# US 2013/0280262 A1 · Polypeptides and their Use in Treating and Limiting Respiratory Syncytial Virus Infection

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- Number: US 2013/0280262 A1
- Document ID: US20130280262A1
- Status: Published application
- Kind: A1
- Application number: 13/878,122
- Filed: 2011-10-06
- Published: 2013-10-24
- Earliest claimed: 2010-10-06
- Assignees: University of Washington through its Center for Commercialization
- Inventors: William R. Schief; Bruno E. Correia; David Baker
- Web page: https://patentgrep.com/patent/US20130280262A1

## CPC

- C07K 14/001: {by chemical synthesis}
- A61K 39/12: Viral antigens
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- C07K 14/005: from viruses
- G16B 15/00: ICT specially adapted for analysing two-dimensional [2D] or three-dimensional [3D] molecular structures, e.g. structural or functional relations or structure alignment
- G16B 15/20: Protein or domain folding
- G16B 15/30: Drug targeting using structural data; Docking or binding prediction
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 2039/552: {Veterinary vaccine}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- A61K 2039/6075: {Viral proteins}
- C12N 2760/18522: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- 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
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- 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 provides polypeptides and compositions thereof for treating or limiting respiratory syncytial virus infection, and computational methods for designing such polypeptides.

## Claims

### Claim 1

An isolated polypeptide, comprising an amino acid sequence according to SEQ ID NO:1

### Claim 2 (depends on 1)

The isolated polypeptide of claim 1, comprising an amino acid sequence according to SEQ ID NO:2.

### Claim 3 (depends on 1)

The isolated polypeptide of claim 1, comprising an amino acid sequence according to SEQ ID NO:3.

### Claim 4 (depends on 1)

The isolated polypeptide of claim 1, wherein the polypeptide comprises a sequence selected from the group consisting of SEQ ID NOS:4-9.

### Claim 5 (depends on 1)

The isolated polypeptide of claim 1, wherein the polypeptide comprises a sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, and SEQ ID NO:9.

### Claim 6 (depends on 1)

The isolated polypeptide of claim 1, wherein the polypeptide comprises a sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:7, and SEQ ID NO:9.

### Claim 7 (depends on 1)

A virus-like particle (VLP) comprising the polypeptide of claim 1.

### Claim 8 (depends on 1)

An isolated nucleic acid encoding the polypeptide of claim 1.

### Claim 9 (depends on 8)

A recombinant expression vector comprising the isolated nucleic acid of claim 8 operatively linked to a promoter.

### Claim 10 (depends on 9)

A recombinant host cell comprising the recombinant expression vector of claim 9.

### Claim 11 (depends on 1)

A pharmaceutical composition, comprising the polypeptide of claim 1, and a pharmaceutically acceptable carrier.

### Claim 12 (depends on 1)

A method for treating a respiratory syncytial virus (RSV) infection, comprising administering to a subject infected with RSV an amount effective to treat the infection of the polypeptide of claim 1.

### Claim 13 (depends on 1)

A method for limiting development of an RSV infection, comprising administering to a subject at risk of RSV infection an amount effective to limit development of an RSV infection of the polypeptide of claim 1.

### Claim 14 (depends on 1)

A method for generating an immune response in a subject, comprising administering to the subject an amount effective to generate an immune response of the polypeptide of claim 1.

### Claim 15 (depends on 8)

A pharmaceutical composition, comprising
(a) the isolated nucleic acid of claim 8; and
(b) a pharmaceutically acceptable carrier.

### Claim 16 (depends on 1)

A method for monitoring an RSV-induced disease in a subject and/or monitoring response of the subject to immunization by an RSV vaccine, comprising contacting the polypeptide of claim 1 with a bodily fluid from the subject and detecting RSV-binding antibodies in the bodily fluid of the subject.

### Claim 17 (depends on 16)

The method of claim 16, wherein the bodily fluid comprises serum or whole blood.

### Claim 18 (depends on 1)

A method for detecting RSV binding antibodies, comprising
(a) contacting the polypeptide of claim 1 with a composition comprising a candidate RSV binding antibody under conditions suitable for binding of RSV antibodies to the polypeptide, VLP, or composition; and
(b) detecting RSV antibody complexes with the polypeptide, VLP, or composition.

### Claim 19 (depends on 18)

The method of claim 18, further comprising isolating the RSV antibodies.

### Claim 20 (depends on 1)

A method for producing RSV antibodies, comprising
(a) administering to a subject an amount effective to generate an antibody response of the polypeptide of claim 1; and
(b) isolating antibodies produced by the subject.

### Claim 21

A computational method for designing a polypeptide scaffold, comprising
(a) defining a polypeptide structural motif to be used as a folding nucleus;
(b) defining (i) a target three dimensional topology for a polypeptide scaffold compatible with the polypeptide structural motif, and (b) a region of the target three dimensional topology to be replaced by the polypeptide structural motif;
(c) growing an extended polypeptide chain from termini of atomic coordinates of the polypeptide structural motif;
(d) folding the extended polypeptide chain while maintaining backbone dihedral angles of the polypeptide structural motif fixed; and
(e) identifying folded polypeptide chains that meet a user-defined threshold of polypeptide backbone root mean square deviation (rmsd) relative to the target three-dimensional topology as polypeptide scaffolds of interest.

### Claim 22 (depends on 21)

The method of claim 21, further comprising determining one or more constraints from the target three-dimensional topology prior to growing the extended polypeptide chain.

### Claim 23 (depends on 21)

The method of claim 21, further comprising recovering original side-chain conformations within the structural motif and keeping them fixed throughout 1 or more rounds of iterative folding and full-atom optimization.

### Claim 24 (depends on 21)

A non-transitory machine readable storage medium, comprising a set of instructions for causing a computing device to carry out the computational methods of claim 21.
