SINGLE-DOMAIN ANTIBODY SPECIFICALLY BINDING TO CLL1 PROTEIN AND ITS APPLICATION

Claims

1. A single-domain antibody that comprises a heavy chain variable region, and this heavy chain variable region comprises a complementarity determining region, CDR1, with an amino acid sequence located at positions 26-35 of SEQ ID NO: 1, a complementarity determining region, CDR2, with an amino acid sequence located at positions 50-59 of SEQ ID NO: 1, and a complementarity determining region, CDR3, with an amino acid sequence located at positions 99-118 of SEQ ID NO:

1.

2. The single-domain antibody of claim 1, wherein the amino acid sequence of the heavy chain variable region is SEQ ID NO: 1 or an amino acid sequence that is at least 80% identical to SEQ ID NO: 1 and has the same function.

3. A biological substance related to a single-domain antibody according to claim 1 or 2, which is any of the following (c1) to (c4): c1) a nucleic acid molecule encoding the variable region of the heavy chain of a single-domain antibody according to claim 1 or 2; c2) an expression cassette containing the nucleic acid molecule described in (c1); c3) a recombinant vector containing the nucleic acid molecule described in (c1) or a recombinant vector containing the expression cassette described in (c2); c4) a recombinant host cell comprising a nucleic acid molecule as described in (c1), or a recombinant host cell comprising an expression cassette as described in (c2), or a recombinant host cell comprising a recombinant vector as described in (c3).

4. The biological material according to claim 3, wherein the nucleic acid molecule is any of the following molecules: d1) a DNA molecule whose nucleotide sequence or coding sequence is SEQ ID NO: 2; d2) a DNA molecule that is 75% or more identical to the nucleotide sequence defined in paragraph (d1) and has the same function.

5. Any of the following uses of a single-domain antibody according to claim 1 or 2 or a biological substance according to claim 3 or 4: E1) use in the manufacture of a medicinal product for the prevention or treatment of tumors or use for the prevention or treatment of tumors; E2) use in the manufacture of a medicament for the prevention or treatment of diseases associated with a CLL1 (C-type lectin-like molecule 1) target, or use for the prevention or treatment of diseases associated with a CLL1 target; E3) use in the manufacture of a product for screening, diagnosis or aiding in the diagnosis of diseases associated with a CLL1 target, or use for screening, diagnosis or aiding in the diagnosis of diseases associated with a CLL1 target; E4) use in detecting CLL1 protein or in producing a product for detecting CLL1 protein; E5) use in obtaining a product for binding to the CLL1 protein; E6) use in mediating the specific recognition of tumors expressing the CLL1 antigen by drugs or in the production of a product for mediating the specific recognition of tumors expressing the CLL1 antigen by drugs; E7) use for visualizing the CLL1 protein in vivo or in obtaining a product for visualizing the CLL1 protein in vivo; E8) application in obtaining a product targeting CLL1.

6. The use according to claim 5, wherein the diseases associated with the CLL1 target are CLL1-positive cancers.

7. The use according to claim 6, wherein the CLL1-positive cancers are acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia.

8. A pharmaceutical composition that contains a single-domain antibody according to claim 1 or 2 or cells modified with a chimeric antigen receptor, wherein the chimeric antigen receptor contains a single-domain antibody according to claim 1 or 2.

9. A reagent or kit comprising a single domain antibody according to claim 1 or 2 and having any of the following uses: g1) detection of CLL1 protein; g2) screening, diagnosis or assistance in diagnosis of diseases associated with the CLL1 target; g3) visualization of CLL1 protein in vivo.

10. A method for producing a single-domain antibody according to claim 1 or 2, comprising: constructing a recombinant expression vector containing a nucleic acid molecule according to claim 3 or 4; introducing the recombinant expression vector into a host cell to produce recombinant cells expressing the single-domain antibody; culturing the recombinant cells and producing the single-domain antibody by separation and purification.

11. A method for diagnosing or assisting in the diagnosis of diseases associated with a CLL1 target, comprising: isolating a sample from a subject, and then determining the content of CLL1 protein in this sample using a single-domain antibody according to claim 1 or 2, and performing a diagnosis or assisting in the diagnosis of diseases associated with a CLL1 target based on the content of CLL1 protein.

12. A method for screening for diseases associated with a CLL1 target, comprising: isolating a sample from a subject, and then determining the CLL1 protein content in the sample using a single-domain antibody according to claim 1 or 2, and screening for diseases associated with a CLL1 target based on the CLL1 protein content.

13. A method for preventing or treating diseases associated with a CLL1 target, comprising administering a single-domain antibody according to claim 1 or 2 or a pharmaceutical composition according to claim 8 to a subject suffering from diseases associated with a CLL1 target.

14. The method according to any one of claims 11-13, wherein the diseases associated with the CLL1 target are tumors associated with the CLL1 target.

15. The method of claim 14, wherein the tumors associated with the CLL1 target are CLL1-positive cancers.

16. The method of claim 15, wherein the CLL1-positive cancers are acute myeloid leukemia, myelodysplastic syndrome, or chronic myeloid leukemia.

17. A method for detecting CLL1 protein in vitro, comprising detecting CLL1 protein using a single-domain antibody according to claim 1 or 2 or a reagent or kit according to claim 9.

18. Antibody conjugate - a medicinal product containing an antibody moiety and a conjugated moiety, wherein the antibody moiety contains a single-domain antibody according to claim 1 or 2.

19. The antibody-drug conjugate of claim 18, wherein the conjugated moiety comprises a detectable label, a chemical drug, or a cytotoxin.