WO2023175171A1 - Anticorps de polyomavirus bk et leurs utilisations - Google Patents

Anticorps de polyomavirus bk et leurs utilisations Download PDF

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WO2023175171A1
WO2023175171A1 PCT/EP2023/056946 EP2023056946W WO2023175171A1 WO 2023175171 A1 WO2023175171 A1 WO 2023175171A1 EP 2023056946 W EP2023056946 W EP 2023056946W WO 2023175171 A1 WO2023175171 A1 WO 2023175171A1
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sequence
seq
amino acid
acid sequence
antibody
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PCT/EP2023/056946
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Inventor
Dorian MCILROY
Xavier SAULQUIN
Ngoc Khanh Nguyen
Céline BRESSOLLETTE-BODIN
Laetitia GAUTREAU-ROLLAND
Cynthia Fourgeux
Marie-Claire DEVILDER
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Inserm (Institut National De La Sante Et De La Recherche Medicale)
Centre National De La Recherche Scientifique
Nantes Université
Chu De Nantes
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Publication of WO2023175171A1 publication Critical patent/WO2023175171A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/081—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from DNA viruses
    • C07K16/084—Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Definitions

  • This application includes a sequence listing in computer readable form in a file named S3_SATT OUEST_PR94463_sequence listing created on March 7, 2023 (161 458 bytes), which is incorporated by reference herein.
  • the present disclosure relates to antibodies, and combinations thereof, targeting BK polyomaviruses (BKPyV), and methods using those antibodies.
  • BKPyV BK polyomaviruses
  • BK polyomavirus is a small double-stranded DNA virus with a non-enveloped icosahedral capsid, first described in 1971.
  • BKPyV has been divided into four major subtypes (genotypes) I, II, III and IV, further divided into subgroups, that are characterized by sequence variation in the major capsid protein VP1 and correspond to distinct neutralizing virus serotypes (Knowles et al. J. Med. Virol. 1989, 28, 118-123 - Pastrana et al. J. Virol. 2013, 87, 10105-10113).
  • Genotype I is the most prevalent BKPyV genotype worldwide, followed by genotype IV in East Asia and Europe, while genotypes II and III are rare throughout the world (Zhong et al. J. Gen. Virol. 2009, 90, 144-152).
  • the distribution of the molecular subgroups of the virus is associated with the region of origin, for instance, BKPyV subtype la is most common in Africa, Ibl in Southeast Asia, and Ib2 in Europe, while Ic is the most common variant in Northeast Asia (Furmaga, Jacek et al. Viruses vol. 13,8 1502. 30 Jul. 2021).
  • BKPyV genotype I-E61K or BKPyV genotype IV-E327K in vitro selected genetic variants of some genotypes of the BKPyV were characterized, such as BKPyV genotype I-E61K or BKPyV genotype IV-E327K (Lindner et al. Immunity. 2019;50:668- 676.e5).
  • the virus capsid is composed of 72 pentamers of the major capsid protein VP1, and each pentamer is associated with one copy of either VP2 or VP3, which are the minor capsid proteins.
  • the circular double-stranded DNA genome is packaged inside the capsid in a condensed form associated with histones from the host cell.
  • the exterior of the virus particle is composed entirely of the VP1 protein, and virus like particles (VLP) composed of VP1 are structurally and antigenically identical to infectious virus particles (Hurdiss et al. Structure 2018, 26, 839-847.e3).
  • BKPyV is a typical opportunistic virus, which provokes overt pathology almost exclusively in the context of immunosuppression. It is estimated that 80% of the adult population is latently infected with BKPyV. After kidney transplantation (KTx), reactivation of BKPyV from sites of persistent infection (mainly kidney epithelial cells) frequently occurs, leading to virus detection in urine (Bressollette-Bodin et al. Am. J. Transplant. 2005, 5, 1926-1933).
  • KTx recipients with persistent BKPyV viremia or PyVAN were found to have an 11 -fold greater risk of bladder carcinoma compared to KTx recipients without evidence of BKPyV replication (Liu et al.
  • BKPyV hemorrhagic cystitis
  • HCT allogeneic hematopoietic cell transplantations
  • BK polyoma virus-associated nephropathy relies on modification or dose reduction of immunosuppressive therapy, with the aim of inducing host antiviral immune responses that may then control viral replication.
  • This strategy is applied in the case of histologically confirmed BK polyomavirus-associated nephropathy (curative treatment), as well as in cases of “presumptive BK PyVAN”, defined by a high viruria and DNAemia (Zhong et al. J. Gen. Virol. 2009, 90, 144-152).
  • BKPyV-HC symptoms can persist for several weeks in subjects with high plasma DNAemia (Imlay et al. Blood Adv 2020, 4, 617-628), and their resolution is thought to depend on the reconstitution of the BK-specific immune response that follows successful engraftment (Espada et al. Blood Adv 2020, 4, 1881-1893). In both clinical situations, patients would benefit from effective antiviral therapy.
  • the incidence of BK PyVAN is higher in kidney transplantation recipients with low neutralizing antibody titers (Solis et al. J. Am. Soc. Nephrol.
  • IVIG intravenous immunoglobulin
  • BKPyV-specific neutralizing antibodies Velay et al. Antimicrob Agents Chemother 2019, 63
  • IVIG intravenous immunoglobulin
  • BKPyV-specific neutralizing antibodies Velay et al. Antimicrob Agents Chemother 2019, 63
  • BK polyomavirus-associated nephropathy Matsumura et al. Ther Clin Risk Manag 2020, 16, 947-952; Pibum et al. Pediatric Transplantation 2020, 24, el3600; Hwang et al. Transplant Proc 2018, 50, 2575-2578.
  • IVIG is a blood product that contains a complex mix of antibody specificities, and although rare, acute antibody-mediated rejection after infusion of IVIG containing donorspecific antibodies has been reported in the literature (Mainra, et al., Transpl Immunol 2013, 28, 145-147).
  • antiviral T-cell therapy has been developed for BKPyV-HC, with reported clinical response rates greater than 80% (Nelson et al. Curr. Opin. Infect. Dis., 2021, 34, 627- 634).
  • at least one fatal outcome associated with cytokine reconstitution syndrome has been reported in a BKPyV-HC patient treated with T-cell therapy.
  • the broadly neutralizing monoclonal antibody 41F17 has been identified as an anti-BKPyV antibody efficiently for binding and neutralizing all of the four genotypes of the BKPyV wildtype (Lindner et al. Immunity. 2019; 50:668-676.e5).
  • BKPyV has the ability to escape selection pressure by antibodies by developing BKPyV variants containing mutations on its VP1 capsid protein.
  • the anti-BKPyV 41F17 antibody may not be enough to efficiently neutralize all the BKPyV variants.
  • Broadly neutralizing antibodies capable of inhibiting the four wildtype BKPyV genotypes and its variants would be potential candidates for therapeutics for the treatment of BKPyV infection-associated diseases, in particular PyVAN and/or BKPyV-HC.
  • BKPyV infection-associated diseases include BK polyomavirus-associated nephropathy, confirmed and presumptive, BKPyV hemorrhagic cystitis, as well as pneumonitis, retinitis, and meningoencephalitis in immunocompromised subjects, and the likely long-term consequences of BKPyV infection-associated diseases such as reno-urinary tumors, for example bladder carcinoma.
  • the present disclosure aims at satisfying all or parts of those needs.
  • the present disclosure relates to an isolated antibody binding a BK polyomavirus (BKPyV) VP1 capsid protein, or an antigen-binding fragment thereof, comprising:
  • CDR1-H comprising an amino acid sequence selected from SEQ ID NOs: 1, 14, 27, 40, 53, 66 and 79, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution;
  • CDR2-H comprising an amino acid sequence selected from SEQ ID NOs: 2, 15, 28, 41, 54, 67 and 80, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution;
  • CDR3-H comprising an amino acid sequence selected from SEQ ID NOs: 3, 16, 29, 42, 55, 68 and 81, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution;
  • CDR1-L comprising an amino acid sequence selected from SEQ ID NOs: 4, 17, 30, 43, 56, 69 and 82, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution;
  • CDR2-L comprising an amino acid sequence selected from DTS, DAS, LGS, GAS, DQS, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution
  • CDR3-L comprising an amino acid sequence selected from SEQ ID NOs: 5, 18, 31, 44, 57, 70 and 83, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution.
  • the present disclosure relates to an isolated antibody binding a BK polyomavirus (BKPyV) VP1 capsid protein, or an antigen-binding fragment thereof, comprising:
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1 or a sequence differing from SEQ ID NO: 1 by one conservative amino acid substitution
  • a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2 or a sequence differing from SEQ ID NO: 2 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3 or a sequence differing from SEQ ID NO: 3 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4 or a sequence differing from SEQ ID NO: 4 by one conservative amino acid substitution
  • a CDR2-L comprising an amino acid sequence of DTS or a sequence differing from DTS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5 or a sequence differing from SEQ ID NO: 5 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14 or a sequence differing from SEQ ID NO: 14 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 15 or a sequence differing from SEQ ID NO: 15 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 16 or a sequence differing from SEQ ID NO: 16 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17 or a sequence differing from SEQ ID NO: 17 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18 or a sequence differing from SEQ ID NO: 18 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27 or a sequence differing from SEQ ID NO: 27 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 28 or a sequence differing from SEQ ID NO: 28 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 29 or a sequence differing from SEQ ID NO: 29 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30 or a sequence differing from SEQ ID NO: 30 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31 or a sequence differing from SEQ ID NO: 31 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40 or a sequence differing from SEQ ID NO: 40 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 41 or a sequence differing from SEQ ID NO: 41 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42 or a sequence differing from SEQ ID NO: 42 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43 or a sequence differing from SEQ ID NO: 43 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of LGS or a sequence differing from LGS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44 or a sequence differing from SEQ ID NO: 44 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53 or a sequence differing from SEQ ID NO: 53 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 54 or a sequence differing from SEQ ID NO: 54 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 55 or a sequence differing from SEQ ID NO: 55 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56 or a sequence differing from SEQ ID NO: 56 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57 or a sequence differing from SEQ ID NO: 57 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66 or a sequence differing from SEQ ID NO: 66 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 67 or a sequence differing from SEQ ID NO: 67 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 68 or a sequence differing from SEQ ID NO: 68 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69 or a sequence differing from SEQ ID NO: 69 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of DQS or a sequence differing from DQS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70 or a sequence differing from SEQ ID NO: 70 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79 or a sequence differing from SEQ ID NO: 79 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 80 or a sequence differing from SEQ ID NO: 80 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81 or a sequence differing from SEQ ID NO: 81 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82 or a sequence differing from SEQ ID NO: 82 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83 or a sequence differing from SEQ ID NO: 83 by one conservative amino acid substitution.
  • the isolated antibody binding a BK polyomavirus (BKPyV) VP1 capsid protein, or an antigen-binding fragment thereof may comprise:
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1 or an amino acid sequence differing from SEQ ID NO: 1 by one conservative amino acid substitution
  • a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2 or an amino acid sequence differing from SEQ ID NO: 2 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3 or an amino acid sequence differing from SEQ ID NO: 3 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4 or an amino acid sequence differing from SEQ ID NO: 4 by one conservative amino acid substitution
  • a CDR2-L comprising an amino acid sequence of DTS or an amino acid sequence differing from DTS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5 or an amino acid sequence differing from SEQ ID NO: 5 by one conservative amino acid substitution.
  • the isolated antibody binding a BK polyomavirus (BKPyV) VP1 capsid protein, or an antigen-binding fragment thereof may comprise:
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79 or an amino acid sequence differing from SEQ ID NO: 79 by one conservative amino acid substitution
  • a CDR2-H comprising an amino acid sequence of SEQ ID NO: 80 or an amino acid sequence differing from SEQ ID NO: 80 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81 or an amino acid sequence differing from SEQ ID NO: 81 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82 or an amino acid sequence differing from SEQ ID NO: 82 by one conservative amino acid substitution
  • a CDR2-L comprising an amino acid sequence of GAS or an amino acid sequence differing from GAS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83 or an amino acid sequence differing from SEQ ID NO: 83 by one conservative amino acid substitution.
  • the inventors have surprisingly identified new antibodies able to strongly neutralize BKPyV infection induced by the different wildtype and naturally occurring variant genotypes in different host cells. Furthermore, it has been shown that combinations of at least two of those antibodies surprisingly were able to neutralize variants of BKPyV escaping neutralization by the benchmark anti-BKPyV antibody 41F17.
  • the disclosed antibodies, and combinations thereof, are able to bind and neutralize BKPyV.
  • antibodies and combinations of antibodies may be implemented in prophylactic and/or therapeutic treatment of BKPyV-induced infections and diseases associated with BKPyV infections in transplanted subjects, such as kidney transplanted subjects.
  • prophylactic and/or therapeutic uses of those antibodies and combinations of antibodies may advantageously be associated with a reduced of occurrence of antibody-resistant variants of BKPyV.
  • An antibody disclosed herein may comprise:
  • an antibody as disclosed herein may comprise a variable domain of heavy chain of the amino acid sequence SEQ ID NO: 6 or an amino acid sequence at least 85% identical thereto and/or a variable domain of light chain of the amino acid sequence SEQ ID NO: 7, or an amino acid sequence at least 85% identical thereto.
  • an antibody as disclosed herein may comprise a variable domain of heavy chain of the amino acid sequence SEQ ID NO: 84 or an amino acid sequence at least 85% identical thereto and/or a variable domain of light chain of the amino acid sequence SEQ ID NO: 85, or an amino acid sequence at least 85% identical thereto.
  • An antibody disclosed herein may comprise:
  • a heavy chain comprising an amino acid sequence of SEQ ID NO: 8 or a sequence at least 85% identical thereto and/or a light chain comprising an amino acid sequence of SEQ ID NO: 9, or a sequence at least 85% identical thereto; or
  • an antibody as disclosed herein may comprise a heavy chain comprising an amino acid sequence of SEQ ID NO: 8 or an amino acid sequence at least 85% identical thereto and/or a light chain comprising an amino acid sequence of SEQ ID NO: 9, or an amino acid sequence at least 85% identical thereto.
  • an antibody as disclosed herein may comprise a heavy chain of amino acid sequence SEQ ID NO: 86 or an amino acid sequence at least 85% identical thereto and/or a light chain of amino acid sequence SEQ ID NO: 87, or an amino acid sequence at least 85% identical thereto.
  • the disclosure relates to an isolated antibody, or an antigen-binding fragment thereof, neutralizing at least one BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 101, or SEQ ID NO: 106, and for example at least one BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97, or SEQ ID NO: 101, with an IC50 of less than 40 nM.
  • An antibody disclosed herein bind and neutralize a BKPy virus variant selected among BKPyV-D58Del_59A, BKPyV-E61K, BKPyV-E327K and BKPyV-K172A, and for example a BKPy virus variant selected among BKPyV-D58Del_59A, BKPyV-E61K, and BKPyV-E327K.
  • Such an antibody may bind and neutralize at least two BKPy virus variants selected among BKPyV-D58Del_59A, BKPyV-E61K and BKPyV-E327K.
  • An antibody disclosed herein may be an antibody fragment.
  • An antibody fragment may be selected from the group consisting of Fv, Fab, F(ab')2, Fab', dsFv, (dsFv)2, scFv, sc(Fv)2, and diabodies.
  • An antibody disclosed herein may be a variable heavy chain of a single domain antibody (VHH). The variable heavy chain may be as defined herein.
  • the present disclosure relates to an immunoconjugate comprising an antibody as disclosed herein conjugated or linked to a detectable probe, label or reporter molecule.
  • Such immunoconjugate may be used as a diagnostic tool for detecting and/or measuring a BKPyV infection in a subject in need thereof.
  • a detectable probe, label or reporter molecule can be a radioisotope, such as 3 H, 14 C, 32 P, 35 S, or 125 I; a fluorescent or chemiluminescent moiety such as fluorescein isothiocyanate, or rhodamine; or an enzyme such as alkaline phosphatase, P-galactosidase, horseradish peroxidase, or luciferase.
  • a radioisotope such as 3 H, 14 C, 32 P, 35 S, or 125 I
  • a fluorescent or chemiluminescent moiety such as fluorescein isothiocyanate, or rhodamine
  • an enzyme such as alkaline phosphatase, P-galactosidase, horseradish peroxidase, or luciferase.
  • the present disclosure relates to a combination of at least a first antibody, or an antigen-binding fragment thereof, and a second antibody, or an antigen-binding fragment thereof, wherein said first and second antibodies may be selected among the groups of antibodies as disclosed herein.
  • the present disclosure relates to an isolated multi-specific antibody comprising at least a first antibody, or an antigen-binding fragment thereof, and a second antibody, or an antigen-binding fragment thereof, joined to each other, wherein said first and second antibodies may be selected among the groups of antibodies as disclosed herein.
  • An isolated multi-specific antibody may be a bispecific antibody.
  • a combination or an isolated multi-specific antibody disclosed herein may comprise:
  • a combination or an isolated multi-specific antibody disclosed herein may comprise:
  • the present disclosure relates to a pharmaceutical composition
  • a pharmaceutical composition comprising at least an antibody as disclosed herein, at least a combination of at least a first and a second antibodies as disclosed herein, or at least a multispecific antibody as disclosed herein, and a pharmaceutically acceptable carrier.
  • the present disclosure relates to an isolated antibody as disclosed herein, at least a combination of at least a first and a second antibodies as disclosed herein, at least a multi-specific antibody as disclosed herein, or a pharmaceutical composition as disclosed herein, for use as a medicament.
  • the present disclosure relates to an isolated antibody as disclosed herein, at least a combination of at least a first and a second antibodies as disclosed herein, at least a multi-specific antibody as disclosed herein, or a pharmaceutical composition as disclosed herein, for use in the prevention and/or treatment of a BKPyV -infection and/or a BKPyV -inf ection associated disease, in a subject in need thereof.
  • a subject in need thereof may be an organ transplant recipient.
  • An organ transplant recipient may be a kidney transplant recipient.
  • a BKPyV-infection associated disease may be a BK polyomavirus-associated nephropathy (BK PyVAN), a hemorrhagic cystitis, (BK Py-HC) a granule cell neuronopathy (GCN), an interstitial kidney disease, an ureteral stenosis, a pneumonitis, a vasculitis, a colitis, a meningitis, a retinitis, a meningoencephalitis, an immune reconstitution inflammatory syndrome (IRIS), or a reno-urinary cancer.
  • BK PyVAN BK polyomavirus-associated nephropathy
  • BK Py-HC hemorrhagic cystitis
  • GCN granule cell neuronopathy
  • IRIS immune reconstitution inflammatory syndrome
  • a disorder induced by a BKPyV infection may be a hemorrhagic cystitis.
  • a disorder induced by a BKPyV infection may be a BK polyomavirus-associated nephropathy.
  • a disorder induced by a BKPyV infection may be a reno- urinary cancer, for example a bladder cancer.
  • nucleic acid sequence disclosed herein may comprise:
  • a nucleic acid sequence disclosed herein may comprise:
  • the present disclosure relates to an isolated or recombinant expression vector comprising a nucleic acid sequence disclosed herein.
  • the present disclosure relates to a recombinant host cell which has been transformed by a nucleic acid or an expression vector disclosed herein.
  • the present disclosure relates to a method for producing an antibody binding a BK polyoma virus (BKPyV) VP1 capsid protein, or an antigenbinding fragment thereof, comprising at least the steps of culturing a host cell disclosed in a culture medium under conditions suitable for producing said antibody or fragment thereof and recovering the antibody or fragment thereof from said cultured cells.
  • BKPyV BK polyoma virus
  • the present disclosure relates to an isolated BKPy VP1 protein of amino acid sequence SEQ ID NO: 96 or an isolated VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence.
  • the present disclosure relates to an isolated BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96 or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence.
  • isolated BKPy virus may be a pseudotype virus or a virus.
  • pseudotype virus and pseudovirus are used interchangeably.
  • the present disclosure relates to a use of a BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96 or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence for screening a candidate antibody able to neutralize a BKPy virus.
  • the BKPy virus may be a pseudotype virus.
  • the BKPy virus pseudotype may be BKPyV g!b2-D58DelP59A.
  • the present disclosure relates to an in vitro method for screening a candidate antibody able to neutralize a BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence, said method comprising at least the steps of:
  • the BKPy virus may be a pseudotype virus.
  • the BKPy virus may be BKPyV g!b2-D58DelP59A.
  • the present disclosure relates to a method for manufacturing a pharmaceutical composition for treating and/or preventing a BKPyV infection or for treating and/or preventing a disorder induced by a BKPyV infection in a subject in need thereof, the method comprising at least the steps of:
  • the present disclosure relates to an in vitro method for measuring a neutralizing activity of an anti -BKPyV antibody isolated from a subject presumed to be infected with a BKPy virus, the method comprising at least the steps of:
  • FIGURES 1A-F represent the binding properties of BK120 (Fig. 1A), BK160- 1 (Fig. IB), BK198 (Fig. 1C), BK206 (Fig. ID), BK256 (Fig. IE), and BK293 (Fig. IF), antibodies measured by ELISA against the four wildtype BKPyV genotypes: gla (•), gll ( ⁇ ), gill (A) and gIVc2 ( ⁇ ).
  • FIGURES 2A-G represent the neutralization capacity of BK120 (Fig. 2A),
  • BK160-1 (Fig. 2B), BK198 (Fig. 2C), BK206 (Fig. 2D), BK256 (Fig. 2E), BK293 (Fig. 2F) and BK304 (Fig. 2G) antibodies on HEK293TT cells infected with wildtype pseudotype viruses
  • BKPyV infection rate in percentage relative to cells infected in the absence of antibody.
