARDWGSLDV (SEQ ID NO: 49), ARDWGNLDI (SEQ ID NO: 56), or ARDWGSLDI (SEQ ID NO: 60), the light chain CDR3 of the anti-Vanin-1 antibody (4) comprises an amino acid sequence represented by QQYHSWPYT (SEQ ID NO: 51), QQYHNWPYT (SEQ ID NO: 54), or QQYYSWPYT (SEQ ID NO: 59), The heavy chain CDR3 of the anti-Vanin-1 antibody (5) comprises the amino acid sequence represented by ARDGGYFH (SEQ ID NO: 64) or ARDRGDFDV (SEQ ID NO: 67), and the light chain CDR3 of the anti-Vanin-1 antibody (5) comprises the amino acid sequence represented by QQYHSWPYA (SEQ ID NO: 66) or QQYQNWPYT (SEQ ID NO: 68).The heavy chain CDR3 of the anti-Vanin-1 antibody (6) comprises the amino acid sequence represented by AREGMVAGFYFDV (SEQ ID NO: 70), the light chain CDR3 of the anti-Vanin-1 antibody (6) comprises the amino acid sequence represented by QQGSSTPYT (SEQ ID NO: 72), the heavy chain CDR3 of the anti-Vanin-1 antibody (7) comprises the amino acid sequence represented by AADPGGNSHPYLDV (SEQ ID NO: 75), AADPGGNYHPYFDV (SEQ ID NO: 79), or AADPGGNSHPYFDV (SEQ ID NO: 82), the light chain CDR3 of the anti-Vanin-1 antibody (7) comprises the amino acid sequence represented by QVWDSDSAGV (SEQ ID NO: 77), QVWDTDSAGV (SEQ ID NO: 80), or QVWDSDSAGL (SEQ ID NO: 83), The heavy chain CDR3 of the anti-Vanin-1 antibody (8) comprises the amino acid sequence represented by AADPGGSGYFGYFDI (SEQ ID NO: 84) or AADPSGSGWTVDV (SEQ ID NO: 88), the light chain CDR3 of the anti-Vanin-1 antibody (8) comprises the amino acid sequence represented by QVWDADSAQYV (SEQ ID NO: 85), the heavy chain CDR3 of the anti-Vanin-1 antibody (9) comprises the amino acid sequence represented by ARHIAAYYFNL (SEQ ID NO: 91), the light chain CDR3 of the anti-Vanin-1 antibody (9) comprises the amino acid sequence represented by QQSSNDLT (SEQ ID NO: 93), the heavy chain CDR3 of the anti-Vanin-1 antibody (10) comprises the amino acid sequence represented by LRNGRYSWGTYHYFDV (SEQ ID NO: 96), the light chain CDR3 of the anti-Vanin-1 antibody (10) comprises the amino acid sequence represented by QHTNSWPQYT (SEQ ID NO: 98), The heavy chain CDR3 of the anti-Vanin-1 antibody (11) comprises the amino acid sequence represented by ARASMGWNEYQYALDI (SEQ ID NO: 101), and the light chain CDR3 of the anti-Vanin-1 antibody (11) comprises the amino acid sequence represented by GMSYSGGFV (SEQ ID NO: 103).The heavy chain CDR3 of the anti-Vanin-1 antibody (12) comprises an amino acid sequence represented by ARPGYGRYSYYTALDI (SEQ ID NO: 106), ARPGYGRYSYYTALDS (SEQ ID NO: 109), ARPGYGTYSYYTALDI (SEQ ID NO: 111), ARPGYGTYSYYTALDF (SEQ ID NO: 114), ARPGYGTYSYYTALDA (SEQ ID NO: 115), ARPGYGTYSYYTALDT (SEQ ID NO: 116), ARPAYGTYSYYTALDI (SEQ ID NO: 118), or ARPAYGTYSYYTALDF (SEQ ID NO: 119), and the light chain CDR3 of the anti-Vanin-1 antibody (12) comprises an amino acid sequence represented by SSWDYSQNVYV (SEQ ID NO: 108), SSWDYSQNVYL (SEQ ID NO: 112), or SSWDYSQNVYI (SEQ ID NO: 121). The anti-vanin-1 antibody or antigen-binding fragment according to claim 1, wherein the heavy chain CDR3 of the anti-vanin-1 antibody (13) comprises the amino acid sequence represented by ASFYSKYV (SEQ ID NO: 124), the light chain CDR3 of the anti-vanin-1 antibody (13) comprises the amino acid sequence represented by MQDYSAPYT (SEQ ID NO: 125), the heavy chain CDR3 of the anti-vanin-1 antibody (14) comprises the amino acid sequence represented by AASLDYYGLDI (SEQ ID NO: 128), the light chain CDR3 of the anti-vanin-1 antibody (14) comprises the amino acid sequence represented by AIALGSGSGFHV (SEQ ID NO: 130), the heavy chain CDR3 of the anti-vanin-1 antibody (15) comprises the amino acid sequence represented by AAGPEYYSRNSYYMPFQY (SEQ ID NO: 132), and the light chain CDR3 of the anti-vanin-1 antibody (15) comprises the amino acid sequence represented by TIWHSGTWV (SEQ ID NO: 135).

