Disclosed herein are engineered nucleases that bind and cleave a recognition sequence within intron 1 of a transferrin gene, and methods of using such engineered nucleases to produce a genetically-modified eukaryotic cell comprising a modified transferrin gene. Further provided are pharmaceutical compositions and methods for treatment of a variety of conditions through expression of a polypeptide of interest encoded by an exogenous nucleic acid molecule inserted in intron 1 of a transferrin gene and expressed under the control of the endogenous transferrin promoter.
Disclosed are engineered nucleases that bind and cleave a recognition sequence within a hydroxyacid oxidase 1 (HAO1) gene. The present invention also encompasses methods of using such engineered nucleases to make genetically-modified cells. Further, the invention encompasses pharmaceutical compositions comprising engineered nuclease proteins or nucleic acids encoding engineered nucleases of the invention, and the use of such compositions for treatment of primary hyperoxaluria type I.
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
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
Disclosed are engineered meganucleases that bind and cleave a recognition sequence within a serine peptidase inhibitor, Clade A, Member 1 (SERPINA1) gene, which encodes alpha-1 antitrypsin (AAT). Further disclosed are donor polynucleotides that encode functional AAT proteins. The present disclosure also encompasses methods of using such engineered meganucleases and donor polynucleotides to make genetically-modified cells and use of such compositions for treatment of AAT deficiency.
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
C12N 15/90 - Stable introduction of foreign DNA into chromosome
4.
OPTIMIZED ENGINEERED MEGANUCLEASES HAVING SPECIFICITY FOR A RECOGNITION SEQUENCE IN THE HEPATITIS B VIRUS GENOME
The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced specificity and/or efficiency of indel formation, when compared to the first-generation meganuclease HBV 11-12x.26. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or hepatocellular carcinoma.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.
Disclosed are rationally-designed, non-naturally-occurring meganucleases in which a pair of enzyme subunits having specificity for different recognition sequence half-sites are joined into a single polypeptide to form a functional heterodimer with a non-palindromic recognition sequence. The invention also relates to methods of producing such meganucleases, and methods of producing recombinant nucleic acids and organisms using such meganucleases.
The present invention encompasses engineered meganucleases which recognize and cleave a recognition sequence within an open reading frame (ORF) of the genome of at least two genotypes of the Hepatitis B virus (HBV). The present invention also encompasses methods of using such engineered meganucleases in a pharmaceutical composition and in methods for treating or reducing the symptoms of a HBV infection, or treating hepatocellular carcinoma (HCC). Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or HCC.
The invention relates to the field of molecular biology and recombinant nucleic acid technology. In particular, the invention relates to a method of treating a patient with Duchenne Muscular Dystrophy comprising the removal of at least one exon from the dystrophin gene using engineered nucleases.
The present invention encompasses engineered meganucleases which recognize and cleave a recognition sequence within the human PCSK9 gene. The present invention also encompasses methods for using such engineered meganucleases in a pharmaceutical composition and in methods for treating or reducing the symptoms of cholesterol-related disorders, such as hypercholesterolemia. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating cholesterol-related disorders, such as hypercholesterolemia.
The present disclosure encompasses engineered meganucleases that comprise two subunits connected by a polypeptide linker that is smaller than polypeptide linkers used in the art. The engineered meganucleases can exhibit at least one improved characteristic, such as increased efficiency of binding and/or cleavage, when compared to meganucleases comprising longer polypeptide linkers. The present disclosure also encompasses methods of using engineered nucleases to make genetically-modified cells and the use of such cells in a pharmaceutical composition and in methods for treating diseases.
The present disclosure encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases described herein can exhibit improved characteristics, such as enhanced specificity and/or efficiency of indel formation, when compared to previously described HBV meganucleases. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or diseases associated with HBV infections.
The application relates to the field of oncology, cancer immunotherapy, molecular biology and recombinant nucleic acid technology. In particular, the invention relates to genetically-modified eukaryotic cells comprising modulated TGF Beta signaling. The application further relates to the use of such genetically-modified eukaryotic cells for treating a disease, including cancer, in a subject.
Disclosed are recombinant meganucleases engineered to recognize and cleave recognition sequences present in a mutant RHO P23H allele. The invention further relates to the use of such recombinant meganucleases in methods for treating retinitis pigmentosa, wherein the mutant RHO P23H allele is preferentially targeted, cleaved, and inactivated.
The present invention provides a method of treating a nucleotide repeat expansion disorder comprising delivering a pair of engineered nucleases, or genes encoding engineered nucleases, to the cells of a patient such that the two nucleases excise the nucleotide repeat responsible for the disease permanently from the genome. The invention provides a general method for treating nucleotide repeat expansion disorders and engineered nucleases suitable for practicing the method. The invention further provides vectors and techniques for delivering engineered nucleases to patient cells.
A method for expressing and delivering a polynucleotide encoding a protein of interest is provided herein. Specifically, the protein of interest can be a nuclease associated with a gene-editing system with increased half-life of the mRNA encoding an engineered nuclease, such that the protein level and the gene editing efficiency of the engineered nuclease is increased. In particular, the mRNA comprises a specific combination of 5′ UTR sequence, Kozak sequence, and 3′ UTR sequence. Further provided herein are pharmaceutical compositions comprising the polynucleotides, and methods of modifying the genome of a eukaryotic cells using the polynucleotides disclosed herein.
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
The present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, used in populations of subjects having cancer who previously received an autologous cell therapy, had a response, and subsequently relapsed.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
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
17.
POLYNUCLEOTIDES ENCODING ENGINEERED MEGANUCLEASES HAVING SPECIFICITY FOR RECOGNITION SEQUENCES IN THE DYSTROPHIN GENE
The present disclosure encompasses engineered meganucleases that bind and cleave recognition sequences within a dystrophin gene. The present disclosure also encompasses methods of using such engineered meganucleases to make genetically modified cells. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or polynucleotides encoding engineered meganucleases of the disclosure, and the use of such compositions for the modification of a dystrophin gene in a subject, or for treatment of Duchenne Muscular Dystrophy.
