Anti-human CEACAM5 antibody Fab fragment

1. An anti-human CEACAM 5 antibody Fab fragment selected from the group consisting of the following (a) and (b):

(a) an anti-human CEACAM5 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region consisting of an amino acid sequence from amino acid positions 1 to 121 of SEQ ID NO: 2 and a light chain comprising a light chain variable region consisting of an amino acid sequence from amino acid positions 1 to 112 of SEQ ID NO: 4; and

(b) an anti-human CEACAM 5 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region derived from a heavy chain variable region consisting of an amino acid sequence from amino acid positions 1 to 121 of SEQ ID NO: 2 by the modification of glutamic acid at amino acid position 1 of SEQ ID NO: 2 into pyroglutamic acid, and a light chain comprising a light chain variable region consisting of an amino acid sequence from amino acid positions 1 to 112 of SEQ ID NO: 4.

2. The anti-human CEACAM 5 antibody Fab fragment according to claim 1 selected from the group consisting of the following (a) and (b):

(a) an anti-human CEACAM 5 antibody Fab fragment comprising a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 2 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 4; and

(b) an anti-human CEACAM 5 antibody Fab fragment comprising a heavy chain fragment derived from a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 2 by the modification of glutamic acid at amino acid position 1 of SEQ ID NO: 2 into pyroglutamic acid, and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 4.

3. The anti-human CEACAM5 antibody Fab fragment according to claim 2 , comprising a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 2 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 4.

4. A conjugate comprising a labeling moiety and an anti-human CEACAM5 antibody Fab fragment according to any one of claims 1 to 3 .

5. The conjugate according to claim 4 , wherein the labeling moiety is (i) a ligand and a linker, (ii) a ligand, (iii) a fluorescent dye and a linker, or (iv) a fluorescent dye.

6. The conjugate according to claim 5 , wherein the labeling moiety is (i) a ligand and a linker, or (ii) a ligand.

7. The conjugate according to claim 6 , wherein the ligand is a ligand represented by the following formula (A):

wherein the wavy line represents binding to the anti-human CEACAMS antibody Fab fragment or the linker.

8. The conjugate according to claim 6 , wherein the labeling moiety is (i) a ligand and a linker, wherein the ligand and the linker are a group represented by the following formula (A′):

wherein the wavy line represents binding to the anti-human CEACAM 5 antibody Fab fragment.

9. The conjugate according to claim 8 , wherein the anti-human CEACAM5 antibody Fab fragment is bound to the carbon atom of a labeling moiety terminal C(═S) group via an amino group in the Fab fragment.

10. The conjugate according to claim 6 represented by the following formula (I):

(L-X) p -Ab  

wherein Ab is the anti-human CEACAM5 antibody Fab fragment;

L is the ligand;

X is the linker or a bond; and

p is a natural number of 1 to 25.

11. The conjugate according to claim 10 , wherein L is a ligand represented by the following formula (A):

wherein the wavy line represents binding to X or Ab when X is a bond.

12. The conjugate according to claim 8 represented by the following formula (II):

wherein Ab is the anti-human CEACAM5 antibody Fab fragment; and

p is a natural number of 1 to 25, wherein Ab is bound to the carbon atom of labeling moiety terminal C(═S) via an amino group in the Ab.

13. The conjugate according to claim 10 , wherein p is a natural number of 1 to 16.

14. The conjugate according to claim 10 , wherein p is a natural number of 1 to 10.

15. The conjugate according to claim 5 , further comprising a metal.

16. The conjugate according to claim 15 , wherein the metal is a metal radioisotope.

17. The conjugate according to claim 15 , wherein the metal is 89 Zr.

18. The conjugate according to claim 16 or 17 which is a PET tracer.

19. A polynucleotide selected from the group consisting of the following (a) and (b):

(a) a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 ; and

(b) a polynucleotide comprising a nucleotide sequence encoding the light chain of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 .

20. A polynucleotide selected from the group consisting of the following (a) and (b):

(a) a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of an anti-human CEACAM5 antibody Fab fragment according to claim 3 ; and

(b) a polynucleotide comprising a nucleotide sequence encoding the light chain of the anti-human CEACAM5 antibody Fab fragment according to claim 3 .

21. An expression vector comprising the following (a) and/or (b):

(a) a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 ; and

(b) a polynucleotide comprising a nucleotide sequence encoding the light chain of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 .