  • FIGURES 3A-G represent the neutralization capacity of BK120 (Fig. 3A), BK160-1 (Fig. 3B), BK198 (Fig. 3C), BK206 (Fig. 3D), BK256 (Fig. 3E), BK293 (Fig. 3F) and BK304 (Fig. 3G) antibodies on RS cells infected with wildtype pseudotype viruses (PSV) gla (•), gll ( ⁇ ), gill (A) and gIVc2 ( ⁇ ). Each antibody was added to BKPyV PSV in serial 5- fold dilutions starting at 10 pg/mL. Abscissa: Antibody concentration in pg/ml in loglO.
  • PSV wildtype pseudotype viruses
  • FIGURES 4A-H represent the viral neutralization capacity of BK120 (Fig. 4A), BK206 (Fig. 4B), BK293 (Fig. 4C), BK304 (Fig. 4D), BK120 + BK206 (Fig. 4E), BK120 + BK293 (Fig. 4F), BK120 + BK304 (Fig. 4G), and 41F17 (Fig. 4H) on HEK293TT cells infected with wildtype and naturally occurring variant pseudotype viruses (PSV) glb2-wt (•), glb2- DNEQ ( ⁇ ), gIb2-VVAE (+), gIVc2 ( ⁇ ) and gIVc2-SDKAN (0).
  • PSV wildtype and naturally occurring variant pseudotype viruses
  • FIGURES 5A-H represent the viral neutralization capacity of BK120 (Fig. 5A), BK206 (Fig. 5B), BK293 (Fig. 5C), BK304 (Fig. 5D), BK120 + BK206 (Fig. 5E), BK120 + BK293 (Fig. 5F), BK120 + BK304 (Fig. 5G), and 41F17 (Fig. 5A), BK206 (Fig. 5B), BK293 (Fig. 5C), BK304 (Fig. 5D), BK120 + BK206 (Fig. 5E), BK120 + BK293 (Fig. 5F), BK120 + BK304 (Fig. 5G), and 41F17 (Fig. 5A), BK206 (Fig. 5B), BK293 (Fig. 5C), BK304 (Fig. 5D), BK120 + BK206 (Fig. 5E), BK120 + BK293 (Fig. 5F), BK120 + BK304 (Fig. 5G), and 41F17 (Fig.
  • FIGURES 6A-D represent the viral neutralization capacity of BK120 (o), compared to P8D11 ( ⁇ ) and 41F17 (A) antibodies on cells infected with wildtype pseudotype viruses (PSV) gl (Fig. 6A), gll (Fig. 6B), gill (Fig. 6C) and gIV (Fig. 6D).
  • P8D11 antibody was added to BKPyV PSV in serial 5-fold dilutions starting at 10 pg/mL
  • BK120 and 41F17 antibodies were added to BKPyV PSV in serial 5-fold dilutions starting at 5 pg/mL .
  • Abscissa Antibody concentration in ng/ml in log 10.
  • Ordinate BKPyV infection rate in percentage relative to cells infected in the absence of antibody.
  • FIGURES 7A-B represent the viral neutralization capacity of BK120 (o), compared to P8D11 ( ⁇ ) and 41F17 (A) on cells infected with variants pseudotype viruses (PSV) g!b2-E61K (Fig. 7A) and g!b2-K172A (Fig. 7B).
  • P8D11 antibody was added to BKPyV PSV in serial 5-fold dilutions starting at 10 pg/mL
  • BK120 and 41F17 antibodies were added to BKPyV PSV in serial 5-fold dilutions starting at 5 pg/mL .
  • Abscissa Antibody concentration in ng/ml in log 10.
  • Ordinate BKPyV infection rate in percentage relative to cells infected in the absence of antibody.
  • FIGURES 8A-B represent the viral neutralization capacity of BK120 (o), compared to P8D11 ( ⁇ ) and 41F17 (A) antibodies on cells infected with variants pseudotype viruses (PSV) g!b2-DNEQ (Fig. 8A) and gIVc2 SDKAN (Fig. 8B).
  • P8D11 antibody was added to BKPyV PSV in serial 5-fold dilutions starting at 10 pg/mL
  • BK120 and 41F17 antibodies were added to BKPyV PSV in serial 5-fold dilutions starting at 5 pg/mL.
  • Abscissa Antibody concentration in ng/ml in log 10.
  • Ordinate BKPyV infection rate in percentage relative to cells infected in the absence of antibody.
  • SEQ ID NO: 1 represents the amino acids sequence of the HCDR1 of BK120.
  • SEQ ID NO: 2 represents the amino acids sequence of the HCDR2 of BK120.
  • SEQ ID NO: 3 represents the amino acids sequence of the HCDR3 of BK120.
  • SEQ ID NO: 4 represents the amino acids sequence of the LCDR1 of BK120.
  • SEQ ID NO: 5 represents the amino acids sequence of the LCDR3 of BK120.
  • SEQ ID NO: 6 represents the amino acids sequence of the heavy chain variable domain (VH) of BK120.
  • SEQ ID NO: 7 represents the amino acids sequence of the light chain variable domain (VL) of BK120.
  • SEQ ID NO 8 represents the amino acids sequence of the heavy chain of BK120.
  • SEQ ID NO 9 represents the amino acids sequence of the light chain of BK120.
  • SEQ ID NO 10 represents the nucleic acids sequence of the VH of BK120.
  • SEQ ID NO 11 represents the nucleic acids sequence of the VL of BK120.
  • SEQ ID NO 12 represents the nucleic acids sequence of the heavy chain of the BK120.
  • SEQ ID NO 13 represents the nucleic acids sequence of the light chain of the BK120.
  • SEQ ID NO 14 represents the amino acids sequence of the HCDR1 of BK160-1.
  • SEQ ID NO 15 represents the amino acids sequence of the HCDR2 of B KI 60-1.
  • SEQ ID NO 16 represents the amino acids sequence of the HCDR3 of B KI 60-1.
  • SEQ ID NO 17 represents the amino acids sequence of the LCDR1 of BK160-1.
  • SEQ ID NO 18 represents the amino acids sequence of the LCDR3 of B KI 60-1.
  • SEQ ID NO 19 represents the amino acids sequence of the VH of B KI 60-1.
  • SEQ ID NO 20 represents the amino acids sequence of the VL of B KI 60-1.
  • SEQ ID NO 21 represents the amino acids sequence of the heavy chain of BK160-1.
  • SEQ ID NO 22 represents the amino acids sequence of the light chain of B KI 60-1.
  • SEQ ID NO 23 represents the nucleic acids sequence of the VH of B KI 60-1.
  • SEQ ID NO 24 represents the nucleic acids sequence of the VL of B KI 60-1.
  • SEQ ID NO 25 represents the nucleic acids sequence of the heavy chain of the B KI 60-1.
  • SEQ ID NO 26 represents the nucleic acids sequence of the light chain of the B KI 60-1.
  • SEQ ID NO 27 represents the amino acids sequence of the HCDR1 of BK198.
  • SEQ ID NO 28 represents the amino acids sequence of the HCDR2 of BK198.
  • SEQ ID NO 29 represents the amino acids sequence of the HCDR3 of BK198.
  • SEQ ID NO 30 represents the amino acids sequence of the LCDR1 of BK198.
  • SEQ ID NO 31 represents the amino acids sequence of the LCDR3 of BK198.
  • SEQ ID NO 32 represents the amino acids sequence of the VH of BK198.
  • SEQ ID NO 33 represents the amino acids sequence of the VL of BK198.
  • SEQ ID NO 34 represents the amino acids sequence of the heavy chain of BK198.
  • SEQ ID NO 35 represents the amino acids sequence of the light chain of BK198.
  • SEQ ID NO 36 represents the nucleic acids sequence of the VH of BK198.
  • SEQ ID NO 37 represents the nucleic acids sequence of the VL of BK198.
  • SEQ ID NO 38 represents the nucleic acids sequence of the heavy chain of the BK198.
  • SEQ ID NO 39 represents the nucleic acids sequence of the light chain of the BK198.
  • SEQ ID NO 40 represents the amino acids sequence of the HCDR1 of BK206.
  • SEQ ID NO 41 represents the amino acids sequence of the HCDR2 of BK206.
  • SEQ ID NO 42 represents the amino acids sequence of the HCDR3 of BK206.
  • SEQ ID NO 43 represents the amino acids sequence of the LCDR1 of BK206.
  • SEQ ID NO 44 represents the amino acids sequence of the LCDR3 of BK206.
  • SEQ ID NO 45 represents the amino acids sequence of the VH of BK206.
  • SEQ ID NO 46 represents the amino acids sequence of the VL of BK206.
  • SEQ ID NO 47 represents the amino acids sequence of the heavy chain of BK206.
  • SEQ ID NO 48 represents the amino acids sequence of the light chain of BK206.
  • SEQ ID NO 49 represents the nucleic acids sequence of the VH of BK206.
  • SEQ ID NO 50 represents the nucleic acids sequence of the VL of BK206.
  • SEQ ID NO 51 represents the nucleic acids sequence of the heavy chain of the BK206.
  • SEQ ID NO 52 represents the nucleic acids sequence of the light chain of the BK206.
  • SEQ ID NO 53 represents the amino acids sequence of the HCDR1 of BK256.
  • SEQ ID NO 54 represents the amino acids sequence of the HCDR2 of BK256.
  • SEQ ID NO 55 represents the amino acids sequence of the HCDR3 of BK256.
  • SEQ ID NO 56 represents the amino acids sequence of the LCDR1 of BK256.
  • SEQ ID NO 57 represents the amino acids sequence of the LCDR3 of BK256.
  • SEQ ID NO 58 represents the amino acids sequence of the VH of BK256.
  • SEQ ID NO 59 represents the amino acids sequence of the VL of BK256.
  • SEQ ID NO 60 represents the amino acids sequence of the heavy chain of BK256.
  • SEQ ID NO 61 represents the amino acids sequence of the light chain of BK256.
  • SEQ ID NO 62 represents the nucleic acids sequence of the VH of BK256.
  • SEQ ID NO 63 represents the nucleic acids sequence of the VL of BK256.
  • SEQ ID NO 64 represents the nucleic acids sequence of the heavy chain of the BK256.
  • SEQ ID NO 65 represents the nucleic acids sequence of the light chain of the BK256.
  • SEQ ID NO 66 represents the amino acids sequence of the HCDR1 of BK293.
  • SEQ ID NO 67 represents the amino acids sequence of the HCDR2 of BK293.
  • SEQ ID NO 68 represents the amino acids sequence of the HCDR3 of BK293.
  • SEQ ID NO: 69 represents the amino acids sequence of the LCDR1 of BK293.
  • SEQ ID NO: 70 represents the amino acids sequence of the LCDR3 of BK293.
  • SEQ ID NO: 71 represents the amino acids sequence of the VH of BK293.
  • SEQ ID NO: 72 represents the amino acids sequence of the VL of BK293.
  • SEQ ID NO: 73 represents the amino acids sequence of the heavy chain of BK293.
  • SEQ ID NO: 74 represents the amino acids sequence of the light chain of BK293.
  • SEQ ID NO: 75 represents the nucleic acids sequence of the VH of BK293.
  • SEQ ID NO: 76 represents the nucleic acids sequence of the VL of BK293.
  • SEQ ID NO: 77 represents the nucleic acids sequence of the heavy chain of the BK293.
  • SEQ ID NO: 78 represents the nucleic acids sequence of the light chain of the BK293.
  • SEQ ID NO: 79 represents the amino acids sequence of the HCDR1 of BK304.
  • SEQ ID NO: 80 represents the amino acids sequence of the HCDR2 of BK304.
  • SEQ ID NO: 81 represents the amino acids sequence of the HCDR3 of BK304.
  • SEQ ID NO: 82 represents the amino acids sequence of the LCDR1 of BK304.
  • SEQ ID NO: 83 represents the amino acids sequence of the LCDR3 of BK304.
  • SEQ ID NO: 84 represents the amino acids sequence of the VH of BK304.
  • SEQ ID NO: 85 represents the amino acids sequence of the VL of BK304.
  • SEQ ID NO: 86 represents the amino acids sequence of the heavy chain of BK304.
  • SEQ ID NO: 87 represents the amino acids sequence of the light chain of BK304.
  • SEQ ID NO: 88 represents the nucleic acids sequence of the VH of BK304.
  • SEQ ID NO: 89 represents the nucleic acids sequence of the VL of BK304.
  • SEQ ID NO: 90 represents the nucleic acids sequence of the heavy chain of the BK304.
  • SEQ ID NO: 91 represents the nucleic acids sequence of the light chain of the BK304.
  • SEQ ID NO: 92 represents the amino acids sequence of the VP1 protein of the wildtype BKPyV. genotype la.
  • SEQ ID NO: 93 represents the amino acids sequence of the VP1 protein of the wildtype BKPyV genotype Ib2.
  • SEQ ID NO: 94 represents the amino acids sequence of the VP1 protein of the DNEQ BKPyV genotype Ib2.
  • SEQ ID NO: 95 represents the amino acids sequence of the VP1 protein of the VVAE BKPyV genotype Ib2.
  • SEQ ID NO: 96 represents the amino acids sequence of the VP1 protein of the D58Del_59A BKPyV genotype Ib2.
  • SEQ ID NO: 97 represents the amino acids sequence of the VP1 protein of the E61K BKPyV genotype Ib2.
  • SEQ ID NO: 98 represents the amino acids sequence of the VP1 protein of the wildtype BKPyV genotype II.
  • SEQ ID NO: 99 represents the amino acids sequence of the VP1 protein of the wildtype BKPyV genotype III.
  • SEQ ID NO: 100 represents the amino acids sequence of the VP1 protein of the wildtype BKPyV genotype IVc2.
  • SEQ ID NO: 101 represents the amino acids sequence of the VP1 protein of the E327K BKPyV genotype IVc2.
  • SEQ ID NO: 102 represents the amino acids sequence of the VP1 protein of the SDKAN BKPyV genotype IVc2.
  • SEQ ID NO: 103 represents the amino acids sequence of the VP1 protein of the wildtype MPyV.
  • SEQ ID NO: 104 represents the nucleic acids sequence of the primer CMV-F.
  • SEQ ID NO: 105 represents the nucleic acids sequence of the primer pEGFP-Nl-R.
  • SEQ ID NO: 106 represents the amino acids sequence of the VP1 protein of the K172A BKPyV genotype Ib2.
  • BKPyV BK polyomavirus
  • a or “an” entity refers to one or more of that entity; for example, “a nucleotide sequence,” is understood to represent one or more nucleotide sequences.
  • the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein.
  • aspects and embodiments of the present disclosure described herein include “comprising”, “having”, “consisting of’, and “consisting essentially of’ aspects and embodiments.
  • the words “have” and “comprise,” or variations such as “has,” “having”, “comprises”, or “comprising”, will be understood to imply the inclusion of the stated element(s) (such as a composition of matter or a method step) but not the exclusion of any other elements.
  • the term “consisting of’ implies the inclusion of the stated element(s), to the exclusion of any additional elements.
  • antibody As used herein the term “antibody” have the same meaning and will be used equally in the present description.
  • the term “antibody” as used herein refers to isolated or recombinant immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that contain an antigen binding site that immunospecifically binds an antigen, such as VP1 capsid protein.
  • the term antibody encompasses not only whole antibody molecules, but also antibody fragments as well as variants (including derivatives) of antibodies and antibody fragments.
  • two heavy chains are linked to each other by disulphide bonds and each heavy chain is linked to a light chain by a disulphide bond.
  • the light chain includes two domains, a variable domain (VL) and a constant domain (CL).
  • the heavy chain includes four domains, a variable domain (VH) and three constant domains (CHI, CH2 and CH3, collectively referred to as CH).
  • VL variable domain
  • VH variable domain
  • CH constant domain
  • the constant region domains of the light (CL) and heavy (CH) chains confer important biological properties such as antibody chain association, secretion, trans-placental mobility, complement binding, and binding to Ec receptors (EcR).
  • the Fv fragment is the N-terminal part of the Fab fragment of an immunoglobulin and consists of the variable portions of one light chain and one heavy chain.
  • the specificity of the antibody resides in the structural complementarity between the antibody combining site and the antigenic determinant.
  • Antibody combining sites are made up of residues that are primarily from the hypervariable or complementarity determining regions (CDRs). Occasionally, residues from nonhypervariable or framework regions (FR) can participate to the antibody binding site or influence the overall domain structure and hence the combining site.
  • Complementarity Determining Regions or CDRs refer to amino acid sequences which together define the binding affinity and specificity of the natural Fv region of a native immunoglobulin binding site.
  • the light and heavy chains of an immunoglobulin each have three CDRs, designated CDR1-L, CDR2-L, L- CDR3-L and CDR1-H CDR2-H, CDR3-H, respectively.
  • An antigen-binding site therefore, typically includes six CDRs, comprising the CDR set from each of a heavy and a light chain V region.
  • Framework Regions refer to amino acid sequences interposed between CDRs.
  • an antibody includes, but is not limited to, monoclonal antibodies, human antibodies, humanized antibodies, camelid antibodies and chimeric antibodies.
  • the antibodies can be of any isotype/class (e.g., IgG, IgE, IgM, IgD, IgA and IgY), or subclass (e.g., IgGl, IgG2, IgG3, IgG4, IgAl and IgA2).
  • an antibody of the present disclosure refers to an anti-BKPyV antibody.
  • an antibody of the present disclosure refers to an antibody binding a BKPyV VP1 capsid protein.
  • an antibody of the present disclosure may refer to BK120 antibody having the amino acid sequences as set forth in Table 3, BK106-1 antibody having the amino acid sequences as set forth in Table 4, BK198 antibody having the amino acid sequences as set forth in Table 5, BK206 antibody having the amino acid sequences as set forth in Table 6, BK256 antibody having the amino acid sequences as set forth in Table 7, BK293 antibody having the amino acid sequences as set forth in Table 8 and/or BK304 antibody having the amino acid sequences as set forth in Table 9.
  • the term “antibody” specifically includes an antibody binding a BK polyomavirus (BKPyV) VP1 capsid protein, a combination of at least two antibodies binding a BKPyV VP1 capsid protein, or a multi-specific antibody binding a BKPyV VP1 capsid protein as described herein.
  • BKPyV BK polyomavirus
  • an "isolated" compound or entity such as an antibody or antigen-binding fragment thereof, a vector or a cell, is one that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would interfere with diagnostic or therapeutic uses for the compound or entity, and may include enzymes, hormones, and other proteinaceous or non- proteinaceous solutes.
  • the compound or entity is partially or substantially purified.
  • the compound or entity may be purified to greater than about 95% by weight of antibody as determined by the Lowry method, for example, more than 95%, 96%, 97%, 98% or 99% by weight of compound or entity.
  • an isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment is not present.
  • an isolated antibody may be prepared by at least one purification step.
  • nucleic acid sequence as applied to an antibody, or an antigen-binding fragment thereof, a nucleic acid sequence, an expression vector or a host cell means that those are the products of various combinations of in vitro cloning, restriction, ligation steps, and other genetic engineering procedures.
  • monoclonal antibody refers to a preparation of antibody molecules of single molecular composition.
  • a monoclonal antibody composition displays a single binding specificity and affinity for a particular epitope on an antigen, in particular VP1 capsid protein of BKPyV.
  • CDRs complementarity-determining regions
  • the expression “complementarity-determining regions” or “CDRs” interchangeably refers to the hypervariable regions of VL and VH.
  • the CDRs are the target protein-binding site of the antibody chains that harbors specificity for such target protein, in particular BKPyV VP1 capsid protein.
  • CDRs can be referred to by their region and order.
  • VHCDR1”, “CDRLH” or “H-CDR1” refer to the first CDR of the heavy chain variable region.
  • the CDRs are structurally complementary to the epitope of the target protein, such as BKPyV VP1 protein, and are thus directly responsible for the binding specificity.
  • the positions of the CDRs and framework regions can be determined using various well-known definitions in the art, e.g., Kabat, Chothia, IMGT, and AbM.
  • the amino acid residues of the antibody of the disclosure are numbered according to the IMGT numbering system.
  • the IMGT unique numbering has been defined to compare the variable domains whatever the antigen receptor, the chain type, or the species (Lefranc M.-P., Immunology Today, 18, 509 (1997) ; Lefranc et al. Dev. Comp. Immunol., 27, 55-77 (2003)).
  • the conserved amino acids always have the same position, for instance cysteine 23, tryptophan 41, hydrophobic amino acid 89, cysteine 104, phenylalanine or tryptophan 118.
  • the IMGT unique numbering provides a standardized delimitation of the framework regions (FR1-IMGT: positions 1 to 26, FR2- IMGT: 39 to 55, FR3-IMGT: 66 to 104 and FR4-IMGT: 118 to 128) and of the complementarity determining regions: CDR1-IMGT: 27 to 38, CDR2-IMGT: 56 to 65 and CDR3-IMGT: 105 to 117. If the CDR3-IMGT length is less than 13 amino acids, gaps are created from the top of the loop, in the following order 111, 112, 110, 113, 109, 114, etc.
  • CDR3-IMGT length is more than 13 amino acids
  • additional positions are created between positions 111 and 112 at the top of the CDR3-IMGT loop in the following order 112.1,111.1, 112.2, 111.2, 112.3, 111.3, etc. (http://www.imgt.org/IMGTScientificChart/Nomenclature/ IM GT -FRCDRdefinition.html).
  • variable domains of both the light (VL) and heavy (VH) chain portions determine antigen recognition and specificity.
  • the constant domains of the light chain (CL) and the heavy chain (CHI, CH2, or CH3) confer important biological properties such as secretion, transplacental mobility, Fc receptor binding, complement binding, and the like.
  • the numbering of the constant region domains increases as they become more distal from the antigen binding site or amino-terminus of the antibody.
  • the N-terminus is a variable region and at the C-terminus is a constant region; the CH3 and CL domains actually comprise the carboxy-terminal domains of the heavy and light chain, respectively.