The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within the int22h-1 sequence of a Factor VIII gene. The present invention also encompasses methods of using such engineered nucleases to make genetically-modified cells, and the use of such cells in a pharmaceutical composition and in methods for treating hemophilia A. Further, the invention encompasses pharmaceutical compositions comprising engineered nuclease proteins, nucleic acids encoding engineered nucleases, or genetically-modified cells of the invention, and the use of such compositions for treating of hemophilia A.
The present disclosure encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, using particular lymphodepletion regimens in combination with particular populations of chimeric antigen receptor T cells.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 35/02 - Antineoplastic agents specific for leukemia
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
20.
GENE EDITING METHODS FOR TREATING ALPHA-1 ANTITRYPSIN (AAT) DEFICIENCY
Disclosed are engineered meganucleases that bind and cleave a recognition sequence within a serine peptidase inhibitor, Clade A, Member 1 (SERPINA1) gene, which encodes alpha-1 antitrypsin (AAT). Further disclosed are donor polynucleotides that encode functional AAT proteins. The present disclosure also encompasses methods of using such engineered meganucleases and donor polynucleotides to make genetically-modified cells and use of such compositions for treatment of AAT deficiency.
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
21.
RECOGNITION SEQUENCES FOR I-CREI-DERIVED MEGANUCLEASES AND USES THEREOF
Methods of cleaving double-stranded DNA that can be recognized and cleaved by a rationally-designed, I-Crel-derived meganuclease are provided. Also provided are recombinant nucleic acids, cells, and organisms containing such recombinant nucleic acids, as well as cells and organisms produced using such meganucleases. Also provided are methods of conducting a custom-designed, I-Crel-derived meganuclease business.
Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human T cell receptor alpha constant region gene. The present disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells.
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/66 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
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
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
Disclosed are engineered meganucleases that bind and cleave a recognition sequence within a hydroxyacid oxidase 1 (HAO1) gene. The present invention also encompasses methods of using such engineered meganucleases to make genetically-modified cells. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or nucleic acids encoding engineered meganucleases of the invention, and the use of such compositions for treatment of primary hyperoxaluria type I (PH1).
The present invention encompasses engineered meganucleases which recognize and cleave a recognition sequence within an open reading frame (ORF) of the genome of at least two genotypes of the Hepatitis B virus (HBV). The present invention also encompasses methods of using such engineered meganucleases in a pharmaceutical composition and in methods for treating or reducing the symptoms of a HBV infection, or treating hepatocellular carcinoma (HCC). Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or HCC.
Disclosed are recombinant meganucleases engineered to recognize and cleave recognition sequences present in a mutant RHO P23H allele. The invention further relates to the use of such recombinant meganucleases in methods for treating retinitis pigmentosa, wherein the mutant RHO P23H allele is preferentially targeted, cleaved, and inactivated.
The present invention encompasses engineered meganucleases that bind and cleave a recognition sequence within the first exon of the human T cell receptor (TCR) alpha constant region gene. The engineered meganucleases can exhibit at least one optimized characteristic, such as increased specificity or efficiency of cleavage, when compared to previous generations of meganucleases. The present invention also encompasses methods of using such engineered nucleases to make genetically-modified cells, and the use of such cells in a pharmaceutical composition and in methods for treating diseases, such as cancer.
Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in combination with mitochondrial transit peptides in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been modified or edited.
The invention relates to the field of molecular biology and recombinant nucleic acid technology. In particular, the invention relates to a method of treating a patient with Duchenne Muscular Dystrophy comprising the removal of at least one exon from the dystrophin gene using engineered nucleases.
Disclosed herein are recombinant meganucleases engineered to bind and cleave a recognition sequence in the mitochondrial DNA (mtDNA) of a eukaryotic cell, such as a plant cell. The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.
The present invention encompasses engineered meganucleases which recognize and cleave a recognition sequence within the human PCSK9 gene. The present invention also encompasses methods for using such engineered meganucleases in a pharmaceutical composition and in methods for treating or reducing the symptoms of cholesterol-related disorders, such as hypercholesterolemia. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating cholesterol-related disorders, such as hypercholesterolemia.
The present invention encompasses engineered meganucleases which recognize and cleave a recognition sequence within the human PCSK9 gene. The present invention also encompasses methods for using such engineered meganucleases in a pharmaceutical composition and in methods for treating or reducing the symptoms of cholesterol-related disorders, such as hypercholesterolemia. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating cholesterol-related disorders, such as hypercholesterolemia.
The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.
Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.
Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human beta-2 microglobulin gene. The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified T cells having reduced cell-surface expression of beta-2 microglobulin.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C12N 15/52 - Genes encoding for enzymes or proenzymes
C12N 15/62 - DNA sequences coding for fusion proteins
37.
OPTIMIZED ENGINEERED MEGANUCLEASES HAVING SPECIFICITY FOR A RECOGNITION SEQUENCE IN THE HEPATITIS B VIRUS GENOME
The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced specificity and/or efficiency of indel formation, when compared to the first-generation meganuclease HBV 11-12x.26. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or hepatocellular carcinoma.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
The present disclosure provides novel co-stimulatory domains useful in genetically-modified cells to promote cell proliferation and/or promote cytokine secretion after antigen recognition. For example, disclosed herein are genetically-modified cells comprising a chimeric antigen receptor or an inducible regulatory construct incorporating the co-stimulatory domains disclosed herein. Also disclosed herein are plasmids and viral vectors comprising a nucleic acid sequence encoding the co-stimulatory domains, and methods of administering compositions comprising the novel co-stimulatory domains to subjects in order to reduce the symptoms, progression, or occurrence of disease, such as cancer.
The present disclosure encompasses engineered meganucleases that bind and cleave recognition sequences within a dystrophin gene. The present disclosure also encompasses methods of using such engineered meganucleases to make genetically modified cells. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or polynucleotides encoding engineered meganucleases of the disclosure, and the use of such compositions for the modification of a dystrophin gene in a subject, or for treatment of Duchenne Muscular Dystrophy.
