Polyomavirus neutralizing antibodies

Patent metadata

Field	Value
Publication number	US-10450366-B2
Application number	US-201615758491-A
Country	US
Kind code	B2
Filing date	Sep 8, 2016
Priority date	Sep 16, 2015
Publication date	Oct 22, 2019
Grant date	Oct 22, 2019

Abstract

The present disclosure is directed to anti-VP1 antibodies, antibody fragments, and their uses for the reducing the likelihood or treatment of polyoma virus infection.

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 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 and a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier contains histidine or a sugar.

3. The pharmaceutical composition of claim 2 , wherein the sugar is sucrose.

4. The pharmaceutical composition of claim 1 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 α2,3linked sialic acid residue.

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

6. A pharmaceutical composition comprising an antibody or antigen binding fragment thereof, wherein said antibody or antigen binding fragment thereof 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 (1) a LCDR3 of SEQ ID NO:18 wherein the composition is prepared as a lyophilisate.

7. 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 .

8. The method of claim 7 , wherein the patient in need is diagnosed with BK viruria or BK viremia.

9. 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 , 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, or immune reconstitution inflammatory syndrome (IRIS).

10. The method of claim 7 or 9 , wherein the pharmaceutical composition is administered in combination with another therapeutic agent.

11. The method of claim 10 , wherein the therapeutic agent is an immunosuppressive agent.

12. The method of claim 11 , wherein the immune suppressive agent is: a monophosphate dehydrogenase inhibitor, a purine synthesis inhibitor, a calcineurin inhibitor or an mTOR inhibitor.

13. The method of claim 12 , wherein the immunosuppressive agent is mycophenolate mofetil (MMF), mycophenolate sodium, azathioprine, tacrolimus, sirolimus or cyclosporine.

14. The method of claim 10 , wherein the therapeutic agent is an additional anti-VP1 antibody.

15. The pharmaceutical composition of claim 6 , wherein the composition is reconstituted prior to injection or infusion.

16. The pharmaceutical composition of claim 6 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 α2,3linked sialic acid residue.

17. The pharmaceutical composition of claim 6 , comprising a plurality of the antibody or antigen binding fragment, wherein none of the antibodies comprise a bisecting GlcNAc.

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

19. 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 6 .

20. 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 6 , 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, or immune reconstitution inflammatory syndrome (IRIS).

21. The pharmaceutical composition of claim 6 wherein the antibody or antigen binding fragment thereof has reduced glycosylation or no glycosylation or is hypofucosylated.

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

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title