Polyomavirus neutralizing antibodies

Patent metadata

Field	Value
Publication number	US-10654914-B2
Application number	US-201816183262-A
Country	US
Kind code	B2
Filing date	Nov 7, 2018
Priority date	Sep 16, 2015
Publication date	May 19, 2020
Grant date	May 19, 2020

Abstract

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.

First claim

What is claimed is:

1. A pharmaceutical composition comprising an antibody or antigen binding fragment thereof, wherein said antibody or antigen binding fragment thereof binds to BK virus VP 1 and comprises: a heavy chain variable region that comprises (a) a HCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO: 6, (b) a HCDR2 of SEQ ID NO: 7, (c) a HCDR3 of SEQ ID NO: 8 and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:16, (e) a LCDR2 of SEQ ID NO: 17, and (f) a LCDR3 of SEQ ID NO: 18.

2. The pharmaceutical composition of claim 1 , wherein the composition is prepared as a lyophilisate.

3. The pharmaceutical composition of claim 1 wherein the antibody or antigen binding fragment thereof 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.

4. The pharmaceutical composition of claim 1 , wherein said antibody or antigen binding fragment thereof comprises:
a heavy chain variable region (vH) that comprises a sequence having at least 95% identity to SEQ ID NO: 12, and a light chain variable region (vL) that comprises a sequence having at least 95% identity to SEQ ID NO: 22.

5. The pharmaceutical composition of claim 4 wherein the vH comprises SEQ ID NO: 12 or a modification thereof selected from one or more of V5Q, G9P, T10G, N30S, N30K, and N30Q, and wherein the vL comprises SEQ ID NO: 22.

6. The pharmaceutical composition of claim 4 wherein the antibody or antigen binding fragment thereof 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.

7. The pharmaceutical composition of claim 1 or claim 4 wherein the antibody or antigen binding fragment thereof has reduced glycosylation or no glycosylation or is hypofucosylated.

8. The pharmaceutical composition of claim 1 or claim 4 further comprising a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8 , wherein the pharmaceutically acceptable carrier contains histidine or a sugar.

10. The pharmaceutical composition of claim 9 , wherein the sugar is sucrose.

11. The pharmaceutical composition of claim 1 or claim 4 comprising a plurality of the antibody or antigen binding fragment, 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.

12. The pharmaceutical composition of claim 1 or claim 4 comprising a plurality of the antibody or antigen binding fragment, wherein none of the antibodies comprise a bisecting GlcNAc.

13. 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 pharmaceutical composition of claim 1 or claim 4 .

14. The method of claim 13 , wherein the patient in need is diagnosed with BK viruria or BK viremia.

15. 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 pharmaceutical composition of claim 1 or claim 4 , 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).

16. The method of claim 15 , wherein 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 16 , wherein the therapeutic agent is an additional anti-VP1 antibody.

21. A pharmaceutical composition, comprising an antibody and a pharmaceutically acceptable carrier, wherein the antibody comprises a heavy chain variable region (vH) that comprises SEQ ID NO: 12, and a light chain variable region (vL) that comprises SEQ ID NO: 22, and wherein the pharmaceutically acceptable carrier contains histidine, sucrose, and a polysorbate.

Assignees

• Novartis Ag

Inventors

• Abend Johanna
• Dragic Zorica
• Feire Adam Lloyd
• Knapp Mark
• Kovacs Steven
• Traggiai Elisabetta
• Wang Lichun
• Wang Yongqiang
• Wu Danqing
• Wu Qilong
• Xu Fangmin

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61P13/10

  of the bladder · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title