  • identity may mean the percentage of nucleotide bases or amino acid residues in the candidate sequence that are identical with the residue of a corresponding sequence to which it is compared, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity for the entire sequence, and not considering any conservative amino acid substitutions as part of the sequence identity. Neither N-terminal or C-terminal extensions nor insertions shall be construed as reducing identity or homology. Methods and computer programs for the alignment are available and well known in the art. Sequence identity may be measured using sequence analysis software. Two examples of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms (the National Center for Biotechnology Information). The BLASTN program is use for nucleotide sequences, whereas the BLASTP program is used for amino acid sequences.
  • antigen binding site or “antigen binding region” as used in the present disclosure refers to the part of the antibody which comprises the area which specifically binds to and is complementary to part or all of an antigen. Where an antigen is large, an antibody may only bind to a particular part of the antigen, which part is termed on epitope.
  • An antigen binding region may be provided by one or more antibody variable domains. Preferably, an antigen binding region is made of the association of an antibody light chain variable domain (VL) and an antibody heavy chain variable domain (VH).
  • VL antibody light chain variable domain
  • VH antibody heavy chain variable domain
  • an antigen can have one or more than one epitope.
  • an antigen may be a VP1 capsid protein of a human BKPyV.
  • an antigen of the disclosure may be a VP1 capsid protein selected among BKPyV VP1 gl wt, BKPyV VP1 gll wt, BKPyV VP1 gill wt, BKPyV VP1 gIV wt, BKPyV glb2 wt, BKPyV VP1 glb2 DNEQ, BKPyV glb2 VVAE, BKPyV VP1 gIVc2 wt, BKPyV VP1 gIV c2 SDKAN, BKPyV VP1 glb2 D58delP59A, BKPyV VP1 glb2 E61K, BKPyV
  • affinity means the strength of the binding of an antibody to an epitope presented on an antigen.
  • the affinity of an antibody is given by the dissociation constant KD, defined as [Ab] x [Ag] I [Ab-Ag], where [Ab-Ag] is the molar concentration of the antibody-antigen complex, [Ab] is the molar concentration of the unbound antibody and [Ag] is the molar concentration of the unbound antigen.
  • KD dissociation constant
  • Ka is defined by 1/Kd.
  • Ka and KD values determined by such standard methods measure the functional affinity, or avidity of the interaction.
  • an antibody is considered to bind an antigen when a functional binding affinity (KD), preferably measured by surface plasmon resonance, is of 10’ 8 mol/1 (M) or less, preferably 10’ 9 M to 10 12 M.
  • KD functional binding affinity
  • parenteral administration designates administration routes other than enteral and topical administration, generally by injection, by intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, epidermal, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal routes, including, without limitation, injections, and perfusions.
  • treat refers to the administration or consumption of a compound or composition according to the disclosure with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect a disorder, the symptoms of the condition, the likelihood of the disorder, or to prevent or delay the onset of the symptoms, complications, or otherwise arrest or inhibit further development of the disorder in a statistically significant manner. More particularly, “treating” or “treatment” includes any approach for obtaining beneficial or desired results in a subject’s BKPyV infection condition.
  • Beneficial or desired clinical results can include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions of BKPyV infection-associated disease, diminishment or reduction of the extent of a BKPyV infection-associated disease or of a symptom-associated BKPyV infection, stabilizing, i.e., not worsening, the state of a BKPyV infection-associated disease or of a symptom-associated BKPyV infection prevention of a BKPyV infection-associated disease, delay or slowing of BKPyV infection-associated disease or symptom-associated BKPyV infection progression, amelioration or palliation of the BKPyV infection-associated disease state, diminishment of the reoccurrence of BKPyV infection- associated disease, and remission, whether partial or total and whether detectable or undetectable.
  • treatment includes any cure, amelioration, or reduction of a BKPyV infection-associated disease or related symptom.
  • a “reduction” of a symptom or a disease means decreasing of the severity or frequency of the disease or symptom, or elimination of the disease or symptom.
  • the terms “prevent” or “preventing” (and grammatical variants thereof) with respect to a disease or disorder relate to prophylactic treatment of a disease, e.g., in a subject suspected to have the disease, or at risk for developing the disease. Prevention may include, but is not limited to, preventing, or delaying onset or progression of the disease and/or maintaining one or more symptoms of the disease at a desired or sub-pathological level.
  • the term “prevent” does not require the 100% elimination of the possibility or likelihood of occurrence of the event. Rather, it denotes that the likelihood of the occurrence of the event has been reduced in the presence of a composition or method as described herein.
  • prevention refers to a decrease in the risk of occurrence of a BKPyV infection- associated disease or symptom in a subject.
  • the prevention may be complete, i.e., no detectable symptoms or disease, or partial, such that fewer symptoms or less severity of the disease are observed than would likely occur absent treatment.
  • disorders and “disease” are used interchangeably herein and comprise any undesired physiological change in a subject or a cell.
  • the term “infection” refers to the presence of BKPyV in a subject, whether the infected subject presents clinical signs of the infection, in particular by the manifestation of a disorder, or not.
  • Subjects that are infected with BKPyV but have not become clinically manifest are called asymptomatic subjects.
  • subjects that are infected with BKPyV may be asymptomatic, i.e., subjects have no clinical signs of a BKPyV infection- associated disease.
  • the terms “therapeutically effective amount” and “prophylactically effective amount” refer to an amount that provides a therapeutic benefit in the treatment, prevention, or management of pathological processes considered.
  • the specific amount that is therapeutically effective can be readily determined by an ordinary medical practitioner and may vary depending on factors such as the type and stage of pathological processes considered, the subject’s medical history and age, and the administration of other therapeutic agents.
  • the term “patient” or “subject” is a mammal. Mammals include, but are not limited to, domesticated animals (e.g., cows, sheep, cats, dogs, and horses), primates (e.g., humans and non-human primates such as monkeys), rabbits, and rodents (e.g., mice and rats).
  • the subject may be a human.
  • a subject may be an immunocompromised subject.
  • immunocompromised subject or “immunosuppressed subject” refers to a subject having a weakened immune system.
  • the immune system of an immunocompromised subjects has a reduced ability to fight virus or bacterial infections and other diseases.
  • An immunocompromised subject includes subjects suffering from a Primary Immune Deficiency Diseases, subjects suffering from a Secondary Immune Deficiency Diseases, subjects being or has been treated with an immunosuppressive therapy; subjects being or has been treated with a chemotherapeutic agent or subjects who has been transplanted.
  • Primary Immune Deficiency Diseases refers to an inherited immune disorders resulting from genetic mutations, usually present at birth and diagnosed in childhood.
  • Secondary Immune Deficiency Diseases refers to an acquired immunodeficiency as a result of disease or environmental factors, such as AIDS, cancer, diabetes, malnutrition, or medical treatment, such as anticancer drugs, radiation therapy, or stem cell or organ transplant.
  • nucleic acid sequence is used herein interchangeably with the term “polynucleotide” and refers to deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or doublestranded form.
  • the term encompasses isolated or recombinant nucleic acids containing known nucleotide analogs or modified backbone residues or linkages, which are synthetic, naturally occurring, and non-naturally occurring, which have similar binding properties as the reference nucleic acid, and which are metabolized in a manner similar to the reference nucleotides.
  • Examples of such analogs include, without limitation, phosphorothioates, phosphor amidates, methyl phosphonates, chiral-methyl phosphonates, 2-O-methyl ribonucleotides, peptide-nucleic acids (PNAs).
  • PNAs peptide-nucleic acids
  • polypeptide and protein are used interchangeably herein to refer to a sequence of amino acid residues.
  • the terms apply to amino acid sequences in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid sequences and non-naturally occurring amino acid sequence. Unless otherwise indicated, a particular polypeptide sequence also implicitly encompasses conservatively modified variants thereof.
  • ICso half-maximal inhibitory concentration
  • IC50 is the concentration of antibody at which 50% of the available binding sites on the VP1 antigen are occupied.
  • target cell herein means any cell that may be infected by a BKPyV.
  • a target cell also includes a cell expressing a target antigen that can be recognized by an anti- BKPyV antibody according to the present disclosure.
  • a target cell may be a kidney cell.
  • a target cell used as cellular model in the binding and neutralization assays may be a 293TT cell line or an RS cell line.
  • virus-like particles are an assembly of VP1 pentamers into viral capsids. VLPs are composed of 72 VP1 pentamers. VLPs are structurally very similar to actual virus without the minor capsid proteins (VP2 and VP3) as well as the viral DNA genome, and therefore are non-infectious. VLPs are useful as viral epitopes are presented in a similar conformation to the actual virus.
  • BK polyomavirus BKPyV
  • the antibodies described herein specifically bind to the capsid protein VP1 of different BK polyomaviruses and BK pseudotype polyoma viruses. Further, the antibodies neutralize BKPy virus and BKPy pseudotype viruses. They can therefore be effectively used for preventing and treating an infection with BKPyV and/or a disorder induced by a BKPyV infection.
  • a pseudovirus or a pseudotype virus is a recombinant viral particle which in addition to its core/backbone, may incorporate envelope proteins derived from different viruses; moreover, the genes inside the pseudovirus are usually altered or modified so that they are unable to produce the surface protein on their own. As such, an additional plasmid or stable cell line expressing the surface proteins is needed to make the pseudovirus.
  • Pseudoviruses are capable of infecting susceptible cells, but they only replicate for 1 round in the infected host cells. Compared with wild-type viruses, pseudoviruses can be safely handled in biosafety level (BSL)- 2 laboratories and are usually easier to manipulate experimentally. Nevertheless, the conformational structure of pseudoviral surface proteins bears high similarity to that of the native viral proteins, and these surface proteins can effectively mediate viral entry into host cells.
  • BK polyoma virus (BKPyV” and “BK virus” are herein used interchangeably and intend to refer to a member of the family Polyomaviridae, genus Betapolyomavirus (Helle, Francois et al. Viruses vol. 9,11 327. 3 Nov. 2017).
  • BK polyomaviruses are icosahedral, non-enveloped, circular double-stranded DNA viruses with a genome of around 5,300 base pairs. They measure approximately 40-45 nM in diameter (Bennett et al., Microbes and Infection. 2012:14(9):672-683). Further, the BKPyVs have been associated with nephropathy, renal dysfunction such as hemorrhagic cystitis, pneumonitis, retinitis, and meningoencephalitis.
  • the BKPyV may be a whole BKPyV, BKPyV virus-like particles (VLPs) composed only of VP1 protein, or pseudotype virus that are incorporate all capsid proteins and are able to infect susceptible target cells. Up to 90% of the population as a whole is persistently infected with BKPyV. The virus reactivates and is asymptomatically shed into the urine in 5-10% of immunocompetent adults at any given time.
  • VLPs BKPyV virus-like particles
  • genotypes Based on the sequence of the VP1 gene, four genotypes have been described, corresponding to the four serologically differentiated subtypes I-IV, with different prevalence and geographic distribution. In each genotype, numerous serotype variants exist. The most common genotype worldwide is genotype I, with a frequency of about 80%, followed by genotype IV (about 15%), while genotypes II and III are isolated only sporadically. The distribution of the molecular variants of the virus is associated with the region of origin. BKPyV subtype la is most common in Africa, Ib-1 in Southeast Asia, and Ib-2 in Europe, while Ic is the most common variant in Northeast Asia.
  • the antibodies or antigen-binding fragments thereof are able to specifically bind and neutralize the BKPyV genotype I wildtype (la, Ib-1, Ib- 2 and Ic), as well as the newly identified variant BKPyV genotype Ib2-D58Del_59A and the known variants BKPyV genotype Ib2-E61K, BKPyV genotype Ib2-DNEQ and BKPyV genotype Ib2-VVAE, the BKPyV genotype II wildtype, the BKPyV genotype III wildtype, the BKPyV genotype IV wildtype (IVa-1, IVa-2, IVb-1, IVb-2, IVc-1 and IVc-2), as well as the variants BKPyV genotype IVc2-E327K and BKPyV genotype IVc2-SDKAN.
  • the BK120 antibody or antigenbinding fragments thereof is also able to specifically bind and/or neutralize the variant BKPyV genotype Ib2-K172A.
  • BKPyV variant refers to a wild-type BKPy virus wherein some mutations are present on the VP1 capsid proteins of the wild-type BKPyV.
  • BKPyV variant encompasses naturally occurring BKPyV variants and in vitro selected BKPyV variants.
  • the expression “naturally occurring BKPyV” intends to refer to variants of BKPyV obtained from subjects, such as genotype Ib2-DNEQ, the BKPyV genotype Ib2-VVAE, and the BKPyV genotype IVc2-SDKAN (McIlroy et al. Viruses 2020).
  • the term 'in vitro selected BKPyV refers to variants of BKPyV obtained by passaging viruses in vitro cell culture under suitable conditions, such as the BKPyV genotype Ia-D58Del_59A, and also the BKPyV genotype Ib2-E61K, the BKPyV genotype Ib2-K172A and the BKPyV genotype IVc2-E327K (Lindner et al. Immunity. 2019;50:668-676.e5 and McIlroy et al. Viruses. 2020 Jul 29; 12(8): 824.).
  • VP1 or “VP1 capsid protein” refers to the major polyoma virus capsid subunit protein. In the virus capsid, the monomers of VP1 oligomerize in pentamers. Expression of the VP1 protein alone is sufficient to produce VLPs that have the same antigenic properties as the infectious virus, since the minor capsid proteins VP2 and VP3 are not exposed on the surface of the virion.
  • VLPs Virus-like particles
  • viruses are molecules that closely resemble viruses but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then selfassemble into the virus-like structure.
  • the antibodies of the disclosure, or the antigen-binding fragments thereof, specifically bind to the VP1 sequences of the BKPyV of Table 1.
  • the VP1 coding region shows very high similarity (over 95%) in all genotypes of BKPyV, but the similarity between the amino acid residues from 61E to 83R is only 61-70%
  • the antibodies of the disclosure, or the antigen-binding fragments thereof specifically may bind to variants VP1 sequences comprising an amino acid sequence having at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequences of the VP1 of BKPyV of Table 1.
  • the antibodies of the disclosure, or the antigen-binding fragments thereof neutralize BKPyV comprising VP1 sequences comprising an amino acid sequence having at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequences of the VP1 of BKPyV of Table 1.
  • variants and/or mutants are described by reference to the amino acid sequences of the VP1 of BKPyV of Table 1 which are amino acid sequences of reference. Such a description by reference is based on the prerequisite of optimal sequence alignment in order to determine the amino acid in the variant sequence that corresponds to the amino acid defined as being in a specific position in the amino acid of reference.
  • variants and/or mutants are also described by percent identity with a sequence of reference. Percent identity between two amino acid sequences or two nucleotide sequences is determined with standard alignment algorithms as those described below.
  • a sequence identity refers to the similarity between amino acid sequences expressed in terms of the similarity between the sequences. Sequence identity is frequently measured in terms of percentage identity (or similarity or homology); the higher the percentage, the more similar the two sequences are. Variants of a polypeptide will possess a relatively high degree of sequence identity when aligned using standard methods.
  • sequence alignment can be achieved and percent identity can be determined Basic Local Alignment Tools (BLASTs, including BLASTP for amino acid sequence alignment and BLASTN for nucleotide sequence alignment; described in Altschul et al., (1990) J. Mol. Biol., 215: 403) available on the National Center for the Biotechnology Information (NCBI) web site at http://www.ncbi.nlm.nih.gov/BLAST and may be used using the default parameters [BLASTP: Expect value E: 10; Word size: 3; Matrix: BLOSUM62; Cost gap: Existence 11, Extension 1; and BLASTN: algorithm by default: Megablast; Expect value E: 10; Word size: 28; Match scores: 1; Mismatch score: -2;
  • variant and mutant amino acid sequences include amino acid sequences that have at least about 90% sequence identity with an amino acid sequence defined herein.
  • a variant or mutant amino acid sequence may have at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity to an amino acid sequence as defined herein.
  • Amino acid sequence identity is defined as the percentage of amino acid residues in the variant sequence that are identical with the amino acid residues in the reference sequence, after aligning the sequences and if necessary, introducing gaps, to achieve the maximum percent sequence identity, and not considering any conservative substitution as part of the sequence identity. Standard alignment algorithms cited above are useful in this regard.
  • the antibodies of the disclosure, or the antigen-binding fragments thereof specifically may bind to variants VP1 sequences of Table 1.
  • the antibodies of the disclosure, or the antigen-binding fragments thereof neutralize BKPyV comprising VP1 sequences of Table 1.
  • An object of the disclosure is an isolated, or recombinant, BKPy VP1 protein of amino acid sequence SEQ ID NO: 96 or an isolated, or recombinant, VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence.
  • BKPy VP1 protein may be useful for producing VLPs and BK PyV pseudotypes usable in neutralizing assay, antibody screening, in diagnosing methods for measuring an immune response to a BK PyV infection in a patient in need thereof, such as KTx patient.
  • the present disclosure also relates to an in vitro selected BKPyV variant having a VP1 capsid protein having an amino acid sequence as set forth in SEQ ID NO: 96.
  • the disclosure relates to an isolated or recombinant BKPy virus comprising a
  • Recombinant BKPyV virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96 or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence may be obtained by any known techniques in the art.
  • a recombinant BKPyV virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96 or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence may be a virus, a virus-like particle (VLP), or a pseudotype virus.
  • VLP virus-like particle
  • a recombinant BKPyV may be a pseudotype virus.
  • a recombinant BKPyV virus may be prepared in any suitable cells or cell lines such as human embryonic kidney cells (HEK 293TT cells).
  • a nucleic acid sequence encoding a VP1 protein of amino acid sequence SEQ ID NO: 96 or a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence may be inserted in any expression vector known in the art, for example an expression plasmid such as pCAG.
  • the minor capsid proteins VP2 and VP3 may be provided in separate plasmids, such as ph2b and ph3b plasmids, or may be inserted in the same expression plasmid used for the VP1 protein.
  • the vector expression may be transfected in suitable cells, such as HEK 293TT cells, using any nucleic acid cell delivery methods.
  • the viral particles may be harvested.
  • Harvest may be carried out by trypsinization, centrifugation and then lysis of the cells in a hypotonic lysis buffer, for example consisting of 25 mM Sodium Citrate pH 6.0, 1 mM CaC12, 1 mM MgC12 and 5mM KC1. Further to exposure to the lysis buffer, the cells may be sonicated.
  • a hypotonic lysis buffer for example consisting of 25 mM Sodium Citrate pH 6.0, 1 mM CaC12, 1 mM MgC12 and 5mM KC1. Further to exposure to the lysis buffer, the cells may be sonicated.
  • the lysate may be clarified, for example by centrifugation.
  • Purification of the viral particles may be carried on density gradient medium, by any known techniques in the art.
  • An object of the invention relates to antibodies, or fragment thereof, binding to the VP1 capsid protein of BKPy viruses.
  • antibody and “antigen-binding fragment” are used interchangeably.
  • the antibodies described herein may be isolated antibodies.
  • the antibodies described herein may be recombinant antibodies.
  • the antibodies may be monoclonal antibodies.
  • the antibodies may be human antibodies or human engineered antibodies.
  • Antigen-binding fragments may be Fv, Fab, F(ab')2, Fab', dsFv, (dsFv)2, scFv, sc(Fv)2, or diabodies.
  • binding fragment refers to a fragment of an intact antibody that retain the ability to specifically binds to a given antigen/ligand.
  • binding fragments include a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CHI domains; a Fab’ fragment, a monovalent fragment consisting of the VL, VH, CL, CHI domains and hinge region; a E(ab’)2 fragment, a bivalent fragment comprising two Lab’ fragments linked by a disulphide bridge at the hinge region; an Ed fragment consisting of VH domains of a single arm of an antibody; a single domain antibody (sdAb) fragment (Ward et al., 1989 Nature 341:544-546), which consists of a VH domain or a VL domain; and an isolated complementary determining region (CDR).
  • Fab fragment a monovalent fragment consisting of the VL, VH, CL and CHI domains
  • a Fab’ fragment a monovalent fragment consisting of the VL,
  • the two domains of the Fv fragment, VL and VH are coded for by separate genes, they can be joined, using recombinant methods, by an artificial peptide linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv (ScFv); see, e.g., Bird et al., 1989 Science 242:423-426; and Huston et al., 1988 proc. Natl. Acad. Sci. 85:5879-5883).
  • dsFv is a VH::VL heterodimer stabilized by a disulfide bond.
  • Divalent and multivalent antibody fragments can form either spontaneously by association of monovalent scFvs or can be generated by coupling monovalent scFvs by a peptide linker, such as divalent sc(Fv)2.
  • Such single chain antibodies include one or more antigen biding portions or fragments of an antibody. These antibody fragments are obtained using conventional techniques known to those skilled in the art, and the fragments are screened for utility in the same manner as are intact antibodies.
  • a unibody is another type of antibody fragment lacking the hinge region of IgG4 antibodies. The deletion of the hinge region results in a molecule that is essentially half the size of traditional IgG4 antibodies and has a univalent binding region rather than the bivalent biding region of IgG4 antibodies.
  • UniBodies may be obtained by reference to WO 2007/059782, which is incorporated by reference in its entirety.
  • Antigen binding fragments can be incorporated into single domain antibodies, SMIP, maxibodies, minibodies, intrabodies, diabodies, triabodies and tetrabodies (see, e.g., Hollinger and Hudson, 2005, Nature Biotechnology, 23, 9, 1126-1136).
  • diabodies tribodies or tetrabodies” refers to small antibody fragments with multivalent antigen-binding sites (2, 3 or four), which fragments comprise a heavy -chain variable domain (VH) connected to a light-chain variable domain (VL) in the same polypeptide chain (VH-VL).
