Humanized anti-BAG3 antibodies
The present invention provides for a humanized anti-BAG3 antibody or a fragment thereof, pharmaceutical compositions comprising said antibody and its use as a medicament, in particular for use in the treatment of pancreatic tumours or other pathologies of an immune, inflammatory, neoplastic, cardiovascular and/or degenerative nature.
1. A humanized antibody or a fragment thereof that binds to BAG3 protein and comprises:
a) a heavy chain comprising the following CDRs: H-CDR1 comprising the amino acids GFNIKDTYMY (SEQ ID NO: 3), H-CDR2 comprising the amino acids GVDPANGNTRYDPKFQG (SEQ ID NO: 4), H-CDR3 comprising the amino acids DGAMDY (SEQ ID NO: 5), and
b) a light chain comprising the following CDRs: L-CDR1 comprising the amino acids KSSQSLLYSSNQKNYLA (SEQ ID NO: 6), L-CDR2 comprising the amino acids WASTRES (SEQ ID NO: 7) and L-CDR3 comprising the amino acids QQYYTYPLT (SEQ ID NO: 8).
2. The humanized antibody or a fragment thereof according to claim 1 , characterized in that the heavy chain comprises an amino acid sequence is selected from SEQ ID NO: 14, SEQ ID NO: 16 or SEQ ID NO: 18.
3. The humanized antibody or a fragment thereof according to claim 1 , characterized in that the light chain comprises an amino acid sequence is selected from SEQ ID NO: 22, SEQ ID NO: 24 or SEQ ID NO: 26.
4. The humanized antibody or a fragment thereof according to claim 1 , characterized in that the heavy chain comprises SEQ ID NO:12 or at least the variable domain thereof or an amino acid sequence having a sequence identity of at least 80% thereof, and the light chain comprises SEQ ID NO:20 or at least the variable domain thereof or an amino acid sequence having a sequence identity of at least 80% thereof.
5. The humanized antibody or a fragment thereof according to claim 1 , characterized in that the heavy chain amino acid sequence comprises SEQ ID NO: 18 and the light chain amino acid sequence comprises SEQ ID No: 22.
6. The humanized antibody or a fragment thereof according to claim 1 , characterized in that it is an antibody of mammalian origin.
7. The humanized antibody or fragment thereof according to claim 1 , characterized in that said antibody is a Fab fragment, a Fab′ fragment, a F(ab′) fragment, a Fv fragment, a diabody, a ScFv, a small modular immunopharmaceutical (SMIP), an affibody, an avimer, a nanobody, a domain antibody and/or single chains.
8. A nucleic acid encoding the antibody or a fragment thereof according to claim 1 .
9. A vector comprising the nucleic acid according to claim 8 .
10. A host cell comprising the nucleic acid of claim 8 .
11. A method for treating a pathological state which involves the activation of macrophages, selected from neoplastic diseases, inflammatory diseases, immune diseases and/or degenerative diseases, comprising the step of administering the humanized antibody or a fragment thereof according to claim 1 to a subject in need thereof.
12. The method according to claim 11 , wherein the method is for treating pancreatic tumour or bladder tumour.
13. A pharmaceutical composition comprising at least one antibody or a fragment thereof according to claim 1 and at least one pharmaceutically acceptable excipient or carrier.
14. The pharmaceutical composition according to claim 13 characterized in that said composition is formulated in a form suitable for oral administration or in a form suitable for parenteral or topical administration.
15. The pharmaceutical composition according to claim 13 characterized in that said composition comprises a further active principle, selected from antimetabolites, camptothecins or taxanes.
16. The humanized antibody or a fragment thereof according to claim 1 , characterized in that the heavy chain amino acid sequence comprises SEQ ID NO: 18 and the light chain amino acid sequence comprises SEQ ID NO: 26.
17. A nucleic acid encoding the antibody or a fragment thereof according to claim 5 .
18. A nucleic acid encoding the antibody or a fragment thereof according to claim 16 .
19. A pharmaceutical composition comprising the antibody or a fragment thereof according to claim 5 and at least one pharmaceutically acceptable excipient or carrier.
20. A pharmaceutical composition comprising the antibody or a fragment thereof according to claim 16 and at least one pharmaceutically acceptable excipient or carrier.