Anti-CD47 monoclonal antibody and use thereof

1 . An antibody or an antigen-binding fragment thereof that specifically binds to CD47, which, comprises HCDR1-3 and LCDR1-3 as shown below, wherein

the amino acid sequences of the 3 CDR regions of the heavy chain variable region are as follows:

HCDR1:

(SEQ ID NO: 5)

GYTFTSYW,

HCDR2:

(SEQ ID NO: 6)

IDPSDSET,

and

HCDR3:

(SEQ ID NO: 7)

ARLYRWYFDV;

and

and

the amino acid sequences of the 3 CDR regions of the light chain variable region are as follows:

LCDR1:

(SEQ ID NO: 8)

EIVGTY,

LCDR2:

(SEQ ID NO: 9)

GAS,

and

LCDR3:

(SEQ ID NO: 10)

GQSYNFPYT

2 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody further comprises a heavy chain constant region and a light chain constant region, and the constant regions are derived from species other than murine.

3 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody comprises a combination of a heavy chain and a light chain selected from the group consisting of the following:

(a) a heavy chain set forth in SEQ ID NO: 59 and a light chain set forth in SEQ ID NO: 60;

(b) a heavy chain set forth in SEQ ID NO: 61 and a light chain set forth in SEQ ID NO: 62;

(c) a heavy chain set forth in SEQ ID NO: 63 and a light chain set forth in SEQ ID NO: 64;

(d) a heavy chain set forth in SEQ ID NO: 65 and a light chain set forth in SEQ ID NO: 66;

(e) a heavy chain set forth in SEQ ID NO: 67 and a light chain set forth in SEQ ID NO: 68; and

(f) a heavy chain set forth in SEQ ID NO: 69 and a light chain set forth in SEQ ID NO: 70.

4 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody further comprises an amino acid mutation introduced at position 234 and/or 235 in the constant region of the heavy chain according to the EU numbering system.

5 . The antibody or the antigen-binding fragment thereof according to claim 4 , wherein the antibody comprises a combination of a heavy chain and a light chain selected from the group consisting of the following:

(a) a heavy chain set forth in SEQ ID NO: 59 and a light chain set forth in SEQ ID NO: 60;

(b) a heavy chain set forth in SEQ ID NO: 61 and a light chain set forth in SEQ ID NO: 62; and

(c) a heavy chain set forth in SEQ ID NO: 63 and a light chain set forth in SEQ ID NO: 64.

6 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antigen-binding fragment is selected from Fab, Fab′, F(ab′) 2 , Fd, Fv, Fab/c, single chain antibody, or bivalent antibody.

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

8 . The antibody or the antigen-binding fragment thereof according to claim 1 , which is encoded by a polynucleotide.

9 . The antibody or antigen-binding fragment thereof according to claim 8 wherein the polynucleotide molecule is contained in a vector or a host cell.

10 . The antibody conjugate comprising the antibody or the antigen-binding fragment thereof according claim 1 , wherein the antibody or the antigen-binding fragment thereof is contained in an antibody conjugate, a pharmaceutical composition, a multiple specific antibody, a fusion protein, a medicament or a kit, wherein the antibody conjugate further comprises a conjugated moiety coupled thereto to the antibody or antigen-binding fragment thereof.

11 . A hybridoma cell line and a monoclonal antibody produced by the hybridoma cell line, wherein the hybridoma cell line is hybridoma cell line LT012 under CCTCC NO. 2018135.

12 . A method, comprising administering a cell comprising the antibody or the antigen-binding fragment thereof according to claim 1 , or administering to a subject in need an effective amount of the antibody or the antigen-binding fragment thereof according to claim 1 , wherein the method is selected from:

a method for blocking the binding of CD47 to human SIRPα,

a method for blocking the activity of human CD47 or down-regulating the level of human CD47,

a method for blocking cellular response mediated by the binding of human SIRPα to CD47, and

a method for treating a tumor.

13 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody is secreted by a hybridoma cell line, wherein the hybridoma cell line is hybridoma cell line LT012 under CCTCC NO. 2018135.

14 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody comprises:

(a) a heavy chain variable region comprising or consisting of: an amino acid sequence set forth in SEQ ID NO: 2, and a light chain variable region comprising or consisting of: an amino acid sequence set forth in SEQ ID NO: 4;

(b) a heavy chain variable region comprising or consisting of: an amino acid sequence set forth in SEQ ID NO: 12; and a light chain variable region comprising or consisting of: an amino acid sequence set forth in SEQ ID NO: 14;

(c) a heavy chain variable region comprising or consisting of: an amino acid sequence set forth in SEQ ID NO: 16; and a light chain variable region comprising or consisting of: an amino acid sequence set forth in SEQ ID NO: 18; or

(d) a heavy chain variable region comprising or consisting of: an amino acid sequence set forth in SEQ ID NO: 20; and a light chain variable region comprising or consisting of: an amino acid sequence set forth in SEQ ID NO: 22.

15 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody further comprises a heavy chain constant region and a light chain constant region, and the heavy chain constant region is Ig gamma-1 chain C region, ACCESSION No. P01857 set forth in SEQ ID NO: 58 or Ig gamma-4 chain C region, ACCESSION No. P01861.1 set forth in SEQ ID NO: 56; the light chain constant region is Ig kappa chain C region, ACCESSION No. P01834 set forth in SEQ ID NO: 57.

16 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody comprises mutation L234A and/or L235A in the constant region of the heavy chain according to the EU numbering system.

17 . The antibody or the antigen-binding fragment thereof according to claim 10 , wherein the conjugated moiety is a purification tag, a cytotoxic agent or a detectable label; or

the multispecific antibody further comprises an antibody or an antigen-binding fragment against another antigen and/or another antigenic epitope, or

the kit further comprises a second antibody that specifically identifies the antibody or the antigen-binding fragment thereof, wherein the second antibody further comprising a detectable label; or

the pharmaceutical composition further comprises a pharmaceutically acceptable carrier and/or excipient, or

the medicament is in a form suitable for injection.

18 . The antibody or the antigen-binding fragment thereof according to claim 17 ,

wherein the purification tag is a His tag, or

the detectable label is a radioisotope, a luminescent substance, a colored substance, an enzyme or polyethylene glycol, or

the medicament is in a form suitable for administration by subcutaneous injection, intradermal injection, intravenous injection, intramuscular injection or intralesional injection.

19 . The method according to claim 12 , wherein the tumor is a tumor expressing CD47.

20 . The method according to claim 12 , wherein the tumor is a hematological malignancy or a solid tumor.

21 . The method according to claim 12 , wherein the tumor is lymphoma, colon cancer or breast cancer.

22 . The method according to claim 12 , wherein the tumor is non-Hodgkin lymphoma.

23 . The method according to claim 12 , wherein the tumor is B cell lymphoma cells.