  • VH heavy -chain variable domain
  • VL light-chain variable domain
  • Antigen binding fragments can be incorporated into single chain molecules comprising a pair of tandem Fv segments (VH-CH1- VH-CH1) Which, together with complementary light chain polypeptides, form a pair of antigen binding regions (Zapata et al., 1995 Protein Eng. 8(10); 1057-1062 and U.S. Pat. No. 5,641,870).
  • Fab fragments can be obtained by treating an antibody with a protease, papain. Also, the Fab can be produced by inserting DNA encoding Fab of the antibody into a vector for prokaryotic expression system, or for eukaryotic expression system, and introducing the vector into a procaryote or eucaryote (as appropriate) to express the Fab.
  • F(ab’)2 can be obtained by treating an antibody with a protease, pepsin. Also, the F(ab’)2 can be produced by binding Fab’ described below via a thioether bond or a disulphide bond.
  • Fab’ can be obtained by treating F(ab’)2 with a reducing agent, dithiothreitol. Also, the Fab’ can be produced by inserting DNA encoding Fab’ fragment of the antibody into an expression vector for prokaryote, or an expression vector for eukaryote, and introducing the vector into a prokaryote or eukaryote (as appropriate) to perform its expression.
  • An antigen-binding fragment may be variable heavy chain of a single domain antibody (VHH).
  • binding or “specifically binding” are used interchangeably and refer to the ability of an antibody or antigen-binding fragment thereof to detectably bind an epitope present on a specific antigen, such as a BKPyV VP1 capsid protein, while having relatively no or little detectable reactivity with different antigen, for example non- BKPyV VP1 capsid proteins or structures, such as the VP1 of the MPyV (Murine polyoma virus).
  • a specific antigen such as a BKPyV VP1 capsid protein
  • a VP1 of the MPyV may be of SEO ID NO: 103:
  • the antibody or antigen-binding fragment thereof forms a complex with an antigen that is relatively stable under physiologic conditions.
  • Specific binding can be characterized by an equilibrium dissociation constant (KD) of at least about IxlO -6 M or less (e.g., a smaller KD denotes a tighter binding).
  • KD equilibrium dissociation constant
  • Methods for determining whether two molecules specifically bind are well known in the art and include, for example, equilibrium dialysis, surface plasmon resonance, and the like. Moreover, multi-specific antibodies that bind to the VP1 protein of a BKPyV and one or more additional antigens or a bi-specific that binds to two different regions of the VP1 protein of a BKPyV are nonetheless considered antibodies that “specifically bind” the VP1 protein of a BKPyV, as used herein.
  • the binding affinity of the antibodies may range from about 10 -12 M to about 5xl0 -8 M, as measured by surface plasmon resonance, e.g., BIACORETM or solution-affinity ELISA, for example as described in the Examples section.
  • the binding affinity of the antibodies on the VP1 capsid protein of gl-IV BKPyV may be of about 10.0xl0 -8 M or less.
  • the binding affinity of the antibodies on the VP1 capsid protein of gl-IV BKPyV may range from about l.OxlO -7 M to about l.OxlO" 10 M, or less.
  • the binding affinity of the antibodies on the VP1 capsid protein of gl-IV BKPyV may be of about l.OxlO -7 M or less, or of about 8.0xl0 -8 M or less, or of about 6.5xl0 -8 M or less, or of about 5.0xl0 -8 M or less, or of about 3.0xl0 -8 M or less, or of about 2.0xl0 -8 M or less, or of about 1.5xl0 -8 M or less, or of about l.OxlO -8 M or less, or of about 9.OxlO -10 M or less, or of about 8.0xl0 -9 M or less, or of about 5.0xl0 -9 M or less, or of about 2.5xl0 -9 M or less, or of about 2.0xl0 -9 M or less, or of about 1.5xl0 -9 M or less, or of about l.OxlO -9 M or less, or of about 8.0xl0 -1 ° M
  • a BKPyV neutralizing antibody intends to refer to an antibody which is capable of specifically binding to an antigen of BKPyV and substantially inhibiting or eliminating infection of a target cell by the BKPyV, or reducing the infectious titer, as demonstrated for example by the absence of viral gene expression of the BKPyV.
  • a neutralizing antibody will inhibit infection activity of a BKPyV, or reduce an infection titer, by at least about 50%, or at least about 60%, or at least about 70%, or at least 80%, or at least 85%, or at least 90%, or at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99%.
  • the neutralizing antibody of the invention is especially useful in therapeutic applications: to prevent or treat infections with BKPyV and/or disorders induced by a BKPyV infection.
  • the ability of an antibody for neutralizing a BKPyV may be determined by the measurement of the IC50, i.e., the concentration of an antibody reducing by 50% the infection of cells by the virus.
  • a neutralization assay may be carried out with a virus or a pseudotype virus, as described in the Examples section.
  • a serial dilution of a predetermined amount of infecting viral particles (virus or pseudotype virus) is used to infect cultured cells.
  • useable cells may be HEK293 TTT cells or RS cells.
  • a 2-, 3-, 4-, 5-, 6-, 7-fold dilution may be used.
  • the antibody to be assayed may be placed in contact with the viral particles before adding the viral particles to the cultured cells.
  • antibody may be placed in contact with the cultured cells before addition of the viral particles.
  • the antibody may be placed in contact with the cultured cells after addition of the viral particles to the cells.
  • the infected cells may be numbered, and the obtained value is compared with, or normalized with, the value obtained with cultured cells infected by viral particles in the absence of the antibody to be assayed .
  • the neutralization activity of the antibodies may be expressed as the IC50.
  • the neutralization activity of the antibodies on the gl-IV BKPyV expressed as the concentration inhibiting at least 50% of the infection, IC50, measured, for example on HEK293 TTT or RS cells, as described in the Examples section, may be of about 50 nM or less.
  • the neutralization activity of the antibodies on the gl-IV BKPyV may range from about 0.01 nM to about 50 nM.
  • the antibodies described herein may neutralize the gl-IV BKPyV in a target cell with a IC50 of about 50.0 nM or less, of about 45.0 nM or less, of about 40.0 nM or less, or of about 35.0 nM or less, or of about 30.0 nM or less, or of about 25.0 nM or less, or of about 20.0 nM or less, or of about 15.0 nM or less, or of about 10.0 nM or less, or of about 8.0 nM or less, or of about 5.0 or less, or of about 3.5 nM or less, or of about 2.5 nM or less, or of about 1.0 nM or less, or of about 0.8 nM or less, or of about 0.5 nM or less, or of about 0.3 nM or less, or of about 0.15 nM or less, or of about 0.10 nM or less, or of about 0.08 nM or less, or of about
  • the antibodies may have a neutralization activity on BKPy virus comprising a VP1 amino acid sequence SEQ ID NO: 97, SEQ ID NO: 98 or SEQ ID NO: 99, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences, with an IC50 of less than about 40 nM, or less than 30 nM, or less than 15 nM, or less than 10 nM, or less than 5 nM, or less than 1 nM.
  • the antibodies may have a neutralization activity on BKPy virus comprising a VP1 amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 101 or SEQ ID NO: 106, and for example comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said amino acid sequences, with an IC50 of less than about 40 nM, or less than 30 nM, or less than 15 nM, or less than 10 nM, or less than 5 nM, or less than 1 nM.
  • the antibodies may have a neutralization activity on BKPy virus comprising a VP1 amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 101 or SEQ ID NO: 106, and for example comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences, with an IC50 of less than about 35 nM, or less than about 30 nM, or less than about 20 nM, or less than about 15 nM, or less than about 10 nM, or less than about 5 nM, or less than about 4 nM, or less than about 2.5 nM, or less than about 2 nM, or less than about 1.5 nM, or less than about 1 nM, or less than about 0.8 nM, or less than about 0.5 nM, or less than about 0.3
  • An antibody may bind and neutralize at least two BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 101, or SEQ ID NO: 106, and for example comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences.
  • An antibody may bind and neutralize at least two BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 101, or SEQ ID NO: 106, and for example comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of less than about 35 nM, or less than about 30 nM, or less than about 20 nM, or less than about 15 nM, or less than about 10 nM, or less than about 5 nM, or less than about 4 nM, or less than about 2.5 nM, or less than about 2 nM, or less than about 1.5 nM, or less than about 1 nM, or less than about 0.8 nM, or less than about 0.5 nM, or less than
  • the BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, SEQ ID NO: 97 or SEQ ID NO: 101, or SEQ ID NO: 106 may be selected among BKPyV- D58Del_59A, BKPyV-E61K, BKPyV-E327K and BKPyV-K172A.
  • An antibody disclosed herein may bind and neutralize at least two BKPy virus selected among BKPyV-D58Del_59A, BKPyV-E61K, BKPyV-E327K and BKPyV-K172A.
  • An antibody disclosed herein may be an antibody from group (i), (ii), (iii), (iv), (v), (vi) or (vii) defined as comprising:
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1 or a sequence differing from SEQ ID NO: 1 by one conservative amino acid substitution
  • a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2 or a sequence differing from SEQ ID NO: 2 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3 or a sequence differing from SEQ ID NO: 3 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4 or a sequence differing from SEQ ID NO: 4 by one conservative amino acid substitution
  • a CDR2-L comprising an amino acid sequence of DTS or a sequence differing from DTS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5 or a sequence differing from SEQ ID NO: 5 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14 or a sequence differing from SEQ ID NO: 14 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 15 or a sequence differing from SEQ ID NO: 15 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 16 or a sequence differing from SEQ ID NO: 16 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17 or a sequence differing from SEQ ID NO: 17 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18 or a sequence differing from SEQ ID NO: 18 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27 or a sequence differing from SEQ ID NO: 27 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 28 or a sequence differing from SEQ ID NO: 28 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 29 or a sequence differing from SEQ ID NO: 29 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30 or a sequence differing from SEQ ID NO: 30 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31 or a sequence differing from SEQ ID NO: 31 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40 or a sequence differing from SEQ ID NO: 40 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 41 or a sequence differing from SEQ ID NO: 41 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42 or a sequence differing from SEQ ID NO: 42 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43 or a sequence differing from SEQ ID NO: 43 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of LGS or a sequence differing from LGS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44 or a sequence differing from SEQ ID NO: 44 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53 or a sequence differing from SEQ ID NO: 53 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 54 or a sequence differing from SEQ ID NO: 54 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 55 or a sequence differing from SEQ ID NO: 55 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56 or a sequence differing from SEQ ID NO: 56 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57 or a sequence differing from SEQ ID NO: 57 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66 or a sequence differing from SEQ ID NO: 66 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 67 or a sequence differing from SEQ ID NO: 67 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 68 or a sequence differing from SEQ ID NO: 68 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69 or a sequence differing from SEQ ID NO: 69 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of DQS or a sequence differing from DQS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70 or a sequence differing from SEQ ID NO: 70 by one conservative amino acid substitution
  • a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79 or a sequence differing from SEQ ID NO: 79 by one conservative amino acid substitution
  • a CDR2- H comprising an amino acid sequence of SEQ ID NO: 80 or a sequence differing from SEQ ID NO: 80 by one conservative amino acid substitution
  • a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81 or a sequence differing from SEQ ID NO: 81 by one conservative amino acid substitution
  • a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82 or a sequence differing from SEQ ID NO: 82 by one conservative amino acid substitution
  • a CDR2- L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution
  • a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83 or a sequence differing from SEQ ID NO: 83 by one conservative amino acid substitution.
  • a “conservative substitution” refers to the replacement of an amino acid with another amino acid of similar chemical structure, similar chemical properties or similar sidechain volume in an amino acid sequence.
  • a conservative amino acid substitution will not substantially change the functional properties of a protein.
  • the amino acids introduced may have similar polarity, hydrophilicity or hydrophobicity to the amino acids they replace.
  • Conservative amino acid changes are well known in the art. Conservative amino acid changes may also be determined by reference to the Point Accepted Mutation (PAM) or BLOcks Substitution Matrix (BLOSUM) family of scoring matrices for conservation of amino acid sequence.
  • PAM Point Accepted Mutation
  • BLOSUM BLOSUM family of scoring matrices for conservation of amino acid sequence.
  • conservative amino acid changes may be members of an equivalence group, being a set of amino acids having mutually positive scores in the similarity representation of the scoring matrix selected for use in an alignment of the reference and mutant polypeptide chains.
  • a conservative substitution may be a substitution of an amino acid of one class by an amino acid of the same class as presented in Table 2.
  • a conservative substitution may be a substitution of an amino acid of one class by an amino acid of another class but with a similar chemical structure, a similar chemical property and/or a similar side -chain volume.
  • a substitution mutation may be a non-conservative mutation, which replaces the amino acid of one class with an amino acid of non-similar chemical structure, non-similar chemical property and/or non-similar side-chain volume.
  • a CDR of an antibody, or antigen-binding fragment thereof may comprise more than one conservative amino acid substitution, for example at least two, or at least three.
  • the full-length heavy chain, the full-length light chain, VH, VL and CDRs of an antibody disclosed herein may comprise at least one conservative substitution.
  • the full-length heavy chain, the full-length light chain, the VH chain, the VL chain, and the CDRs of antibodies disclosed herein, or an antigen-binding fragments thereof may comprise:
  • amino acid sequence having at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the corresponding amino acid sequences set forth in any of Tables 3 to 9 and having CDRs sequences differing from the sequences CDRs set forth in any of Tables 3 to 9 by one conservative amino acid substitution, or
  • amino acid sequence having at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the corresponding amino acid sequences set forth in any of Tables 3 to 9 and having CDRs sequences identical to the sequences CDRs set forth in any of Tables 3 to 9, or
  • nucleic acid sequence having at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence as set forth in any of Tables 3 to 9, or
  • nucleic acid sequence having at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence as set forth in any of Tables 3 to 9, and having nucleic acid sequences coding for CDRs differing from the CDRs set forth in any of Tables 3 to 9 by one conservative amino acid substitution, or
  • nucleic acid sequence having at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence as set forth in any of Tables 3 to 9, and having nucleic acid sequences coding for CDRs identical to the CDRs set forth in any of Tables 3 to 9, or
  • Percent identity between amino acid sequences may be determined with standard alignment algorithms as those described herein.
  • sequence comparison For sequence comparison of nucleic acid sequences, typically one sequence acts as a reference sequence, to which test sequences are compared.
  • test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters are used.
  • Methods of alignment of sequences for comparison are well known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482, 1981, by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443, 1970, by the search for similarity method of Pearson & Lipman, Proc.
  • PILEUP uses a simplification of the progressive alignment method of Feng & Doolittle, J. Mol. Evol. 35:351-360, 1987. The method used is similar to the method described by Higgins & Sharp, CABIOS 5:151-153, 1989.
  • a reference sequence is compared to other test sequences to determine the percent sequence identity relationship using the following parameters: default gap weight (3.00), default gap length weight (0.10), and weighted end gaps.
  • PILEUP can be obtained from the GCG sequence analysis software package, e.g., version 7.0 (Devereaux et al., Nuc. Acids Res. 12:387- 395, 1984).
  • BLAST Altschul et al., J. Mol. Biol. 215:403-410, 1990 and Altschul et al., Nucleic Acids Res. 25:3389-3402, 1977.
  • Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (ncbi.nlm.nih.gov).
  • the BLASTP program (for amino acid sequences) uses as defaults a word length (W) of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915, 1989).
  • an antibody disclosed herein may comprise:
  • a CDR1-H comprising an amino acid sequence selected from SEQ ID NOs: 1, 14, 27, 40, 53, 66 and 79, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution;
  • a CDR2-H comprising an amino acid sequence selected from SEQ ID NOs: 2,
  • a CDR3-H comprising an amino acid sequence selected from SEQ ID NOs: 3,
  • CDR2-L comprising an amino acid sequence selected from DTS, DAS, LGS, GAS, DQS, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution
  • an antibody disclosed herein may comprise:
  • an antibody disclosed herein may comprise:
  • an antibody disclosed herein may comprise:
  • CDR1-L comprising an amino acid sequence selected from SEQ ID NOs: 4, 17, 30, 43, 56, 69 and 82; a CDR2-L comprising an amino acid sequence selected from DTS, DAS, LGS, GAS, DQS; and a CDR3-L comprising an amino acid sequence selected from SEQ ID NOs: 5, 18, 31, 44, 57, 70.
  • an antibody disclosed herein may comprise:
  • a heavy chain comprising an amino acid sequence selected from SEQ ID NO: 8, 21, 34, 47, 60, 73and 86, or a sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto; and/or
  • an antibody disclosed herein may comprise:
  • a heavy chain comprising an amino acid sequence selected from SEQ ID NO: 8, 21, 34, 47, 60, 73and 86, or a sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, and a CDR1-H comprising an amino acid sequence selected from SEQ ID NOs: 1, 14, 27, 40, 53, 66 and 79, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution; a CDR2-H comprising an amino acid sequence selected from SEQ ID NOs: 2, 15, 28, 41, 54, 67 and 80, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution; and a CDR3-H comprising an amino acid sequence selected from SEQ ID NOs: 3, 16, 29, 42, 55, 68 and 81, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution; and/
  • a light chain comprising an amino acid sequence from SEQ ID NO: 9, 22, 35, 48, 61, 74 and 87, or a sequence at least 85%%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, and a CDR1-L comprising an amino acid sequence selected from SEQ ID NOs: 4, 17, 30, 43, 56, 69 and 82, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution; a CDR2-L comprising an amino acid sequence selected from DTS, DAS, LGS, GAS, DQS, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution; and a CDR3-L comprising an amino acid sequence selected from SEQ ID NOs: 5, 18, 31, 44, 57, 70 and 83, or an amino acid sequence differing from said sequences by at least one conservative amino acid substitution.
  • an antibody disclosed herein may comprise:
  • a heavy chain comprising an amino acid sequence selected SEQ ID NO: 8, 21, 34, 47, 60, 73and 86, or a sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, and a CDR1-H comprising an amino acid sequence selected from SEQ ID NOs: 1, 14, 27, 40, 53, 66 and 79; a CDR2-H comprising an amino acid sequence selected from SEQ ID NOs: 2, 15, 28, 41, 54, 67 and 80; and a CDR3-H comprising an amino acid sequence selected from SEQ ID NOs: 3, 16, 29, 42, 55, 68 and 81; and/or
  • a light chain comprising an amino acid sequence from SEQ ID NO: 9, 22, 35, 48, 61, 74 and 87, or a sequence at least 85%%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, and a CDR1-L comprising an amino acid sequence selected from SEQ ID NOs: 4, 17, 30, 43, 56, 69 and 82; a CDR2-L comprising an amino acid sequence selected from DTS, DAS, LGS, GAS, DQS; and a CDR3-L comprising an amino acid sequence selected from SEQ ID NOs: 5, 18, 31, 44, 57, 70.
  • Group (i) of antibodies comprising an amino acid sequence from SEQ ID NO: 9, 22, 35, 48, 61, 74 and 87, or a sequence at least 85%%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,
  • the group (i) of antibodies is illustrated by the antibody B KI 20 of the Example section.
  • an antibody of group (i) may efficiently neutralize BKPyV escaping neutralization by both the antibodies 41F17 and P8D11.
  • the antibodies of group (i) may comprise a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1 or a sequence differing from SEQ ID NO: 1 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2 or a sequence differing from SEQ ID NO: 2 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3 or a sequence differing from SEQ ID NO: 3 by one conservative amino acid substitution, a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4 or a sequence differing from SEQ ID NO: 4 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DTS or a sequence differing from DTS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5 or a sequence differing from SEQ ID NO: 5 by one conservative amino acid substitution.
  • the CDRs may comprise at least two, or at least 3 conservative amino acid substitution.
  • the conservative amino acid substitution may be as above described.
  • the antibodies of group (i) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 6.
  • the antibodies of group (i) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 6 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1 or a sequence differing from SEQ ID NO: 1 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2 or a sequence differing from SEQ ID NO: 2 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3 or a sequence differing from SEQ ID NO: 3 by one conservative amino acid substitution.
  • the antibodies of group (i) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 6 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3.
  • the amino acid sequence of the variable domain of heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 6.
  • the antibodies of group (i) may comprise a variable domain of heavy chain of sequence SEQ ID NO: 6.
  • the antibodies of group (i) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 7.
  • the antibodies of group (i) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 7 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4 or a sequence differing from SEQ ID NO: 4 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DTS or a sequence differing from DTS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5 or a sequence differing from SEQ ID NO: 5 by one conservative amino acid substitution.
  • the antibodies of group (i) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 7 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4, a CDR2-L comprising an amino acid sequence of DTS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5.
  • the amino acid sequence of the variable domain of light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 7.
  • the antibodies of group (i) may comprise a variable domain of light chain of sequence SEQ ID NO: 7.
  • the antibodies of group (i) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 8.
  • the antibodies of group (i) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 8 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1 or a sequence differing from SEQ ID NO: 1 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2 or a sequence differing from SEQ ID NO: 2 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3 or a sequence differing from SEQ ID NO: 3 by one conservative amino acid substitution.
  • the antibodies of group (i) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 8 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3.
  • the amino acid sequence of the heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 8.
  • the antibodies of group (i) may comprise a heavy chain of sequence SEQ ID NO: 8.
  • the antibodies of group (i) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 9.
  • the antibodies of group (i) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 9 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4 or a sequence differing from SEQ ID NO: 4 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DTS or a sequence differing from DTS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5 or a sequence differing from SEQ ID NO: 5 by one conservative amino acid substitution.
  • the antibodies of group (i) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 9 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4, a CDR2-L comprising an amino acid sequence of DTS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5.
  • the amino acid sequence of the light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 9.
  • the antibodies of group (i) may comprise a light chain of sequence SEQ ID NO: 9.
  • an antibody of group (i) may be the antibody referred to as antibody BK120 in the Examples section.
