# US 11,441,160 B2 · Compositions and methods for viral delivery of neoepitopes and uses thereof

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- Number: US 11,441,160 B2
- Document ID: US11441160B2
- Status: Granted
- Kind: B2
- Application number: 16/836,515
- Filed: 2020-03-31
- Published: 2020-09-17
- Granted: 2022-09-13
- Earliest claimed: 2015-12-07
- Assignees: Nant Holdings IP, LLC
- Applicants: Nant Holdings IP, LLC
- Inventors: Patrick Soon-Shiong; Shahrooz Rabizadeh; Kayvan Niazi
- Web page: https://patentgrep.com/patent/US11441160B2

## CPC

- C12N 15/86: Viral vectors
- A61K 35/761: Adenovirus
- A61K 38/19: Cytokines; Lymphokines; Interferons
- A61K 38/2013: {IL-2}
- A61K 38/2046: {IL-7}
- A61K 38/208: {IL-12}
- A61K 38/2086: {IL-13 to IL-16}
- A61K 39/0011: {Cancer antigens}
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2039/5256: {expressing foreign proteins}
- C12N 2710/10021: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2710/10043: viral genome or elements thereof as genetic vector
- C12N 2710/10343: viral genome or elements thereof as genetic vector
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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

## Abstract

Cancer immunotherapy is enhanced by co-expression of cancer associated or tumor-specific (neo)epitopes with co-stimulatory molecules and/or other immune activators. Where desired, treatment may be enhanced by administration of a immune checkpoint inhibitor.

## Claims

### Claim 1

A method of generating a recombinant nucleic acid, comprising:
assaying deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and inferred protein from matched tumor and histologically normal tissue samples from a patient to identify a patient-specific cancer-related neoepitope of the patient;
determining binding of the patient-specific cancer-related neoepitope to an HLA-type of the same patient, and determining an expression level of the patient-specific cancer-related neoepitope, wherein the determination of expression level uses mass spectroscopy based sequencing;
selecting at least one co-stimulatory molecule; and
genetically modifying an expression vector to include a nucleic acid encoding the at least one costimulatory molecule and the patient-specific cancer-related neoepitope, wherein the expression vector is an adenoviral or yeast or bacterial expression vector.

### Claim 2 (depends on 1)

The method of claim 1 wherein the cancer-related neoepitope of the patient is identified in silico by location-guided synchronous alignment of omics data of tumor and matched normal samples.

### Claim 3 (depends on 1)

The method of claim 1 further comprising a step of predicting the HLA type of the patient in silico.

### Claim 4 (depends on 1)

The method of claim 1 wherein the expression level of the patient-specific cancer-related neoepitope is at least 20% compared to a matched normal sample.

### Claim 5 (depends on 1)

The method of claim 1 wherein the co-stimulatory molecule is selected from the group of B7.1 (CD80), B7.2 (CD86), CD30L, CD40, CD40L, CD48, CD70, CD112, CD155, ICOS-L, 4-1BB, GITR-L, LIGHT, TIM3, TIM4, ICAM-1, and LFA3 (CD58).

### Claim 6 (depends on 1)

The method of claim 1 wherein the nucleic acid further comprises a sequence encoding a cytokine.

### Claim 7 (depends on 6)

The method of claim 6 wherein the cytokine is selected from the group consisting of IL-2, IL-7, IL-12, IL-15, an IL-15 superagonist (IL-15N72D), and an IL-15 superagonist/IL-15RαSushi-Fc fusion complex.

### Claim 8 (depends on 1)

The method of claim 1 wherein the nucleic acid further comprises a sequence encoding at least one component of a SMAC (supramolecular activation cluster).

### Claim 9 (depends on 8)

The method of claim 8 wherein the at least one component of the SMAC is selected form the group consisting of CD2, CD4, CD8, CD28, Lck, Fyn, LFA-1,CD43, and CD45 or their respective binding counterparts.

### Claim 10 (depends on 1)

The method of claim 1 wherein the nucleic acid further comprises a sequence encoding an activator of a STING (Stimulator of Interferon Gene) pathway.

### Claim 11 (depends on 10)

The method of claim 10 wherein the activator of the STING pathway comprises a chimeric protein in which a transmembrane domain of Latent membrane protein-1 (LMP1) of Epstein-Barr Virus (EBV) is fused to a signaling domain of Interferon Promoter Stimulator-1 (IPS-1).

### Claim 12 (depends on 1)

The method of claim 1 wherein the nucleic acid further comprises a sequence encoding at least a second distinct cancer-related neoepitope.

### Claim 13 (depends on 1)

The method of claim 1 wherein the nucleic acid that encodes the patient-specific cancer-related neoepitope further includes a trafficking sequence that directs the neoepitope to an endosomal or lysosomal compartment of a cell.