CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Alain, Tommy
Hoang, Huy-Dung
Graber, Tyson
Abstract
The present invention is directed to nucleic acids, vectors, compositions, kits, and cell lines comprising US11 5' leader sequence (SEQ ID NO: 1 or SEQ ID NO: 4), UL27 5' leader sequence (SEQ ID NO: 7 or SEQ ID NO: 10), or UL19 5' leader sequence (SEQ ID NO: 13 or SEQ ID NO: 16) whereby the leader sequences are capable of enhancing translation of a downstream gene encoding a protein of interest, resulting in increased protein production, expression or synthesis in HSV1 infected cells. The 5' leader increases protein expression by several fold compared to protein expression in the absence of the leader sequence. Methods of increasing protein production, methods of increasing efficiency of existing gene therapies, and methods of treating a medical condition, cellular defect, disease or disorder are also provided.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David F.
Abstract
The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynucleotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David F.
Abstract
The present disclosure provides a Farmington virus formulated to induce an immune response in a mammal against a tumour associated antigen. The Farmington virus may express an antigenic protein that includes an epitope from the tumour associated antigen. The Farmington virus may be formulated in a composition where the virus is separate from an antigenic protein that includes an epitope from the tumour associated antigen. The present disclosure also provides a prime:boost therapy for use in inducing an immune response in a mammal. The boost includes a Farmington virus, or a composition that includes a Farmington virus.
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
4.
METHODS FOR INDUCING AN IMMUNE RESPONSE AGAINST NEOANTIGENS
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David
Kmiecik, Justyna
Burgess, Michael F.
Abstract
In one aspect, provided herein is a heterologous boost method for inducing an immune response to at least one neoantigen, the method comprising administering to a subject a first boost and subsequently administering to the subject a second boost, wherein the first boost comprises a first oncolytic virus comprising a genome that expresses, in the subject, a first peptide, or the first boost comprises a first oncolytic virus and a second peptide, wherein the second boost comprises a second oncolytic virus comprising a genome that expresses, in the subject, a third peptide, or the second boost comprises a second oncolytic virus and a fourth peptide, wherein the first peptide, the second peptide, the third peptide, and the fourth peptide are each capable of inducing an immune response to at least one neoantigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus. The subject may have pre-existing immunity to the at least one neoantigen. The subject may have been administered a priming composition before receiving the first boost, wherein the priming composition is capable of inducing an immune response to the at least one neoantigen.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
TURNSTONE BIOLOGICS INC. (Canada)
Inventor
Stojdl, David
Kmiecik, Justyna
Burgess, Michael F.
Abstract
The present disclosure relates to a sequential boost oncolytic viral immunotherapy and compositions for use in the same. More particularly, the disclosure relates to oncolytic viruses that significantly increase antigen-specific T cell-mediated immune responses when combined in a sequential heterologous boost treatment regimen.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David F.
Abstract
The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynuclotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David
Kmiecik, Justyna
Burgess, Michael F.
Abstract
In one aspect, provided herein is a heterologous boost method for inducing an immune response to at least one neoantigen, the method comprising administering to a subject a first boost and subsequently administering to the subject a second boost, wherein the first boost comprises a first oncolytic virus comprising a genome that expresses, in the subject, a first peptide, or the first boost comprises a first oncolytic virus and a second peptide, wherein the second boost comprises a second oncolytic virus comprising a genome that expresses, in the subject, a third peptide, or the second boost comprises a second oncolytic virus and a fourth peptide, wherein the first peptide, the second peptide, the third peptide, and the fourth peptide are each capable of inducing an immune response to at least one neoantigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus. The subject may have pre-existing immunity to the at least one neoantigen. The subject may have been administered a priming composition before receiving the first boost, wherein the priming composition is capable of inducing an immune response to the at least one neoantigen.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David
Kmiecik, Justyna
Burgess, Michael F.
Abstract
The present disclosure relates to a sequential boost oncolytic viral immunotherapy and compositions for use in the same. More particularly, the disclosure relates to oncolytic viruses that significantly increase antigen-specific T cell-mediated immune responses when combined in a sequential heterologous boost treatment regimen.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
UNIVERSITY OF OTTAWA (Canada)
Inventor
Persano, Stefano
Stojdl, David
Abstract
A lipid nanoparticle composition is disclosed. The lipid nanoparticle composition includes: a core, and a lipid mixture encapsulating the core. The core includes: (i) a complex of a poly-(beta-amino ester) polymer with DNA or RNA; or (ii) a peptide. The lipid mixture encapsulating the core includes: (a) N1-[2-((1S)-1-[(3-aminopropyl)amino]-4-[di(3-amino-propyl)amino]butylcarboxamido)ethyl]-3,4-di[oleyloxy]-benzamide (MVL5); (b) 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE); and (c) a polyethylene glycol (PEG)-modified lipid. Uses and methods associated with the lipid nanoparticle composition are also disclosed.
