# US 2022/0033784 A1 · Recombinant vaccinia virus

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- Number: US 2022/0033784 A1
- Document ID: US20220033784A1
- Status: Published application
- Kind: A1
- Application number: 17/371,206
- Filed: 2021-07-09
- Published: 2022-02-03
- Earliest claimed: 2020-07-14
- Assignees: Pfizer Inc.
- Applicants: Pfizer Inc.
- Inventors: Joseph John Binder; Michael Dale Eisenbraun; Clare Lees; Jeremy Shawn Myers; James Travis Patterson
- Web page: https://patentgrep.com/patent/US20220033784A1

## CPC

- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 35/768: Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
- A61P 35/00: Antineoplastic agents
- C07K 14/005: from viruses
- C07K 14/55: IL-2
- C12N 15/86: Viral vectors
- 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)
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C12N 2710/16622: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2710/24121: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2710/24143: 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
- 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

The present disclosure provides human IL-2 variants, recombinant oncolytic viruses comprising the IL-2 variant, compositions comprising the IL-2 variant or recombinant oncolytic virus, and use of the IL-2 variants, recombinant oncolytic virus, or compositions for treating cancer in an individual.

## Claims

### Claim 1

An isolated human interleukin 2 (IL-2) variant comprising at least one amino acid substitution as compared to wild-type human IL-2 having the amino acid sequence as shown in SEQ ID NO: 1, wherein the IL-2 variant comprises one or more substitutions at amino acid positions selected from the group consisting of:
a) K35,
b) both R38 and L40,
c) both T41 and K43,
d) both K43 and Y45,
e) both E62 and K64, and
f) both L72 and Q74.

### Claim 2 (depends on 1)

An isolated fusion protein, comprising: a) an IL-2 variant of claim 1; and b) an Fc region of a human antibody, wherein the IL-2 variant is covalently linked to the Fc region.

### Claim at position 3

3-5. (canceled)

### Claim 6 (depends on 1)

A method for treating cancer in a subject, comprising administering to the subject in need thereof an effective amount of the IL-2 variant of claim 1.

### Claim 7 (depends on 1)

A recombinant oncolytic virus (OV), which comprises a nucleotide sequence encoding an IL-2 variant of claim 1.

### Claim at position 6

8-14. (canceled)

### Claim 15 (depends on 7)

The OV according to claim 7, wherein the IL-2 variant comprises the amino acid substitutions R38N, L40T, K43N, and Y45T.

### Claim 16 (depends on 7)

The OV according to claim 7, wherein the IL-2 variant comprises the amino acid sequence of SEQ ID NO:29 or SEQ ID NO:31.

### Claim 17 (depends on 7)

The OV according to claim 7, wherein the IL-2 variant comprises substitutions at amino acid positions K43, Y45, L72, and Q74.

### Claim 18 (depends on 7)

The OV according to claim 7, wherein the IL-2 variant comprises the amino acid substitutions K43N, Y45T, L72N, and Q74T.

### Claim 19 (depends on 7)

The OV according to claim 7, wherein the IL-2 variant comprises the amino acid sequence of SEQ ID NO:33 or SEQ ID NO:35.

### Claim 20

(canceled)

### Claim 21

(canceled)

### Claim 22 (depends on 7)

The OV of claim 7, which further comprises a nucleotide sequence encoding heterologous thymidine kinase (TK) polypeptide.

### Claim 23

(canceled)

### Claim 24 (depends on 22)

The OV of claim 22, wherein the heterologous TK polypeptide is a variant herpes simplex virus (HSV) TK polypeptide.

### Claim at position 17

25-28. (canceled)

### Claim 29 (depends on 24)

The OV of claim 24, wherein the variant HSV TK polypeptide comprises the amino acid sequence of SEQ ID NO: 26, 27, or 28.

### Claim 30 (depends on 7)

The OV of claim 7, wherein the virus comprises an A34R gene comprising a K151E substitution.

### Claim 31 (depends on 7)

The OV of claim 7, wherein the virus comprises a modification that renders the vaccinia thymidine kinase deficient.

### Claim 32

(canceled)

### Claim 33 (depends on 7)

The OV of claim 7, wherein the virus is a vaccinia virus.

### Claim 34 (depends on 33)

The OV of claim 33, wherein the vaccinia virus is a Copenhagen strain.

### Claim 35

(canceled)

### Claim 36 (depends on 7)

The OV of claim 7, comprising, in its genome: (1) a nucleotide sequence encoding a variant interleukin-2 (IL-2v) polypeptide comprising amino acid sequence of SEQ ID NO:29; (2) a nucleotide sequence encoding a heterologous thymidine kinase (TK) polypeptide comprising the amino acid sequence of SEQ ID NO: 28; and (3) a K151E substitution in the A34R gene, wherein the virus is a Copenhagen strain vaccinia virus and is vaccinia thymidine kinase deficient.

### Claim 37 (depends on 7)

A composition comprising: a) the OV of claim 7; and b) a pharmaceutically acceptable carrier.

### Claim 38 (depends on 37)

A method of treating cancer in an individual having a cancer, the method comprising administering to the individual an effective amount of the composition of claim 37.

### Claim at position 28

39-48. (canceled)

### Claim 49 (depends on 22)

A method of treating cancer in an individual, comprising administering to the individual: a) an effective amount of a recombinant oncolytic virus of claim 22; and b) a synthetic analog of 2′-deoxy-guanosine in an amount that is effective to reduce an adverse side effect of the oncolytic virus.

### Claim 50

(canceled)