# US 10,765,754 B2 · Compositions and methods related to inhibition of respiratory syncytial virus entry

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- Number: US 10,765,754 B2
- Document ID: US10765754B2
- Status: Granted
- Kind: B2
- Application number: 15/753,950
- Filed: 2016-08-26
- Published: 2018-10-04
- Granted: 2020-09-08
- Earliest claimed: 2015-08-28
- Assignees: Navigen, Inc.; University of Utah Research Foundation
- Applicants: Navigen, Inc.; University of Utah Research Foundation
- Inventors: Brett D. Welch; Michael S. Kay; Debra Muir Eckert; Rena McKinnon; Michael Thomas Jacobsen
- Web page: https://patentgrep.com/patent/US10765754B2

## CPC

- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61K 38/02: Peptides of undefined number of amino acids; Derivatives thereof
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61K 38/162: {from virus}
- A61P 31/14: for RNA viruses
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- 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
- 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)
- 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)

## Abstract

Disclosed herein are compositions and methods for inhibiting respiratory syncytial virus (RSV) entry into a host cell. Also provided herein are methods of identifying a peptide that interacts with the N-trimer of RSV F protein.

## Claims

### Claim 1

An isolated D-peptide comprising the amino acid sequence of SEQ ID NO:42, wherein the amino acids of the D-peptide have a D-configuration with the exception of glycine and the D-peptide is capable of interacting with the N-trimer groove of respiratory syncytial virus (RSV) F protein.

### Claim 2 (depends on 1)

The isolated D-peptide of claim 1, wherein the D-peptide is linked to an identical D-peptide.

### Claim 3 (depends on 1)

The isolated D-peptide of claim 1, wherein the D-peptide is linked to two identical D-peptides.

### Claim 4 (depends on 1)

The isolated D-peptide of claim 1, wherein the D-peptide comprises an amino acid sequence selected from any one of SEQ ID NOS:23-31, 122-124, 128-146, 214-216, 152, and 159.

### Claim 5 (depends on 1)

The isolated D-peptide of claim 1, wherein the N-terminus of the D-peptide is capped with an acetyl group.

### Claim 6 (depends on 1)

The isolated D-peptide of claim 1, wherein the C-terminus of the D-peptide is capped with an amide group.

### Claim 7

An isolated composition comprising a first D-peptide comprising the amino acid sequence of SEQ ID NO:42, wherein the amino acids of the first D-peptide have a D-configuration with the exception of glycine and the first D-peptide is capable of interacting with the N-trimer groove of respiratory syncytial virus (RSV) F protein.

### Claim 8 (depends on 7)

The isolated composition according to claim 7, wherein the first D-peptide is linked to a second D-peptide, wherein the amino acids of the second D-peptide have a D-configuration with the exception of glycine.

### Claim 9 (depends on 8)

The isolated composition according to claim 8, wherein the second D-peptide is identical to the first D-peptide.

### Claim 10 (depends on 7)

The isolated composition according to claim 7, wherein the first D-peptide is linked to a second D-peptide and a third D-peptide, wherein the amino acids of the third D-peptide have a D-configuration with the exception of glycine.

### Claim 11 (depends on 10)

The isolated composition according to claim 10, wherein the first D-peptide, second D-peptide, and third D-peptide are identical.

### Claim 12 (depends on 10)

The isolated composition according to claim 10, wherein the first D-peptide, the second D-peptide, and the third D-peptide, are multimerized through a cross-linker.

### Claim 13 (depends on 12)

The isolated composition of claim 12, wherein the cross-linker is a polyethylene glycol (PEG) linker.

### Claim 14 (depends on 12)

The isolated composition according to claim 12, wherein the N-termini of the D-peptides are cross-linked.

### Claim 15 (depends on 12)

The isolated composition according to claim 12, wherein the C-termini of the D-peptides are cross-linked.

### Claim 16 (depends on 12)

The isolated composition according to claim 12, wherein the N-terminus or C-terminus of each D-peptide is cross-linked.

### Claim 17 (depends on 12)

The isolated composition according to claim 12, wherein the first D-peptide, the second D-peptide, and the third D-peptide, are multimerized through a scaffold having the following structure:

### Claim 18 (depends on 17)

The isolated composition according to claim 17, wherein:
the N-termini of the D-peptides are attached to the scaffold;
the C-termini of the D-peptides are attached to the scaffold; or
the N-terminus or C-terminus of each D-peptide is attached to the scaffold.

