RNA viruses expressing IL-12 for immunovirotherapy

• US 10,344,067 B2
• Filed: 02/24/2017
• Issued: 07/09/2019
• Est. Priority Date: 02/25/2016
• Status: Active Grant

• Current Assignee: Deutsches Krebsforschungszentrum, Ruprecht-Karls Universitaet
• Original Assignee: Deutsches Krebsforschungszentrum
• Inventors: Ungerechts, Guy, Engeland, Christine, Veinalde, Ruta
• Primary Examiner(s): Leavitt, Maria G
• Application Number:
  US15/441,545
• Publication Number:
  US 20170247425A1
• Time in Patent Office: 865 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: 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
• CPC Class Codes: C07K 14/5434 IL-12
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 16/3007 Carcino-embryonic Antigens
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C12N 2760/18043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2760/18432 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2760/18443 viral genome or elements thereof as genetic vector

Abstract

The present invention relates to a recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding an IL-12 polypeptide, wherein said IL-12 polypeptide is an IL-12 fusion polypeptide comprising a p35 subunit of an IL-12 and a p40 subunit of an IL-12; to a polynucleotide encoding the same, and to a kit comprising the same. Moreover, the present invention relates to a method for treating cancer in a subject afflicted with cancer, comprising contacting said subject with a recombinant virus of the family Paramyxoviridae of the invention, and thereby, treating cancer in a subject afflicted with cancer.

Claims

1. A recombinant virus of the family Paramyxoviridae comprising at least one expressible polynucleotide encoding an interleukin 12 (IL-12) polypeptide wherein said IL-12 polypeptide is a fusion protein comprising a p35 subunit of an IL-12 and a p40 subunit of an IL-12, wherein said polynucleotide optionally encodes a ligand for an immune checkpoint blockade protein or a binding domain to a tumor associated antigen, and wherein said recombinant virus is encoded by a polynucleotide comprising the nucleic acid sequence selected from the group consisting of SEQ ID NOS 4 to 7, 14 and 15.

2. A host cell comprising the recombinant virus of the family Paramyxoviridae according to claim 1.

3. A medicament comprising

(a) (i) the recombinant virus of the family Paramyxoviridae according to claim 1;

and/or

(a)(ii) a host cell comprising the recombinant virus of the family Paramyxoviridae according to claim 1; and

(b) at least one pharmacological acceptable excipient.

4. A method for treating cancer in a subject afflicted with cancer, comprising administering to said subject a therapeutically effective amount of the medicament according to claim 3, thereby treating cancer in a subject afflicted with cancer.

5. The method of claim 4, wherein said cancer is a solid cancer, a metastasis, or a relapse thereof.

6. The method of claim 4, wherein treating cancer is reducing tumor burden.

7. The method of claim 4, wherein said cancer is malignant melanoma, head and neck cancer, hepatocellular carcinoma, pancreatic carcinoma, prostate cancer, renal cell carcinoma, gastric carcinoma, colorectal carcinoma, lymphomas or leukemias.