The present invention encompasses engineered meganucleases that bind and cleave a recognition sequence within a TTR gene. The present invention also encompasses methods of using such engineered meganucleases to make genetically-modified cells. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or nucleic acids encoding engineered meganucleases of the invention, and the use of such compositions for treatment of TTR-associated diseases, such as transthyretin amyloidosis.
The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within the first exon of the human T cell receptor (TCR) alpha constant region gene. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced (i.e., increased) specificity or efficiency of cleavage, when compared to the first-generation meganuclease TRC 1-2x.87EE. The present invention also encompasses methods of using such engineered nucleases to make genetically-modified cells, and the use of such cells in a pharmaceutical composition and in methods for treating diseases, such as cancer.
Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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
43.
Polynucleotides encoding engineered meganucleases having specificity for recognition sequences in the dystrophin gene
The present disclosure encompasses engineered meganucleases that bind and cleave recognition sequences within a dystrophin gene. The present disclosure also encompasses methods of using such engineered meganucleases to make genetically modified cells. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or polynucleotides encoding engineered meganucleases of the disclosure, and the use of such compositions for the modification of a dystrophin gene in a subject, or for treatment of Duchenne Muscular Dystrophy.
Disclosed are rationally-designed, non-naturally-occurring meganucleases in which a pair of enzyme subunits having specificity for different recognition sequence half-sites are joined into a single polypeptide to form a functional heterodimer with a non-palindromic recognition sequence. The invention also relates to methods of producing such meganucleases, and methods of producing recombinant nucleic acids and organisms using such meganucleases.
The invention provides engineered meganucleases, derived from I-Cre1, which have substitutions at particular positions that increase the activity of the nucleases for recognition sequences containing certain center sequences. The invention also provides methods of cleaving double-stranded DNA using such engineered meganucleases. The invention further provides methods for improving the activity of engineered meganucleases for recognition sequences containing certain center sequences.
Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.
The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.
C07H 21/02 - 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 ribosyl as saccharide radical
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A method for expressing and delivering a polynucleotide encoding a protein of interest is provided herein. Specifically, the protein of interest can be a nuclease associated with a gene-editing system with increased half-life of the mRNA encoding an engineered nuclease, such that the protein level and the gene editing efficiency of the engineered nuclease is increased. In particular, the mRNA comprises a specific combination of 5' UTR sequence, Kozak sequence, and 3' UTR sequence. Further provided herein are pharmaceutical compositions comprising the polynucleotides, and methods of modifying the genome of a eukaryotic cells using the polynucleotides disclosed herein.
The present invention provides a method of treating a nucleotide repeat expansion disorder comprising delivering a pair of engineered nucleases, or genes encoding engineered nucleases, to the cells of a patient such that the two nucleases excise the nucleotide repeat responsible for the disease permanently from the genome. The invention provides a general method for treating nucleotide repeat expansion disorders and engineered nucleases suitable for practicing the method. The invention further provides vectors and techniques for delivering engineered nucleases to patient cells.
Disclosed are recombinant meganucleases engineered to bind and cleave a recognition sequence present in a mutant RHO P23H allele. The invention further relates to the use of such recombinant meganucleases in a method for treating retinitis pigmentosa, wherein the mutant RHO P23H allele is preferentially targeted, cleaved, and inactivated.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
The present invention encompasses methods for reducing the number of target cells in a subject, such as cancer cells. The methods include administration of genetically-modified human immune cells expressing a chimeric antigen receptor or exogenous T cell receptor, which have specificity for an antigen on the target cells Administration of the genetically-modified immune cells can be preceded by the administration of a lymphodepletion region and/or an immunosuppression regimen, to improve efficacy of the therapy and persistence of the cells in vivo.
A61K 31/7056 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
Disclosed herein are viral vectors for use in recombinant molecular biology techniques. In particular, the present disclosure relates to self-limiting viral vectors comprising genes encoding site-specific endonucleases as well as recognition sequences for site-specific endonucleases such that expression of the endonuclease in a cell cleaves the viral vector and limits its persistence time. In some embodiments, the viral vectors disclosed herein also carry directives to delete, insert, or change a target sequence.
Disclosed herein are viral vectors for use in recombinant molecular biology techniques. In particular, the present disclosure relates to self-limiting viral vectors containing nucleic acid sequences that encode engineered nucleases as well as nuclease recognition sequences such that expression of the engineered nuclease in a cell cleaves the viral vector and limits its persistence time. In some embodiments, the viral vectors disclosed herein also carry directives to delete, insert, or change a target sequence.
The present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, used in populations of subjects having cancer who previously received an autologous cell therapy, had a response, and subsequently relapsed.
The present invention encompasses compositions and methods for the sequential stacking of donor nucleic acids into a single genomic locus within a cell to allow for the introduction of relatively long nucleic sequences. This allows for insertion into the genome of a donor nucleic acid sequence that exceeds the packaging capacity of a single adeno-associated viral vector.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
The present disclosure encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, using particular lymphodepletion regimens in combination with particular populations of chimeric antigen receptor T cells.
The present invention encompasses methods of reducing the number of target cells in a subject, reducing host rejection of genetically-modified immune cells, and/or reducing the killing of genetically-modified immune cells by nucleoside analogs. In particular, the methods of the invention utilize genetically-modified immune cells comprising an engineered antigen receptor that have reduced expression of deoxycytidine kinase (dCK) protein.
SERPINA1SERPINA1) gene, which encodes alpha- 1 antitrypsin (AAT). Further disclosed are donor polynucleotides that encode functional AAT proteins. The present disclosure also encompasses methods of using such engineered meganucleases and donor polynucleotides to make genetically-modified cells and use of such compositions for treatment of AAT deficiency.
SERPINA1SERPINA1) gene, which encodes alpha-1 antitrypsin (AAT). Further disclosed are donor polynucleotides that encode functional AAT proteins. The present disclosure also encompasses methods of using such engineered meganucleases and donor polynucleotides to make genetically-modified cells and use of such compositions for treatment of AAT deficiency.
