Methods of treating Fabry disease via administration of stabilized plant recombinant human alpha galactosidase protein comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety, and unit dosages of protein are disclosed herein. The disclosed protocols are safe, have greater than 2 week intervals between administrations and exhibit important improvement in patient's disease parameters, in terms of reduced Gb3 accumulation, pain and GI parameters, kidney and cardiac stabilization in the clinical setting.
A method of treating a disease or disorder associated with excessive uric acid levels is disclosed herein. The method comprises administering to the subject by i.v. infusion an amount of a recombinant homotetrameric uricase enzyme comprising four uricase polypeptides having the amino acid sequence as set forth in SEQ ID NO: 2, wherein the polypeptides are crosslinked by polyethylene glycol (PEG) bis-aldehyde having a molecular weight of 2-3.5 kDa.
A modified uricase is described herein, as well as a method of reducing a level of uric acid by contacting a medium with the modified uricase. The modified uricase comprises a uricase polypeptide crosslinked by at least one bifunctional linking moiety that comprises a poly(alkylene glycol) moiety. A molecular weight of the bifunctional linking moiety is from about 1.5 kDa to about 4 kDa, and/or the modified uricase comprises a plurality of polypeptides having the amino acid sequence SEQ ID NO: 2. Further described is a polypeptide having the amino acid sequence SEQ ID NO: 2. A process of preparing the modified uricase is also described, comprising contacting the polypeptide with a crosslinking agent that comprises a poly(alkylene glycol) moiety and at least two aldehyde groups, to obtain a conjugate; and contacting the conjugate with a reducing agent.
A modified DNase protein is described herein as well as pharmaceutical compositions comprising same, the modified DNase protein comprising a DNase polypeptide attached to at least two poly(alkylene glycol) moieties. Further described herein is a process of preparing a modified DNase protein, the process comprising: contacting the polypeptide with an agent that comprises a poly(alkylene glycol) attached to an aldehyde group, to obtain a conjugate of the polypeptide and the agent; and contacting the conjugate with a reducing agent.
A61K 47/60 - 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
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
DICER-liker knock-out plant cells are provided. Accordingly, there is provided an isolated plant cell in suspension comprising loss of function mutations in all alleles of at least two genes selected from the group consisting of DCL2, DCL4, RDR1, RDR2 and RDR6 in said plant cell. Also provided are methods of abolishing expression and/or activity of at least two genes selected from the group consisting of DCL2, DCL4, RDR1, RDR2 and RDR6 in a plant cell.
Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and/or a longer lasting activity under both lysosomal conditions and in a serum environment.
A modified uricase is described herein, as well as a method of reducing a level of uric acid by contacting a medium with the modified uricase. The modified uricase comprises a uricase polypeptide crosslinked by at least one bifunctional linking moiety that comprises a poly(alkylene glycol) moiety. A molecular weight of the bifunctional linking moiety is from about 1.5 kDa to about 4 kDa, and/or the modified uricase comprises a plurality of polypeptides having the amino acid sequence SEQ ID NO: 2. Further described is a polypeptide having the amino acid sequence SEQ ID NO: 2. A process of preparing the modified uricase is also described, comprising contacting the polypeptide with a crosslinking agent that comprises a poly(alkylene glycol) moiety and at least two aldehyde groups, to obtain a conjugate; and contacting the conjugate with a reducing agent.
A61K 47/60 - 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
C12N 9/06 - Oxidoreductases (1.), e.g. luciferase acting on nitrogen containing compounds as donors (1.4, 1.5, 1.7)
DICER-liker knock-out plant cells are provided. Accordingly, there is provided an isolated plant cell in suspension comprising loss of function mutations in all alleles of at least two genes selected from the group consisting of DCL2, DCL4, RDR1, RDR2 and RDR6 in said plant cell. Also provided are methods of abolishing expression and/or activity of at least two genes selected from the group consisting of DCL2, DCL4, RDR1, RDR2 and RDR6 in a plant cell.
A modified DNase protein is described herein as well as pharmaceutical compositions comprising same, the modified DNase protein comprising a DNase polypeptide attached to at least two poly(alkylene glycol) moieties. Further described herein is a process of preparing a modified DNase protein, the process comprising: contacting the polypeptide with an agent that comprises a poly(alkylene glycol) attached to an aldehyde group, to obtain a conjugate of the polypeptide and the agent; and contacting the conjugate with a reducing agent.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 47/60 - 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
Modified DNase I protein in which one or more amino acids of a DNase I protein are modified non-cellularly, are provided. The modified DNase I protein exhibits a DNA hydrolytic activity in the presence of actin and an improved DNA hydrolytic activity compared to a homologous non-modified DNase I protein. Processes of preparing the modified DNase I protein and uses thereof in, for example, reducing a DNA content in sputum and/or in treating a disease or condition associated with excess extracellular DNA in a fluid, secretion or tissue of a subject, are also provided.
Methods of treating Fabry disease via administration of stabilized plant recombinant human alpha galactosidase protein comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety, and unit dosages of protein are disclosed herein. The disclosed protocols are safe, have greater than 2 week intervals between administrations and exhibit important improvement in patient's disease parameters, in terms of reduced Gb3 accumulation, pain and GI parameters, kidney and cardiac stabilization in the clinical setting.
Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and/or a longer lasting activity under both lysosomal conditions and in a serum environment.
(ii) a second domain which comprises an Fc domain of an immunoglobulin, wherein the first domain and the second domain are N-terminally to C-terminally respectively sequentially translationally fused and wherein the chimeric polypeptide specifically binds TNF Alpha.