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David F.
Abstract
The present disclosure provides a Farmington virus formulated to induce an immune response in a mammal against a tumour associated antigen. The Farmington virus may express an antigenic protein that includes an epitope from the tumour associated antigen. The Farmington virus may be formulated in a composition where the virus is separate from an antigenic protein that includes an epitope from the tumour associated antigen. The present disclosure also provides a prime:boost therapy for use in inducing an immune response in a mammal. The boost includes a Farmington virus, or a composition that includes a Farmington virus.
C07K 14/025 - Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Mccart, Judith, Andrea
Stojdl, David, Francis
Ho, Tiffany, Yun-Yee
Abstract
The disclosure provides a recombinant oncolytic poxvirus including vaccinia virus comprising one or more inactivated immunomodulatory gene selected from NIL, K1L, K3L, A46R, and/or A52R, optionally further comprising inactivated TK and/or VGF genes. The disclosure also provides methods and for the use of these recombinant oncolytic poxvirus in oncolytic virotherapy. Also provided in the disclosure are vector constructs for generating recombinant oncolytic poxviruses including for example vaccinia viruses that have one or more inactivated immunomodulatory genes.
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12N 15/39 - Poxviridae, e.g. vaccinia virus, variola virus
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE (Canada)
Inventor
Figeys, Joseph Michel Daniel
Stintzi, Alain Christophe
Mack, David R.
Zhang, Xu
Ning, Zhibin
Abstract
A method of isotope-labelling a microbiota sample. It involves providing a first microbiota sample that was obtained from a given source; exposing the first microbiota sample to an isotope enriched medium; and culturing the exposed first microbiota sample in the isotope enriched medium to obtain an isotope-labelled microbiota sample, wherein the isotope labelled metaproteome of the isotope-labelled microbiota sample is taxon specific for taxa present in the first microbiota sample when initially obtained from the given source.
C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving viable microorganisms
C12N 1/00 - Microorganisms, e.g. protozoaCompositions thereofProcesses of propagating, maintaining or preserving microorganisms or compositions thereofProcesses of preparing or isolating a composition containing a microorganismCulture media therefor
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Korneluk, Robert G.
Lacasse, Eric C.
Beug, Shawn T.
Tang, Vera A.
Abstract
The present invention includes methods and compositions for enhancing the efficacy of SMCs in the treatment of cancer. In particular, the present invention includes methods and compositions for combination therapies that include an SMC and at least a second agent that stimulates one or more apoptotic or immune pathways. The second agent may be, e.g., an immunostimulatory or immunomodulatory compound or oncolytic virus.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Korneluk, Robert G.
Beug, Shawn T.
Lacasse, Eric C.
Tang, Vera A.
Abstract
The present inventionIncludes methods and compositions for enhancing the efficacy of SMCs in the treatment of cancer. In particular, the present invention includes methods and compositions for combination therapies that include an SMC and at least a second agent that stimulates one or more apoptotic or immune pathways. The second agent may be, e.g., an immunostimulatory or immunomodulatory compound or oncolytic virus.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David F.
Abstract
The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynucleotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.
Disclosed are new approaches to detecting adenosine deaminase (ADA) deficiency. There is provided a method of determining ADA activity, comprising: dividing a sample obtained from blood into two portions, adding an ADA inhibitor to one portion, measuring levels of ADA activity in both portions, and determining the ADA activity. Also provided is a method of measuring ADA substrate, comprising: measuring an ADA substrate in a sample obtained from blood of subject, and comparing this to at least one control sample obtained from blood and comprising an ADA inhibitor, and a known quantity of the ADA substrate. Multiplexed methods of measuring ADA enzymatic activity along with other metabolic markers are also provided. The methods are particularly useful for the analysis of samples obtained from dried blood spots (DBSs), and may be incorporated into existing newborn screening programs. Associated diagnostic methods, control samples, and apparatuses are also disclosed.
C12Q 1/34 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase
G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers
G01N 33/483 - Physical analysis of biological material
G01N 33/49 - Physical analysis of biological material of liquid biological material blood
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
17.