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
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 11/00 - Drugs for disorders of the respiratory system
The present disclosure provides antibodies, and fragments thereof, having specificity for human B cell maturation antigen (BCMA), as well as chimeric antigen receptors (CARs) comprising such antibodies and antigen-binding fragments, and genetically modified cells comprising such CARs. Also provided are methods of using such cells in combination with gamma secretase inhibitors for the treatment of disorders and diseases associated with BCMA, such as cancer.
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 5/0783 - T cellsNK cellsProgenitors of T or NK cells
61.
Polynucleotides encoding engineered meganucleases having specificity for recognition sequences in the dystrophin gene
The present disclosure encompasses engineered meganucleases that bind and cleave recognition sequences within a dystrophin gene. The present disclosure also encompasses methods of using such engineered meganucleases to make genetically modified cells. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or polynucleotides encoding engineered meganucleases of the disclosure, and the use of such compositions for the modification of a dystrophin gene in a subject, or for treatment of Duchenne Muscular Dystrophy.
The present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, using particular lymphodepletion regimens in combination with particular populations of chimeric antigen receptor T cells expressing anti CD19 CAR PBCAR0191, anti CD20 CAR PBCAR20A or anti BCMA CAR PBCAR269A.
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
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
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced specificity and/or efficiency of indel formation, when compared to previously described HBV meganucleases. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or hepatocellular carcinoma.
Provided herein are compositions and methods for the treatment of a disease, such as cancer, using a chimeric antigen receptor or genetically-modified cells comprising a chimeric antigen receptor having specificity for CD20. The invention provides polynucleotides encoding such chimeric antigen receptors, and genetically-modified cells comprising such chimeric antigen receptors. Also provided are methods for making such genetically-modified cells and pharmaceutical compositions comprising the same. The invention further provides methods for treating a disease (e.g., cancer) in a subject by administering such genetically-modified cells or compositions. The main embodiments concern CARs with an scFv specific for CD20, the hinge and transmembrane domains from CD8, the costimulatory cytoplasmic or signalling domain from co-stimulatory molecules Novell (N1) or Novel6 (N6) and the CD3zeta intracellular signaling domain.
Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in combination with mitochondrial transit peptides in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been modified or edited.
Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.
Disclosed herein are recombinant meganucleases engineered to bind and cleave a recognition sequence in the mitochondrial DNA (mtDNA) of a eukaryotic cell, such as a plant cell. The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.
Methods of inserting genes into defined locations in the chromosomal DNA of cultured mammalian cell lines which are subject to gene amplification are disclosed. In particular, sequences of interest (e.g., genes encoding biotherapeutic proteins) are inserted proximal to selectable genes in amplifiable loci, and the transformed cells are subjected to selection to induce co-amplification of the selectable gene and the sequence of interest. The invention also relates to meganucleases, vectors and engineered cell lines necessary for performing the methods, to cell lines resulting from the application of the methods, and use of the cell lines to produce protein products of interest.
The present invention encompasses methods and compositions including genetically-modified cells expressing chimeric antigen receptors or exogenous T cell receptors, and pharmaceutical compositions thereof, for the treatment of cancer and other disorders and diseases. Further, provided herein are methods for depleting lymphocytes in a subject in need of treatment prior to, concomitant with, or following administration of the genetically-modified cells provided herein.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 38/50 - Hydrolases (3) acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The application relates to the field of oncology, cancer immunotherapy, molecular biology and recombinant nucleic acid technology. In particular, the invention relates to genetically-modified eukaryotic cells comprising modulated TGF Beta signaling. The application further relates to the use of such genetically-modified eukaryotic cells for treating a disease, including cancer, in a subject.
A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
71.
NUCLEIC ACID MOLECULES ENCODING AN ENGINEERED ANTIGEN RECEPTOR AND AN INHIBITORY NUCLEIC ACID MOLECULE AND METHODS OF USE THEREOF
The present disclosure provides nucleic acid molecules encoding an engineered antigen receptor, such as a chimeric antigen receptor or exogenous T cell receptor, and an inhibitory nucleic acid molecule, such as an RNA interference molecule. The present disclosure further relates to nucleic acids, DNA constructs, vectors, pharmaceutical compositions, genetically-modified cells, and methods of treatment that utilize the nucleic acid molecules of the invention.
C07K 14/74 - Major histocompatibility complex [MHC]
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 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
72.
ENGINEERED MEGANUCLEASES HAVING SPECIFICITY FOR A RECOGNITION SEQUENCE IN THE HYDROXYACID OXIDASE 1 GENE
Disclosed are engineered meganucleases that bind and cleave a recognition sequence within a hydroxyacid oxidase 1 (HAO1) gene. The present invention also encompasses methods of using such engineered meganucleases to make genetically-modified cells. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or nucleic acids encoding engineered meganucleases of the invention, and the use of such compositions for treatment of primary hyperoxaluria type I (PH1).
The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.
C07H 21/02 - 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 ribosyl as saccharide radical
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 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
74.
METHODS OF PREPARING POPULATIONS OF GENETICALLY-MODIFIED IMMUNE CELLS
The present disclosure provides methods for preparing a population of genetically-modified immune cells. The methods include contacting a population of immune cells with lipid nanoparticles in the presence of an apolipoprotein. The lipid nanoparticles include mRNA encoding an engineered nuclease having specificity for a recognition sequence in the genome of the immune cells. The mRNA is delivered into the immune cells and the engineered nuclease is expressed, generating a cleavage site at the recognition sequence. Further provided are populations of genetic ally-modified immune cells produced according to the disclosed methods, pharmaceutical compositions containing such cells, and methods of treating diseases with the genetically-modified immune cells.
