# US 10,478,510 B2 · Plant virus particles for delivery of antimitotic agents

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- Number: US 10,478,510 B2
- Document ID: US10478510B2
- Status: Granted
- Kind: B2
- Application number: 15/745,358
- Filed: 2016-07-18
- Published: 2018-07-19
- Granted: 2019-11-19
- Earliest claimed: 2015-07-16
- Assignees: Case Western Resrve University
- Applicants: Case Western Resrve University
- Inventors: Nicole F. Steinmetz
- Web page: https://patentgrep.com/patent/US10478510B2

## CPC

- A61K 47/6901: {Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors}
- A61K 31/401: Proline; Derivatives thereof, e.g. captopril
- A61K 39/12: Viral antigens
- A61K 47/646: {the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines}
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61K 47/6811: {the drug being a protein or peptide, e.g. transferrin or bleomycin}
- A61P 35/00: Antineoplastic agents
- C07K 5/06052: {Val-amino acid}
- 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)

## Abstract

Anti-lymphoma plant virus particles are described. The anti-lymphoma plant virus particles include a filamentous or rod-shaped plant virus particle linked to an antimitotic agent. A therapeutically effective amount of an anti-lymphoma plant virus particle can be administered to a subject to provide a method of treating lymphoma.

## Claims

### Claim 1

A method of treating lymphoma in a subject in need thereof: comprising ay administering to the subject a therapeutically effective amount of an anti-lymphoma virus particle, the anti-lymphoma virus particle comprising a tobacco mosaic virus particle linked to an antimitotic agent, wherein the antimitotic agent is covalently conjugated to the exterior of the plant virus particle.

### Claim 2 (depends on 1)

The method of claim 1, wherein the lymphoma is non-Hodgkin's lymphoma.

### Claim 3 (depends on 1)

The method of claim 1, wherein the anti-lymphoma virus particle is administered together with a pharmaceutically acceptable carrier.

### Claim 4 (depends on 1)

The method of claim 1, wherein the antimitotic agent is a dolastatin.

### Claim 5 (depends on 4)

The method of claim 4, wherein the doloastatin is monomethyl-auristatin-E (MMAE).

### Claim 6 (depends on 4)

The method of claim 4, wherein the dolastatin is valine-citrulline monomethyl-auristatin-E (vcMMAE).

### Claim 7 (depends on 1)

The method of claim 1, wherein a targeting ligand is attached to the exterior of the plant virus particle.

### Claim 8 (depends on 1)

The method of claim 1, wherein the plant virus particle is linked to an antimitotic agent with a linker that is cleavable during or upon internalization into a cell.

### Claim 9 (depends on 8)

The method of claim 8, wherein the antimitotic agent is non-active when linked to the plant virus particle and toxic when released within the endolysosome of the cell.

### Claim 10

A method of treating lymphoma in a subject in need thereof; comprising administering to the subject a therapeutically effective amount of an antilymphoma virus particle, the anti-lymphoma virus particle comprising a tobacco mosaic virus particle linked to an antimitotic agent with a linker that is cleavable during or upon internalization into a lymphoma cell, wherein the antimitotic agent is non-active when linked to the plant virus particle and toxic when released within the endolysosome of the cell.

### Claim 11 (depends on 10)

The method of claim 10, wherein the lymphoma is non-Hodgkin's lymphoma.

### Claim 12 (depends on 10)

The method of claim 10, wherein the antimitotic agent is a dolastatin.

### Claim 13 (depends on 12)

The method of claim 12, wherein the dolastatin is valine-citrulline monomethyl-auristatin-E (vcMMAE).