  • variable domain of heavy chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 10.
  • a variable domain of heavy chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 10 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1 or a sequence differing from SEQ ID NO: 1 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2 or a sequence differing from SEQ ID NO: 2 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3 or a sequence differing from SEQ ID NO: 3 by one conservative amino acid substitution.
  • variable domain of heavy chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 10 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3.
  • variable domain of heavy chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 10.
  • variable domain of heavy chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 10.
  • variable domain of light chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 11.
  • a variable domain of light chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 11 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4 or a sequence differing from SEQ ID NO: 4 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DTS or a sequence differing from DTS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5 or a sequence differing from SEQ ID NO: 5 by one conservative amino acid substitution.
  • a variable domain of light chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 11 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4, a CDR2-L comprising an amino acid sequence of DTS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5.
  • variable domain of light chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 11.
  • variable domain of light chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 11.
  • a heavy chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 12.
  • a heavy chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 12 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1 or a sequence differing from SEQ ID NO: 1 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2 or a sequence differing from SEQ ID NO: 2 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3 or a sequence differing from SEQ ID NO: 3 by one conservative amino acid substitution.
  • a heavy chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 12 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 1, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 2, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 3.
  • a heavy chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 12.
  • a heavy chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 12.
  • a light chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 13.
  • a light chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 13 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4 or a sequence differing from SEQ ID NO: 4 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DTS or a sequence differing from DTS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5 or a sequence differing from SEQ ID NO: 5 by one conservative amino acid substitution.
  • a light chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 13 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 4, a CDR2-L comprising an amino acid sequence of DTS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 5.
  • a light chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 13.
  • a light chain of an antibody of group (i) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 13.
  • the antibodies of group (i) may (a) bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about l.OxlO -9 mol/1 (M) or less, and (b) neutralize a BKPyV with an IC50 of about 2.0 nM or less.
  • KD binding affinity
  • the antibodies of group (i) may bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about l.OxlO -9 mol/1 (M) or less, or of about 9.OxlO -10 M or less, or of about 5.0xl0 -1 ° M or less, or of about 2.5xlO -10 M or less, or of about 2.OxlO -10 M or less, or of about 1.5xl0 -10 M or less, or of about l.lxlO" 10 M or less, or of about l.OxlO 10 M or less, or of about 0.5 xlO -10 M or less.
  • KD binding affinity
  • the antibodies of group (i) may bind to BKPyV VP1 capsid protein of genotype I BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 1.5xl0 -10 M or less, or of about l.lxlO -10 M or less.
  • KD binding affinity
  • the antibodies of group (i) may bind to BKPyV VP1 capsid protein of genotype II BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.OxlO -10 M or less, or of about 1.6xlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (i) may bind to BKPyV VP1 capsid protein of genotype III BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.5xlO -10 M or less, or of about 2.1xlO -10 M or less.
  • KD binding affinity
  • the antibodies of group (i) may bind to BKPyV VP1 capsid protein of genotype IV BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 9.OxlO 10 M or less, or of about 8.6xlO -10 M or less.
  • KD binding affinity
  • the antibodies of group (i) may neutralize a BKPyV with an IC50 of about 2 nM or less, or of about 1.5 nM or less, or of about 1.0 nM or less, or of about 0.8 nM or less, or of about 0.5 nM or less, or of about 0.2 or less, or of about 0.1 nM or less, or of about 0.08 nM or less, or of about 0.06 nM or less, or of about 0.05 nM or less, or about 0.01 nM or less.
  • the antibodies of group (i) may neutralize a BKPyV of genotype I with an IC50 of about 2 nM or less, or of about 1.5 nM or less, or of about 1 nM or less, or of about 0.2 nM or less, or of about 0.1 nM or less, or of about 0.05 nM or less, or of about 0.01 nM or less.
  • the antibodies of group (i) may neutralize a BKPyV of genotype I comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96 or 97 or 106, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences, with an IC50 of about 2 nM or less, or of about 1.5 nM or less, or of about 1.1 nM or less, or of about 0.13 nM or less, or of about 0.08 nM or less, or of about 0.01 nM or less.
  • the antibodies of group (i) may neutralize a BKPyV of genotype II with an IC50 of about 1 nM or less, or of about 0.5 nM or less, or of about 0.27 nM or less, or of about 0.23 nM or less.
  • the antibodies of group (i) may neutralize a BKPyV of genotype III with an IC50 of about 1 nM or less, or of about 0.6 nM or less, or of about 0.2 nM or less, or of about 0.15 nM or less.
  • the antibodies of group (i) may neutralize a BKPyV of genotype IV with an IC50 of about 1 nM or less, or of about 0.5 nM or less, or of about 0.3 nM or less, or of about 0.15 nM or less, or of about 0.14 nM or less.
  • IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured with a neutralization assay as disclosed in the Examples section.
  • the IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured on HEK293 TTT or RS cells as described in the Examples section.
  • the group (ii) of antibodies is illustrated by the antibody B KI 60-1 of the Example section.
  • the antibodies of group (ii) may comprise a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14 or a sequence differing from SEQ ID NO: 14 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 15 or a sequence differing from SEQ ID NO: 15 by one conservative amino acid substitution, a CDR3- H comprising an amino acid sequence of SEQ ID NO: 16 or a sequence differing from SEQ ID NO: 16 by one conservative amino acid substitution, a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17 or a sequence differing from SEQ ID NO: 17 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18 or a sequence differing from SEQ ID NO: 18 by one conservative amino acid substitution.
  • the antibodies of group (ii) may comprise
  • the conservative amino acid substitution may be as above described.
  • the antibodies of group (ii) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 19.
  • the antibodies of group (ii) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 19 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14 or a sequence differing from SEQ ID NO: 14 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 15 or a sequence differing from SEQ ID NO: 15 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 16 or a sequence differing from SEQ ID NO: 16 by one conservative amino acid substitution.
  • the antibodies of group (ii) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 19 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 15, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 16.
  • the amino acid sequence of the variable domain of heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 19.
  • the antibodies of group (ii) may comprise a variable domain of heavy chain of sequence SEQ ID NO: 19.
  • the antibodies of group (ii) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 20.
  • the antibodies of group (ii) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 20 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17 or a sequence differing from SEQ ID NO: 17 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18 or a sequence differing from SEQ ID NO: 18 by one conservative amino acid substitution.
  • the antibodies of group (ii) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 20 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17, a CDR2-L comprising an amino acid sequence of DAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18.
  • the amino acid sequence of the variable domain of light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 20.
  • the antibodies of group (ii) may comprise a variable domain of light chain of sequence SEQ ID NO: 20.
  • the antibodies of group (ii) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 21.
  • the antibodies of group (ii) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 21 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14 or a sequence differing from SEQ ID NO: 14 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 15 or a sequence differing from SEQ ID NO: 15 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 16 or a sequence differing from SEQ ID NO: 16 by one conservative amino acid substitution.
  • the antibodies of group (ii) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 21 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 15, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 16.
  • the amino acid sequence of the heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 21.
  • the antibodies of group (ii) may comprise a heavy chain of sequence SEQ ID NO: 21.
  • the antibodies of group (ii) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 22.
  • the antibodies of group (ii) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 22 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17 or a sequence differing from SEQ ID NO: 17 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18 or a sequence differing from SEQ ID NO: 18 by one conservative amino acid substitution.
  • the antibodies of group (ii) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 22 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17, a CDR2-L comprising an amino acid sequence of DAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18.
  • the amino acid sequence of the light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 22.
  • the antibodies of group (ii) may comprise a light chain of sequence SEQ ID NO: 22.
  • an antibody of group (ii) may be the antibody referred to as antibody B KI 60-1 in the Examples section.
  • variable domain of heavy chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 23.
  • a variable domain of heavy chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 23 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14 or a sequence differing from SEQ ID NO: 14 by one conservative amino acid substitution, a CDR2- H comprising an amino acid sequence of SEQ ID NO: 15 or a sequence differing from SEQ ID NO: 15 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 16 or a sequence differing from SEQ ID NO: 16 by one conservative amino acid substitution.
  • variable domain of heavy chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 23 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 15, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 16.
  • variable domain of heavy chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 23.
  • variable domain of heavy chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 23.
  • variable domain of light chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 24.
  • a variable domain of light chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 24 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17 or a sequence differing from SEQ ID NO: 17 by one conservative amino acid substitution, a CDR2- L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18 or a sequence differing from SEQ ID NO: 18 by one conservative amino acid substitution.
  • a variable domain of light chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 24 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17, a CDR2-L comprising an amino acid sequence of DAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18.
  • variable domain of light chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 24.
  • variable domain of light chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 24.
  • a heavy chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 25.
  • a heavy chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 25 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14 or a sequence differing from SEQ ID NO: 14 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 15 or a sequence differing from SEQ ID NO: 15 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 16 or a sequence differing from SEQ ID NO: 16 by one conservative amino acid substitution.
  • a heavy chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 25 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 14, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 15, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 16.
  • a heavy chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 25.
  • a heavy chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 25.
  • a light chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 26.
  • a light chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 26 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17 or a sequence differing from SEQ ID NO: 17 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18 or a sequence differing from SEQ ID NO: 18 by one conservative amino acid substitution.
  • a light chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 26 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 17, a CDR2-L comprising an amino acid sequence of DAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 18.
  • a light chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 26.
  • a light chain of an antibody of group (ii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 26.
  • the antibodies of group (ii) may (a) bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about 5.OxlO 10 mol/1 (M) or less, and (b) neutralize a BKPyV with an IC50 of about 10 nM or less.
  • KD binding affinity
  • the antibodies of group (ii) may bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about 5.OxlO 10 M or less, or of about 4.OxlO 10 M or less, or of about 3xlO 10 M or less, or of about 2.5xlO 10 M or less, or of about 2.OxlO 10 M or less, or of about 1.8xlO 10 M or less, or of about 1.7xlO 10 M or less, or of about 1.5xlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (ii) may bind to BKPyV VP1 capsid protein of genotype I BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance of about 2.5xlO 10 M or less, or of about 2.3xlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (ii) may bind to BKPyV VP1 capsid protein of genotype II BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 3.OxlO 10 M or less, or of about 2.8xlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (ii) may bind to BKPyV VP1 capsid protein of genotype III BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.OxlO 10 M or less, or of about 1.7xlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (ii) may bind to BKPyV VP1 capsid protein of genotype IV BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 3.OxlO 10 M or less, or of about 2.7xlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (ii) may neutralize a BKPyV with an IC50 of about 10 nM or less, or of about 8.0 nM or less, or of about 5.0 nM or less, or of about 2.5 nM or less, or of about 2.0 nM or less, or of about 1.5 or less, or of about 1.0 nM or less, or of about 0.80 nM or less, or of about 0.50 nM or less, or of about 0.30 nM or less, or of about 0.25 nM or less, or of about 0.10 nM or less, or of about 0.05 nM or less.
  • the antibodies of group (ii) may neutralize a BKPyV of genotype I with an IC50 of about 0.5 nM or less, or of about 0.44 nM or less, of about 0.2 nM or less, or of about 0.15 nM or less, or of about 0.12 nM or less.
  • the antibodies of group (ii) may neutralize a BKPyV of genotype II with an IC50 of about 5.5 nM or less, or of about 4.9 nM or less.
  • the antibodies of group (ii) may neutralize a BKPyV of genotype III with an IC50 of about 1 nM or less, or of about 0.25 nM or less.
  • the antibodies of group (ii) may neutralize a BKPyV of genotype IV with an IC50 of about 1 nM or less, or of about 0.6 nM or less, or about 0.2 nM or less.
  • the IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured with a neutralization assay as disclosed in the Examples section.
  • the IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured on HEK293 TTT or RS cells as described in the Examples section.
  • the antibodies of group (iii) may comprise a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27 or a sequence differing from SEQ ID NO: 27 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 28 or a sequence differing from SEQ ID NO: 28 by one conservative amino acid substitution, a CDR3- H comprising an amino acid sequence of SEQ ID NO: 29 or a sequence differing from SEQ ID NO: 29 by one conservative amino acid substitution, a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30 or a sequence differing from SEQ ID NO: 30 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31 or a sequence differing from SEQ ID NO: 31 by one conservative amino acid substitution.
  • the CDRs may comprise at least two, or at least 3 conservative amino acid substitution.
  • the conservative amino acid substitution may be as above described.
  • the antibodies of group (iii) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 32.
  • the antibodies of group (iii) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 32 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27 or a sequence differing from SEQ ID NO: 27 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 28 or a sequence differing from SEQ ID NO: 28 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 29 or a sequence differing from SEQ ID NO: 29 by one conservative amino acid substitution.
  • the antibodies of group (iii) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 32 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 28, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 29.
  • the amino acid sequence of the variable domain of heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 32.
  • the antibodies of group (iii) may comprise a variable domain of heavy chain of sequence SEQ ID NO: 32.
  • the antibodies of group (iii) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 33.
  • the antibodies of group (iii) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 33 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30 or a sequence differing from SEQ ID NO: 30 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31 or a sequence differing from SEQ ID NO: 31 by one conservative amino acid substitution.
  • the antibodies of group (iii) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 33 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30, a CDR2-L comprising an amino acid sequence of DAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31.
  • the amino acid sequence of the variable domain of light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 33.
  • the antibodies of group (iii) may comprise a variable domain of light chain of sequence SEQ ID NO: 33.
  • the antibodies of group (iii) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 34.
  • the antibodies of group (iii) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 34 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27 or a sequence differing from SEQ ID NO: 27 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 28 or a sequence differing from SEQ ID NO: 28 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 29 or a sequence differing from SEQ ID NO: 29 by one conservative amino acid substitution.
  • the antibodies of group (iii) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 34 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 28, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 29.
  • the amino acid sequence of the heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 34.
  • the antibodies of group (iii) may comprise a heavy chain of sequence SEQ ID NO: 34.
  • the antibodies of group (iii) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 35.
  • the antibodies of group (iii) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 35 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30 or a sequence differing from SEQ ID NO: 30 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31 or a sequence differing from SEQ ID NO: 31 by one conservative amino acid substitution.
  • the antibodies of group (iii) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 35 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30, a CDR2-L comprising an amino acid sequence of DAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31.
  • the amino acid sequence of the light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 35.
  • the antibodies of group (iii) may comprise a light chain of sequence SEQ ID NO: 35.
  • an antibody of group (iii) may be the antibody referred to as antibody BK198 in the Examples section.
  • variable domain of heavy chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 36.
  • a variable domain of heavy chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 36 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27 or a sequence differing from SEQ ID NO: 27 by one conservative amino acid substitution, a CDR2- H comprising an amino acid sequence of SEQ ID NO: 28 or a sequence differing from SEQ ID NO: 28 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 29 or a sequence differing from SEQ ID NO: 29 by one conservative amino acid substitution.
  • variable domain of heavy chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 36 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 28, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 29.
  • variable domain of heavy chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 36.
  • variable domain of heavy chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 36.
  • variable domain of light chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 37.
  • a variable domain of light chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 37 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30 or a sequence differing from SEQ ID NO: 30 by one conservative amino acid substitution, a CDR2- L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31 or a sequence differing from SEQ ID NO: 31 by one conservative amino acid substitution.
  • a variable domain of light chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 37 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30, a CDR2-L comprising an amino acid sequence of DAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31.
  • variable domain of light chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 37.
  • variable domain of light chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 37.
  • a heavy chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 38.
  • a heavy chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 38 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27 or a sequence differing from SEQ ID NO: 27 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 28 or a sequence differing from SEQ ID NO: 28 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 29 or a sequence differing from SEQ ID NO: 29 by one conservative amino acid substitution.
  • a heavy chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 38 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 27, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 28, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 29.
  • a heavy chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 38.
  • a heavy chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO:
  • a light chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 39.
  • a light chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 39 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30 or a sequence differing from SEQ ID NO: 30 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DAS or a sequence differing from DAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31 or a sequence differing from SEQ ID NO: 31 by one conservative amino acid substitution.
  • a light chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 39 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 30, a CDR2-L comprising an amino acid sequence of DAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 31.
  • a light chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 39.
  • a light chain of an antibody of group (iii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO:
  • the antibodies of group (iii) may (a) bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about 5.OxlO 10 mol/1 (M) or less, and (b) neutralize a BKPyV with an IC50 of about 10 nM or less.
  • KD binding affinity
  • the antibodies of group (iii) may bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about 5.0xl0 -9 M or less, or of about 2.5xl0 -9 M or less, or of about l.OxlO -9 M or less, of about 5.OxlO 10 M or less, or of about 4.OxlO 10 M or less, or of about 3xlO 10 M or less, or of about 2.OxlO 10 M or less, or of about 1.8xlO 10 M or less, or of about 1.5xlO 10 M or less, or about l.lxlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (iii) may bind to BKPyV VP1 capsid protein of genotype I BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.0xl0 -9 M or less, or of about 1.6xl0 -9 M or less.
  • KD binding affinity
  • the antibodies of group (iii) may bind to BKPyV VP1 capsid protein of genotype II BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.5xl0 -9 M or less, or of about 2.3xl0 -9 M or less.
  • KD binding affinity
  • the antibodies of group (iii) may bind to BKPyV VP1 capsid protein of genotype III BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 1.5xlO 10 M or less, or of about l.lxlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (iii) may bind to BKPyV VP1 capsid protein of genotype IV BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 3.OxlO 10 M or less, or of about 2.8xlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (iii) may neutralize a BKPyV with an IC50 of about 10 nM or less, or of about 8.0 nM or less, or of about 5.0 nM or less, or of about 2.5 nM or less, or of about 2.0 nM or less, or of about 1.5 or less, or of about 1.0 nM or less, or of about 0.80 nM or less, or of about 0.50 nM or less, or of about 0.30 nM or less, or of about 0.25 nM or less.
  • the antibodies of group (iii) may neutralize a BKPyV of genotype I with an IC50 of about 2 nM or less, or of about 1.3 nM or less, or of about 1 nM or less, or of about 0.8 nM or less, or of about 0.79 nM or less.
  • the antibodies of group (iii) may neutralize a BKPyV of genotype II with an IC50 of about 10 nM or less, or of about 9 nM or less, or of about 5 nM or less, or of about 3.9 nM or less.
  • the antibodies of group (iii) may neutralize a BKPyV of genotype III with an IC50 of about 3 nM or less, or of about 2.8 nM or less.
  • the antibodies of group (iii) may neutralize a BKPyV of genotype IV with an IC50 of about 4 nM or less, or of about 3.5 nM or less, or of about 3.3 nM or less, or of about 1.7 nM or less.
  • IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured on HEK293 TTT or RS cells as described in the Examples section.
  • IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured with a neutralization assay as disclosed in the Examples section.
  • the antibodies of group (iv) may comprise a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40 or a sequence differing from SEQ ID NO: 40 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 41 or a sequence differing from SEQ ID NO: 41 by one conservative amino acid substitution, a CDR3- H comprising an amino acid sequence of SEQ ID NO: 42 or a sequence differing from SEQ ID NO: 42 by one conservative amino acid substitution, a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43 or a sequence differing from SEQ ID NO: 43 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of LGS or a sequence differing from LGS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44 or a sequence differing from SEQ ID NO: 44 by one conservative amino acid substitution.
  • the CDRs may comprise at least two, or at least 3 conservative amino acid substitution.
  • the antibodies of group (iv) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 45.
  • the antibodies of group (iv) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 45 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40 or a sequence differing from SEQ ID NO: 40 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 41 or a sequence differing from SEQ ID NO: 41 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42 or a sequence differing from SEQ ID NO: 42 by one conservative amino acid substitution.
  • the antibodies of group (iv) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 45 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 41, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42.
  • the amino acid sequence of the variable domain of heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 45.
  • the antibodies of group (iv) may comprise a variable domain of heavy chain of sequence SEQ ID NO: 45.
  • the antibodies of group (iv) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 46.
  • the antibodies of group (iv) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 46 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43 or a sequence differing from SEQ ID NO: 43 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of LGS or a sequence differing from LGS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44 or a sequence differing from SEQ ID NO: 44 by one conservative amino acid substitution.
  • the antibodies of group (iv) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 46 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43, a CDR2-L comprising an amino acid sequence of LGS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44.
  • the amino acid sequence of the variable domain of light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 46.
  • the antibodies of group (iv) may comprise a variable domain of light chain of sequence SEQ ID NO: 46.
  • the antibodies of group (iv) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 47.
  • the antibodies of group (iv) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 47 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40 or a sequence differing from SEQ ID NO: 40 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 41 or a sequence differing from SEQ ID NO: 41 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42 or a sequence differing from SEQ ID NO: 42 by one conservative amino acid substitution.
  • the antibodies of group (iv) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 47 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 41, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42.
  • the amino acid sequence of the heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 47.
  • the antibodies of group (iv) may comprise a heavy chain of sequence SEQ ID NO: 47.
  • the antibodies of group (iv) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 48.
  • the antibodies of group (iv) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 48 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43 or a sequence differing from SEQ ID NO: 43 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of LGS or a sequence differing from LGS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44 or a sequence differing from SEQ ID NO: 44 by one conservative amino acid substitution.
  • the antibodies of group (iv) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 48 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43, a CDR2-L comprising an amino acid sequence of LGS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44.
  • the amino acid sequence of the light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 48.
  • the antibodies of group (iv) may comprise a light chain of sequence SEQ ID NO: 48.
  • an antibody of group (iv) may be the antibody referred to as antibody BK206 in the Examples section.
  • variable domain of heavy chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 49.