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/62 - DNA sequences coding for fusion proteins
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Genome editing reagents (term considered too vague by the
International Bureau - Rule 13 (2) (b) of the Regulations);
chemical, biochemical, biotechnological products intended
for industry, agriculture, horticulture, namely polypeptides
for in vivo and in vitro genetic engineering, natural and
engineered meganucleases and endonucleases, nucleic acid
vectors, molecular scissors; chemical, biochemical,
biotechnological and bacteriological products intended for
research laboratories and control laboratories, namely
polypeptides for in vivo and in vitro genetic engineering;
biochemicals and biologics, namely, engineered proteins for
gene regulation, genome engineering, gene modulation,
transcriptional regulation, transcriptional modulation, gene
modification, and gene correction, all for use in scientific
research, pharmaceutical research, agricultural
biotechnology, diagnostics, and industrial biotechnology;
engineered proteins for use in scientific research and
analysis relating to genetic diseases, gene therapy, and
cell therapy; biochemicals and biologics, namely, engineered
nucleic acids, viral vectors, non-viral vectors, gene
therapy vectors, gene editing vectors, genetically modified
cells, engineered proteins for multiplexed gene editing,
mRNA and recombinant adeno-associated virus (AAV) vectors
for delivery of therapeutic DNA or mRNA sequences to cells,
antibody preparations, CAR T-cell preparations, T-cell
preparations, B-cell preparations, Treg preparations, and NK
cell preparations, all for use in scientific research and
analysis and diagnostics. Pharmaceutical preparations, namely, cell therapy products
utilizing T-cell therapy for use in treating disease;
pharmaceuticals for the treatment of cancer; pharmaceutical
preparations in the nature of genetically modified cells,
namely genetically modified immune cells for use in human
therapeutics and in the treatment of cancer; pharmaceutical
and biological preparations based on gene, genome and
cellular editing, modulation, modification, engineering,
regulation, repair and therapy for use in human
therapeutics, namely, therapeutic pharmaceuticals developed
through genome modifications for the treatment of
cardiovascular, central nervous system, endocrine,
gastrointestinal, genetic immunological, infectious,
inflammatory, menopausal, metabolic, autoimmune,
musculoskeletal, neurological, ophthalmological,
psychiatric, respiratory, urogenital, urological,
hematologic and viral diseases and disorders; pharmaceutical
preparations, namely, therapeutic pharmaceuticals developed
through genome modifications for the treatment of erectile
dysfunction, sexual dysfunction, cancer, pain and diabetes;
pharmaceutical preparations, namely, therapeutic
pharmaceuticals developed through genome modifications,
namely, antifungal preparations, dermatological
preparations, smoking cessation preparations and tissue
repair preparations; engineered nucleic acids, viral
vectors, non-viral vectors, gene therapy vectors, gene
editing vectors, genetically modified cells, engineered
proteins for multiplexed gene editing, mRNA and recombinant
adeno-associated virus (AAV) vectors for delivery of
therapeutic DNA or mRNA sequences to cells, antibody
preparations, CAR T-cell preparations, T-cell preparations,
B-cell preparations, Treg preparations, and NK cell
preparations, all for clinical use, medical use, clinical
laboratory use, and medical laboratory use. Research in the fields of genome editing, gene editing,
genome engineering, gene modulation, transcriptional
regulation, transcriptional modulation, genetic disease,
gene therapy and cell therapy; pharmaceutical research and
development services; scientific and industrial research;
research in genetic, medical, pharmaceutical and veterinary
fields; research in chemistry, biology, biochemistry,
molecular biology, bacteriology; scientific analysis. Cellular immunotherapy programs utilizing chimeric antigen
receptor t cells for use in treating disease, namely, the
treatment of cancer; cell-based immunotherapeutic treatment
by way of genetically modified cells for use in human
therapeutics and the treatment of cancer.
76.
NUCLEIC ACIDS ENCODING ENGINEERED MEGANUCLEASES WITH RECOGNITION SEQUENCES FOUND IN THE HUMAN T CELL RECEPTOR ALPHA CONSTANT REGION GENE
Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human T cell receptor alpha constant region gene. The present disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells.
A61K 47/66 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
The present disclosure encompasses engineered meganucleases that bind and cleave recognition sequences within a dystrophin gene. The present disclosure also encompasses methods of using such engineered meganucleases to make genetically modified cells. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or polynucleotides encoding engineered meganucleases of the disclosure, and the use of such compositions for the modification of a dystrophin gene in a subject, or for treatment of Duchenne Muscular Dystrophy.
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
78.
GENETICALLY-MODIFIED CELLS COMPRISING A MODIFIED TRANSFERRIN GENE
Disclosed herein are engineered nucleases that bind and cleave a recognition sequence within intron 1 of a transferrin gene, and methods of using such engineered nucleases to produce a genetically-modified eukaryotic cell comprising a modified transferrin gene. Further provided are pharmaceutical compositions and methods for treatment of a variety of conditions through expression of a polypeptide of interest encoded by an exogenous nucleic acid molecule inserted in intron 1 of a transferrin gene and expressed under the control of the endogenous transferrin promoter.
The present invention provides lipid nanoparticle compositions, and methods of using the same, that are useful for introducing nucleic acids into eukaryotic cells, such as human immune cells. Generally, the lipid nanoparticles described herein comprise an apolipoprotein that is bound to one component of the lipid nanoparticles. The apolipoprotein can be bound to the lipid nanoparticle components by various types of bonds, including covalent bonds. The invention further provides methods for transfecting eukaryotic cells with such lipid nanoparticles, populations of eukaryotic cells, pharmaceutical compositions, and methods of treatment and use.
A61K 9/00 - Medicinal preparations characterised by special physical form
C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
80.
GENETIC MODIFICATION OF THE HYDROXYACID OXIDASE 1 GENE FOR TREATMENT OF PRIMARY HYPEROXALURIA
Disclosed are engineered nucleases that bind and cleave a recognition sequence within a hydroxyacid oxidase 1 (HAO1) gene. The present invention also encompasses methods of using such engineered nucleases to make genetically-modified cells. Further, the invention encompasses pharmaceutical compositions comprising engineered nuclease proteins or nucleic acids encoding engineered nucleases of the invention, and the use of such compositions for treatment of primary hyperoxaluria type I.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
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
The present invention encompasses engineered meganucleases that bind and cleave a recognition sequence within a TTR gene. The present invention also encompasses methods of using such engineered meganucleases to make genetically-modified cells. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or nucleic acids encoding engineered meganucleases of the invention, and the use of such compositions for treatment of TTR-associated diseases, such as transthyretin amyloidosis.
