Abstract

Provided are nucleic acid molecules encoding mutant Seneca Valley Virus (SVV) that evade neutralizing antibodies with a binding specificity to SVV, as well as nanoparticles containing rapamycin and SVV or mutant SVV. The mutant SVV comprise one or more mutations in one or more SVV epitopes that prevent binding of the mutant SVV to the neutralizing antibodies. The one or more mutations of the mutant SVV may be in one or more SVV epitopes. The epitopes may be inVP1, VP2, and/or VP3 subunits of SVV. Also provided are methods of producing and using the mutant SVV for treating cancer. Also provided are methods of treating a subject comprising administering to the subject the nanoparticles comprising SVV, or mutant SVV, and rapamycin. Also provided are methods of treating a subject comprising administering to the subject SVV or mutant SVV, and cyclophosphamide.

IPC Classes  ?

• A61K 39/125 - Picornaviridae, e.g. calicivirus
• C12N 15/09 - Recombinant DNA-technology
• G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
• A61K 35/768 - Oncolytic viruses not provided for in groups

Abstract

Provided herein in are armed Seneca Valley Viruses which have been altered to carry a therapeutic payload, i.e. to encode an agent for treating cancer. These armed Seneca Valley Viruses are oncolytic and express a cancer treating agent. Also provided herein are compositions and methods of using an armed Seneca Valley Virus to treat cancer in a subject.

IPC Classes  ?

• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• A61K 38/18 - Growth factorsGrowth regulators
• A61K 38/19 - CytokinesLymphokinesInterferons
• A61K 38/20 - Interleukins
• A61K 38/50 - Hydrolases (3) acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• C12N 15/86 - Viral vectors

Abstract

Provided herein are compositions and methods of using Seneca Valley Vims (SVV) or SVV derivative in combination with a checkpoint inhibitor for treating a cancer that is refractive to treatment by the checkpoint inhibitor. Also provided herein are kits containing a Seneca Valley Vims (SVV) or SVV derivative and a checkpoint inhibitor for treating a cancer that is refractive to treatment by the checkpoint inhibitor.

IPC Classes  ?

• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61P 35/00 - Antineoplastic agents
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Abstract

in vitro in vitro screening methods for cancers that are susceptible to treatment with SVV as well as methods of treating such cancers. Also provided herein are kits containing agents that may be used to screen for the biomarkers. Also disclosed methods of using the biomarkers to identify and treat poorly differentiated neuroendocrine carcinomas (NECs) and well-differentiated neuroendocrine tumors (NETs) with SVV-001 in combination with the programmed death receptor 1 (PD-1) immune checkpoint blocker (ICB: nivolumab).

IPC Classes  ?

• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12Q 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
• C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material

Abstract

Provided herein are compositions and methods of using Seneca Valley Virus (SVV) or a derivative thereof and an interferon type I (IFN-I) inhibiting agent comprising an mTOR inhibitor for treating a cancer in a subject. The disclosed methods particularly rely upon the expression level of an ANTXR1 and the expression level of IFN-I in the cancer from the subject. Also provided herein are methods for predicting the efficacy of an SVV treatment comprising IFN-I inhibiting agent.

IPC Classes  ?

• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
• A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Abstract

i.e i.e. to encode an agent for treating cancer. These armed Seneca Valley Viruses are oncolytic and express a cancer treating agent. Also provided herein are compositions and methods of using an armed Seneca Valley Virus to treat cancer in a subject.

IPC Classes  ?

• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C07K 14/55 - IL-2
• A61P 35/00 - Antineoplastic agents
• C12N 15/09 - Recombinant DNA-technology
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

Provided herein are compositions and methods of using Seneca Valley Vims (SVV) or SVV derivative in combination with a checkpoint inhibitor for treating a cancer that is refractive to treatment by the checkpoint inhibitor. Also provided herein are kits containing a Seneca Valley Virus (SVV) or SVV derivative and a checkpoint inhibitor for treating a cancer that is refractive to treatment by the checkpoint inhibitor.

IPC Classes  ?

• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material

Abstract

Provided herein are compositions and methods of using Seneca Valley Virus (SW), or a derivative thereof, combined with an IFN-I inhibitor for treating a cancer in a subject. The disclosed methods particularly rely upon the expression level of an ANTXR1 and the expression level of IFN-I in the cancer from the subject. Also provided herein are methods for predicting the efficacy of an SW treatment and a kit for determining the same.

IPC Classes  ?

• A61K 35/76 - VirusesSubviral particlesBacteriophages
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• A61P 35/00 - Antineoplastic agents

Abstract

Provided herein are compositions and methods of using Seneca Valley Virus (SW),or a derivative thereof, combined with an IFN-I inhibitor for treating a cancer in a subject. The disclosed methods particularly rely upon the expression level of an ANTXR1 and the expression level of IFN-I in the cancer from the subject. Also provided herein are methods for predicting the efficacy of an SW treatment and a kit for determining the same.

IPC Classes  ?

• A61K 35/76 - VirusesSubviral particlesBacteriophages
• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61K 38/21 - Interferons
• A61P 31/12 - Antivirals
• A61P 35/00 - Antineoplastic agents
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof