RI-LABELED HUMANIZED ANTIBODY

1 - 20 . (canceled)

21 . A conjugate comprising:

an antibody,

a peptide linker,

and a chelating agent comprising a chelate linker and a chelate site; wherein the chelate site is chelated with a radionuclide comprising a positron emitting metallic nuclide;

wherein the antibody is a humanized antibody specifically binding to MUC5AC, comprising a heavy chain variable region selected from the group consisting of

(1) the amino acid sequence shown in SEQ ID NO: 1 (H01),

(2) the amino acid sequence shown in SEQ ID NO: 2 (H02),

(3) the amino acid sequence shown in SEQ ID NO: 3 (H03), and

(4) the amino acid sequence shown in SEQ ID NO: 4 (H04), and

a light chain variable region selected from the group consisting of

(5) the amino acid sequence shown in SEQ ID NO: 5 (L01),

(6) the amino acid sequence shown in SEQ ID NO: 6 (L02),

(7) the amino acid sequence shown in SEQ ID NO: 7 (L03), and

(8) the amino acid sequence shown in SEQ ID NO: 8 (L04);

wherein the chelating site specifically modifies an Fc region of the antibody via the peptide linker;

wherein the peptide linker comprises an antibody modification peptide and an antibody modification linker;

wherein the antibody modification peptide consists of not less than 13 and not more than 17 amino acid residue and is represented by the following formula (i):

wherein Xa, Xb, Xc and Xd are each continuous X in the number of a, continuous X in the number of b, continuous X in the number of c, and continuous X in the number of d, respectively,

X is an amino acid residue having neither a thiol group nor a haloacetyl group in the side chain,

a, b, c and d are each independently an integer of not less than one and not more than 5, and satisfy a+b+c+d<14,

Xaa1 and Xaa3 are each independently an amino acid residue derived from an amino acid having a thiol group in the side chain, or

Xaa1 is an amino acid residue derived from an amino acid having a thiol group in the side chain and the Xaa3 is an amino acid residue derived from an amino acid having a haloacetyl group in the side chain, or

Xaa3 is an amino acid residue derived from an amino acid having a thiol group in the side chain and the Xaa1 is an amino acid residue derived from an amino acid having a haloacetyl group in the side chain,

and Xaa1 and Xaa3 are linked through their side chains, and

Xaa2 is a lysine residue, arginine residue, cysteine residue, aspartic acid residue, glutamic acid residue, 2-aminosuberic acid, or diamino propionic acid, wherein Xaa2 is modified with the crosslinking agent with a structure of

wherein the Fc region is bound to the crosslinking agent at the position of A*, and

is the binding site with Xaa2; and

wherein the antibody-modification linker is derived from a structure of:

wherein:

the antibody modification peptide is bound to the antibody modification linker at ;

and

n is 2 to 10

wherein the chelate site is represented by the following formula (A) or a salt thereof

wherein:

R 11 , R 13 , and R 14 are each independently selected from the group consisting of —(CH 2 ) p COOH, —(CH 2 ) p C 5 H 5 N, —(CH 2 ) p PO 3 H 2 , —(CH 2 ) p CONH 2 or —(CHCOOH)(CH 2 ) p COOH; and

p is an integer of not less than 0 and not more than 3;

R 15 is a hydrogen atom; and

R 12 is a binding site derived from a substituent having the structure of:

wherein C* is the binding site with the chelate linker after ring opening;

wherein the chelate linker has a structure derived from:

wherein:

is the binding site with the chelate site; and

wherein the peptide linker and the chelating agent are linked via a triazole moiety derived from the azide group in the antibody-modification linker and the dibenzocyclooctyne group in the chelate linker represented by formula (10a) and (10b):

wherein (10a) and (10b) are isomers that may be present at any ratio; and

R 1A is a binding site with the remaining portion of the chelate linker, and R 2A is a binding site with the remaining portion of the antibody-modification linker.

22 . The conjugate according to claim 21 , wherein the antibody comprises

(1) a heavy chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 1 (H01), and

(7) a light chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 7 (L03).

23 . The conjugate according to claim 21 , wherein the antibody modification peptide comprises the amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, or SEQ ID NO: 21; wherein Xaa2 is a lysine residue.

24 . The conjugate according to claim 23 , wherein the antibody modification peptide comprises the amino acid sequence of SEQ ID NO: 10, SEQ ID NO: 16, SEQ ID NO: 17, or SEQ ID NO: 18; wherein Xaa2 is a lysine residue.

25 . The conjugate according to claim 21 , wherein R 1 , R 13 , and R 14 are each independently a group consisting of —(CH 2 ) p COOH or —(CHCOOH)(CH 2 ) p COOH, and p is 1.

26 . The conjugate according to claim 21 , wherein the chelating agent has a structure derived from a compound represented by the following formula or a salt thereof:

27 . The conjugate according to claim 21 , wherein the antibody comprises:

(1) the heavy chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 1 (H01), and

(7) the light chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 7 (L03);

wherein the antibody-modification peptide comprises the amino acid sequence of SEQ ID NO: 10,

wherein Xaa2 is a lysine residue; and

wherein the chelating agent has a structure derived from a compound represented by the following formula or a salt thereof:

28 . The conjugate according to claim 21 , wherein the antibody comprises:

(1) the heavy chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 1 (H01), and

(7) the light chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 7 (L03);

wherein the antibody modification peptide comprises the amino acid sequence of SEQ ID NO: 16, wherein Xaa2 is a lysine residue; and

wherein the chelating agent has a structure derived from a compound represented by the following formula or a salt thereof:

29 . The conjugate according to claim 21 , wherein the antibody comprises:

