# US 11,440,952 B2 · Compositions for preventing or treating viral and other microbial infections

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- Number: US 11,440,952 B2
- Document ID: US11440952B2
- Status: Granted
- Kind: B2
- Application number: 17/501,955
- Filed: 2021-10-14
- Published: 2022-04-21
- Granted: 2022-09-13
- Earliest claimed: 2020-10-16
- Assignees: Invisishield Technologies Ltd.
- Applicants: InvisiShield Technologies Ltd.
- Inventors: Cheng Liu; Hongbing Zhang; Zhiyuan Yang; Jingyi Xiang; Ziyou Cui; Jianying Liu
- Web page: https://patentgrep.com/patent/US11440952B2

## CPC

- A61K 9/0043: {Nose}
- 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 38/17: from animals; from humans {(enzyme inhibitors A61K38/005)}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- 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 14/47: from mammals
- C07K 16/102: Coronaviridae (F)
- C07K 16/104: Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]
- C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes}
- C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/505: {comprising antibodies}
- A61K 2039/543: {intranasal}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/00: Fusion polypeptide
- C07K 2319/01: containing a localisation/targetting motif
- C07K 2319/035: containing a signal for targeting to the external surface of a cell, e.g. to the outer membrane of Gram negative bacteria, GPI- anchored eukaryote proteins
- C07K 2319/21: containing a His-tag
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C12N 15/1037: {Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display}
- 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)
- 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 application relates to compositions for preventing or treating viral and other microbial infections. In some embodiments, the present application provides chimeric proteins comprising a target-binding moiety that specifically binds to a pathogen that infects through a mucosa, and a positively charged mucoadhesive peptide fragment. Also provided are antibodies and constructs thereof that specifically binds to an S1 subunit of a spike protein of SARS-CoV-2. Compositions comprising the chimeric proteins, antibodies, or constructs described herein are useful for preventing or treating a microbial infection in an individual, such as a coronavirus infection.

## Claims

### Claim 1

A chimeric protein comprising:
(a) an antibody or antigen binding fragment thereof that specifically binds to a SARS-CoV-2 spike (S) protein; and
(b) a mucoadhesive peptide fragment comprising about 5 to about 50 contiguous positively charged amino acid residues, wherein the mucoadhesive peptide fragment facilitates attachment of the chimeric protein to a mucosa.

### Claim 2 (depends on 1)

The chimeric protein of claim 1, wherein the mucoadhesive peptide fragment comprises at least about 6 contiguous positively charged amino acid residues.

### Claim 3 (depends on 1)

The chimeric protein of claim 1, wherein the chimeric protein comprises two or more mucoadhesive peptide fragments.

### Claim 4 (depends on 3)

The chimeric protein of claim 3, wherein each of the two or more mucoadhesive peptide fragments comprises about 11 to about 15 positively charged amino acid residues.

### Claim 5 (depends on 1)

The chimeric protein of claim 1, wherein the positively charged amino acid residues are selected from the group consisting of lysine, arginine, histidine, ornithine, and combinations thereof.

### Claim 6 (depends on 5)

The chimeric protein of claim 5, wherein the positively charged amino acid residues are lysines.

### Claim 7 (depends on 5)

The chimeric protein of claim 5, wherein the positively charged amino acid residues are histidines.

### Claim 8 (depends on 1)

The chimeric protein of claim 1, wherein the antibody or antigen binding fragment thereof inhibits binding of the SARS-CoV-2 S protein to a receptor of the SARS-CoV-2 S protein on a cell of the mucosa.

### Claim 9 (depends on 1)

The chimeric protein of claim 1, wherein the SARS-CoV-2 S protein is from SARS-CoV-2 or a variant thereof.

### Claim 10 (depends on 9)

The chimeric protein of claim 9, wherein the SARS-CoV-2 or variant thereof is selected from the group consisting of WIV4, a B.1.1.7 variant, a B.1.351 variant, a B.1.526 variant, a B1.526.1 variant, a B1.617 variant, a B.1.617.1 variant, a B.1.617.2 variant, a B1.617.3 variant, a P.2 variant, a P.1 variant, an A.23.1 variant, a CAL.20C variant, a B.1.427 variant, a B.1.429 variant, a B.1.525 variant, and a P.1.351 variant.

### Claim 11 (depends on 1)

The chimeric protein of claim 1, wherein the antibody or antigen binding fragment thereof comprises a heavy chain complementarity determining region (HC-CDR)1 comprising the amino acid sequence of SEQ ID NO: 37, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 38, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39, a light chain complementarity determining region (LC-CDR)1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 41, and an LC CDR3 comprising the amino acid sequence of SEQ ID NO: 42.

### Claim 12 (depends on 1)

The chimeric protein of claim 1, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 75, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 76.

### Claim 13 (depends on 1)

The chimeric protein of claim 1, wherein the antibody or antigen binding fragment thereof comprises:
(1) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 3, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 6;
(2) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 9, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 10, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12;
(3) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 13, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 15, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 16, the HC-LDR2 comprises the amino acid sequence of SEQ ID NO: 17, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18;
(4) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 21, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 22, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24;
(5) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 28, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30;
(6) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 35, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36;
(7) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 47, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 48;
(8) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 54; or
(9) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 57, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 58, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60.

### Claim 14 (depends on 1)

A pharmaceutical composition comprising the chimeric protein of claim 1 and a pharmaceutically acceptable carrier.

### Claim 15 (depends on 14)

The pharmaceutical composition of claim 14, comprising a plurality of chimeric proteins, wherein the antibodies or antigen binding fragments thereof of the chimeric proteins are different from each other.

### Claim 16 (depends on 14)

The pharmaceutical composition of claim 14, wherein the pharmaceutical composition is for nasal administration.

### Claim 17 (depends on 1)

An isolated nucleic acid or a set of isolated nucleic acids encoding the chimeric protein of claim 1.

### Claim 18 (depends on 1)

The chimeric protein of claim 1, wherein the antibody or antigen binding fragment thereof specifically binds an S1 subunit of the S protein of SARS-CoV-2.

### Claim 19 (depends on 1)

The chimeric protein of claim 1, wherein the antibody or antigen binding fragment thereof is a human antibody or antigen binding fragment thereof.

### Claim 20 (depends on 1)

The chimeric protein of claim 1, wherein the antibody is a full-length antibody.

### Claim 21 (depends on 20)

The chimeric protein of claim 20, wherein the full-length antibody is selected from the group consisting of an IgG, an IgA, an IgM, and an IgD.

### Claim 22 (depends on 1)

The chimeric protein of claim 1, wherein the antibody or antigen binding fragment thereof comprises an scFv comprising the amino acid sequence of SEQ ID NO: 87.