# US 11,773,143 B2 · Conformational epitopes in respiratory syncytial virus G protein central conserved region

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- Number: US 11,773,143 B2
- Document ID: US11773143B2
- Status: Granted
- Kind: B2
- Application number: 16/159,497
- Filed: 2018-10-12
- Published: 2019-05-09
- Granted: 2023-10-03
- Earliest claimed: 2017-10-13
- Assignees: Trellis Bioscience, LLC; The Regents of the University of California
- Applicants: Trellis Bioscience, LLC; The Regents of the University of California
- Inventors: Rebecca Dubois; Stas Fedechkin; Lawrence M. Kauvar
- Web page: https://patentgrep.com/patent/US11773143B2

## CPC

- C07K 14/135: Respiratory syncytial virus
- A61K 39/12: Viral antigens
- A61K 39/155: Paramyxoviridae, e.g. parainfluenza virus
- A61P 31/14: for RNA viruses
- C07K 14/005: from viruses
- C07K 16/11: Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV]
- A61K 2039/552: {Veterinary vaccine}
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/55: Fab or Fab'
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2760/18522: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/18533: Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory
- 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

X-ray crystallography has defined conformational properties of a key functional region of the G protein of respiratory syncytial virus (RSV). Mimics of these epitopes have utility as immunogens, as tools for discovery of antibodies and other monoclonal binding agents, and as pharmacological agents to modulate activity of the host receptors for this viral protein.

## Claims

### Claim 1

A mutant peptide or peptidomimetic thereof, the mutant peptide or peptidomimetic comprising:
(a) amino acid residues 161-197 of respiratory syncytial virus (RSV) G protein, as set forth as SEQ ID NO: 1, with at least one amino acid substitution at amino acid residue 162, 164, 166, 177, 187, 192, or 193 thereof;
(b) amino acid residues 162-172 of RSV G protein, as set forth as SEQ ID NO: 2, with at least one amino acid substitution at amino acid residue 162, 164, or 166 thereof;
(c) amino acid residues 169-198 of RSV G protein, as set forth as SEQ ID NO: 3, with at least one amino acid substitution at amino acid residue 177, 187, 192, or 193 thereof;
(d) amino acid residues 157-197 of RSV G protein, as set forth as SEQ ID NO: 4, with at least one amino acid substitution at amino acid residue 162, 164, 166, 177, 187, 192, or 193 thereof;
(e) amino acid residues 148-197 of RSV G protein, as set forth as SEQ ID NO: 5, with at least one amino acid substitution at amino acid residue 162, 164, 166, 177, 187, 192, or 193 thereof; or
(f) amino acid residues 161-191 of RSV G protein, as set forth as SEQ ID NO: 6, with at least one amino acid substitution at amino acid residue 162, 164, 166, 177, or 187 thereof;
wherein the mutant peptide or peptidomimetic (i) comprises diminished activation of CX3CR1 (chemokine receptor responsive to fractalkine) as compared to the respective unmodified peptide comprising SEQ ID NOS: 1-6, (ii) is immunoreactive with mAb 3D3, and/or 2D10 and/or 3G12, and (iii) is chemically stabilized to maintain its native conformation when binding to mAb 3D3, and/or 2D10 and/or 3G12.

### Claim 2 (depends on 1)

The mutant or peptidomimetic of claim 1 which elicits sub-nM affinity antibodies immunoreactive with an epitope of RSV G protein conserved between A and B strains of the virus.

### Claim 3 (depends on 1)

The mutant or peptidomimetic of claim 1, wherein the substituted amino acid of (a)-(f) comprises a different charge than the unsubstituted amino acid.

### Claim 4 (depends on 1)

The mutant or peptidomimetic of claim 1, wherein the substituted amino acid of (a)-(f) comprises a different size or shape than the unsubstituted amino acid.

### Claim 5 (depends on 1)

The mutant or peptidomimetic of claim 1, wherein the substituted amino acid of (a)-(f) comprises a different side chain than the unsubstituted amino acid.

### Claim 6 (depends on 1)

The mutant or peptidomimetic of claim 1, wherein the at least one substitution provided in (a)-(f) comprises a tyrosine for histidine at amino acid position 164, a lysine for glutamate at amino acid position 166, a tryptophan for serine at amino acid position 177, or arginine for serine at amino acid position 177, or combination thereof.

### Claim 7 (depends on 1)

The mutant or peptidomimetic of claim 1, wherein the at least one substitution provided in (a)-(f) comprises a lysine for glutamate at amino acid position 166 and glutamate for lysine at amino acid position 187.

### Claim 8 (depends on 1)

The mutant or peptidomimetic of claim 1, wherein the at least one substitution provided in (a) and (c) comprises a glutamate for lysine at amino acid positions 192 and 193.

### Claim 9 (depends on 1)

A pharmaceutical or veterinary composition or vaccine that comprises as active agent the mutant or peptidomimetic of claim 1.
