Anti-BTLA antibody

1. An isolated anti-BTLA antibody or an antigen-binding fragment thereof wherein the amino acid sequences of the LCDR1, LCDR2 and LCDR3 of the light chain CDR and the amino acid sequences of the HCDR1, HCDR2 and HCDR3 of the heavy chain CDR of the isolated antibody or the antigen-binding fragment thereof are selected from any one of the following groups I-IX:

Group

LCDR1

LCDR2

LCDR3

I

SEQ ID NO: 7

SEQ ID NO: 8

SEQ ID NO: 9

II

SEQ ID NO: 10

SEQ ID NO: 11

SEQ ID NO: 12

III

SEQ ID NO: 16

SEQ ID NO: 17

SEQ ID NO: 18

IV

SEQ ID NO: 22

SEQ ID NO: 23

SEQ ID NO: 24

V

SEQ ID NO: 22

SEQ ID NO: 23

SEQ ID NO: 24

VI

SEQ ID NO: 31

SEQ ID NO: 32

SEQ ID NO: 33

VII

SEQ ID NO: 7

SEQ ID NO: 8

SEQ ID NO: 9

VIII

SEQ ID NO: 10

SEQ ID NO: 11

SEQ ID NO: 12

IX

SEQ ID NO: 10

SEQ ID NO: 11

SEQ ID NO: 12

Group

HCDR1

HCDR2

HCDR3

I

SEQ ID NO: 1

SEQ ID NO: 2

SEQ ID NO: 3

II

SEQ ID NO: 4

SEQ ID NO: 5

SEQ ID NO: 6

III

SEQ ID NO: 13

SEQ ID NO: 14

SEQ ID NO: 15

IV

SEQ ID NO: 19

SEQ ID NO: 20

SEQ ID NO: 21

V

SEQ ID NO: 25

SEQ ID NO: 26

SEQ ID NO: 27

VI

SEQ ID NO: 28

SEQ ID NO: 29

SEQ ID NO: 30

VII

SEQ ID NO: 4

SEQ ID NO: 5

SEQ ID NO: 6

VIII

SEQ ID NO: 1

SEQ ID NO: 2

SEQ ID NO: 3

IX

SEQ ID NO: 13

SEQ ID NO: 14

SEQ ID NO: 15.

2. The anti-BTLA antibody or the antigen-binding fragment thereof according to claim 1 , comprising:

a light chain variable region having an amino acid sequence selected from any one of amino acid sequences set forth in SEQ ID NOs: 36, 37, 39, 41, 44, 46, 47 and 48; and

a heavy chain variable region having an amino acid sequence selected from any one of amino acid sequences set forth in SEQ ID NOs: 34, 35, 38, 40, 42, 43 and 45.

3. The anti-BTLA antibody or the antigen-binding fragment thereof according to claim 2 , wherein,

the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 36, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 34 or 35;

the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 37, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 34 or 35;

the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 39, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 38;

the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 41, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 40 or 42;

the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 44, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 43; or

the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 46, 47 or 48, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 45.

4. The anti-BTLA antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody is a chimeric antibody, or a humanized antibody.

5. An isolated nucleic acid molecule, comprising (1) a polynucleotide sequence encoding the anti-BTLA antibody or the antigen-binding fragment thereof according to claim 1 , and (2) a complementary sequence of the polynucleotide sequence of (1).

6. The isolated nucleic acid molecule of claim 5 , wherein the light chain variable region of the antibody or the antigen-binding fragment thereof comprises an amino acid sequence as set forth in SEQ ID NO: 46, 47 or 48; and the heavy chain variable region of the antibody or the antigen-binding fragment thereof comprises an amino acid sequence as set forth in SEQ ID NO: 45.

7. An expression vector comprising the isolated nucleic acid molecule according to claim 5 .

8. The expression vector of claim 7 comprising the nucleic acid molecule encoding an antibody comprising a heavy chain variable region selected from the amino acid sequence of SEQ ID NO: 45, and a light chain variable region selected from the group consisting of the amino acid sequence of SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48, or an antigen-binding fragment thereof.

9. A host cell comprising the nucleic acid molecule according to claim 5 .

10. The host cell of claim 9 comprising the nucleic acid molecule encoding an antibody comprising a heavy chain variable region selected from the amino acid sequence of SEQ ID NO: 45, and a light chain variable region selected from the group consisting of the amino acid sequence of SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48, or an antigen-binding fragment thereof.

11. A pharmaceutical composition comprising the anti-BTLA antibody or the antigen-binding fragment thereof according to claim 1 , a nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof, an expression vector comprising the nucleic acid molecule, or a host cell comprising the nucleic acid molecule or the expression vector, or any combination thereof; and a pharmaceutically acceptable carrier.

12. A method for treating a BTLA-mediated disease by eliminating, inhibiting, or reducing BTLA activity, comprising administering to a subject in need thereof a therapeutically effective amount of antibodies or the antigen-binding fragments thereof of claim 1 , or an nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof, an expression vector comprising the nucleic acid molecule, or a host cell comprising the nucleic acid molecule or the expression vector, an immunoconjugate comprising the antibody an antigen-binding fragment thereof, or a pharmaceutical composition comprising the antibody or the antigen-binding fragment thereof, the expression vector, the host cell or the immunoconjugate, wherein the BTLA-mediated disease is a cancer.

13. An immunoconjugate comprising the antibody or an antigen-binding fragment thereof according to claim 1 conjugated with a therapeutic agent.

14. The immunoconjugate of claim 13 , wherein the antibody comprises a heavy chain variable region selected from the amino acid sequence of SEQ ID NO: 45, and a light chain variable region selected from the group consisting of the amino acid sequence of SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48.

15. The immunoconjugate of claim 13 , wherein the therapeutic agent is a toxin, a radioisotope, or a cytotoxic agent.