Nectin-4 binding proteins and methods of use thereof

1. An antibody or antigen-binding fragment thereof that binds to an epitope of human Nectin-4 comprising a light chain variable region (VL) comprising a VL CDR1 having the amino acid sequence selected from the group consisting of SEQ ID NO:7 and 8, a VL CDR2 having the amino acid sequence selected from the group consisting of SEQ ID NO:9, 10, and 11, and a VL CDR3 having the amino acid sequence selected from the group consisting of SEQ ID NO:12, and 13;

and a light chain variable region (VH) comprising a VH CDR1 having the amino acid sequence selected from the group consisting of SEQ ID NO:14, 15, 16, and 17, a VH CDR2 having the amino acid sequence selected from the group consisting of SEQ ID NO:18, 19, 20, and 21, and a VH CDR3 having the amino acid sequence selected from the group consisting of SEQ ID NO:22, 23, and 24.

2. The antibody or antigen-binding fragment thereof of claim 1 , wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS: 7, 10, and 12, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS: 15, 19, and 23, respectively, wherein said VL and VH CDR sequences are determined according to Kabat CDR definition.

3. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 3 and a VH comprising the amino acid sequence of SEQ ID NO: 4.

4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a mouse IgG2 Fc, human IgG1 Fc region, or a mutant thereof.

5. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises: a light chain constant region comprising the amino acid sequence of SEQ ID NO: 33 and a heavy chain Fc region comprising the amino acid sequence of SEQ ID NO: 35.

6. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises: a light chain comprising the amino acid sequence of SEQ ID NO: 5 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 6.

7. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a monoclonal antibody, a humanized antibody, a chimeric antibody, or a deimmunized humanized antibody or the antibody or antigen-binding fragment thereof is a Fab, a Fab′, a F(ab′) 2 , a Fv, a scFv, a dsFv, a diabody, a triabody, or a tetrabody formed from antibody fragments.

8. The antibody or antigen-binding fragment thereof of claim 3 , wherein the glutamine at the first residue of SEQ ID NO: 4 is substituted with a pyroglutamate.

9. A polynucleotide comprising nucleotide sequences encoding the VH and the VL of the antibody or antigen-binding fragment thereof of claim 1 or nucleotide sequences encoding the heavy chain and the light chain of the antibody or antigen-binding fragment thereof of claim 1 .

10. A vector comprising the polynucleotide of claim 9 .

11. A cell comprising a polynucleotide encoding the VH and a polynucleotide encoding the VL, or comprising a polynucleotide encoding both the VH and VL of the antibody or antigen-binding fragment of claim 1 ; or comprising a polynucleotide encoding the heavy chain and a polynucleotide encoding the light chain or comprising a polynucleotide encoding both the heavy chain and the light chain of the antibody or antigen-binding fragment thereof of claim 1 .

12. A method of making an antibody or antigen-binding fragment thereof which specifically binds to an epitope of human Nectin-4, comprising culturing the cell of claim 11 to express the antibody or antigen-binding fragment thereof.

13. A kit comprising the antibody or antigen-binding fragment thereof of claim 1 .

14. A method for assessing Nectin-4 expression in a tissue sample from a subject suspected of having cancer, comprising:

(a) contacting said tissue sample with the antibody or antigen binding fragment thereof of claim 1 ;

(b) detecting the binding of said antibody or antigen binding fragment thereof to said tissue sample;

(c) measuring the expression of Nectin-4 in the tissue sample, wherein the expression level of Nectin-4 in the tissue sample is compared with a reference expression level of Nectin-4.

15. A method for assessing Nectin-4 expression in a tissue sample from a subject suspected of having cancer, comprising:

(a) performing an immunohistochemistry assay on the tissue sample with the antibody or antigen binding fragment thereof of claim 1 ;

(b) measuring the expression of Nectin-4 in the tissue sample.

16. A method for assessing responsiveness of a cancer patient to an anti-cancer therapeutic agent, said method based on Nectin-4 expression in a tissue sample from said patient, comprising:

(a) contacting said tissue sample with the antibody or antigen binding fragment thereof of claim 1 ;

(b) detecting the binding of said antibody or antigen binding fragment thereof to said tissue sample;

(c) measuring the expression level of Nectin-4 in the tissue sample, wherein the expression level of Nectin-4 in the tissue sample is compared with a reference expression level of Nectin-4;

wherein an increased expression level of Nectin-4 compared to the reference is indicative of responsiveness to said anti-cancer therapy.

17. A method for assessing responsiveness of a cancer patient to an anti-cancer therapeutic agent, said method based on Nectin-4 expression in a tissue sample from said patient, comprising:

(a) performing an immunohistochemistry assay on the tissue sample with the antibody or antigen binding fragment thereof of claim 1 ;

(b) measuring the expression level of Nectin-4 in the tissue sample, wherein the expression level of Nectin-4 in the tissue sample is compared with a reference expression level of Nectin-4,

wherein an increased expression level of Nectin-4 in the tissue sample compared to the reference is indicative of responsiveness to said anti-cancer therapy.