JPWO2021190622A5

JPWO2021190622A5 -

Info

Publication number: JPWO2021190622A5
Application number: JP2022547787A
Authority: JP
Publication date: 2023-06-12
Anticipated expiration: 2041-03-26

Claims

An isolated antibody that specifically binds to Siglec15, comprising:
i) A heavy chain variable region comprising a VH CDR1 region, a VH CDR2 region and a VH CDR3 region, wherein said VH CDR1 region, said VH CDR2 region and said VH CDR3 region are SEQ ID NOS: 1, 2 (where X1 is D and X2 is K, or X1 is D and X2 is Q, or X1 is E and X2 is Q) and 3 amino acid sequences, respectively; and
ii) a light chain variable region comprising a VL CDR1 region, a VL CDR2 region and a VL CDR3 region, wherein said VL CDR1 region, said VL CDR2 region and said VL CDR3 region comprise the amino acid sequences of SEQ ID NOS: 4, 5 and 6; An isolated antibody comprising, respectively;

2. The isolated antibody of Claim 1, wherein said VH CDR2 region comprises the amino acid sequence of SEQ ID NO:2, wherein X1 is D and X2 is K.

(a) said heavy chain variable region comprises an amino acid sequence having at least 85% identity to SEQ ID NO:7; and/or said light chain variable region has at least 85% identity to SEQ ID NO:8 comprising an amino acid sequence; or
(b) said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:7; and/or said light chain variable region comprises the amino acid sequence of SEQ ID NO:8;
2. The isolated antibody of claim 1.

4. The isolated antibody of Claim 3, wherein said heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:7, wherein X1 is D and X2 is K.

5. The isolated antibody of any one of claims 1-4, which is of the IgG1, IgG2 or IgG4 isotype.

6. The isolated antibody of any one of claims 1-5, comprising a heavy chain constant region having the amino acid sequence of SEQ ID NO: 17, linked to said heavy chain variable region.

7. The isolated antibody of any one of claims 1-6, comprising a human kappa or human lambda light chain constant region.

8. The isolated antibody of any one of claims 1-7, comprising a light chain constant region having the amino acid sequence of SEQ ID NO: 18, linked to said light chain variable region.

An isolated antibody that specifically binds to Siglec15, comprising SEQ ID NO: 7 (X1 is D and X2 is K, X1 is D and X2 is Q, or X1 is E and X2 is Q and a light chain variable region comprising the amino acid sequence of SEQ ID NO:8.

10. The isolated antibody of Claim 9, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:7, wherein X1 is D and X2 is K.

a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 17 linked to the heavy chain variable region, and a light chain constant region comprising the amino acid sequence of SEQ ID NO: 18 linked to the light chain variable region; 11. The isolated antibody of claim 9 or 10.

12. The isolated antibody of any one of claims 1-11, which is a murine, human, chimeric or humanized antibody.

13. The isolated antibody of any one of claims 1-12 conjugated to a cytotoxic agent, toxin, or radioisotope.

(a) the heavy and light chain variable regions of the isolated antibody of any one of claims 1-13; or
(b) the heavy and light chains of the isolated antibody of any one of claims 1-13;
A polynucleotide encoding a

A vector containing the polynucleotide of claim 14 .

(a) the polynucleotide of claim 14;
(b) the vector of claim 15;
(c) a first polynucleotide encoding the heavy chain variable region or heavy chain of the isolated antibody of any one of claims 1-13; a second polynucleotide encoding the light chain variable region or light chain of the isolated antibody; or
(d) a first vector comprising a first polynucleotide encoding the heavy chain variable region or heavy chain of the isolated antibody of any one of claims 1-13; and any one of claims 1-13. a second vector comprising a second polynucleotide encoding the light chain variable region or light chain of the isolated antibody of claim 1;
A host cell comprising

A method of producing an isolated antibody that specifically binds to Siglec15, said method comprising:
(a) polynucleotides encoding the heavy and light chain variable regions, or heavy and light chains, of the isolated antibody of any one of claims 1-13;
(b) a heavy chain variable region and a first nucleotide encoding the heavy chain of the isolated antibody of any one of claims 1-13; a second polynucleotide encoding the light chain variable region and the light chain of the isolated antibody;
(c) a vector comprising polynucleotides encoding the heavy and light chain variable regions, or the heavy and light chains, of the isolated antibody of any one of claims 1-13; or
(d) a first vector comprising a first polynucleotide encoding the heavy chain variable region or heavy chain of the isolated antibody of any one of claims 1-13; and any one of claims 1-13. a second vector comprising a second polynucleotide encoding the light chain variable region or light chain of the isolated antibody of claim 1;
, under suitable conditions such that said isolated antibody is produced.

an isolated antibody according to any one of claims 1 to 13, a polynucleotide according to claim 14, a vector according to claim 15, or a host cell according to claim 16;
and a pharmaceutically acceptable carrier or excipient.

A method of treating cancer in a subject, comprising a therapeutically effective amount of the isolated antibody of any one of claims 1 to 13, the polynucleotide of claim 14, the vector of claim 15, 19. A method comprising administering the host cell of claim 16 or the pharmaceutical composition of claim 18 to said subject.

20. The method of claim 19, wherein said cancer is a solid tumor.

21. The method of claim 20, wherein the solid tumor is non-small cell lung cancer, ovarian cancer, melanoma, colorectal cancer, breast cancer, endometrial cancer, or squamous cell carcinoma.

15. A method of inhibiting bone loss or increasing bone mass in a subject, comprising a therapeutically effective amount of the isolated antibody of any one of claims 1 to 13, the polynucleotide of claim 14. , the vector of claim 15, the host cell of claim 16, or the pharmaceutical composition of claim 18, to said subject.

(a) treating cancer in a subject in need thereof;
(b) inhibit bone loss in a subject; or
(c) increases bone mass in a subject;
An isolated antibody according to any one of claims 1 to 13, a polynucleotide according to claim 14, a vector according to claim 15, a host according to claim 16, for the manufacture of a medicament for Use of a cell or a pharmaceutical composition according to claim 18.

24. Use according to claim 23, wherein said cancer is a solid tumor.

25. Use according to claim 24, wherein the solid tumor is non-small cell lung cancer, ovarian cancer, melanoma, colorectal cancer, breast cancer, endometrial cancer, or squamous cell carcinoma.

(a) treating cancer in a subject in need thereof;
(b) inhibit bone loss in a subject; or
(c) increases bone mass in a subject;
The isolated antibody of any one of claims 1 to 13, the polynucleotide of claim 14, the vector of claim 15, the host cell of claim 16, or the host cell of claim 16, or 19. A pharmaceutical composition according to claim 18.

27. The isolated antibody, polynucleotide, vector, host cell, or pharmaceutical composition of claim 26, wherein said cancer is a solid tumor.

28. The isolated antibody, polynucleotide, vector, host cell of claim 27, wherein said solid tumor is non-small cell lung cancer, ovarian cancer, melanoma, colorectal cancer, breast cancer, endometrial cancer, or squamous cell carcinoma. , or a pharmaceutical composition.