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
82.
Polynucleotides encoding optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome
The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced specificity and/or efficiency of indel formation, when compared to the first-generation meganuclease HBV 11-12x.26. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or hepatocellular carcinoma.
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
The present disclosure provides antibodies, and fragments thereof, having specificity for human B cell maturation antigen, pharmaceutical compositions thereof, and uses thereof. Also provided are chimeric antigen receptors (CARs) comprising such antibodies or antibody fragments, genetically-modified cells comprising such CARs, pharmaceutical compositions comprising such cells, methods for making such cells, and methods of using such cells for the treatment of disorders and diseases, such as cancer.
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
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.
Disclosed are recombinant meganucleases engineered to bind and cleave a recognition sequence present in a mutant RHO P23H allele. The invention further relates to the use of such recombinant meganucleases in a method for treating retinitis pigmentosa, wherein the mutant RHO P23H allele is preferentially targeted, cleaved, and inactivated.
The present invention encompasses methods for reducing the number of target cells in a subject, such as cancer cells. The methods include administration of genetically-modified human immune cells expressing a chimeric antigen receptor or exogenous T cell receptor, which have specificity for an antigen on the target cells. Administration of the genetically-modified immune cells can be preceded by the administration of a lymphodepletion region and/or an immunosuppression regimen, to improve efficacy of the therapy and persistence of the cells in vivo.
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
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
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
(1) Genome editing reagents for research purposes; chemical, biochemical, biotechnological products intended for industry, agriculture, horticulture, namely polypeptides for in vivo and in vitro genetic engineering, natural and engineered meganucleases and endonucleases, nucleic acid vectors, molecular scissors; chemical, biochemical, biotechnological and bacteriological products intended for research laboratories and control laboratories, namely polypeptides for in vivo and in vitro genetic engineering; biochemicals and biologics, namely, engineered proteins for gene regulation, genome engineering, gene modulation, transcriptional regulation, transcriptional modulation, gene modification, and gene correction, all for use in scientific research, pharmaceutical research, agricultural biotechnology, diagnostics, and industrial biotechnology; engineered proteins for use in scientific research and analysis relating to genetic diseases, gene therapy, and cell therapy; biochemicals and biologics, namely, engineered nucleic acids, viral vectors, non-viral vectors, gene therapy vectors, gene editing vectors, genetically modified cells, engineered proteins for multiplexed gene editing, mRNA and recombinant adeno-associated virus (AAV) vectors for delivery of therapeutic DNA or mRNA sequences to cells, antibody preparations, CAR T-cell preparations, T-cell preparations, B-cell preparations, Treg preparations, and NK cell preparations, all for use in scientific research and analysis and diagnostics.
(2) Pharmaceutical preparations, namely, cell therapy products utilizing T-cell therapy for use in treating disease; pharmaceuticals for the treatment of cancer; pharmaceutical preparations in the nature of genetically modified cells, namely genetically modified immune cells for use in human therapeutics and in the treatment of cancer; pharmaceutical and biological preparations based on gene, genome and cellular editing, modulation, modification, engineering, regulation, repair and therapy for use in human therapeutics, namely, therapeutic pharmaceuticals developed through genome modifications for the treatment of cardiovascular, central nervous system, endocrine, gastrointestinal, genetic immunological, infectious, inflammatory, menopausal, metabolic, autoimmune, musculoskeletal, neurological, ophthalmological, psychiatric, respiratory, urogenital, urological, hematologic and viral diseases and disorders; pharmaceutical preparations, namely, therapeutic pharmaceuticals developed through genome modifications for the treatment of erectile dysfunction, sexual dysfunction, cancer, pain and diabetes; pharmaceutical preparations, namely, therapeutic pharmaceuticals developed through genome modifications, namely, antifungal preparations, dermatological preparations for the treatment of genetic conditions, namely, cancer, smoking cessation preparations and tissue repair preparations; engineered nucleic acids, viral vectors, non-viral vectors, gene therapy vectors, gene editing vectors, genetically modified cells, engineered proteins for multiplexed gene editing, mRNA and recombinant adeno-associated virus (AAV) vectors for delivery of therapeutic DNA or mRNA sequences to cells, antibody preparations, CAR T-cell preparations, T-cell preparations, B-cell preparations, Treg preparations, and NK cell preparations, all for clinical use, medical use, clinical laboratory use, and medical laboratory use. (1) Research in the fields of genome editing, gene editing, genome engineering, gene modulation, transcriptional regulation, transcriptional modulation, genetic disease, gene therapy and cell therapy; pharmaceutical research and development services; scientific research in genetic, medical, pharmaceutical, and veterinary fields; scientific research for medical purposes in the field of cancerous diseases; scientific analysis in the field of immunotherapy; scientific research in the field of cellular immunotherapy utilizing chimeric antigen receptor t cells for use in treating cancer; scientific research in genetic, medical, pharmaceutical and veterinary fields; scientific research in chemistry, biology, biochemistry, molecular biology, bacteriology.
(2) Medical services, namely, cellular immunotherapy programs utilizing chimeric antigen receptor t cells for use in treating disease, namely, the treatment of cancer; cell-based immunotherapeutic treatment by way of genetically modified cells for use in human therapeutics and the treatment of cancer.
Disclosed herein are viral vectors for use in recombinant molecular biology techniques. In particular, the present disclosure relates to self-limiting viral vectors containing nucleic acid sequences that encode engineered nucleases as well as nuclease recognition sequences such that expression of the engineered nuclease in a cell cleaves the viral vector and limits its persistence time. In some embodiments, the viral vectors disclosed herein also carry directives to delete, insert, or change a target sequence.