  • a variable domain of heavy chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 49 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40 or a sequence differing from SEQ ID NO: 40 by one conservative amino acid substitution, a CDR2- H comprising an amino acid sequence of SEQ ID NO: 41 or a sequence differing from SEQ ID NO: 41 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42 or a sequence differing from SEQ ID NO: 42 by one conservative amino acid substitution.
  • variable domain of heavy chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 49 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 41, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42.
  • variable domain of heavy chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 49.
  • a variable domain of heavy chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 49.
  • variable domain of light chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 50.
  • a variable domain of light chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 50 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43 or a sequence differing from SEQ ID NO: 43 by one conservative amino acid substitution, a CDR2- L comprising an amino acid sequence of LGS or a sequence differing from LGS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44 or a sequence differing from SEQ ID NO: 44 by one conservative amino acid substitution.
  • a variable domain of light chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 50 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43, a CDR2-L comprising an amino acid sequence of LGS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44.
  • variable domain of light chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 50.
  • variable domain of light chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 50.
  • a heavy chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 51.
  • a heavy chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 51 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40 or a sequence differing from SEQ ID NO: 40 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 41 or a sequence differing from SEQ ID NO: 41 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42 or a sequence differing from SEQ ID NO: 42 by one conservative amino acid substitution.
  • a heavy chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 51 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 41, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42.
  • a heavy chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 51.
  • a heavy chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 51.
  • a light chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 52.
  • a light chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 52 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43 or a sequence differing from SEQ ID NO: 43 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of LGS or a sequence differing from LGS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44 or a sequence differing from SEQ ID NO: 44 by one conservative amino acid substitution.
  • a light chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 52 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43, a CDR2-L comprising an amino acid sequence of LGS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44.
  • a light chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 52.
  • a light chain of an antibody of group (iv) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 52.
  • the antibodies of group (iv) may (a) bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about 3. Ox 10’ 9 mol/1 (M) or less, and (b) neutralize a BKPyV with an IC50 of about 10.0 nM or less.
  • KD binding affinity
  • the antibodies of group (iv) may bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about 3.0xl0 -9 mol/1 (M) or less, or of about 2.5xl0 -9 M or less, or of about 2.0xl0 -9 M or less, or of about 1.8xl0 -9 M or less, or of about 1.5xl0 -9 M or less, or of about l.OxlO’ 9 M or less, or of about 8.OxlO 10 M or less, or of about 5.OxlO 10 M or less, or of about 2.5xlO 10 M or less, or of about 2.OxlO 10 M or less, or of about 1.5xl0’ 10 M or less, or of about 1.2xlO’ 10 M or less, or of about l.lxlO 10 M or less, or of about l.OxlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (iv) may bind to BKPyV VP1 capsid protein of genotype I BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.5xlO 10 M or less, or of about 2.OxlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (iv) may bind to BKPyV VP1 capsid protein of genotype II BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.5xl0 -9 M or less, or of about 2.2xl0 -9 M or less.
  • KD binding affinity
  • the antibodies of group (iv) may bind to BKPyV VP1 capsid protein of genotype III BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 4xl0 -9 M or less, or of about 3.1xl0 -9 M or less.
  • KD binding affinity
  • the antibodies of group (iv) may bind to BKPyV VP1 capsid protein of genotype IV BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 3.OxlO 10 M or less, or of about 2.5xlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (iv) may neutralize a BKPyV with an IC50 of about 40.0 nM or less, or of about 10.0 nM or less, or of about 8.0 nM or less, or of about 5.0 nM or less, or of about 3.5 nM or less, or of about 3.0 nM or less, or of about 2.8 or less, or of about 2.5 nM or less, or of about 2.0 nM or less, or of about 1.5 nM or less, or of about 1.0 nM or less, or of about 0.8 nM or less, or of about 0.5 nM or less, or of about 0.2 nM or less, or about 0.16 nM or less.
  • the antibodies of group (iv) may neutralize a BKPyV of genotype I with an IC50 of about 0.3 nM or less, or of about 0.2 nM or less, or of about 0.18 nM or less, or of about 0.16 nM or less.
  • the antibodies of group (iv) may neutralize a BKPyV of genotype I comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96 or 97, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences, with an IC50 of about 3 nM or less, or of about 2.64 nM or less, or of about 1 nM or less, or of about 0.96 nM or less, or of about 0.5 nM or less.
  • the antibodies of group (iv) may neutralize a BKPyV of genotype II with an IC50 of about 35 nM or less, or of about 34 nM or less.
  • the antibodies of group (iv) may neutralize a BKPyV of genotype III with an IC50 of about 40 nM or less, or of about 35 nM or less.
  • the antibodies of group (iv) may neutralize a BKPyV of genotype IV with an IC50 of about 0.3 nM or less, or of about 0.24 nM or less, or of about 0.19 nM or less.
  • the IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured with a neutralization assay as disclosed in the Examples section.
  • the IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured on HEK293 TTT or RS cells as described in the Examples section.
  • the antibodies of group (v) may comprise a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53 or a sequence differing from SEQ ID NO: 53 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 54 or a sequence differing from SEQ ID NO: 54 by one conservative amino acid substitution, a CDR3- H comprising an amino acid sequence of SEQ ID NO: 55 or a sequence differing from SEQ ID NO: 55 by one conservative amino acid substitution, a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56 or a sequence differing from SEQ ID NO: 56 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57 or a sequence differing from SEQ ID NO: 57 by one conservative amino acid substitution.
  • the CDRs may comprise at least two, or at least 3 conservative amino acid substitution.
  • the conservative amino acid substitution may be as above described.
  • the antibodies of group (v) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 58.
  • the antibodies of group (v) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 58 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53 or a sequence differing from SEQ ID NO: 53 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 54 or a sequence differing from SEQ ID NO: 54 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 55 or a sequence differing from SEQ ID NO: 55 by one conservative amino acid substitution.
  • the antibodies of group (v) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 58 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 54, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 55.
  • the amino acid sequence of the variable domain of heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 58.
  • the antibodies of group (v) may comprise a variable domain of heavy chain of sequence SEQ ID NO: 58.
  • the antibodies of group (v) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 59.
  • the antibodies of group (v) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 59 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56 or a sequence differing from SEQ ID NO: 56 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57 or a sequence differing from SEQ ID NO: 57 by one conservative amino acid substitution.
  • the antibodies of group (v) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 59 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56, a CDR2-L comprising an amino acid sequence of GAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57.
  • the amino acid sequence of the variable domain of light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 59.
  • the antibodies of group (v) may comprise a variable domain of light chain of sequence SEQ ID NO: 59.
  • the antibodies of group (v) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 60.
  • the antibodies of group (v) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 60 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53 or a sequence differing from SEQ ID NO: 53 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 54 or a sequence differing from SEQ ID NO: 54 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 55 or a sequence differing from SEQ ID NO: 55 by one conservative amino acid substitution.
  • the antibodies of group (v) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 60 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 54, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 55.
  • the amino acid sequence of the heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 60.
  • the antibodies of group (v) may comprise a heavy chain of sequence SEQ ID NO: 60.
  • the antibodies of group (v) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 61.
  • the antibodies of group (v) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 61 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56 or a sequence differing from SEQ ID NO: 56 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57 or a sequence differing from SEQ ID NO: 57 by one conservative amino acid substitution.
  • the antibodies of group (v) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 61 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56, a CDR2-L comprising an amino acid sequence of GAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57.
  • the amino acid sequence of the light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 61.
  • the antibodies of group (v) may comprise a light chain of sequence SEQ ID NO: 61.
  • an antibody of group (v) may be the antibody referred to as antibody BK256 in the Examples section.
  • an isolated nucleic acid sequence comprising a sequence encoding an antibody of group (v) of antibodies.
  • variable domain of heavy chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 62.
  • a variable domain of heavy chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 62 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53 or a sequence differing from SEQ ID NO: 53 by one conservative amino acid substitution, a CDR2- H comprising an amino acid sequence of SEQ ID NO: 54 or a sequence differing from SEQ ID NO: 54 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 55 or a sequence differing from SEQ ID NO: 55 by one conservative amino acid substitution.
  • variable domain of heavy chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 62 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 54, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 55.
  • variable domain of heavy chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 62.
  • variable domain of heavy chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 62.
  • variable domain of light chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 63.
  • a variable domain of light chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 63 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56 or a sequence differing from SEQ ID NO: 56 by one conservative amino acid substitution, a CDR2- L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57 or a sequence differing from SEQ ID NO: 57 by one conservative amino acid substitution.
  • a variable domain of light chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 63 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56, a CDR2-L comprising an amino acid sequence of GAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57.
  • variable domain of light chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 63.
  • variable domain of light chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 63.
  • a heavy chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 64.
  • a heavy chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 64 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53 or a sequence differing from SEQ ID NO: 53 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 54 or a sequence differing from SEQ ID NO: 54 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 55 or a sequence differing from SEQ ID NO: 55 by one conservative amino acid substitution.
  • a heavy chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 64 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 53, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 54, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 55.
  • a heavy chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 64.
  • a heavy chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO:
  • a light chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 65.
  • a light chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 65 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56 or a sequence differing from SEQ ID NO: 56 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57 or a sequence differing from SEQ ID NO: 57 by one conservative amino acid substitution.
  • a light chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 65 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 56, a CDR2-L comprising an amino acid sequence of GAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 57.
  • a light chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 65.
  • a light chain of an antibody of group (v) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO:
  • the antibodies of group (v) may (a) bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about 5. Ox 10’ 8 mol/1 (M) or less, and (b) neutralize a BKPyV with an IC50 of about 30.0 nM or less.
  • KD binding affinity
  • the antibodies of group (v) may bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about 5.0xl0 -8 mol/1 (M) or less, or of about 3.0xl0 -8 M or less, or of about 2.0xl0 -8 M or less, or of about l.OxlO -8 M or less, or of about 9.5xl0 -9 M or less, or of about 9.0xl0 -9 M or less, or of about 8.0xl0 -9 M or less, or of about 5.0xl0 -9 M or less, or of about 2.5xl0 -9 M or less, or of about 2.0xl0 -9 M or less, or of about l.OxlO -9 M or less, or of about 8.OxlO 10 M or less, or of about 5.OxlO 10 M or less, or of about 2.5xlO -10 M or less, or of about 2.Ox
  • KD binding affinity
  • the antibodies of group (v) may bind to BKPyV VP1 capsid protein of genotype I BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 1.5xl0 -10 M or less, or of about 1.2xlO -10 M or less.
  • KD binding affinity
  • the antibodies of group (v) may bind to BKPyV VP1 capsid protein of genotype II BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 1.5xl0 -10 M or less, or of about 1.2xlO -10 M or less.
  • KD binding affinity
  • the antibodies of group (v) may bind to BKPyV VP1 capsid protein of genotype III BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 5.0xl0 -8 M or less, or of about 2.0xl0 -8 M or less.
  • KD binding affinity
  • the antibodies of group (v) may bind to BKPyV VP1 capsid protein of genotype IV BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about l.OxlO -8 M or less, or of about 9.5xl0 -9 M or less, or of about 9.3 xlO -9 M or less.
  • KD binding affinity
  • the antibodies of group (v) may neutralize a BKPyV with an IC50 of about 30.0 nM or less, or of about 25.0 nM or less, or of about 20.0 nM or less, or of about 15.0 nM or less, or of about 10.0 nM or less, or of about 5.0 or less, or of about 2.5 nM or less, or of about 1.0 nM or less, or of about 0.8 nM or less, or of about 0.5 nM or less, or of about 0.25 nM or less, or of about 0.15 nM or less, or of about 0.10 nM or less.
  • the antibodies of group (v) may neutralize a BKPyV of genotype I with an IC50 of about 1 nM or less, or of about 0.23 nM or less, or of about 0.11 nM or less.
  • the antibodies of group (v) may neutralize a BKPyV of genotype II with an IC50 of about 8 nM or less, or of about 1 nM or less, or of about 0.79 nM or less.
  • the antibodies of group (v) may neutralize a BKPyV of genotype III with an IC50 of about 30 nM or less, or of about 23.5 nM or less.
  • IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured with a neutralization assay as disclosed in the Examples section.
  • IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured on HEK293 TTT or RS cells as described in the Examples section.
  • the antibodies of group (vi) may comprise a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66 or a sequence differing from SEQ ID NO: 66 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 67 or a sequence differing from SEQ ID NO: 67 by one conservative amino acid substitution, a CDR3- H comprising an amino acid sequence of SEQ ID NO: 68 or a sequence differing from SEQ ID NO: 68 by one conservative amino acid substitution, a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69 or a sequence differing from SEQ ID NO: 69 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DQS or a sequence differing from DQS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70 or a sequence differing from SEQ ID NO: 70 by one conservative amino acid substitution.
  • the CDRs may comprise at least two, or at least 3 conservative amino acid substitution.
  • the antibodies of group (vi) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 71.
  • the antibodies of group (vi) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 71 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66 or a sequence differing from SEQ ID NO: 66 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 67 or a sequence differing from SEQ ID NO: 67 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 68 or a sequence differing from SEQ ID NO: 68 by one conservative amino acid substitution.
  • the antibodies of group (vi) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 71 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 67, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 68.
  • the amino acid sequence of the variable domain of heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 71.
  • the antibodies of group (vi) may comprise a variable domain of heavy chain of sequence SEQ ID NO: 71.
  • the antibodies of group (vi) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 72.
  • the antibodies of group (vi) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 72 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69 or a sequence differing from SEQ ID NO: 69 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DQS or a sequence differing from DQS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70 or a sequence differing from SEQ ID NO: 70 by one conservative amino acid substitution.
  • the antibodies of group (vi) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 72 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69, a CDR2-L comprising an amino acid sequence of DQS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70.
  • the amino acid sequence of the variable domain of light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 72.
  • the antibodies of group (vi) may comprise a variable domain of light chain of sequence SEQ ID NO: 72.
  • the antibodies of group (vi) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 73.
  • the antibodies of group (vi) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 73 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66 or a sequence differing from SEQ ID NO: 66 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 67 or a sequence differing from SEQ ID NO: 67 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 68 or a sequence differing from SEQ ID NO: 68 by one conservative amino acid substitution.
  • the antibodies of group (vi) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 73 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 67, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 68.
  • the amino acid sequence of the heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 73.
  • the antibodies of group (vi) may comprise a heavy chain of sequence SEQ ID NO: 73.
  • the antibodies of group (vi) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 74.
  • the antibodies of group (vi) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 74 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69 or a sequence differing from SEQ ID NO: 69 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DQS or a sequence differing from DQS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70 or a sequence differing from SEQ ID NO: 70 by one conservative amino acid substitution.
  • the antibodies of group (vi) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 74 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69, a CDR2-L comprising an amino acid sequence of DQS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70.
  • the amino acid sequence of the light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 74.
  • the antibodies of group (vi) may comprise a light chain of sequence SEQ ID NO: 74.
  • an antibody of group (vi) may be the antibody referred to as antibody BK293 in the Examples section.
  • variable domain of heavy chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 75.
  • a variable domain of heavy chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 75 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66 or a sequence differing from SEQ ID NO: 66 by one conservative amino acid substitution, a CDR2- H comprising an amino acid sequence of SEQ ID NO: 67 or a sequence differing from SEQ ID NO: 67 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 68 or a sequence differing from SEQ ID NO: 68 by one conservative amino acid substitution.
  • variable domain of heavy chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 75 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 67, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 68.
  • variable domain of heavy chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 75.
  • variable domain of heavy chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 75.
  • variable domain of light chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 76.
  • a variable domain of light chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 76 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69 or a sequence differing from SEQ ID NO: 69 by one conservative amino acid substitution, a CDR2- L comprising an amino acid sequence of DQS or a sequence differing from DQS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70 or a sequence differing from SEQ ID NO: 70 by one conservative amino acid substitution.
  • a variable domain of light chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 76 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69, a CDR2-L comprising an amino acid sequence of DQS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70.
  • variable domain of light chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 76.
  • variable domain of light chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 76.
  • a heavy chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 77.
  • a heavy chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 77 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66 or a sequence differing from SEQ ID NO: 66 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 67 or a sequence differing from SEQ ID NO: 67 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 68 or a sequence differing from SEQ ID NO: 68 by one conservative amino acid substitution.
  • a heavy chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 77 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 66, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 67, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 68.
  • a heavy chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 77.
  • a heavy chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 77.
  • a light chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 78.
  • a light chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 78 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69 or a sequence differing from SEQ ID NO: 69 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of DQS or a sequence differing from DQS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70 or a sequence differing from SEQ ID NO: 70 by one conservative amino acid substitution.
  • a light chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 78 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 69, a CDR2-L comprising an amino acid sequence of DQS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 70.
  • a light chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 78.
  • a light chain of an antibody of group (vi) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 78.
  • the antibodies of group (vi) may (a) bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about lO.OxlO -8 mol/1 (M) or less, and (b) neutralize a BKPyV with an IC50 of about 40.0 nM or less.
  • KD binding affinity
  • the antibodies of group (vi) may bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about lO.OxlO -8 M or less, or of about 8.0xl0 -8 M or less, or of about 6.5xl0 -8 M or less, or of about 5.0xl0 -8 M or less, or of about 3.0xl0 -8 M or less, or of about 2.0xl0 -8 M or less, or of about 1.5xl0 -8 M or less, or of about l.OxlO -8 M or less, or of about 8.0xl0 -9 M or less, or of about 5.0xl0 -9 M or less, or of about 2.5xl0 -9 M or less, or of about 2.0xl0 -9 M or less, or of about 1.5xl0 -9 M or less, or of about l.OxlO -9 M or less, or of about 8.5xl
  • KD binding affinity
  • the antibodies of group (vi) may bind to BKPyV VP1 capsid protein of genotype I BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 9.0xl0 -8 M or less, or of about 7.0xl0 -8 M or less or of about 6.5xl0 -8 M or less.
  • KD binding affinity
  • the antibodies of group (vi) may bind to BKPyV VP1 capsid protein of genotype II BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.5xl0 -9 M or less, or of about 2.0xl0 -9 M or less, or of about 1.6xl0 -9 M or less.
  • KD binding affinity
  • the antibodies of group (vi) may bind to BKPyV VP1 capsid protein of genotype III BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 1.5xl0 -9 M or less, or of about l.OxlO -9 M or less, or of about 8.5xlO -10 M or less.
  • KD binding affinity
  • the antibodies of group (vi) may bind to BKPyV VP1 capsid protein of genotype IV BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.0xl0 -8 M or less, or about 1.5xl0 -8 M or less, or of about 1.3xl0 -8 M or less.
  • KD binding affinity
  • the antibodies of group (vi) may neutralize a BKPyV with an IC50 of about 40.0 nM or less, or of about 35.0 nM or less, or of about 30.0 nM or less, or of about 15.0 nM or less, or of about 10.0 nM or less, or of about 5.0 or less, or of about 2.5 nM or less, or of about 2 nM or less, or of about 1.5 nM or less, or of about 1.0 nM or less, or of about 0.8 nM or less, or of about 0.5 nM or less, or of about 0.3 nM or less, or of about 0.2 or less, or of about 0.15 nM or less, or of about 0.10 nM or less, or of about 0.08 nM or less, or of about 0.05 nM or less, or of about 0.03 nM or less, or of about 0.01 nM or less.
  • the antibodies of group (vi) may neutralize a BKPyV of genotype II with an IC50 of about 0.5 nM or less, or of about 0.3 nM or less, or of about 0.24 nM or less, or of about 0.05 nM or less, or of about 0.03 nM or less.
  • the antibodies of group (vi) may neutralize a BKPyV of genotype III with an IC50 of about 0.5 nM or less, or of about 0.3 nM or less, or of about 0.27 nM or less, or of about 0.25 nM or less.
  • the antibodies of group (vi) may neutralize a BKPyV of genotype IV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence, with an IC50 of about 40 nM or less, or of about 35.0 nM or less, or of about 32.0 nM or less.
  • the IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured on HEK293 TTT or RS cells as described in the Examples section.
  • IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured with a neutralization assay as disclosed in the Examples section.
  • the group (vii) of antibodies is illustrated by the antibody BK304 of the Example section.
  • the antibodies of group (vii) may comprise a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79 or a sequence differing from SEQ ID NO: 79 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 80 or a sequence differing from SEQ ID NO: 80 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81 or a sequence differing from SEQ ID NO: 81 by one conservative amino acid substitution, a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82 or a sequence differing from SEQ ID NO: 82 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83 or a sequence differing from SEQ ID NO: 83 by one conservative amino acid substitution.
  • the conservative amino acid substitution may be as above described.
  • the antibodies of group (vii) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 84.
  • the antibodies of group (vii) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 84 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79 or a sequence differing from SEQ ID NO: 79 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 80 or a sequence differing from SEQ ID NO: 80 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81 or a sequence differing from SEQ ID NO: 81 by one conservative amino acid substitution.
  • the antibodies of group (vii) may comprise a variable domain of heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 84 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 80, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81.
  • the amino acid sequence of the variable domain of heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 84.
  • the antibodies of group (vii) may comprise a variable domain of heavy chain of sequence SEQ ID NO: 84.
  • the antibodies of group (vii) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 85.
  • the antibodies of group (vii) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 85 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82 or a sequence differing from SEQ ID NO: 82 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83 or a sequence differing from SEQ ID NO: 83 by one conservative amino acid substitution.
  • the antibodies of group (vii) may comprise a variable domain of light chain of sequence at least about 85% identical to sequence SEQ ID NO: 85 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82, a CDR2-L comprising an amino acid sequence of GAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83.
  • the amino acid sequence of the variable domain of light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 85.
  • the antibodies of group (vii) may comprise a variable domain of light chain of sequence SEQ ID NO: 85.
  • the antibodies of group (vii) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 86.
