# US 2023/0053473 A1 · Enhancing expression of line-1 encoded orf2p for cancer therapeutics

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- Number: US 2023/0053473 A1
- Document ID: US20230053473A1
- Status: Published application
- Kind: A1
- Application number: 17/789,099
- Filed: 2020-12-26
- Published: 2023-02-23
- Earliest claimed: 2019-12-26
- Applicants: The Johns Hopkins University
- Inventors: Kathleen H. Burns
- Web page: https://patentgrep.com/patent/US20230053473A1

## CPC

- A61K 31/69: Boron compounds
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 31/24: having an amino or nitro group
- A61K 31/4015: having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
- A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles
- A61K 31/428: condensed with carbocyclic rings
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/52: Purines, e.g. adenine
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 38/05: Dipeptides
- A61K 38/06: Tripeptides
- A61K 38/07: Tetrapeptides
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07K 16/30: from tumour cells
- C07K 16/40: against enzymes
- G01N 33/575: for cancer
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C12N 2320/31: Combination therapy
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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

Methods for treating a neoplasia are provided. Further provided are novel targets for cancer chemotherapy including ORF2p Protein and methods for increasing expression of ORF2p in neoplasias. Monoclonal antibodies are also provided to various epitopes of ORF2p and their use in research and diagnostivds.

## Claims

### Claim 1

A method for treatment of a neoplasia in a cell or population of cells comprising:
increasing expression of ORF2p in the cell or population of cells.

### Claim 2 (depends on 1)

The method of claim 1 wherein the cell or cells are identified and/or selected for treatment based on an assessed level of ORF1p and/or ORF2p expression.

### Claim 3 (depends on 1)

The method of claim 1 wherein the cell or cells are identified and/or selected for treatment based on assessing reduced ORF2p expression as compared to ORF1p expression.

### Claim 4 (depends on 1)

The method of claim 1 wherein ORF2p expression is assessed to be less than ORF1p expression.

### Claim 5 (depends on 1)

The method of claim 1 wherein one or more PKR targeting agents are administered to the cell or cells.

### Claim 6 (depends on 1)

The method of claim 1 wherein a PKR targeting agent is administered to the cell or cells that is selected from 2-aminopurine, 6,8-dihydro-8-(1H-imidazol-5-ylmethylene)-7H-pyrrolo[2,3-g]benzothiazol-7-one, 6-amino-3-methyl-2-oxo-N-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-carboxamide, and 3-methyl-6-(methylsulphonamido)-2-oxo-N-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-carboxamide.

### Claim 7 (depends on 1)

The method of claim 1 wherein the method comprises contacting the cell or population of cells with a small RNA or SINEUP nucleic acid molecule that affects ORF2p translation. For SINEUP molecules, these might be specific for the inter-ORF spacer near the start codon of open reading frame 2 (ORF2).

### Claim 8 (depends on 1)

The method of claim 1 wherein one or more proteasomal inhibitors is administered to the cell or cells.

### Claim 9 (depends on 8)

The method of claim 8 wherein the proteasomal inhibitor is selected from the group consisting of: peptide aldehydes, peptide boronates, and nonpeptide inhibitors.

### Claim 10 (depends on 8)

The method of claim 8 wherein the proteasomal inhibitor is selected from the group consisting of: Epoxomicin, Lactacystin, Bortezomib, MG-132, Carfilzomib, MLN9708, Ixazomib, PI-1840, ONX-0914, Oprozomib, CEP-18770, and Gabexate Mesylate.

### Claim 11

A method for treatment of a neoplasia in a subject in need thereof, comprising administering to the subject a biologically active agent which increases expression of ORF2p in the neoplasia of the subject.

### Claim 12 (depends on 11)

The method of claim 11 further comprising:
identifying and/or selecting the subject for treatment based on an assessed level of ORF1p and/or ORF2p expression of a suspected neoplasia of the subject; and
administering to the subject a biologically active agent which increases expression of ORF2p in the neoplasia of the subject.

### Claim 13 (depends on 11)

The method of claim 11 further comprising:
identifying and/or selecting a subject's neoplasia for treament based on an assessed level of ORF1p and/or ORF2p expression of a suspected neoplasia of the subject; and
administering to the subject a biologically active agent which increases expression of ORF2p in the neoplasia of the subject.

### Claim 14 (depends on 11)

The method of claim 11 wherein ORF2p expression is reduced as compared to ORF1p expression.

### Claim 15 (depends on 11)

The method of claim 11 wherein the subject and/or neoplasia is selected for treatment based on assessing reduced ORF2p expression as compared to ORF1p expression.

### Claim 16 (depends on 11)

The method of claim 11 wherein the biologically active agent is a small RNA or SINEUP nucleic acid molecule that affects ORF2p translation.

### Claim 17 (depends on 11)

The method of claim 11 comprising administering to the subject a proteasomal inhibitor.

### Claim 18

(canceled)

### Claim 19 (depends on 17)

The method of claim 17 wherein the proteasomal inhibitor is selected from the group consisting of: Epoxomicin, Lactacystin, Bortezomib, MG-132, Carfilzomib, MLN9708, Ixazomib, PI-1840, ONX-0914, Oprozomib, CEP-18770, and Gabexate Mesylate.

### Claim 20 (depends on 1)

The method of claim 1 further comprising administering to the subject one or more additional chemotherapeutic agents.

### Claim 21

A monoclonal antibody that specifically binds ORF2p antigenic epitopes.

### Claim at position 22

22-25. (canceled)