The present invention encompasses methods for reducing the number of target cells in a subject, such as cancer cells. The methods include administration of genetically-modified human immune cells expressing a chimeric antigen receptor or exogenous T cell receptor, which have specificity for an antigen on the target cells. Administration of the genetically- modified immune cells is preceded by the administration of a tolerance regimen, followed by administration of a lymphodepletion regimen, to improve efficacy of the therapy and persistence of the cells in vivo.
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
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
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
genome editing reagents for research purposes; Chemical, biochemical, biotechnological products intended for industry, agriculture, horticulture, namely, polypeptides for in vivo and in vitro genetic engineering, natural and engineered meganucleases and endonucleases, nucleic acid vectors, molecular scissors; chemical, biochemical, biotechnological and bacteriological products intended for research laboratories and control laboratories, namely, polypeptides for in vivo and in vitro genetic engineering; Biochemicals and biologics, namely, engineered proteins for gene regulation, genome engineering, gene modulation, transcriptional regulation, transcriptional modulation, gene modification, and gene correction, all for use in scientific research, pharmaceutical research, agricultural biotechnology, diagnostics, and industrial biotechnology; engineered proteins for use in scientific research and analysis relating to genetic diseases, gene therapy, and cell therapy; biochemicals and biologics, namely, engineered nucleic acids, viral vectors, non-viral vectors, gene therapy vectors, gene editing vectors, genetically modified cells, engineered proteins for multiplexed gene editing, mRNA and recombinant adeno-associated virus (AAV) vectors for delivery of therapeutic DNA or mRNA sequences to cells, antibody preparations, CAR T-cell preparations, T-cell preparations, B-cell preparations, Treg preparations, and NK cell preparations, all for use in scientific research and analysis and diagno pharmaceutical preparations, namely, cell therapy products utilizing t-cell therapy for use in treating disease; cell-based immunotherapeutic treatment by way of genetically modified cells for use in human therapeutics and the treatment of cancer; pharmaceuticals for the treatment of cancer; pharmaceutical preparations in the nature of genetically modified cells, namely, genetically modified immune cells for use in human therapeutics and in the treatment of cancer; pharmaceutical and biological preparations based on gene, genome and cellular editing, modulation, modification, engineering, regulation, repair and therapy for use in human therapeutics, namely, therapeutic pharmaceuticals developed through genome modifications for the treatment of cardiovascular, central nervous system, endocrine, gastrointestinal, genetic immunological, infectious, inflammatory, menopausal, metabolic, autoimmune, musculoskeletal, neurological, ophthalmological, psychiatric, respiratory, urogenital, urological, hematologic and viral diseases and disorders; pharmaceutical preparations, namely, therapeutic pharmaceuticals developed through genome modifications for the treatment of erectile dysfunction, sexual dysfunction, cancer, pain and diabetes; pharmaceutical preparations, namely, therapeutic pharmaceuticals developed through genome modifications, namely, antifungal preparations, dermatological preparations, smoking cessation preparations and tissue repair preparations; engineered nucleic acids, viral vectors, non-viral vectors, gene therapy vectors, gene editing vectors, genetically modified cells, engineered proteins for multiplexed gene editing, mRNA and recombinant adeno-associated virus (AAV) vectors for delivery of therapeutic DNA or mRNA sequences to cells, antibody preparations, CAR T-cell preparations, T-cell preparations, B-cell preparations, Treg preparations, and NK cell preparations, all for clinical use, medical use, clinical laboratory use, and medical laboratory use research in the fields of genome editing, gene editing, genome engineering, gene modulation, transcriptional regulation, transcriptional modulation, genetic disease, gene therapy and cell therapy; pharmaceutical research and development services; Scientific research; scientific research in genetic, medical, pharmaceutical and veterinary fields; scientific research in chemistry, biology, biochemistry, molecular biology, bacteriology; scientific analysis in the field of immunotherapy; scientific research in the field of cellular immunotherapy utilizing chimeric antigen receptor t cells for use in treating cancer Medical services, namely, cellular immunotherapy treatments utilizing chimeric antigen receptor t cells for use in treating disease, namely, the treatment of cancer
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
genome editing reagents for research purposes; Chemical, biochemical, biotechnological products intended for industry, agriculture, horticulture, namely, polypeptides for in vivo and in vitro genetic engineering, natural and engineered meganucleases and endonucleases, nucleic acid vectors, molecular scissors; chemical, biochemical, biotechnological and bacteriological products intended for research laboratories and control laboratories, namely, polypeptides for in vivo and in vitro genetic engineering; Biochemicals and biologics, namely, engineered proteins for gene regulation, genome engineering, gene modulation, transcriptional regulation, transcriptional modulation, gene modification, and gene correction, all for use in scientific research, pharmaceutical research, agricultural biotechnology, diagnostics, and industrial biotechnology; engineered proteins for use in scientific research and analysis relating to genetic diseases, gene therapy, and cell therapy; biochemicals and biologics, namely, engineered nucleic acids, viral vectors, non-viral vectors, gene therapy vectors, gene editing vectors, genetically modified cells, engineered proteins for multiplexed gene editing, mRNA and recombinant adeno-associated virus (AAV) vectors for delivery of therapeutic DNA or mRNA sequences to cells, antibody preparations, CAR T-cell preparations, T-cell preparations, B-cell preparations, Treg preparations, and NK cell preparations, all for use in scientific research and analysis and diagno pharmaceutical preparations, namely, cell therapy products utilizing t-cell therapy for use in treating disease; cell-based immunotherapeutic treatment by way of genetically modified cells for use in human therapeutics and the treatment of cancer; pharmaceuticals for the treatment of cancer; pharmaceutical preparations in the nature of genetically modified cells, namely, genetically modified immune cells for use in human therapeutics and in the treatment of cancer; pharmaceutical and biological preparations based on gene, genome and cellular editing, modulation, modification, engineering, regulation, repair and therapy for use in human therapeutics, namely, therapeutic pharmaceuticals developed