RECOMBINANT HUMAN ANTIBODIES FOR THERAPY AND PREVENTION OF POLYOMAVIRUS-RELATED DISEASES

• US 20180037635A1
• Filed: 08/16/2017
• Published: 02/08/2018
• Est. Priority Date: 12/31/2012
• Status: Active Grant

• Current Assignee: Neurimmune Holding AG, University of Zurich
• Original Assignee: Neurimmune Holding AG, University of Zurich
• Inventors: GRIMM, Jan, MARTIN, Roland, COMBALUZIER, Benoit, JELCIC, Ivan
• Granted Patent: US 10,450,365 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 39/42 viral
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 16/081 from DNA viruses
• CPC Class Codes: C07K 16/084 Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12N 2710/22022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: G01N 2333/025 : Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
• CPC Class Codes: G01N 33/56983 : Viruses
• CPC Class Codes: G01N 33/6893 : related to diseases not provided for elsewhere
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Provided are novel human-derived antibodies specifically recognizing polyomavirus polypeptides, preferably capable of binding to polyomaviruses of the type of JC virus (JCV) and/or BK virus (BKV) as well as methods related thereto. Furthermore, assays and kits related to antibodies specific for polyomaviruses, polyomavirus VP1 and or polyomavirus VP1 Virus-Like Particles (VLPs), preferably of the type of JCV and/or BKV, are disclosed. The human-derived antibodies as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for polyomavirus targeted immunotherapy and diagnostics.

Claims

1-29. -29. (canceled)

30. A polynucleotide encoding at least a binding domain of a variable region of an immunoglobulin chain of a human monoclonal antibody or an antigen-binding fragment thereof capable of binding to a polyomavirus and/or antigen thereof.

31. A vector comprising the polynucleotide of claim 30.

32. The vector of claim 31, further comprising a polynucleotide encoding at least a binding domain of a variable region of an immunoglobulin chain of a human monoclonal antibody or an antigen-binding fragment thereof capable of binding to a polyomavirus and/or antigen thereof, wherein the polyomavirus is JC virus (JCV) or BK virus (BKV), wherein the polynucleotide further encodes the variable region of the other immunoglobulin chain of the antibody or an antigen-binding fragment thereof.

33. A host cell comprising a polynucleotide of claim 30.

34. A composition comprising a polynucleotide of claim 30.

35. The composition of claim 34, wherein the composition:

(a) is a pharmaceutical composition and further comprises a pharmaceutical acceptable carrier, or

(b) is a diagnostic composition, and further comprises reagents conventionally used in immune- or nucleic acid based diagnostic methods.

36. The composition of claim 34, further comprising an immunomodulatory agent.

37. A kit useful in the diagnosis or monitoring of the progression of Progressive Multifocal Leukoencephalopathy (PML) and/or transplant rejection following clinical bone marrow, kidney, and other solid organs transplantations, said kit comprising a polynucleotide of claim 30.

38. The kit of claim 37, further comprising reagents and/or instructions for use.

39. The composition of claim 34, wherein:

(a) the disease is Progressive Multifocal Leukoencephalopathy (PML), infection of granule neurons, hyperchromatic nuclei, granule cell neuronopathy, cerebral autothrophy, encephalopathy, meningitis, Polyoma-induced tumors, immune reconstitution inflammatory syndrome (IRIS), hemorrhagic cystitis, pneumonia, retinitis, colitis, vasculitis, interstitial kidney disease, infections of respiratory tract, JCV nephropathy, BKV nephropathy, meningitis, Merkel cell carcinoma, trichodysplasia spinulosa, or malignant pleural mesothelioma; and

/or

(b) the agent is natalizumab, efalizumab, rituximab, infliximab, ocrelizumab, alemtuzumab, bentuximab, or vedotin.

42. The polynucleotide of claim 30, wherein the polyomavirus is JC virus (JCV) or BK virus (BKV).

43. The polynucleotide of claim 30, wherein the antibody or antigen-binding fragment thereof is capable of binding VP1 protein or a fragment thereof.

44. The polynucleotide of claim 30, wherein the antibody or antigen-binding fragment thereof is capable of recognizing an epitope exposed on the surface of the virus.

45. The polynucleotide of claim 30, wherein the antibody or antigen-binding fragment thereof does not substantially recognize serum albumin.

46. The polynucleotide of claim 45, wherein the serum albumin is bovine serum albumin (BSA).

47. The polynucleotide of claim 30, wherein the antibody or antigen-binding fragment thereof recognizes progressive multifocal leukoencephalopathy (PML)-associated VP1 mutants.

48. The polynucleotide of claim 30, wherein the antibody or antigen-binding fragment thereof is detectably labelled.

49. The polynucleotide of claim 30, wherein the antibody or antigen-binding fragment thereof is attached to a drug.

40. A complementary DNA (cDNA) molecule encoding at least a binding domain of a variable region of an immunoglobulin chain of an antibody or antigen binding fragment thereof, wherein the antibody or antigen-binding fragment thereof is capable of binding to a polyomavirus or an antigen thereof.

41. A vector comprising the cDNA of claim 40, wherein the vector encodes the variable region of the other immunoglobulin chain of the antibody or an antigen-binding fragment thereof.