# US 11,078,280 B2 · Oncolytic viral delivery of therapeutic polypeptides

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- Number: US 11,078,280 B2
- Document ID: US11078280B2
- Status: Granted
- Kind: B2
- Application number: 16/775,164
- Filed: 2020-01-28
- Published: 2020-05-21
- Granted: 2021-08-03
- Earliest claimed: 2016-06-30
- Assignees: Oncorus, Inc.
- Applicants: Oncorus, Inc.
- Inventors: Luke Evnin; Mitchell H. Finer
- Web page: https://patentgrep.com/patent/US11078280B2

## CPC

- C07K 16/2818: {against CD28 or CD152}
- A61K 35/76: Viruses; Subviral particles; Bacteriophages
- A61K 35/768: Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- C07K 14/4703: {Inhibitors; Suppressors}
- C07K 14/522: {Alpha-chemokines, e.g. NAP-2, ENA-78, GRO-alpha/MGSA/NAP-3, GRO-beta/MIP-2alpha, GRO-gamma/MIP-2beta, IP-10, GCP-2, MIG, PBSF, PF-4, KC}
- C07K 14/5434: {IL-12}
- C07K 14/5443: {IL-15}
- C07K 14/70503: {Immunoglobulin superfamily}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70532: {B7 molecules, e.g. CD80, CD86}
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/3092: {against tumour-associated mucins}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 9/6491: {Matrix metalloproteases [MMP's], e.g. interstitial collagenase (3.4.24.7); Stromelysins (3.4.24.17; 3.2.1.22); Matrilysin (3.4.24.23)}
- C12N 15/86: Viral vectors
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/31: multispecific
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/00: Fusion polypeptide
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C12N 2710/16633: Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory
- C12N 2710/16641: Use of virus, viral particle or viral elements as a vector
- C12N 2740/16032: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2740/16043: viral genome or elements thereof as genetic vector
- C12N 2760/20232: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2760/20243: viral genome or elements thereof as genetic vector
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Described herein are pseudotyped oncolytic viruses comprising nucleic acids encoding an engager molecule. In some embodiments, the pseudotyped oncolytic viruses comprises nucleic acids encoding an engager molecule and one or more therapeutic molecules. Pharmaceutical compositions containing the pseudotyped oncolytic virus and methods of treating cancer using the pseudotyped oncolytic viruses are further provided herein.

## Claims

### Claim 1

An oncolytic herpes simplex virus (HSV) comprising a recombinant nucleic acid comprising: i) a first nucleic acid sequence encoding a polypeptide comprising a first domain specific for an antigen expressed on an effector cell and a second domain that hinds to an antigen expressed on a target cell, wherein the antigen expressed on the target cell is FAP, PDL1 or CD47, and wherein the antigen expressed on the effector cell is CD3, CD16 or NKp46, and ii) a second nucleic acid sequence encoding an immune modulator polypeptide selected from the group consisting of a cytokine, a costimulatory molecule, an immune checkpoint polypeptide, an anti-angiogenesis factor, and a matrix metalloprotease (MMP).

### Claim 2 (depends on 1)

The oncolytic HSV of claim 1, wherein the antigen expressed on the target cell is FAP.

### Claim 3 (depends on 1)

The oncolytic HSV of claim 1, wherein the antigen expressed on the target cell is PDL1.

### Claim 4 (depends on 1)

The oncolytic HSV of claim 1, wherein the antigen expressed on the target cell is CD47.

### Claim 5 (depends on 1)

The oncolytic HSV of claim 1, wherein the antigen expressed on the effector cell is CD3.

### Claim 6 (depends on 1)

The oncolytic HSV of claim 1, wherein the first and second nucleic acid sequences are expressed from a single promoter sequence present in the recombinant nucleic acid.

### Claim 7 (depends on 1)

The oncolytic HSV of claim 1, wherein the first and second nucleic acids have a size of 7.2-38 kb.

### Claim 8 (depends on 1)

The oncolytic HSV of claim 1, wherein the HSV is HSV-1.

### Claim 9 (depends on 1)

The oncolytic HSV of claim 1, wherein the immune modulator polypeptide is a cytokine selected from IL-15, IL-12, and CXCL10.

### Claim 10 (depends on 1)

The oncolytic HSV of claim 1, wherein one or more HSV glycoproteins are modified to alter the tropism of the oncolytic HSV.

### Claim 11 (depends on 1)

The oncolytic HSV of claim 1, wherein the immune modulator polypeptide comprises (i) an inhibitor of any one of PD-1, CTLA-4, LAG3, TIM 3, neuropilin, or CCR4; (ii) an agonist of any one of GITR, OX-40, or CD28; or (iii) a combination of (i) and (ii).

### Claim 12 (depends on 1)

A pharmaceutical composition comprising the oncolytic HSV of claim 1.

### Claim 13 (depends on 12)

The pharmaceutical composition of claim 12, further comprising a pharmaceutically acceptable carrier.