(1) the heavy chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 1 (H01), and

(7) the light chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 7 (L03);

wherein the antibody modification peptide comprises the amino acid sequence of SEQ ID NO: 17, wherein Xaa2 is a lysine residue; and

wherein the chelating agent has a structure derived from a compound represented by the following formula or a salt thereof:

30 . The conjugate according to claim 21 , wherein the antibody comprises:

(1) the heavy chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 1 (H01), and

(7) the light chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 7 (L03);

wherein the antibody modification peptide comprises the amino acid sequence of SEQ ID NO: 18, wherein Xaa2 is a lysine residue; and

wherein the chelating agent has a structure derived from a compound represented by the following formula or a salt thereof:

31 . The conjugate of claim 21 , wherein the radionuclide comprising a positron emitting metallic nuclide is Zirconium-89 ( 89 Zr).

32 . The conjugate of claim 21 wherein the radionuclide comprising a positron emitting metallic nuclide selected from the group consisting of 64 Cu, 68 Ga, and 86 Y.

33 . The conjugate according to claim 21 , wherein the chelate site has a structure derived from a compound represented by the following formula (A-12) or a salt thereof:

wherein the chelate site is chelated with a radionuclide comprising a positron emitting metallic nuclide.

34 . The conjugate according to claim 22 , wherein the antibody comprises:

a heavy chain constant region consisting of the amino acid sequence shown in SEQ ID NO: 25, and

a light chain constant region consisting of the amino acid sequence shown in SEQ ID NO: 26.

35 . The conjugate according to claim 21 , wherein the peptide linker comprises the structure of formula (L):

wherein Lys252 of the Fc region of the antibody by EU numbering is bound through Fc* and the chelating agent is bound via a triazole derived from the azide group.

36 . The conjugate of claim 21 , wherein the antibody modification linker is bound at the N-terminus of the antibody modification peptide.

37 . A conjugate comprising an antibody,

wherein the antibody is a humanized antibody specifically binding to MUC5AC, comprising a heavy chain variable region selected from the group consisting of

(1) the amino acid sequence shown in SEQ ID NO: 1 (H01),

(2) the amino acid sequence shown in SEQ ID NO: 2 (H02),

(3) the amino acid sequence shown in SEQ ID NO: 3 (H03), and

(4) the amino acid sequence shown in SEQ ID NO: 4 (H04), and

a light chain variable region selected from the group consisting of

(5) the amino acid sequence shown in SEQ ID NO: 5 (L01),

(6) the amino acid sequence shown in SEQ ID NO: 6 (L02),

(7) the amino acid sequence shown in SEQ ID NO: 7 (L03), and

(8) the amino acid sequence shown in SEQ ID NO: 8 (L04); and

a compound comprising a peptide and a chelating agent, or a pharmaceutically acceptable salt thereof, having the structure of

wherein the chelating agent is chelated with a positron emitting metallic nuclide; and Lys252 of the Fc region of the antibody by EU numbering is bound through Fc*.

38 . The conjugate of claim 37 , wherein the compound comprising a peptide and a chelating agent, or a pharmaceutically acceptable salt thereof, has the structure of:

39 . The conjugate of claim 37 , wherein the compound comprising a peptide and a chelating agent, or a pharmaceutically acceptable salt thereof, has the structure of:

40 . The conjugate of claim 37 , wherein the antibody comprises:

(1) the heavy chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 1 (H01), and

(7) the light chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 7 (L03).

41 . The conjugate according to claim 40 , wherein the antibody comprises:

a heavy chain constant region consisting of the amino acid sequence shown in SEQ ID NO: 25, and

a light chain constant region consisting of the amino acid sequence shown in SEQ ID NO: 26.

42 . A conjugate comprising an antibody,

wherein the antibody is a humanized antibody specifically binding to MUC5AC, comprising a heavy chain variable region selected from the group consisting of

(1) the amino acid sequence shown in SEQ ID NO: 1 (H01),

(2) the amino acid sequence shown in SEQ ID NO: 2 (H02),

(3) the amino acid sequence shown in SEQ ID NO: 3 (H03), and

(4) the amino acid sequence shown in SEQ ID NO: 4 (H04), and

a light chain variable region selected from the group consisting of

(5) the amino acid sequence shown in SEQ ID NO: 5 (L01),

(6) the amino acid sequence shown in SEQ ID NO: 6 (L02),

(7) the amino acid sequence shown in SEQ ID NO: 7 (L03), and

(8) the amino acid sequence shown in SEQ ID NO: 8 (L04); and

a compound comprising a peptide and a chelating agent, or a pharmaceutically acceptable salt thereof, having the structure of

wherein the chelating agent is chelated with Zr-89; and Lys252 of the Fc region of the antibody by EU numbering is bound through Fc*.

43 . The conjugate of claim 42 , wherein the compound comprising a peptide and a chelating agent chelated with Zr-89, or a pharmaceutically acceptable salt thereof, has the structure of:

44 . The conjugate of claim 42 , wherein the compound comprising a peptide and a chelating agent chelated with Zr-89, or a pharmaceutically acceptable salt thereof, has the structure of:

45 . The conjugate of claim 42 , wherein the antibody comprises:

(1) the heavy chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 1 (H01), and

(7) the light chain variable region consisting of the amino acid sequence shown in SEQ ID NO: 7 (L03).

46 . The conjugate according to claim 45 , wherein the antibody comprises:

a heavy chain constant region consisting of the amino acid sequence shown in SEQ ID NO: 25, and

a light chain constant region consisting of the amino acid sequence shown in SEQ ID NO: 26.