4. The heavy chain CDR1 of the anti-Vanin-1 antibody (1) includes the amino acid sequence indicated by GFSITTTNYW (SEQ ID NO: 1), the heavy chain CDR2 includes the amino acid sequence indicated by ISYDGNT (SEQ ID NO: 2), the heavy chain CDR3 includes the amino acid sequence indicated by TSGWLLSLAEWG (SEQ ID NO: 3), the light chain CDR1 includes the amino acid sequence indicated by SEHSSSY (SEQ ID NO: 4), the light chain CDR2 includes the amino acid sequence indicated by LKSDGSH (SEQ ID NO: 5), and the light chain CDR3 includes the amino acid sequence indicated by GVAYSGGYV (SEQ ID NO: 6). The heavy chain CDR1 of the anti-Vanin-1 antibody (2) includes the amino acid sequence indicated by GFTFSNYW (SEQ ID NO: 13), the heavy chain CDR2 includes the amino acid sequence indicated by INSDSSTM (SEQ ID NO: 14), the heavy chain CDR3 includes the amino acid sequence indicated by MTSGGLWG (SEQ ID NO: 15), the light chain CDR1 includes the amino acid sequence indicated by QSLLYSGNNNNY (SEQ ID NO: 16), the light chain CDR2 includes the amino acid sequence indicated by LAS, and the light chain CDR3 includes the amino acid sequence indicated by MQTFGIPRT (SEQ ID NO: 17). The heavy chain CDR1 of the anti-Vanin-1 antibody (3) includes the amino acid sequence indicated by GFTFSNWY (SEQ ID NO: 34), the heavy chain CDR2 includes the amino acid sequence indicated by ISADSSDI (SEQ ID NO: 35), the heavy chain CDR3 includes the amino acid sequence indicated by ADISGSGI (SEQ ID NO: 36), the light chain CDR1 includes the amino acid sequence indicated by QSLLSSGNNKNY (SEQ ID NO: 37), the light chain CDR2 includes the amino acid sequence indicated by LAS, and the light chain CDR3 includes the amino acid sequence indicated by MQDYSVPLT (SEQ ID NO: 38). The heavy chain CDR1 of the anti-Vanin-1 antibody (4) includes the amino acid sequence indicated by GFSLTSYS (SEQ ID NO: 47), the heavy chain CDR2 includes the amino acid sequence indicated by IWSDGSP (SEQ ID NO: 48), the heavy chain CDR3 includes the amino acid sequence indicated by ARDWGSLDV (SEQ ID NO: 49), the light chain CDR1 includes the amino acid sequence indicated by QSISRY (SEQ ID NO: 50), the light chain CDR2 includes the amino acid sequence indicated by YTN, and the light chain CDR3 includes the amino acid sequence indicated by QQYHSWPYT (SEQ ID NO: 51).The heavy chain CDR1 of the anti-Vanin-1 antibody (5) includes the amino acid sequence shown by GFPLTSYS (SEQ ID NO: 63), the heavy chain CDR2 includes the amino acid sequence shown by IWSDGSS (SEQ ID NO: 55), the heavy chain CDR3 includes the amino acid sequence shown by ARDGGYFH (SEQ ID NO: 64), the light chain CDR1 includes the amino acid sequence shown by QSVNSY (SEQ ID NO: 65), the light chain CDR2 includes the amino acid sequence shown by NAY, and the light chain CDR3 includes the amino acid sequence shown by QQYHSWPYA (SEQ ID NO: 66). The heavy chain CDR1 of the anti-Vanin-1 antibody (6) includes the amino acid sequence indicated by GFSITTTNYW (SEQ ID NO: 1), the heavy chain CDR2 includes the amino acid sequence indicated by INYDGNT (SEQ ID NO: 69), the heavy chain CDR3 includes the amino acid sequence indicated by AREGMVAGFYFDV (SEQ ID NO: 70), the light chain CDR1 includes the amino acid sequence indicated by QGIDNG (SEQ ID NO: 71), the light chain CDR2 includes the amino acid sequence indicated by DAT, and the light chain CDR3 includes the amino acid sequence indicated by QQGSSTPYT (SEQ ID NO: 72). The heavy chain CDR1 of the anti-Vanin-1 antibody (7) includes the amino acid sequence indicated by GFTFSNSW (SEQ ID NO: 73), the heavy chain CDR2 includes the amino acid sequence indicated by INGDSSNI (SEQ ID NO: 74), the heavy chain CDR3 includes the amino acid sequence indicated by AADPGGNSHPYLDV (SEQ ID NO: 75), the light chain CDR1 includes the amino acid sequence indicated by NIGRKS (SEQ ID NO: 76), the light chain CDR2 includes the amino acid sequence indicated by ADY, and the light chain CDR3 includes the amino acid sequence indicated by QVWDSDSAGV (SEQ ID NO: 77). The heavy chain CDR1 of the anti-Vanin-1 antibody (8) includes the amino acid sequence indicated by GFTFSNSW (SEQ ID NO: 73), the heavy chain CDR2 includes the amino acid sequence indicated by INGDSSNI (SEQ ID NO: 74), the heavy chain CDR3 includes the amino acid sequence indicated by AADPGGSGYFGYFDI (SEQ ID NO: 84), the light chain CDR1 includes the amino acid sequence indicated by NIGRKS (SEQ ID NO: 76), the light chain CDR2 includes the amino acid sequence indicated by ADY, and the light chain CDR3 includes the amino acid sequence indicated by QVWDADSAQYV (SEQ ID NO: 85).The heavy chain CDR1 of the anti-Vanin-1 antibody (9) includes the amino acid sequence indicated by GFTFSNDY (SEQ ID NO: 89), the heavy chain CDR2 includes the amino acid sequence indicated by ISGDSNYI (SEQ ID NO: 90), the heavy chain CDR3 includes the amino acid sequence indicated by ARHIAAYYFNL (SEQ ID NO: 91), the light chain CDR1 includes the amino acid sequence indicated by SVNNNF (SEQ ID NO: 92), the light chain CDR2 includes the amino acid sequence indicated by RTS, and the light chain CDR3 includes the amino acid sequence indicated by QQSSNDLT (SEQ ID NO: 93). The heavy chain CDR1 of the anti-Vanin-1 antibody (10) includes the amino acid sequence indicated by GFLFNTFY (SEQ ID NO: 94), the heavy chain CDR2 includes the amino acid sequence indicated by ISHTGGST (SEQ ID NO: 95), the heavy chain CDR3 includes the amino acid sequence indicated by LRNGRYSWGTYHYFDV (SEQ ID NO: 96), the light chain CDR1 includes the amino acid sequence indicated by QGISKN (SEQ ID NO: 97), the light chain CDR2 includes the amino acid sequence indicated by YAT, and the light chain CDR3 includes the amino acid sequence indicated by QHTNSWPQYT (SEQ ID NO: 98). The heavy chain CDR1 of the anti-Vanin-1 antibody (11) includes the amino acid sequence indicated by GFTFSDYW (SEQ ID NO: 99), the heavy chain CDR2 includes the amino acid sequence indicated by INYDGDST (SEQ ID NO: 100), the heavy chain CDR3 includes the amino acid sequence indicated by ARASMGWNEYQYALDI (SEQ ID NO: 101), the light chain CDR1 includes the amino acid sequence indicated by SAHSSYY (SEQ ID NO: 102), the light chain CDR2 includes the amino acid sequence indicated by LKSDGSH (SEQ ID NO: 5), and the light chain CDR3 includes the amino acid sequence indicated by GMSYSGGFV (SEQ ID NO: 103). The heavy chain CDR1 of the anti-Vanin-1 antibody (12) includes the amino acid sequence indicated by GFSLTSYG (SEQ ID NO: 104), the heavy chain CDR2 