### Claim 19 (depends on 7)

The isolated composition of claim 7, wherein the first D-peptide comprises an amino acid sequence selected from any one of SEQ ID NOS:23-31, 122-124, 128-146, 214-216, 152, and 159.

### Claim 20 (depends on 19)

The isolated composition of claim 19, wherein the N-terminus of the D-peptide is capped with an acetyl group.

### Claim 21 (depends on 19)

The isolated composition of claim 19, wherein the C-terminus of the D-peptide is capped with an amide group.

### Claim 22 (depends on 17)

The isolated composition of claim 17, wherein:
the first, second, and third D-peptide each comprises the amino acid sequence of Ac-K(PEG4)-DDG-GECVNRPEWLLDWCGT-NH2 (SEQ ID NO:142); or
the first, second, and third D-peptide each comprises the amino acid sequence of Ac-K(PEG4)-EEG-GECVNRPEWLLDWCGT-NH2 (SEQ ID NO:214).

### Claim 23 (depends on 7)

The isolated composition of claim 7, wherein the first D-peptide is linked to a potency enhancing cargo molecule.

### Claim 24 (depends on 23)

The isolated composition of claim 23, wherein the potency enhancing cargo molecule is a cholesterol, sterol, sugar, maltose binding protein, ubiquitin, streptavidin, immunoglobulin domain, keyhole limpet hemacyanin, sperm whale myoovalbumin, bovine pancreatic trypsin inhibitor, green fluorescent protein, gold particle, magnetic particle, agarose bead, lactose bead, fatty acid, a high molecular weight PEG, or serum albumin.

### Claim 25 (depends on 23)

The isolated composition of claim 23, wherein the potency enhancing cargo molecule is linked to the first D-peptide with a PEG linker.

### Claim 26 (depends on 10)

The isolated composition according to claim 10, wherein a trimer of the first, second, and third D-peptides exhibits enhanced binding affinity or anti-viral activity as compared with the binding affinity or anti-viral activity of an isolated composition comprising the first D-peptide as a monomer.

### Claim 27 (depends on 10)

The isolated composition according to claim 10, wherein the composition further comprises a pharmaceutically acceptable carrier.

### Claim 28 (depends on 1)

A method for inhibiting entry of respiratory syncytial virus (RSV) into a host cell, comprising exposing the RSV virus to the D-peptide of claim 1, thereby inhibiting entry of the virus into the host cell.

### Claim 29 (depends on 28)

The method according to claim 28, wherein the D-peptide comprises an amino acid sequence as set forth in SEQ ID NO:142 or SEQ ID NO:214.

### Claim 30

A method for inhibiting entry of RSV into a host cell, comprising exposing the RSV virus to a composition comprising a first D-peptide, a second D-peptide, and a third D-peptide that are multimerized through a scaffold having the following structure:
wherein each of the first, second, and third D-peptides comprises an amino acid sequence as set forth in SEQ ID NO:142; or each of the first, second, and third D-peptides comprises an amino acid sequence as set forth in SEQ ID NO:214; and wherein the amino acids of the first, second, and third D-peptides have a D-configuration with the exception of glycine.

### Claim 31 (depends on 1)

A method of treating respiratory syncytial virus (RSV) infection in a subject, comprising administering to the subject a therapeutically effective amount of the D-peptide of claim 1.

### Claim 32 (depends on 4)

A method of treating RSV infection in a subject, comprising administering to the subject a therapeutically effective amount of a D-peptide according to claim 4.

### Claim 33 (depends on 22)

A method of treating RSV infection in a subject comprising administering to the subject a therapeutically effective amount of a composition according to claim 22.

### Claim 34 (depends on 31)

The method of claim 31, wherein the D-peptide w is administered concurrently or sequentially with at least one additional anti-viral agent.

### Claim 35 (depends on 34)

The method of claim 34, wherein the at least one additional anti-viral agent is a viral fusion inhibitor, viral attachment inhibitor, viral replication inhibitor, a viral protease inhibitor, an inhibitor antibody, a biologic, an antisense molecule, an RNA interference agent, a peptide, or a small molecule.

### Claim 36 (depends on 1)

The isolated D-peptide of claim 1, wherein the D-peptide is 8 to 30 amino acids in length.