COMPOSITIONS AND METHODS FOR GLIOBLASTOMA TREATMENT
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David F.
Abstract
The present disclosure concerns a Farmington rhabdovirus for the treatment of cancer, for example brain cancer, such as glioblastoma. The virus has a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6, 7, and at least one additional protein implicated in cell death; or variants thereof. Examples of such an additional protein include: mixed lineage kinase domain-like (MLKL), casepase 2 (CASP2), p15 BH3 interacting-domain death agonist, transcript variant 2 (BIDv2), and Bcl-2- associated death promoter (BAD). Specific examples of these proteins have the sequences shown in SEQ ID NOs: 13, 15, 17 and 19, respectively.
C07K 14/145 - Rhabdoviridae, e.g. rabies virus, Duvenhage virus, Mokola virus or vesicular stomatitis virus
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Korneluk, Robert G.
Lacasse, Eric C.
Beug, Shawn T.
Tang, Vera A.
Abstract
The present invention includes methods and compositions for enhancing the efficacy of SMCs in the treatment of cancer. In particular, the present invention includes methods and compositions for combination therapies that include an SMC and at least a second agent that stimulates one or more apoptotic or immune pathways. The second agent may be, e.g., an immunostimulatory compound or oncolytic virus.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
OTTAWA HOSPITAL RESEARCH INSTITUTE (Canada)
MCMASTER UNIVERSITY (Canada)
Inventor
Stojdl, David, F.
Bell, John, Cameron
Lichty, Brian
Pol, Jonathan
Abstract
There is described a kit for use in inducing an immune response in a mammal, the kit includes: a first virus that expresses MAGEA3, Human Papilloma Virus E6/E7 fusion protein, human Six-Transmembrane Epithelial Antigen of the Prostate protein, or Cancer Testis Antigen 1, or a variant thereof as an antigenic protein and that is formulated to generate an immunity to the protein or variant thereof in the mammal. The kit also includes a Maraba MG1 virus encoding the same antigen, or a variant of the same antigen. The Maraba MG1 virus is formulated to induce the immune response in the mammal. The first virus is immunologically distinct from the Maraba MG1 virus.
C07K 14/145 - Rhabdoviridae, e.g. rabies virus, Duvenhage virus, Mokola virus or vesicular stomatitis virus
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
OTTAWA HOSPITAL RESEARCH INSTITUTE (Canada)
Inventor
Stojdl, David
Bell, John, Cameron
Abstract
Described herein is an isolated viral particle having a genome that includes open reading frames that encode: Maraba proteins N, P, and L, or variants thereof; as well as Maraba protein M or protein delta 51M, or variants thereof; and a Bahia Grande G protein, a LCMV G protein, or an Ebola G protein. Maraba protein N may have a sequence which includes SEQ ID NO: 1. Maraba protein P may have a sequence which includes SEQ ID NO: 2. Maraba protein L may have a sequence which includes SEQ ID NO: 3. Maraba proteins M and delta 1M may have sequence which include SEQ ID NO: 4 and 5, respectively. Bahia Grande G protein may have a sequence which includes SEQ ID NO: 6. LCMV G protein may have a sequence which includes SEQ ID NO: 7. Ebola G protein may have a sequence which includes SEQ ID NO: 8.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David F.
Abstract
The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynucleotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David, F.
Abstract
The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynuclotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Bell, John, C.
Stojdl, David, F.
Abstract
Embodiments of the invention include compositions and methods related to Maraba virus and their use as anti-cancer therapeutics. Such rhabdoviruses possess tumor cell killing properties in vitro and in vivo.
CHILDREN'S HOSPITAL OF EASTERN ONTARIO RESEARCH INSTITUTE INC. (Canada)
Inventor
Stojdl, David
Abstract
Embodiments of the invention include compositions and methods related to non- VSV rhabdoviruses and their use as anti-cancer therapeutics. Such rhabdo viruses possess tumor cell killing properties in vitro and in vivo.
The invention features a method for identifying a compound that inhibits apoptosis (e.g., ER stress-induced apoptosis). This method includes the steps of (a) contacting a polypeptide having a HIAP2 BIR2 or HIAP2 BIR1-BIR2 linker region (e.g., a human HIAP2 BIR2 or HIAP2 BIR1-BIR2 linker region) with a candidate compound; and (b) determining whether the candidate compound binds the polypeptide.
G01N 33/566 - ImmunoassayBiospecific binding assayMaterials therefor using specific carrier or receptor proteins as ligand binding reagent
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
patents
