# US 10,501,528 B2 · Immunoglobulin single variable domain antibody against RSV prefusion F protein

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- Number: US 10,501,528 B2
- Document ID: US10501528B2
- Status: Granted
- Kind: B2
- Application number: 15/736,663
- Filed: 2016-06-20
- Published: 2018-06-28
- Granted: 2019-12-10
- Earliest claimed: 2015-06-18
- Assignees: V18 Vzw; Universiteit Gent; The United States of America as represented by the Secretary of Health and Human Services; Trustees of Dartmouth College
- Applicants: Vib Vzw; Universiteit Gent; The United States of America, AS Represented By the Secretary, Department of Health and Human Services; Trustees of Dartmouth College
- Inventors: Xavier Saelens; Bert Schepens; Iebe Rossey; Barney Graham; Jason McLellan; Morgan Gilman
- Web page: https://patentgrep.com/patent/US10501528B2

## CPC

- C07K 16/11: Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV]
- A61K 39/12: Viral antigens
- A61P 31/14: for RNA viruses
- A61K 2039/505: {comprising antibodies}
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- C07K 2317/22: from camelids, e.g. camel, llama or dromedary
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2760/18534: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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)

## Abstract

The present invention relates to immunoglobulin single variable domains (ISVDs) that are directed against respiratory syncytial virus (RSV). More specifically, it relates to ISVDs that bind to the prefusion form of the fusion (F) protein of RSV. The invention relates further to the use of these ISVDs for prevention and/or treatment of RSV infections, and to pharmaceutical compositions comprising these ISVDs.

## Claims

### Claim 1

An immunoglobulin single variable domain (ISVD) that binds specifically to the prefusion form of the fusion (F) protein of respiratory syncytial virus (RSV), characterized in that the ISVD shows in monovalent format a neutralization activity of RSV serotypes A and B for which the IC50 value differs ten-fold or less, and in that the ISVD binds to a conformational epitope of RSV prefusion F protein comprising amino acids 50-52, 180, 184, 185, 265-270, 305, 307, 308, 345-347, 421, 425, 427-431, 451, 453, 454, 456 and 458 as depicted in SEQ ID NO: 17, characterized in that said ISVD comprises CDR1 sequence SEQ ID NO: 1, a CDR2 sequence selected from the group consisting of SEQ ID NO: 3 and SEQ ID NO: 4, and a CDR3 sequence selected from the group consisting of SEQ ID NO: 5 and SEQ ID NO: 6.

### Claim 2 (depends on 1)

A RSV binding construct, characterized in that said RSV binding construct comprises the ISVD according to claim 1.

### Claim 3 (depends on 1)

A purified nucleic acid, characterized in that said nucleic acid encodes the ISVD according to claim 1.

### Claim 4 (depends on 3)

A cultured host cell, characterized in that said host cell is transformed or transfected with the nucleic acid according to claim 3.

### Claim 5 (depends on 4)

A method of producing an ISVD comprising culturing the host cell according to claim 4.

### Claim 6 (depends on 1)

A method of inhibiting RSV infection in a subject comprising administering the ISVD according to claim 1.

### Claim 7 (depends on 1)

A method of inhibiting RSV infection in a subject comprising administering the ISVD according to claim 1, wherein the ISVD is administered prophylactically.

### Claim 8 (depends on 1)

A pharmaceutical composition, characterized in that said pharmaceutical composition comprises at least one ISVD according to claim 1.

### Claim 9 (depends on 8)

A method of inhibiting RSV infection in a subject comprising administering the pharmaceutical composition according to claim 8.

### Claim 10 (depends on 8)

A method of inhibiting RSV infection in a subject comprising administering the pharmaceutical composition according to claim 8, wherein the pharmaceutical composition is administered prophylactically.

### Claim 11 (depends on 2)

A method of inhibiting RSV infection in a subject comprising administering the RSV binding construct according to claim 2.

### Claim 12 (depends on 2)

A method of inhibiting RSV infection in a subject comprising administering the RSV binding construct according to claim 2, wherein the RSV binding construct is administered prophylactically.
