# US 2014/0154284 A1 · Methods and compositions for inhibiting polyomavirus-associated pathology

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2014/0154284 A1
- Document ID: US20140154284A1
- Status: Published application
- Kind: A1
- Application number: 14/233,582
- Filed: 2012-07-17
- Published: 2014-06-05
- Earliest claimed: 2011-07-18
- Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Inventors: Christopher B. Buck; Diana V. Pastrana
- Web page: https://patentgrep.com/patent/US20140154284A1

## CPC

- A61K 39/12: Viral antigens
- A61P 13/10: of the bladder
- A61P 13/12: of the kidneys
- A61P 31/12: Antivirals
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12Q 1/70: involving virus or bacteriophage {(immunoassay for viruses G01N33/56983)}
- G01N 33/56983: {Viruses}
- A61K 2039/5258: {Virus-like particles}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- A61K 2039/70: {Multivalent vaccine}
- C12N 2710/22023: Virus like particles [VLP]
- C12N 2710/22034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- G01N 2333/025: Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
- G01N 2469/20: Detection of antibodies in sample from host which are directed against antigens from microorganisms
- G01N 2800/347: Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Disclosed herein are methods of eliciting an immune response against a polyomavirus (for example, BKV serotype I (BKV-I), BKV serotype II (BKV-II), BKV serotype III (BKV-III) and/or BKV serotype IV (BKV-IV)) and methods of treating or inhibiting polyomavirus-associated pathology (such as polyomavirus-associated nephropathy, BKV-associated hemorrhagic cystitis, or JC virus-associated progressive multifocal leukoencephalopathy; PML). Further disclosed are immunogenic compositions of use in the disclosed methods. Also disclosed are methods of selecting an organ transplant donor and/or recipient including detecting whether the prospective donor and/or recipient has BKV serotype-specific (such as BKV serotype IV-specific) neutralizing antibodies.

## Claims

### Claim 1

A method of eliciting an immune response against a BK polyomavirus (BKV) in a subject, comprising administering to a subject in need of enhanced immunity to BKV:
a therapeutically effective amount of at least one isolated BKV serotype I (BKV-I) capsid polypeptide or a nucleic acid encoding the at least one BKV-I capsid polypeptide; and
a therapeutically effective amount of at least one isolated BKV serotype IV (BKV-IV) capsid polypeptide or a nucleic acid encoding the at least one BKV-IV capsid polypeptide, wherein the at least one BKV-I capsid polypeptide and the at least one BKV-IV capsid polypeptide are different, thereby eliciting an immune response against the BKV.

### Claim 2 (depends on 1)

The method of claim 1, wherein the at least one BKV-I capsid polypeptide and the at least one BKV-IV capsid polypeptide are administered concurrently or sequentially.

### Claim 3 (depends on 1)

The method of claim 1, wherein:
administering the at least one isolated BKV-I capsid polypeptide comprises administering a virus-like particle comprising the at least one BKV-I capsid polypeptide; and/or
administering the at least one isolated BKV-IV capsid polypeptide comprises administering a virus-like particle comprising the at least one BKV-IV capsid polypeptide.

### Claim 4

(canceled)

### Claim 5 (depends on 1)

The method of claim 1, wherein:
the at least one isolated BKV-I capsid polypeptide comprises BKV-I VP1, BKV-I VP2, BKV-I VP3, or a combination of two or more thereof; and/or
the at least one BKV-IV capsid polypeptide comprises BKV-IV VP1, BKV-IV VP2, BKV-IV VP3 or a combination of two or more thereof.

### Claim 6 (depends on 5)

The method of claim 5, wherein:
the BKV-I VP1 polypeptide comprises one or more of a BKV-Ia VP1 polypeptide, a BKV-Ib1 VP1 polypeptide, a BKV-Ib2 VP1 polypeptide, and a BKV-Ic VP1 polypeptide; and/or
the BKV-IV VP1 polypeptide comprises one or more of a BKV-IVb1 VP1 polypeptide and a BKV-IVc2 VP1 polypeptide.

### Claim at position 7

7-8. (canceled)

### Claim 9 (depends on 1)

The method of claim 1, wherein:
the at least one isolated BKV-IV capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 4-6, 16, and 110-125; and/or
the at least one isolated BKV-I capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 1-3, 13-15, and 52-103.

### Claim 10 (depends on 1)

The method of claim 1, further comprising:
administering to the subject a therapeutically effective amount of at least one isolated BKV serotype II (BKV-II) capsid polypeptide or a nucleic acid encoding the at least one BKV-II capsid polypeptide; and/or
administering to the subject a therapeutically effective amount of at least one isolated BKV serotype III (BKV-III) capsid polypeptide or a nucleic acid encoding the at least one BKV-III capsid polypeptide,
wherein the BKV-II capsid polypeptide and the BKV-III capsid polypeptide are different.

### Claim at position 10

11-13. (canceled)

### Claim 14 (depends on 1)

The method of claim 1, further comprising administering to the subject a therapeutically effective amount of at least one isolated JC polyomavirus capsid polypeptide or a nucleic acid encoding the at least one JC polyomavirus capsid polypeptide.

### Claim 15 (depends on 1)

The method of claim 1, further comprising administering an adjuvant to the subject.

### Claim 16 (depends on 1)

The method of claim 1, wherein the subject is an immunocompromised subject, a subject who has been treated with or is a candidate for treatment with an immunosuppressant, or a subject who has received, or is a candidate for an organ transplant.