includes the amino acid sequence indicated by IWDGGTT (SEQ ID NO: 105), the heavy chain CDR3 includes the amino acid sequence indicated by ARPGYGRYSYYTALDI (SEQ ID NO: 106), the light chain CDR1 includes the amino acid sequence indicated by SSNVGSYG (SEQ ID NO: 107), the light chain CDR2 includes the amino acid sequence indicated by GTT, and the light chain CDR3 includes the amino acid sequence indicated by SSWDYSQNVYV (SEQ ID NO: 108).The heavy chain CDR1 of the anti-Vanin-1 antibody (13) includes the amino acid sequence indicated by GFTFSTYY (SEQ ID NO: 122), the heavy chain CDR2 includes the amino acid sequence indicated by ISNDGSST (SEQ ID NO: 123), the heavy chain CDR3 includes the amino acid sequence indicated by ASFYSKYV (SEQ ID NO: 124), the light chain CDR1 includes the amino acid sequence indicated by QSLLSSGNNKNY (SEQ ID NO: 37), the light chain CDR2 includes the amino acid sequence indicated by LAS, and the light chain CDR3 includes the amino acid sequence indicated by MQDYSAPYT (SEQ ID NO: 125). The heavy chain CDR1 of the anti-Vanin-1 antibody (14) includes the amino acid sequence indicated by GLTLSNSW (SEQ ID NO: 126), the heavy chain CDR2 includes the amino acid sequence indicated by INGDSRNI (SEQ ID NO: 127), the heavy chain CDR3 includes the amino acid sequence indicated by AASLDYYGLDI (SEQ ID NO: 128), the light chain CDR1 includes the amino acid sequence indicated by GLGNKY (SEQ ID NO: 129), the light chain CDR2 includes the amino acid sequence indicated by EDS, and the light chain CDR3 includes the amino acid sequence indicated by AIALGSGSGFHV (SEQ ID NO: 130). The anti-vanin-1 antibody (15) according to claim 1, wherein the heavy chain CDR1 comprises the amino acid sequence shown by GFTFSNSW (SEQ ID NO: 73), the heavy chain CDR2 comprises the amino acid sequence shown by INGDSTNI (SEQ ID NO: 131), the heavy chain CDR3 comprises the amino acid sequence shown by AAGPEYYSRNSYYMPFQY (SEQ ID NO: 132), the light chain CDR1 comprises the amino acid sequence shown by SDISVGRKS (SEQ ID NO: 133), the light chain CDR2 comprises the amino acid sequence shown by YYSDSDK (SEQ ID NO: 134), and the light chain CDR3 comprises the amino acid sequence shown by TIWHSGTWV (SEQ ID NO: 135).

5. The anti-vanin-1 antibody or antigen-binding fragment thereof according to claim 1, wherein the anti-vanin-1 antibody is a monoclonal antibody.

6. A polynucleotide comprising the coding sequence of the anti-Vanin-1 antibody or its antigen-binding fragment as described in claim 1.

7. A cell comprising the polynucleotide described in claim 6.

8. A reagent or pharmaceutical comprising the anti-Vanin-1 antibody or its antigen-binding fragment according to claim 1, the polynucleotide according to claim 6, or the cells according to claim 7.

9. A kit for detecting Vanin-1 protein, comprising the anti-Vanin-1 antibody or its antigen-binding fragment as described in claim 1.

10. A kit for detecting the Vanin-1 protein, comprising two or more anti-Vanin-1 antibodies or antigen-binding fragments thereof as described in claim 1, wherein at least two of the anti-Vanin-1 antibodies or antigen-binding fragments thereof bind to different regions of the Vanin-1 protein.

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