22. An expression vector comprising the following (a) and/or (b):

(a) a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of an anti-human CEACAM5 antibody Fab fragment according to claim 3 ; and

(b) a polynucleotide comprising a nucleotide sequence encoding the light chain of the anti-human CEACAM5 antibody Fab fragment according to claim 3 .

23. A host cell selected from the group consisting of the following (a) to (d):

(a) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 ;

(b) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the light chain of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 ;

(c) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 and a polynucleotide comprising a nucleotide sequence encoding the light chain of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 ; and

(d) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 and an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the light chain of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 .

24. A host cell selected from the group consisting of the following (a) to (d):

(a) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of an anti-human CEACAM5 antibody Fab fragment according to claim 3 ;

(b) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the light chain of the anti-human CEACAM5 antibody Fab fragment according to claim 3 ;

(c) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of the anti-human CEACAM5 antibody Fab fragment according to claim 3 and a polynucleotide comprising a nucleotide sequence encoding the light chain of the anti-human CEACAM5 antibody Fab fragment according to claim 3 ; and

(d) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of the anti-human CEACAM5 antibody Fab fragment according to claim 3 and an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the light chain of the anti-human CEACAM5 antibody Fab fragment according to claim 3 .

25. A method for producing an anti-human CEACAM5 antibody Fab fragment, comprising the step of culturing a host cell selected from the group consisting of the following (a) to (c) to express the anti-human CEACAM5 antibody Fab fragment:

(a) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 and a polynucleotide comprising a nucleotide sequence encoding the light chain of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 ;

(b) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 and an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the light chain of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 ; and

(c) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 , and a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the light chain of anti-human CEACAM5 antibody Fab fragment (a) according to claim 1 .

26. A method for producing an anti-human CEACAM5 antibody Fab fragment, comprising the step of culturing a host cell selected from the group consisting of the following (a) to (c) to express the anti-human CEACAM5 antibody Fab fragment:

(a) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of an anti-human CEACAM5 antibody Fab fragment according to claim 3 and a polynucleotide comprising a nucleotide sequence encoding the light chain of the anti-human CEACAM5 antibody Fab fragment according to claim 3 ;

(b) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of the anti-human CEACAM5 antibody Fab fragment according to claim 3 and an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the light chain of the anti-human CEACAM5 antibody Fab fragment according to claim 3 ; and

(c) a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the heavy chain fragment of the anti-human CEACAM5 antibody Fab fragment according to claim 3 , and a host cell transformed with an expression vector comprising a polynucleotide comprising a nucleotide sequence encoding the light chain of the anti-human CEACAM5 antibody Fab fragment according to claim 3 .

27. A method for producing a conjugate comprising a labeling moiety and an anti-human CEACAM5 antibody Fab fragment, comprising the steps of: preparing the anti-human CEACAM5 antibody Fab fragment by a method according to claim 25 or 26 ; and covalently binding the Fab fragment to the labeling moiety.

28. A method for producing a conjugate comprising a ligand and an anti-human CEACAM5 antibody Fab fragment, comprising the steps of: preparing the anti-human CEACAM5 antibody Fab fragment by a method according to claim 25 or 26 ; and covalently binding the Fab fragment to the ligand via a linker or directly.

29. A method for producing a conjugate comprising a labeling moiety labeled with a metal radioisotope and an anti-human CEACAM5 antibody Fab fragment, comprising the steps of: producing a conjugate comprising a ligand and an anti-human CEACAM5 antibody Fab fragment by a method according to claim 28 ; and binding the metal radioisotope to the ligand of the conjugate through a coordinate bond.

30. A composition for diagnosis comprising a conjugate according to claim 15 , and a pharmaceutically acceptable carrier.

31. The composition for diagnosis according to claim 30 which is a clinical staging drug.

32. A method for diagnosing a cancer selected from colorectal cancer, breast cancer, lung cancer, thyroid gland cancer or a cancer resulting from the metastasis thereof, comprising administering a conjugate according to claim 15 to a subject.

33. The method according to claim 32 , wherein the cancer is colorectal cancer or a cancer resulting from the metastasis of colorectal cancer.

34. The method according to claim 33 , wherein the cancer resulting from the metastasis of colorectal cancer is metastatic liver cancer.

35. The conjugate according to claim 12 , wherein p is a natural number of 1 to 10 and the conjugate further comprises a metal and the metal is 89 Zr.