through genome modifications for the treatment of cardiovascular, central nervous system, endocrine, gastrointestinal, genetic immunological, infectious, inflammatory, menopausal, metabolic, autoimmune, musculoskeletal, neurological, ophthalmological, psychiatric, respiratory, urogenital, urological, hematologic and viral diseases and disorders; pharmaceutical preparations, namely, therapeutic pharmaceuticals developed through genome modifications for the treatment of erectile dysfunction, sexual dysfunction, cancer, pain and diabetes; pharmaceutical preparations, namely, therapeutic pharmaceuticals developed through genome modifications, namely, antifungal preparations, dermatological preparations, smoking cessation preparations and tissue repair preparations; engineered nucleic acids, viral vectors, non-viral vectors, gene therapy vectors, gene editing vectors, genetically modified cells, engineered proteins for multiplexed gene editing, mRNA and recombinant adeno-associated virus (AAV) vectors for delivery of therapeutic DNA or mRNA sequences to cells, antibody preparations, CAR T-cell preparations, T-cell preparations, B-cell preparations, Treg preparations, and NK cell preparations, all for clinical use, medical use, clinical laboratory use, and medical laboratory use research in the fields of genome editing, gene editing, genome engineering, gene modulation, transcriptional regulation, transcriptional modulation, genetic disease, gene therapy and cell therapy; pharmaceutical research and development services; Scientific research; scientific research in genetic, medical, pharmaceutical and veterinary fields; scientific research in chemistry, biology, biochemistry, molecular biology, bacteriology; scientific analysis in the field of immunotherapy; scientific research in the field of cellular immunotherapy utilizing chimeric antigen receptor t cells for use in treating cancer Medical services, namely, cellular immunotherapy treatments utilizing chimeric antigen receptor t cells for use in treating disease, namely, the treatment of cancer
92.
GENETICALLY-MODIFIED T CELLS COMPRISING A MODIFIED INTRON IN THE T CELL RECEPTOR ALPHA GENE
The present invention provides a genetically-modified T cell comprising in its genome a modified human T cell receptor alpha gene. The modified T cell receptor alpha gene comprises an exogenous sequence of interest inserted into an intron within the T cell receptor alpha gene that is positioned 5′ upstream of TRAC exon 1. The exogenous sequence of interest can comprise an exogenous splice acceptor site and/or a poly A signal, which disrupts expression of the T cell receptor alpha subunit. The sequence of interest can also include a coding sequence for a polypeptide, such as a chimeric antigen receptor. Additionally, the endogenous splice donor site and the endogenous splice acceptor site flanking the intron are unmodified and/or remain functional. The invention further provides compositions and methods for producing the genetically-modified cell, and populations of the cell, and methods for the treatment of a disease, such as cancer, using such cells.
The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.
C07H 21/02 - 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 ribosyl as saccharide radical
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
94.
RECOMBINANT ADENO-ASSOCIATED VIRUS COMPOSITIONS AND METHODS FOR PRODUCING AND USING THE SAME
The present invention encompasses improved methods for separating full recombinant adeno-associated virus (rAAV) particles from empty rAAV particles using anion exchange chromatography with an isocratic elution gradient of magnesium chloride. The improved methods allow for the production of viral compositions comprising optimized percentages of full rAAV particles, wherein the AAV can be of any serotype. The optimized viral compositions find use in delivering genes of interest to cells by contacting the cells with the viral compositions.
Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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
96.
Engineered meganucleases specific for recognition sequences in the Hepatitis B virus genome
The present invention encompasses engineered meganucleases which recognize and cleave a recognition sequence within an open reading frame (ORF) of the genome of at least two genotypes of the Hepatitis B virus (HBV). The present invention also encompasses methods of using such engineered meganucleases in a pharmaceutical composition and in methods for treating or reducing the symptoms of a HBV infection, or treating hepatocellular carcinoma (HCC). Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or HCC.
The present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, using particular lymphodepletion regimens in combination with particular populations of chimeric antigen receptor T cells expressing anti CD19 CAR PBCAR0191, anti CD20 CAR PBCAR20A or anti BCMA CAR PBCAR269A.
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
98.
OPTIMIZED ENGINEERED MEGANUCLEASES HAVING SPECIFICITY FOR A RECOGNITION SEQUENCE IN THE HEPATITIS B VIRUS GENOME
The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced specificity and/or efficiency of indel formation, when compared to previously described HBV meganucleases. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or hepatocellular carcinoma.
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
99.
CD20 CHIMERIC ANTIGEN RECEPTORS AND METHODS OF USE FOR IMMUNOTHERAPY
Provided herein are compositions and methods for the treatment of a disease, such as cancer, using a chimeric antigen receptor or genetically-modified cells comprising a chimeric antigen receptor having specificity for CD20. The invention provides polynucleotides encoding such chimeric antigen receptors, and genetically-modified cells comprising such chimeric antigen receptors. Also provided are methods for making such genetically-modified cells and pharmaceutical compositions comprising the same. The invention further provides methods for treating a disease (e.g., cancer) in a subject by administering such genetically-modified cells or compositions. The main embodiments concern CARs with an scFv specific for CD20, the hinge and transmembrane domains from CD8, the costimulatory cytoplasmic or signalling domain from co-stimulatory molecules Novel1 (N1) or Novel6 (N6) and the CD3zeta intracellular signaling domain.
A61P 35/02 - Antineoplastic agents specific for leukemia
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 5/0783 - T cellsNK cellsProgenitors of T or NK cells
100.
Optimized engineered nucleases having specificity for the human T cell receptor alpha constant region gene
The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within the first exon of the human T cell receptor (TCR) alpha constant region gene. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced (i.e., increased) specificity or efficiency of cleavage, when compared to the first-generation meganuclease TRC 1-2x.87EE. The present invention also encompasses methods of using such engineered nucleases to make genetically-modified cells, and the use of such cells in a pharmaceutical composition and in methods for treating diseases, such as cancer.
