Polyomavirus neutralizing antibodies
The present invention relates to anti-VP1 antibodies, antibody fragments, and their uses for the prevention and treatment of polyoma virus infection and associated diseases.
1. An isolated antibody or antigen binding fragment thereof, wherein said antibody or antigen binding fragment thereof comprises: (i) a heavy chain variable region that comprises (a) a HCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:186, (b) a HCDR2 of SEQ ID NO:187, (c) a HCDR3 of SEQ ID NO:188; and alight chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:196, (e) a LCDR2 of SEQ ID NO:197, and (f) a LCDR3 of SEQ ID NO:198; or
(ii) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:206, (b) a HCDR2 of SEQ ID NO:207, (c) a HCDR3 of SEQ ID NO:208; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:216, (e) a LCDR2 of SEQ ID NO:217, and (f) a LCDR3 of SEQ ID NO:218.
2. The antibody of claim 1 wherein the antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human engineered antibody, a human antibody, a single chain antibody (scFv) or an antibody fragment.
3. An isolated antibody or antigen binding fragment thereof, wherein said antibody or antigen binding fragment thereof comprises:
(i) a heavy chain variable region (vH) that comprises SEQ ID NO:192, and a light chain variable region (vL) that comprises SEQ ID NO:202; or
(ii) a heavy chain variable region (vH) that comprises SEQ ID NO:212, and a light chain variable region (vL) that comprises SEQ ID NO:222.
4. The antibody of claim 3 wherein the antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human engineered antibody, a human antibody, a single chain antibody (scFv) or an antibody fragment.
5. The antibody of claim 1 or 3 wherein the antibody or fragment thereof has reduced glycosylation or no glycosylation or is hypofucosylated.
6. A pharmaceutical composition comprising the antibody or fragment thereof, of claim 1 or 3 further comprising a pharmaceutically acceptable carrier.
7. The pharmaceutical composition of claim 6 , wherein the pharmaceutically acceptable carrier contains histidine or a sugar.
8. The pharmaceutical composition of claim 7 , wherein the sugar is sucrose.
9. A pharmaceutical composition comprising a plurality of an antibody or antigen binding fragment of claim 1 or 3 , wherein at least 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 5% or more or more of the antibodies in the composition have an α2,3-linked sialic acid residue.
10. A pharmaceutical composition comprising a plurality of an antibody or antigen binding fragment of claim 1 or 3 , wherein none of the antibodies comprise a bisecting GlcNAc.
11. The pharmaceutical composition comprising the antibody or fragment thereof, of claim 1 or 3 , wherein the composition is prepared as a lyophilisate.
12. A method of neutralizing a BK virus or JC virus infection comprising administering via injection or infusion to a patient in need an effective amount of the antibody or the pharmaceutical composition of claim 1 .
13. The method of claim 12 , wherein the patient in need is diagnosed with BK viruria or BK viremia.
14. A method of treating or reducing the likelihood of a BK virus or JC virus associated disorder, comprising administering via injection or infusion to a patient in need an effective amount of the antibody or the pharmaceutical composition of claim 1 , and wherein the disorder is: nephropathy, BKVAN, hemorrhagic cystitis (HC), Progressive Multifocal Leukoencephalopathy (PML), granule cell neuronopathy (GCN), interstitial kidney disease, ureteral stenosis, vasculitis, colitis, retinitis, meningitis, and immune reconstitution inflammatory syndrome (IRIS).
15. The method of claim 12 or 14 , wherein the antibody or composition is reconstituted prior to injection or infusion.
16. The method of claim 12 or 14 , wherein the antibody or the pharmaceutical composition is administered in combination with another therapeutic agent.
17. The method of claim 16 , wherein the therapeutic agent is an immunosuppressive agent.
18. The method of claim 17 , wherein the immune suppressive agent is: a monophosphate dehydrogenase inhibitor, a purine synthesis inhibitor, a calcineurin inhibitor or an mTOR inhibitor.
19. The method of claim 18 , wherein the immunosuppressive agent is mycophenolate mofetil (MMF), mycophenolate sodium, azathioprine, tacrolimus, sirolimus or cyclosporine.
20. The method of claim 19 , wherein the therapeutic agent is an additional anti-VP1 antibody.
21. A nucleic acid that encodes the antibody or antigen binding fragment of claim 1 or claim 3 .
22. A vector comprising the nucleic acid of claim 21 .
23. An isolated host cell comprising the vector of claim 22 .
24. A process for producing an antibody or antigen binding fragment comprising cultivating the host cell of claim 23 and recovering the antibody from the culture.
25. A diagnostic reagent comprising the antibody or antigen binding fragment thereof of claim 1 or claim 3 which is labeled.
26. The diagnostic reagent of claim 25 , wherein the label is selected from the group consisting of a radiolabel, a fluorophore, a chromophore, an imaging agent, and a metal ion.