  • the antibodies of group (vii) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 86 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79 or a sequence differing from SEQ ID NO: 79 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 80 or a sequence differing from SEQ ID NO: 80 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81 or a sequence differing from SEQ ID NO: 81 by one conservative amino acid substitution.
  • the antibodies of group (vii) may comprise a heavy chain of sequence at least about 85% identical to sequence SEQ ID NO: 86 and a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 80, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81.
  • the amino acid sequence of the heavy chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 86.
  • the antibodies of group (vii) may comprise a heavy chain of sequence SEQ ID NO: 86.
  • the antibodies of group (vii) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 87.
  • the antibodies of group (vii) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 87 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82 or a sequence differing from SEQ ID NO: 82 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution, and a CDR3-L Ill comprising an amino acid sequence of SEQ ID NO: 83 or a sequence differing from SEQ ID NO: 83 by one conservative amino acid substitution.
  • the antibodies of group (vii) may comprise a light chain of sequence at least about 85% identical to sequence SEQ ID NO: 87 and a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82, a CDR2-L comprising an amino acid sequence of GAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83.
  • the amino acid sequence of the light chain may have at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to sequence SEQ ID NO: 87.
  • the antibodies of group (vii) may comprise a light chain of sequence SEQ ID NO: 87.
  • an antibody of group (vii) may be the antibody referred to as antibody BK304 in the Examples section.
  • variable domain of heavy chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 88.
  • a variable domain of heavy chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 88 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79 or a sequence differing from SEQ ID NO: 79 by one conservative amino acid substitution, a CDR2- H comprising an amino acid sequence of SEQ ID NO: 80 or a sequence differing from SEQ ID NO: 80 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81 or a sequence differing from SEQ ID NO: 81 by one conservative amino acid substitution.
  • variable domain of heavy chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 88 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 80, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81.
  • variable domain of heavy chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 88.
  • variable domain of heavy chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 88.
  • variable domain of light chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 89.
  • a variable domain of light chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 89 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82 or a sequence differing from SEQ ID NO: 82 by one conservative amino acid substitution, a CDR2- L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83 or a sequence differing from SEQ ID NO: 83 by one conservative amino acid substitution.
  • a variable domain of light chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 89 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82, a CDR2-L comprising an amino acid sequence of GAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83.
  • variable domain of light chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 89.
  • variable domain of light chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 89.
  • a heavy chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 90.
  • a heavy chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 90 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79 or a sequence differing from SEQ ID NO: 79 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 80 or a sequence differing from SEQ ID NO: 80 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81 or a sequence differing from SEQ ID NO: 81 by one conservative amino acid substitution.
  • a heavy chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 90 and nucleic acid sequences coding: a CDR1-H comprising an amino acid sequence of SEQ ID NO: 79, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 80, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 81.
  • a heavy chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 90.
  • a heavy chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 90.
  • a light chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 91.
  • a light chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 91 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82 or a sequence differing from SEQ ID NO: 82 by one conservative amino acid substitution, a CDR2-L comprising an amino acid sequence of GAS or a sequence differing from GAS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83 or a sequence differing from SEQ ID NO: 83 by one conservative amino acid substitution.
  • a light chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 85% identical to a nucleic acid of sequence SEQ ID NO: 91 and nucleic acid sequences coding: a CDR1-L comprising an amino acid sequence of SEQ ID NO: 82, a CDR2-L comprising an amino acid sequence of GAS, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 83.
  • a light chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of a sequence at least about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid of sequence SEQ ID NO: 91.
  • a light chain of an antibody of group (vii) of antibodies may be encoded by a nucleic acid sequence comprising a nucleic acid of sequence SEQ ID NO: 91.
  • the antibodies of group (vii) may (a) bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.0x1 O’ 9 mol/1 (M) or less, and (b) neutralize a BKPyV with an IC50 of about 25.0 nM or less.
  • KD binding affinity
  • the antibodies of group (vii) may bind to BKPyV VP1 capsid protein with a binding affinity (KD), for example measured by surface plasmon resonance, of about 5.0xl0 -9 M or less, or of about 2.5xl0 -9 M or less, or of about 2.0xl0 -9 M or less, or of about 1.5xl0 -9 M or less, or of about l.OxlO -9 M or less, or of about 9.OxlO 10 M or less, or of about 8.OxlO 10 M or less, or of about 5.OxlO 10 M or less, or of about 4.OxlO 10 M or less, or of about 3.OxlO 10 M or less, or of about 2.OxlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (vii) may bind to BKPyV VP1 capsid protein of genotype I BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 5.OxlO 10 M or less, or of about 3.2xlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (vii) may bind to BKPyV VP1 capsid protein of genotype II BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2.0xl0 -9 M or less, or of about 1.3xl0 -9 M or less.
  • the antibodies of group (vii) may bind to BKPyV VP1 capsid protein of genotype III BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 2xl0 -9 M or less, or of about 1.6xl0 -9 M or less.
  • the antibodies of group (vii) may bind to BKPyV VP1 capsid protein of genotype IV BKPyV with a binding affinity (KD), for example measured by surface plasmon resonance, of about 9.OxlO 10 M or less, or of about 7.6xlO 10 M or less.
  • KD binding affinity
  • the antibodies of group (vii) may neutralize a BKPyV with an IC50 of about 25.0 nM or less, or of about 22.5 nM or less, or of about 20.0 nM or less, or of about 18.0 nM or less, or of about 15.0 nM or less, or of about 10.0 nM or less, or of about 8.0 nM or less, or of about 5.0 nM or less, or of about 2.5 nM or less, or of about 2.0 nM or less, or of about 1.5 nM or less, or of about 1.0 nM or less, or of about 0.80 nM or less, or of about 0.50 nM or less, or of about 0.35 nM or less, or of about 0.25 nM or less, or of about 0.12 nM or less, or of about 0.10 nM or less, or of about 0.08 nM or less, or of about 0.06 nM or less, or of about 0.04 nM
  • the antibodies of group (vii) may neutralize a BKPyV of genotype I with an IC50 of about 15.3 nM or less, or of about 10.0 nM or less, or of about 8.0 nM or less, or of about 6.2 nM or less, or of about 6.0 nM or less, or of about 2.5 nM or less, or of about 1.0 nM or less, or of about 0.8 nM or less, or of about 0.5 nM or less, or of about 0.25 nM or less, or of about 0.10 nM or less, or of about 0.05 nM or less, or of about 0.03 nM or less, or of about 0.02 nM or less, or of about 0.01 nM or less.
  • the antibodies of group (vii) may neutralize a BKPyV of genotype I comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96 or 97, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences, with an IC50 of about 0.5 nM or less, or of about 0.25 nM or less, or of about 0.23 nM or less, or of about 0.1 nM or less.
  • the antibodies of group (vii) may neutralize a BKPyV of genotype II with an IC50 of about 25 nM or less, or of about 21 nM or less.
  • the antibodies of group (vii) may neutralize a BKPyV of genotype III with an IC50 of about 15 nM or less, or of about 13.5 nM or less, or about 13 nM or less.
  • the antibodies of group (vii) may neutralize a BKPyV of genotype IV with an IC50 of about 2.5 nM or less, or of about 2.0 nM or less, or of about 1.8 nM or less, or of about 1.6 nM or less, or of about 1.5 nM or less, or of about 1.0 nM or less, or of about 0.8 nM or less, or of about 0.5 nM or less, or of about 0.3 nM or less, or of about 0.28 nM or less, or about 0.2 nM or less, or of about 0.10 nM or less.
  • the antibodies of group (vii) may neutralize a BKPyV of genotype IV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence, with an IC50 of about 1 nM or less, or of about 0.5 nM or less, or of about 0.1 nM or less, or of about 0.08 nM or less, or of about 0.06 nM or less.
  • the IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured on HEK293 TTT or RS cells as described in the Examples section.
  • IC50 of the inhibition or neutralization effect of the antibodies disclosed herein may be measured with a neutralization assay as disclosed in the Examples section.
  • the inventors have surprisingly demonstrated that a combination of at least two of the antibodies described herein induced an improve neutralizing activity against the BKPyV.
  • the combinations of antibodies may efficiently neutralize BKPyV escaping neutralization by the benchmark antibody 41F17.
  • a combination of antibodies may comprise at least a first antibody and a second antibody, or antigen-binding fragments thereof.
  • the first antibody, or antigen-binding fragment thereof, and the second antibody, or antigen-binding fragment thereof may be selected among the antibodies of groups (i) to (vii) described herein.
  • a first antibody is selected from a first group of antibodies selected from groups (i) to (vii) of antibodies and a second antibody is selected from a second group of antibodies selected from groups (i) to (vii) of antibodies, the first and second groups of antibodies being different.
  • the antibodies of a combination of antibodies may bind to distinct VP1 capsid proteins from, for example, from at least two distinct BKPyV genotypes, serotypes, or variants.
  • the antibodies of a combination of antibodies may bind to a same VP1 capsid protein, but on distinct epitopes of a same VP1 capsid protein, for example on at least two distinct epitopes of a same VP1 capsid protein.
  • a combination of at least two antibodies disclosed herein may neutralize a
  • a combination of at least two antibodies disclosed herein may neutralize a
  • a combination of at least two antibodies disclosed herein may neutralize a
  • a combination of at least two antibodies disclosed herein may neutralize a
  • a combination of at least two antibodies disclosed herein may neutralize a BKPyV of genotype I-IV with an IC50 of about 70 nM or less, or of about 68 nM or less, or of about 65 nM or less, or of about 62 nM or less, or of about 60 nM or less, or of about 58 nM or less, or of about 55 nM or less, or of about 52 nM or less, or of about 50 nM or less, or of about 45 nM or less, or of about 40 nM or less, or of about 30 nM or less, or of about 20 nM or less, or of about 15 nM or less, or of about 10 nM or less, or of about 8 nM or less, or of about 5 nM or less, or of about 2.5 nM or less, or of about 2 nM or less, or of about 1 nM or less, or of about 0.9 nM or less, or of about 0.8 n
  • a combination of at least two antibodies disclosed herein may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences.
  • a combination of at least two antibodies disclosed herein may neutralize a BKPyV of genotype I comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96 or 97, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences.
  • a combination of at least two antibodies disclosed herein may neutralize a BKPyV of genotype IV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence.
  • a combination of at least two antibodies disclosed herein may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 70 nM or less.
  • a combination of at least two antibodies disclosed herein may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 ranging from about 70 nM or less to about 0.1 nM or less.
  • a combination of at least two antibodies disclosed herein may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 70 nM or less, or of about 68 nM or less, or of about 65 nM or less, or of about 62 nM or less, or of about 60 nM or less, or of about 58 nM or less, or of about 55 nM or less, or of about 52 nM or less, or of about 50 nM or less, or of about 45 nM or less, or of about 40 nM or less, or of about 30 nM or less, or of about 20 nM or less, or of about 15 nM or less, or of about 10 nM or less, or of about 8 nM or less, or of about 6 nM or less, or
  • a combination of at least two antibodies disclosed herein may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96 or 97, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 5 nM or less, or of about 4 nM or less, or of about 3 nM or less, or of about 2.5 nM or less, or of about 2 nM or less, or of about 1 nM or less, or of about 0.9 nM or less, or of about 0.8 nM or less, or of about 0.7 nM or less, or of about 0.6 nM or less, or of about 0.5 nM or less, or of about 0.4 nM or less, or of about 0.3 nM or less, or of about 0.2 nM or less, or of about 0.1 nM or less.
  • a combination of at least two antibodies disclosed herein may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 6 nM or less, or of about 5 nM or less, or of about 4 nM or less, or of about 3 nM or less, or of about 2.5 nM or less, or of about 2 nM or less, or of about 1 nM or less, or of about 0.9 nM or less, or of about 0.8 nM or less, or of about 0.7 nM or less, or of about 0.6 nM or less, or of about 0.5 nM or less, or of about 0.4 nM or less, or of about 0.3 nM or less, or of about 0.2 nM or less.
  • a combination of at least two antibodies disclosed herein may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence, with an ICsoof about 70 nM or less, or of about 68 nM or less, or of about 65 nM or less, or of about 62 nM or less, or of about 60 nM or less, or of about 58 nM or less, or of about 55 nM or less, or of about 52 nM or less, or of about 50 nM or less, or of about 45 nM or less, or of about 40 nM or less, or of about 30 nM or less, or of about 20 nM or less, or of about 15 nM or less, or of about 10 nM or less, or of about 8 nM or less, or of about 6 nM or less, or of about 4 nM or less
  • a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101 may be selected among BKPyV g!b2-D58delP59A, BKPyV g!b2-E61K and BKPyV gIVc2-E327K.
  • a combination of antibodies may comprise:
  • a combination of antibodies may comprise:
  • a combination of antibodies may comprise:
  • a combination of antibodies may comprise:
  • a combination of antibodies may comprise:
  • a combination of antibodies may comprise as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (iv) of antibodies.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (iv) of antibodies, may neutralize a BKPyV of genotype I-IV with an IC50 of about 60 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (iv) of antibodies, may neutralize a BKPyV of genotype I-IV with an IC50 ranging from about 60 nM or less to about 0.01 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (iv) of antibodies, may neutralize a BKPyV of wildtype genotype I-IV with an IC50 ranging from about 1 nM or less to about 0.01 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (iv) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 60 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (iv) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 ranging from about 60 nM or less to about 0.1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (iv) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96 or 97, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 5 nM or less, or of about 4 nM or less, or of about 3 nM or less, or of about 2.27 nM or less, or of about 1 nM or less, or of about 0.5 nM or less, or of about 0.36 nM or less, or of about 0.1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (iv) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 3 nM or less, or of about 2.5 nM or less, or of about 2.2 nM or less, or of about 1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (iv) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 60 nM or less, or of about 55 nM or less, or of about 52 nM or less, or of about 50 nM or less, or of about 45 nM or less.
  • a combination of antibodies may comprise:
  • a combination of antibodies may comprise:
  • an antibody selected from group (iv) of antibodies comprising a variable domain of heavy chain of sequence SEQ ID NO: 45 or a sequence at least 85% identical thereto and/or a variable domain of light chain of sequence SEQ ID NO: 46, or a sequence at least 85% identical thereto.
  • a combination of antibodies may comprise:
  • an antibody selected from group (iv) of antibodies comprising a heavy chain of sequence SEQ ID NO: 47 or a sequence at least 85% identical thereto and/or a light chain of sequence SEQ ID NO: 48, or a sequence at least 85% identical thereto.
  • a combination of antibodies may comprise as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (iv) of antibodies, may comprise as a first antibody, the antibody BK120, and as a second antibody, the antibody BK206.
  • a combination of antibodies may comprise as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV of genotype I-IV with an IC50 of about 70 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV of genotype I-IV with an IC50 ranging from about 70 nM or less to about 0.01 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV of wildtype genotype I-IV with an IC50 ranging from about 1 nM or less to about 0.01 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 70 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 ranging from about 70 nM or less to about 0.1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96 or 97, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 5 nM or less, or of about 3 nM or less, or of about 4 nM or less, or of about 1 nM or less, or of about 0.5 nM or less, or of about 0.4 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 5 nM or less, or of about 4 nM or less, or of about 3.4 nM or less, or of about 2.5 nM or less, or of about 2 nM or less, or of about 1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 70 nM or less, or of about 65 nM or less, or of about 60 nM or less, or of about 55 nM or less.
  • a combination of antibodies may comprise:
  • a combination of antibodies may comprise:
  • an antibody selected from group (vi) of antibodies comprising a variable domain of heavy chain of sequence SEQ ID NO: 71 or a sequence at least 85% identical thereto and/or a variable domain of light chain of sequence SEQ ID NO: 72, or a sequence at least 85% identical thereto.
  • a combination of antibodies may comprise:
  • an antibody selected from group (vi) of antibodies comprising a heavy chain of sequence SEQ ID NO: 73 or a sequence at least 85% identical thereto and/or a light chain of sequence SEQ ID NO: 74, or a sequence at least 85% identical thereto.
  • a combination of antibodies may comprise as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may comprise as a first antibody, the antibody BK120, and as a second antibody, the antibody BK293.
  • a combination of antibodies may comprise as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vii) of antibodies.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vii) of antibodies, may neutralize a BKPyV of genotype I-IV with an IC50 of about 1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vii) of antibodies, may neutralize a BKPyV of genotype I-IV with an IC50 ranging from about 1 nM or less to about 0.01 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vii) of antibodies, may neutralize a BKPyV of wildtype genotype I-IV with an IC50 ranging from about 0.5 nM or less to about 0.01 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vii) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vii) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 ranging from about 1 nM or less to about 0.1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vii) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96 or 97, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 1 nM or less, or of about 0.9 nM or less, or of about 0.8 nM or less, or of about 0.7 nM or less, or of about 0.6 nM or less, or of about 0.5 nM or less, or of about 0.4 nM or less, or of about 0.3 nM or less, or of about 0.2 nM or less, or of about 0.1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vii) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 1 nM or less, or of about 0.8 nM or less, or of about 0.6 nM or less, or of about 0.5 nM or less, or of about 0.39 nM or less, or of about 0.3 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vii) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 1 nM or less, or of about 0.9 nM or less, or of about 0.8 nM or less, or of about 0.7 nM or less, or of about 0.6 nM or less, or of about 0.5 nM or less, or of about 0.4 nM or less, or of about 0.3 nM or less, or of about 0.2 nM or less, or of about 0.16 nM or less, or of about 0.1 nM or less, or of about 0.05 nM or less.
  • a combination of antibodies may comprise:
  • a combination of antibodies may comprise:
  • an antibody selected from group (vii) of antibodies comprising a variable domain of heavy chain of sequence SEQ ID NO: 84 or a sequence at least 85% identical thereto and/or a variable domain of light chain of sequence SEQ ID NO: 85, or a sequence at least 85% identical thereto.
  • a combination of antibodies may comprise:
  • an antibody selected from group (vii) of antibodies comprising a heavy chain of sequence SEQ ID NO: 86 or a sequence at least 85% identical thereto and/or a light chain of sequence SEQ ID NO: 87, or a sequence at least 85% identical thereto.
  • a combination of antibodies may comprise as a first antibody, an antibody selected from group (i) of antibodies, and as a second antibody, an antibody selected from group (vii) of antibodies, may comprise as a first antibody, the antibody BK120, and as a second antibody, the antibody BK304.
  • a combination of antibodies may comprise as a first antibody, an antibody selected from group (iv) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (iv) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV of genotype I-IV with an IC50 of about 40 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (iv) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV of genotype I-IV with an IC50 ranging from about 40 nM or less to about 0.1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (iv) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV of wildtype genotype I-IV with an IC50 ranging from about 5 nM or less to about 0.1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (iv) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 40 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (iv) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 ranging from about 40 nM or less to about 1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (iv) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96 or 97, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an ICsoof about 10 nM or less, or of about 9 nM or less, or of about 8 nM or less, or of about 7 nM or less, or of about 6 nM or less, or of about 5 nM or less, or of about 4 nM or less, or of about 3 nM or less, or of about 2 nM or less, or of about 1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (iv) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 8 nM or less, or of about 7 nM or less, or of about 6 nM or less, or of about 5 nM or less, or of about 4 nM or less, or of about 3 nM or less, or of about 2 nM or less, or of about 1 nM or less.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (iv) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences with an IC50 of about 40 nM or less, or of about 38 nM or less, or of about 35 nM or less, or of about 32 nM or less, or of about 30nM or less, or of about 25 nM or less.
  • a combination of antibodies may comprise: [0819] - as a first antibody, an antibody selected from group (iv) of antibodies comprising a CDR1-H comprising an amino acid sequence of SEQ ID NO: 40 or a sequence differing from SEQ ID NO: 40 by one conservative amino acid substitution, a CDR2-H comprising an amino acid sequence of SEQ ID NO: 41 or a sequence differing from SEQ ID NO: 41 by one conservative amino acid substitution, a CDR3-H comprising an amino acid sequence of SEQ ID NO: 42 or a sequence differing from SEQ ID NO: 42 by one conservative amino acid substitution, a CDR1-L comprising an amino acid sequence of SEQ ID NO: 43 or a sequence differing from SEQ ID NO: 43 by one conservative amino acid substitution, a CDR2- L comprising an amino acid sequence of LGS or a sequence differing from LGS by one conservative amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO: 44 or a sequence differing from SEQ ID NO
  • a combination of antibodies may comprise:
  • an antibody selected from group (vi) of antibodies comprising a variable domain of heavy chain of sequence SEQ ID NO: 71 or a sequence at least 85% identical thereto and/or a variable domain of light chain of sequence SEQ ID NO: 72, or a sequence at least 85% identical thereto.
  • a combination of antibodies may comprise: [0825] - as a first antibody, an antibody selected from group (iv) of antibodies comprising a heavy chain of sequence SEQ ID NO: 47 or a sequence at least 85% identical thereto and/or a light chain of sequence SEQ ID NO: 48, or a sequence at least 85% identical thereto, and
  • an antibody selected from group (vi) of antibodies comprising a heavy chain of sequence SEQ ID NO: 73 or a sequence at least 85% identical thereto and/or a light chain of sequence SEQ ID NO: 74, or a sequence at least 85% identical thereto.
  • a combination of antibodies may comprise as a first antibody, an antibody selected from group (iv) of antibodies, and as a second antibody, an antibody selected from group (vi) of antibodies, may comprise as a first antibody, the antibody BK206, and as a second antibody, the antibody BK293.