### Claim at position 14

17-18. (canceled)

### Claim 19 (depends on 1)

The method of claim 1, wherein the subject does not have BKV-I neutralizing antibodies and/or BKV-IV neutralizing antibodies.

### Claim 20

(canceled)

### Claim 21

A multivalent BK polyomavirus (BKV) immunogenic composition comprising:
a virus-like particle comprising at least one BKV serotype IV capsid polypeptide;
a virus-like particle comprising at least one BKV serotype I capsid polypeptide; and
a pharmaceutically acceptable carrier.

### Claim 22 (depends on 21)

The immunogenic composition of claim 21, wherein:
the at least one isolated BKV-IV capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 4-6, 16, and 110-125; and/or
the at least one isolated BKV-I capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 1-3, 13-15, and 52-103.

### Claim 23 (depends on 21)

The immunogenic composition of claim 21, further comprising:
a virus-like particle comprising at least one BKV serotype II capsid polypeptide;
a virus-like particle comprising at least one BKV serotype III capsid polypeptide; or
a combination thereof.

### Claim 24

(canceled)

### Claim 25 (depends on 21)

The immunogenic composition of claim 21, wherein:
the at least one BKV serotype IV capsid polypeptide comprises one or more of a BKV-IVb1 VP1 polypeptide and a BKV-IVc2 VP1 polypeptide; and/or
the at least one BKV serotype I capsid polypeptide comprises one or more of a BKV-Ia VP1 polypeptide, a BKV-Ib1 VP1 polypeptide, a BKV-Ib2 VP1 polypeptide, and a BKV-Ic VP1 polypeptide.

### Claim at position 22

26-27. (canceled)

### Claim 28 (depends on 21)

The immunogenic composition of claim 21, further comprising an adjuvant.

### Claim 29

A method of monitoring development of an immune response to BKV in a subject who has been administered an immunogenic composition comprising at least one isolated BKV capsid polypeptide or a nucleic acid encoding a BKV capsid polypeptide, comprising detecting presence of BK polyomavirus serotype-specific neutralizing antibodies in the subject.

### Claim 30 (depends on 29)

The method of claim 29, wherein the serotype-specific neutralizing antibodies are BKV-I-specific, BKV-II-specific, BKV-III-specific, or BKV-IV-specific.

### Claim 31

(canceled)

### Claim 32 (depends on 29)

The method of claim 29, wherein the presence of BK polyomavirus serotype-specific neutralizing antibodies is detected in a sample from the subject.

### Claim 33

(canceled)

### Claim 34

A method of treating or inhibiting BK polyomavirus-associated nephropathy or BK polyomavirus-associated hemorrhagic cystitis in a subject, comprising administering to a subject in need of treatment for or inhibition of BK polyomavirus-associated nephropathy or BK polyomavirus-associated hemorrhagic cystitis a therapeutically effective amount of at least one isolated BKV serotype IV (BKV-IV) capsid polypeptide or a nucleic acid encoding the at least one BKV-IV capsid polypeptide, thereby treating or inhibiting the BK polyomavirus-associated nephropathy or the BK polyomavirus-associated hemorrhagic cystitis.

### Claim 35 (depends on 34)

The method of claim 34, further comprising administering to the subject a therapeutically effective amount of:
at least one isolated BKV serotype I (BKV-I) capsid polypeptide or a nucleic acid encoding the at least one BKV-I capsid polypeptide;
at least one isolated BKV serotype II (BKV-II) capsid polypeptide or a nucleic acid encoding the at least one BKV-II capsid polypeptide;
at least one isolated BKV serotype III (BKV-III) capsid polypeptide or a nucleic acid encoding the at least one BKV-III capsid polypeptide;
at least one isolated JC polyomavirus capsid polypeptide or a nucleic acid encoding the at least one JC polyomavirus capsid polypeptide; or
a combination of two or more thereof.

### Claim at position 31

36-39. (canceled)

### Claim 40 (depends on 34)

The method of claim 34, wherein the subject is a candidate for an organ transplant and the therapeutically effective amount of the at least one BKV-IV capsid polypeptide or nucleic acid encoding the at least one BKV-IV capsid polypeptide is administered to the subject a sufficient time prior to the organ transplant to produce an immune response in the subject.

### Claim 41 (depends on 34)

The method of claim 34, wherein the subject does not have BKV-IV neutralizing antibodies.

### Claim at position 34

42-43. (canceled)

### Claim 44

A method of selecting a renal transplant donor, comprising selecting a subject as a renal transplant donor if BKV-IV neutralizing antibodies are not present in the subject.

### Claim 45 (depends on 44)

The method of claim 44, further comprising selecting a second subject as a renal transplant recipient if BKV-IV neutralizing antibodies are not present in the second subject.

### Claim at position 37

46-47. (canceled)

### Claim 48

A method of treating or inhibiting BK polyomavirus-associated nephropathy or BK polyomavirus-associated hemorrhagic cystitis in a subject, comprising administering to a subject in need of treatment for or inhibition of BK polyomavirus-associated nephropathy or BK polyomavirus-associated hemorrhagic cystitis a therapeutically effective amount of gamma globulin comprising one or more of BKV-I neutralizing antibodies, BKV-II neutralizing antibodies, BKV-III neutralizing antibodies, and BKV-IV neutralizing antibodies.

### Claim at position 39

49-50. (canceled)