Binding members for human c-MAF
The disclosure relates to binding members, especially antibody molecules, which bind to human Maf. The binding members are useful for the determination of the expression level of Maf.
1. A binding member that specifically binds to human c-MAF, wherein the binding member comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 38, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 40, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 42, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 28 and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 30.
2. The binding member of claim 1 , wherein said binding member is an antibody.
3. The binding member of claim 2 , wherein the antibody is a rabbit antibody, a chimeric antibody or a humanized antibody.
4. The binding member of claim 1 , wherein said binding member comprises a VH domain with a sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17.
5. The binding member of claim 1 , wherein the binding member comprises a V L domain with a sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 21.
6. The binding member of claim 1 , wherein the binding member comprises a heavy chain sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 16.
7. The binding member of claim 1 , wherein the binding member comprises a light chain sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 20.
8. A polynucleotide encoding the binding member of claim 1 .
9. The polynucleotide of claim 8 , wherein the polynucleotide encodes an antigen binding molecule.
10. The polynucleotide of claim 8 , wherein the binding member is an antibody.
11. The polynucleotide of claim 8 , wherein the polynucleotide comprises a VH domain with a sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 99%, or 100% identical to the nucleotide sequence of SEQ ID NO: 15.
12. The polynucleotide of claim 8 , wherein the polynucleotide encodes a V L domain with a sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 99%, or 100% identical to the nucleotide sequence of SEQ ID NO: 20.
13. The polynucleotide of claim 8 , wherein the polynucleotide encodes a heavy chain with a sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 99%, or 100% identical to the nucleotide sequence of SEQ ID NO: 14.
14. The polynucleotide of claim 8 , wherein the polynucleotide encodes a light chain with a sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 99%, or 100% identical to the nucleotide sequence of SEQ ID NO: 18.
15. The binding member of claim 1 , wherein the binding member binds to the epitope encoded by SEQ ID NO: 22.
16. The binding member of claim 1 , wherein the binding member binds to human c-MAF with an affinity (KD) of at least about 1.5 nM or less, at least about 1.2 nM or less, or at least about 1.1 nM or less.
17. A vector comprising the polynucleotide of claim 8 .
18. A host cell expressing the binding member of claim 1 .
19. A method of producing an antigen binding member comprising culturing the host cell of claim 18 .
20. A method of using an antigen binding member produced by the host cell of claim 18 to detect c-MAF.
21. An in vitro method for the diagnosis of metastasis in a subject with cancer or for the prognosis of the tendency to develop metastasis in a subject with cancer, said method comprising:
(i) quantifying the c-MAF gene expression level in a tumor sample of said subject using the binding member of claim 1 , and
(ii) comparing the expression level obtained in (i) with the expression level of the c-MAF gene in a control sample,
wherein if the expression level of the c-MAF gene in said tumor sample is increased with respect to the expression level of the c-MAF gene in the control sample, then said subject has a positive diagnosis for metastasis or a greater tendency to develop metastasis.
22. An in vitro method for designing a customized therapy for a subject with cancer and an increased c-MAF expression level, said method comprising:
(i) quantifying the c-MAF gene expression level in a tumor sample of said subject using the binding member of claim 1 , and
(ii) comparing the expression level obtained in (i) with the expression level of the c-MAF gene in a control sample,
wherein if the expression level of the c-MAF gene in said tumor sample is increased with respect to the expression level of the c-MAF gene in the control sample, then said subject is susceptible to receive a therapy aiming to prevent, inhibit, and/or treat metastasis or a therapy to prevent, inhibit, and/or treat bone degradation.