  • a combination of antibodies may comprise as a first antibody, an antibody selected from group (ii) of antibodies, and as a second antibody, an antibody selected from group (iii) of antibodies.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (ii) of antibodies, and as a second antibody, an antibody selected from group (iii) of antibodies, may neutralize a BKPyV of genotype I-IV.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (ii) of antibodies, and as a second antibody, an antibody selected from group (iii) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, 97 or 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (ii) of antibodies, and as a second antibody, an antibody selected from group (iii) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96 or 97, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequences.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (ii) of antibodies, and as a second antibody, an antibody selected from group (iii) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 96, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence.
  • a combination of antibodies comprising as a first antibody, an antibody selected from group (ii) of antibodies, and as a second antibody, an antibody selected from group (iii) of antibodies, may neutralize a BKPyV comprising a VP1 capsid protein of amino acid sequence SEQ ID NO: 101, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence.
  • a combination of antibodies may comprise:
  • a combination of antibodies may comprise:
  • an antibody selected from group (iii) of antibodies comprising a variable domain of heavy chain of sequence SEQ ID NO: 32 or a sequence at least 85% identical thereto and/or a variable domain of light chain of sequence SEQ ID NO: 33, or a sequence at least 85% identical thereto.
  • a combination of antibodies may comprise:
  • an antibody selected from group (iii) of antibodies comprising a heavy chain of sequence SEQ ID NO: 34 or a sequence at least 85% identical thereto and/or a light chain of sequence SEQ ID NO: 35, or a sequence at least 85% identical thereto.
  • a combination of antibodies may comprise as a first antibody, an antibody selected from group (ii) of antibodies, and as a second antibody, an antibody selected from group (iii) of antibodies, may comprise as a first antibody, the antibody B KI 60-1, and as a second antibody, the antibody BK198.
  • the antibodies may be provided as separate antibodies or as multi-specific antibodies where the antibodies are joined together.
  • Multi-specific antibodies refers to monoclonal antibodies that have binding specificities for at least two different epitopes of one antigen or for at least two distinct antigens.
  • a multi-specific antibody may be a bispecific antibody.
  • multi-specific antibodies are described in US20090232811, US9382323, US9890204 or US8796424.
  • a multi-specific antibodies may be a bispecific antibodies.
  • bispecific antibodies refers to molecules which combine the antigen-binding sites of two antibodies within a single molecule. Thus, a bispecific antibody is able to bind two different antigens or to two distinct epitopes of a same antigen, simultaneously. The distinct epitope may be overlapping epitopes or non-overlapping epitopes.
  • Multi-specific or bispecific antibodies can be prepared as full-length antibodies or antibody fragments.
  • the multi-specific or bispecific antibody described herein may comprise a combination of antibodies as described herein.
  • the multi-specific or bispecific antibody may be an isolated or a recombinant bispecific antibody.
  • a multi-specific or a bispecific antibody may comprise at least a first antibody, or an antigen-binding fragment thereof, and at least a second antibody, or an antigen-binding fragment thereof, joined to each other, wherein said first and second antibodies may be selected among the antibodies of groups (i) to (vii) described herein.
  • a multi-specific or a bispecific may comprise:
  • a multi-specific or a bispecific may comprise:
  • a multi-specific antibody is a bispecific antibody.
  • An antibody of the multi-specific or a bispecific antibody can be linked to or coexpressed with another antibody by any known techniques in the art.
  • an antibody or fragment thereof can be functionally linked, e.g., by chemical coupling, genetic fusion, noncovalent association or otherwise, to one or more other antibody or antibody fragment to produce a bispecific or a multispecific antibody.
  • bispecific formats that can be used include, without limitation, e.g., scFv-based or diabody bispecific formats, IgG-scFv fusions, dual variable domain (DVD)-Ig, Quadroma, knobs-into-holes, common light chain (e.g., common light chain with knobs-into-holes, etc.), CrossMab, CrossFab, (SEED)body, leucine zipper, Duobody, IgGl/IgG2, dual acting Fab (DAF)-IgG, and Mab2 bispecific formats.
  • Immunoconj ugates e.g., scFv-based or diabody bispecific formats, IgG-scFv fusions, dual variable domain (DVD)-Ig, Quadroma, knobs-into-holes, common light chain (e.g., common light chain with knobs-into-holes, etc.), CrossMab, CrossFab, (SEED)body, leu
  • An immunoconjugate comprising an antibody, or a fragment thereof, as disclosed herein may prepared according to any known methods in the art.
  • An antibody, or a fragment thereof, may be conjugated or linked to detectable label or reporter molecule.
  • Such immunoconjugate may be used as a diagnostic tool for detecting and/or measuring a BKPyV infection in a subject in need thereof.
  • a detectable label or reporter molecule can be a radioisotope, such as 3 H, 14 C, 32 P, 35 S, or 125 I; a fluorescent or chemiluminescent moiety such as fluorescein isothiocyanate, or rhodamine; or an enzyme such as alkaline phosphatase, P-galactosidase, horseradish peroxidase, or luciferase.
  • a radioisotope such as 3 H, 14 C, 32 P, 35 S, or 125 I
  • a fluorescent or chemiluminescent moiety such as fluorescein isothiocyanate, or rhodamine
  • an enzyme such as alkaline phosphatase, P-galactosidase, horseradish peroxidase, or luciferase.
  • the term “labeled”, with regard to the antibody according to the disclosure, is intended to encompass direct labeling of the antibody by coupling (i.e., physically linking) a detectable substance, such as a radioactive agent or a fluorophore (e.g. fluorescein isothiocyanate (FITC) or phycoerythrin (PE) or Indocyanine (Cy5)) to the polypeptide, as well as indirect labeling of the polypeptide by reactivity with a detectable substance.
  • a detectable substance such as a radioactive agent or a fluorophore (e.g. fluorescein isothiocyanate (FITC) or phycoerythrin (PE) or Indocyanine (Cy5)
  • radioactive molecules include but are not limited radioactive atom for scintigraphic studies such as 3 H, 14 C, 32 P, 35 S, I 123 , I 124 , or 125 I, In 111 , Re 186 , Re 188 , Tc".
  • Polypeptides of the invention may be also labelled with a spin label for nuclear magnetic resonance (NMR) imaging (also known as magnetic resonance imaging, MRI), such as iodine- 123, indium-ill, fluorine-19, carbon-13, nitrogen-15, oxygen-17, gadolinium, manganese or iron.
  • NMR nuclear magnetic resonance
  • MRI magnetic resonance imaging
  • immunoconjugates according to the present invention can be prepared as described in the application W02004/091668.
  • the antibodies may be covalently attached, directly or via a cleavable or non- cleavable linker, to at least one detectable probe.
  • Linker means a chemical moiety comprising a covalent bond or a chain of atoms that covalently attaches a polypeptide to a detectable probe.
  • the conjugates may be prepared by in vitro methods.
  • a linking group is used. Suitable linking groups are well known in the art and include disulfide groups, thioether groups, acid labile groups, photolabile groups, peptidase labile groups and esterase labile groups.
  • Conjugation of an antibody of the invention with a detectable probe may be made using a variety of bifunctional protein coupling agents including but not limited to N-succinimidyl pyridyldithiobutyrate (SPDB), butanoic acid 4-[(5- nitro-2-pyridinyl)dithio]-2,5-dioxo-l-pyrrolidinyl ester (nitro-SPDB), 4-(Pyridin-2- yldisulfanyl)-2-sulfo-butyric acid (sulfo-SPDB), N-succinimidyl (2-pyridyldithio) propionate (SPDP), succinimidyl (N-maleimidomethyl) cyclohexane- 1 -carboxylate (SMCC), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimid
  • a ricin immunotoxin can be prepared as described in Vitetta et al (1987).
  • Carbon labeled 1- isothiocyanatobenzyl methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody (WO 94/11026).
  • the linker may be a “cleavable linker” or a “non-cleavable linker” (for example SMCC linker).
  • a fusion protein comprising an antibody disclosed herein and a detectable probe may be made, by recombinant techniques or peptide synthesis.
  • the length of DNA may comprise respective regions encoding the two portions of the conjugate either adjacent one another or separated by a region encoding a linker peptide which does not destroy the desired properties of the conjugate.
  • a conjugate can be obtained by a process comprising the steps of:
  • the aqueous solution of cell-binding agent can be buffered with buffers such as, e.g. potassium phosphate, acetate, citrate or N-2-Hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes buffer).
  • buffers such as, e.g. potassium phosphate, acetate, citrate or N-2-Hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes buffer).
  • the reaction temperature is usually comprised between 20 and 40° C.
  • the reaction time can vary from 1 to 24 hours.
  • the reaction between the antibody and the detectable probe can be monitored by size exclusion chromatography (SEC) with a refractometric and/or UV detector. If the conjugate yield is too low, the reaction time can be extended.
  • SEC size exclusion chromatography
  • the conjugate can be purified e.g. by SEC, adsorption chromatography (such as ion exchange chromatography, IEC), hydrophobic interaction chromatograhy (HIC), affinity chromatography, mixed-support chromatography such as hydroxyapatite chromatography, or high performance liquid chromatography (HPLC). Purification by dialysis or diafiltration can also be used.
  • SEC adsorption chromatography
  • IEC hydrophobic interaction chromatograhy
  • HPLC high performance liquid chromatography
  • the term “aggregates” means the associations which can be formed between two or more antibodies, being modified or not by conjugation.
  • the aggregates can be formed under the influence of a great number of parameters, such as a high concentration of cell-binding agent in the solution, the pH of the solution, high shearing forces, the number of bonded dimers and their hydrophobic character, the temperature (see Wang & Gosh, 2008, J. Membrane Sci., 318: 311-316, and references cited therein); note that the relative influence of some of these parameters is not clearly established.
  • the person skilled in the art will refer to Cromwell et al. (2006, AAPS Journal, 8(3): E572-E579).
  • the content in aggregates can be determined with techniques well known to the skilled person, such as SEC (see Walter et al., 1993, Anal. Biochem., 212(2): 469-480).
  • step (i) or (ii) the conjugate-containing solution can be submitted to an additional step (iii) of chromatography, ultrafiltration and/or diafiltration.
  • the present disclosure relates to a use of a BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96, or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence for screening a candidate antibody able to neutralize a BKPy virus.
  • the present disclosure relates to in vitro methods for screening a candidate antibody or a candidate combination of antibodies able to neutralize a BKPy.
  • An in vitro method for screening a candidate antibody may be used to screen antibodies able to neutralize a BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96 or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence.
  • An in vitro method for screening a candidate antibody able to neutralize a BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96 or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence may comprise at least the steps of:
  • the infected cells may be counted, and the obtained value is compared to, or normalized with, the value obtained with cultured cells infected with said virus in the absence of the candidate antibody.
  • An in vitro method for screening a candidate combination of antibodies able to neutralize a BKPy virus may comprise at least the steps of:
  • a number of infected cells obtained at step (a) lower than the number of cells obtained at step (b) may indicative of a neutralizing activity of said candidate combination.
  • the virus may be a BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96 or comprising a VP1 sequence comprising an amino acid sequence having at least about 90% identity with said sequence.
  • a BKPy virus comprising a VP1 protein of amino acid sequence SEQ ID NO: 96 may be BKPyV-D58DelP59A.
  • the methods may be carried out with a virus, or a pseudotype virus (generally referred as viral particles). Methods for preparing virus-like particles and pseudotype virus are known in the art. [0899]
  • the antibodies to be screened may be placed in contact with the viral particles before adding the viral particles and the antibody to the cultured cells.
  • the antibodies to be screened may be placed in contact with the cultured cells before addition of the viral particles.
  • the antibodies to be screened may be placed in contact with the cultured cells after addition of the viral particles to the cells.
  • a serial dilution of a predetermined amount of infecting viral particles may be used to infect cultured cells.
  • a 2-, 3-, 4-, 5-, 6- , 7-fold dilution may be used.
  • Useable cells may be HEK293 TTT cells or RS cells.
  • the neutralization activity of the antibodies may be expressed as an IC50.
  • virus infection of target cells in vitro may be measured by immunofluorescence analysis using markers for intracellular BKPyV antigen expression as disclosed in, for example, Moriyama T, Sorokin A. Curr Protoc Cell Biol. 2009 Mar;Chapter 26:Unit 26.2.
  • An antibody disclosed herein may be produced by any technique known in the art, such as, without limitation, any chemical, biological, genetic, or enzymatic technique, either alone or in combination.
  • an antibody can be synthesized by recombinant DNA techniques well-known in the art.
  • an antibody can be obtained as DNA expression products after incorporation of DNA sequences encoding the antibody into expression vectors and introduction of such vectors into suitable eukaryotic or prokaryotic host cells that will express the desired antibody, from which it can be later isolated using well-known techniques, such as described in the Examples.
  • Another aspect of the present disclosure relates to a method for producing an antibody binding a BK polyomavirus (BKPyV) VP1 capsid protein, or an antigen-binding fragment thereof, comprising at least the steps of culturing a host cell transformed by a nucleic acid sequence encoding an antibody disclosed herein, or by an expression vector comprising such nucleic acid, in a culture medium under conditions suitable for producing said antibody or fragment thereof and recovering the antibody or fragment thereof from said cultured cells.
  • a method for producing an antibody binding a BK polyomavirus (BKPyV) VP1 capsid protein, or an antigen-binding fragment thereof implements culture medium suitable for producing said antibody or fragment.
  • the cell culture medium under conditions suitable for producing said antibody or antigen-binding fragment thereof typically contains a large number of ingredients, which are necessary to support maintenance of the cultured host cells. Suitable combinations of ingredients can readily be formulated by the skilled person.
  • a culture medium to be used herein will generally be a nutrient solution comprising standard cell culture ingredients, such as amino acids, vitamins, inorganic salts, a carbon energy source, and a buffer, as described in the art.
  • a cell culture medium useable may be formulated in deionized, distilled water.
  • a culture medium may be sterilized prior to use to prevent contamination, e.g., by ultraviolet light, heating, gamma-irradiation, or filtration.
  • a cell culture medium may be frozen (e.g., at - 20°C or -80°C) for storage or transport.
  • the medium may contain one or more antibiotics to prevent contamination.
  • a cell culture medium may be a defined synthetic medium that is buffered at a pH of 7.4 (preferably with a pH 7.2 - 7.6 or at least 7.2 and not higher than 7.6) with a carbonate -based buffer, while the cells are cultured in an atmosphere comprising between 5 % and 10% CO2, or at least 5% and not more than 10% CO2, for example 5% CO2.
  • a potentially suitable cell culture medium may be available commercially, and includes, but is not limited to, Dulbecco's Modified Eagle Media (DMEM), Minimal Essential Medium (MEM), Knockout-DMEM (KO-DMEM), Glasgow Minimal Essential Medium (G- MEM), Basal Medium Eagle (BME), DMEM/Ham’s F12, Advanced DMEM/Ham’s F12, Iscove’s Modified Dulbecco’s Media (IMDM), Ham's F-10, Ham’s F-12, Medium 199, RPMI 1640 Media, and Hepatocyte cell culture media.
  • DMEM Dulbecco's Modified Eagle Media
  • MEM Minimal Essential Medium
  • Knockout-DMEM KO-DMEM
  • Glasgow Minimal Essential Medium G- MEM
  • Basal Medium Eagle BME
  • DMEM/Ham’s F12 DMEM/Ham’s F12
  • Advanced DMEM/Ham’s F12 Iscove’s Modified Dulbecco’s Media
  • a nucleic acid sequence may be used to produce an antibody, or an antigenbinding fragment thereof as described in the disclosure.
  • the nucleic acid sequence may be a DNA or a RNA molecule, which may be included in any suitable expression vector, such as a plasmid, cosmid, episome, artificial chromosome, phage, or a viral vector.
  • a nucleic acid sequence encoding an antibody, or an antigen-binding fragment thereof, as described may be an isolated nucleic acid sequence or a recombinant nucleic acid sequence.
  • a nucleic acid sequence usable for producing an antibody, or an antigen-binding fragment thereof, may be as disclosed herein.
  • a nucleic acid as described herein encodes the heavy chain (VH), the light chain (VL), the full-length heavy chain, and the full-length light chain of an antibody of the present disclosure for the groups (i) to (vii) of antibodies.
  • a nucleic acid sequence can be produced by de novo solid-phase DNA synthesis or by PCR mutagenesis of an existing sequence encoding an antibody as described herein or its antigen-binding fragment thereof.
  • Direct chemical synthesis of nucleic acids can be accomplished by methods known in the art, such as the phosphotriester method of Narang et al, Meth. Enzymol. 68:90, 1979; the phosphodiester method of Brown / al, Meth. Enzymol. 68: 109, 1979; the diethylphosphoramidite method of Beaucage et al , Tetra. Lett., 22: 1859, 1981; and the solid support method of U.S. Patent No. 4,458,066.
  • An expression vector may be an isolated or a recombinant expression vector.
  • a host cell may be an isolated or a recombinant host cell.
  • An expression vector may comprise a nucleic acid sequence as described herein.
  • Such a vector may comprise regulatory elements, such as a promotor, enhancer, terminator, and the like, to cause or direct expression of said antibody upon transfection into the host cell.
  • vectors will depend upon a variety of factors such as the type of host cell in which propagation is desired and the purpose of propagation. Some vectors are useful for amplifying and making large amounts of the desired DNA sequence. Other vectors are suitable for expression in cells in culture. Still other vectors are suitable for transfer and expression in cells in a whole animal. The choice of appropriate vector is well within the skill of the art. Many such vectors are available commercially.
  • Any expression vector for animal cell can be used, so long as a gene encoding the human antibody C region can be inserted and expressed.
  • suitable vectors include pAGE107, pAGE103, pHSG274, pKCR, pSGl, pCAG and the like.
  • Other examples of vectors include replicating plasmids comprising an origin of replication, or integrative plasmids, such as for instance pUC, pcDNA, pBR, and the like.
  • Other examples of viral vector include adenoviral, retroviral, herpes virus and AAV vectors. Such recombinant viruses may be produced by techniques known in the art, such as by transfecting packaging cells or by transient transfection with helper plasmids or viruses.
  • virus packaging cells include PA317 cells, PsiCRIP cells, Gpenv+ cells, 293 cells, RS cells, etc.
  • a detailed protocol for producing such replication-defective recombinant viruses may be found for instance in Pastrana et al. (PloS Pathog. 2012, 8, el002650).
  • promoters and enhancers used in the expression vector for animal cell include early promoter and enhancer of SV40, LTR promoter and enhancer of Moloney mouse leukemia virus, promoter and enhancer of immunoglobulin H chain and the like.
  • Vectors can be prepared by, for example, inserting a polynucleotide of interest into a construct backbone, typically by means of DNA ligase attachment to a cleaved restriction enzyme site in the vector.
  • the desired nucleotide sequence can be inserted by homologous recombination or site-specific recombination.
  • homologous recombination is accomplished by attaching regions of homology to the vector on the flanks of the desired nucleotide sequence, while site-specific recombination can be accomplished through use of sequences that facilitate site-specific recombination (e.g., ere -lox, att sites, etc.).
  • Nucleic acid containing such sequences can be added by, for example, ligation of oligonucleotides, or by polymerase chain reaction using primers comprising both the region of homology and a portion of the desired nucleotide sequence.
  • Expression vectors generally have convenient restriction sites located near the promoter sequence to provide for the insertion of nucleic acid sequences encoding proteins of interest.
  • a selectable marker operative in the expression host may be present to facilitate selection of cells containing the vector.
  • the expression construct may include additional elements.
  • the expression vector may have one or two replication systems, thus allowing it to be maintained in organisms, for example in mammalian or insect cells for expression and in a prokaryotic host for cloning and amplification.
  • the expression construct may contain a selectable marker gene to allow the selection of transformed host cells. Selection genes are well known in the art and will vary with the host cell used.
  • vectors encoding both the heavy and light chains may be co-expressed in the host cell for expression of the entire antibody.
  • the expression vector is transferred to a host cell by conventional techniques and the transfected cells then are cultured by conventional techniques to produce an antibody or an antigen-binding fragment thereof of the present disclosure.
  • Isolated or recombinant host cells may be transfected, infected, or transformed by a nucleic acid sequence and/or an expression vector as disclosed herein.
  • Such host cells may be used for the production of an antibody as described herein.
  • transformation means the introduction of a “foreign” (i.e., extrinsic, or extracellular) gene, DNA or RNA sequence to a host cell, so that the host cell will express the introduced gene or sequence to produce a desired substance, typically a protein or enzyme coded by the introduced gene or sequence.
  • a host cell that receives and expresses introduced DNA or RNA bas been “transformed”.
  • the present disclosure further provides a recombinant, or isolated, host cell transformed with a nucleic acid sequence encoding an antibody or antigen-binding fragment thereof as disclosed herein, or with an expression vector comprising such nucleic acid sequence.
  • any of a number of suitable host cells can be used in the production of an antibody or antigen-binding fragment thereof.
  • the antibody or antigen-binding fragment thereof described herein may be expressed in prokaryotes or eukaryotes (eukaryotic unicellular organism), e.g., bacteria such as Escherichia coli, yeasts, such as Saccharomyces sp., or mammalian cell lines, such as Vero cells, HEK293, or CHO, in accordance with conventional techniques.

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Abstract

La présente divulgation concerne un anticorps isolé se liant à une protéine de capside VP1 du polyomavirus BK (BKPyV), ou un fragment de liaison à l'antigène de celle-ci, comprenant des H-CDR1, H-CDR2, H-CDR3, L-CDR1, L-CDR2 et L-CDR3 spécifiques. L'invention concerne également un acide nucléique, des vecteurs d'expression et des cellules hôtes comprenant des séquences codant les anticorps. Les anticorps et les combinaisons de ceux-ci peuvent être utilisés pour la prévention et/ou le traitement d'une infection induite par le BKPyV et/ou d'un trouble induit par une infection par le BKPyV.
PCT/EP2023/056946 2022-03-18 2023-03-17 Anticorps de polyomavirus bk et leurs utilisations WO2023175171A1 (fr)

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