C12N 15/62 - DNA sequences coding for fusion proteins
C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells
A61K 36/81 - Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
Methods of treating Fabry disease via administration of stabilized plant recombinant human alpha galactosidase protein comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety, and unit dosages of protein are disclosed herein. The disclosed protocols are safe, have greater than 2 week intervals between administrations and exhibit important improvement in patient's disease parameters, in terms of reduced Gb3 accumulation, pain and GI parameters, kidney and cardiac stabilization in the clinical setting.
Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and/or a longer lasting activity under both lysosomal conditions and in a serum environment.
Modified DNase I protein in which one or more amino acids of a DNase I protein are modified non-cellularly, are provided. The modified DNase I protein exhibits a DNA hydrolytic activity in the presence of actin and an improved DNA hydrolytic activity compared to a homologous non-modified DNase I protein. Processes of preparing the modified DNase I protein and uses thereof in, for example, reducing a DNA content in sputum and/or in treating a disease or condition associated with excess extracellular DNA in a fluid, secretion or tissue of a subject, are also provided.
Modified DNase I protein in which one or more amino acids of a DNase I protein are modified non-cellularly, are provided. The modified DNase I protein exhibits a DNA hydrolytic activity in the presence of actin and an improved DNA hydrolytic activity compared to a homologous non-modified DNase I protein. Processes of preparing the modified DNase I protein and uses thereof in, for example, reducing a DNA content in sputum and/or in treating a disease or condition associated with excess extracellular DNA in a fluid, secretion or tissue of a subject, are also provided.
Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and/or a longer lasting activity under both lysosomal conditions and in a serum environment.
A61K 38/54 - Mixtures of enzymes or proenzymes covered by more than a single one of groups or
C12N 9/40 - Hydrolases (3.) acting on glycosyl compounds (3.2) acting on alpha-galactose-glycoside bonds, e.g. alpha-galactosidase
C12N 9/96 - Stabilising an enzyme by forming an adduct or a compositionForming enzyme conjugates
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
C07K 1/00 - General processes for the preparation of peptides
A method of maintaining disease stability in a subject having Gaucher's disease following switch from enzyme replacement therapy (ERT) is provided. The method comprising orally administering to the subject a therapeutically effective amount of recombinant glucocerebrosidase (GCD) comprised in plant cells, thereby maintaining disease stability following switch.
DNase I formulations for pulmonary administration and, more particularly, but not exclusively, a dry powder formulation comprising, as an active ingredient, human DNase I, methods, dry powder inhalation devices and systems for the therapeutic use thereof are provided.
An inhalable pharmaceutical composition for pulmonary administration comprising human DNase I and a liquid carrier and, more particularly, but not exclusively, to methods, liquid pharmaceutical inhalation devices and systems for the therapeutic use thereof are provided.
A plant produced chimeric polypeptide is provided. The plant produced chimeric polypeptide comprising: (i) a first domain which comprises a TNF Alpha binding domain of a TNF receptor, and (ii) a second domain which comprises an Fc domain of an immunoglobulin, wherein the first domain and the second domain are N-terminally to C-terminally respectively sequentially translationally fused and wherein the chimeric polypeptide specifically binds TNF Alpha.
HADASIT MEDICAL RESEARCH SERVICES AND DEVELOPMENT LTD. (Israel)
Inventor
Ilan, Yaron
Shaaltiel, Yoseph
Hanania, Uri
Kizhner, Tali
Ariel, Tami
Gingis-Velitski, Svetlana
Abstract
A method of treating a TNF Alpha associated medical condition selected from the group consisting of obesity, metabolic syndrome, diabetes and a liver disease or disorder is provided. The method comprising enterally administering to a subject in need thereof a therapeutically effective amount of plant cells expressing a TNF Alpha polypeptide inhibitor, thereby treating the TNF Alpha associated medical condition.
Nucleic acid expression constructs are provided and, more particularly, nucleic acid constructs for expression of human alpha-galactosidase in plant cells, cells expressing the nucleic acid construct, producing the human alpha-galactosidase and uses thereof.
A method of treating Gaucher's disease in a subject in need thereof is provided. The method comprising orally administering to the subject a therapeutically effective amount of recombinant glucocerecbrosidase (GCD) comprised in plant cells, wherein said therapeutically effective amount of GCD corresponds to 1-1920 units/Kg/14 days, thereby treating Gaucher's disease. Also provide unit dosage forms which comprise the glucocerecbrosidase (GCD) comprised in plant cells.
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
DNase I formulations for pulmonary administration and, more particularly, but not exclusively, a dry powder formulation comprising, as an active ingredient, human DNase I, methods, dry powder inhalation devices and systems for the therapeutic use thereof are provided.
An inhalable pharmaceutical composition for pulmonary administration comprising human DNase I and a liquid carrier and, more particularly, but not exclusively, to methods, liquid pharmaceutical inhalation devices and systems for the therapeutic use thereof are provided.
Plant-expressed human recombinant DNase proteins, nucleic acid constructs for expression of the human recombinant DNase I in plant cells, cells expressing the nucleic acid construct and therapeutic uses thereof are disclosed. Particularly, compositions and methods for treating pulmonary and/or respiratory conditions by inhalation of the plant- expressed human recombinant DNase I are provided.
Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and/or a longer lasting activity under both lysosomal conditions and in a serum environment.
A61K 38/54 - Mixtures of enzymes or proenzymes covered by more than a single one of groups or
C12N 9/96 - Stabilising an enzyme by forming an adduct or a compositionForming enzyme conjugates
C12N 9/40 - Hydrolases (3.) acting on glycosyl compounds (3.2) acting on alpha-galactose-glycoside bonds, e.g. alpha-galactosidase
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
C07K 1/00 - General processes for the preparation of peptides
34.
NUCLEIC ACID CONSTRUCT FOR EXPRESSION OF ALPHA-GALACTOSIDASE IN PLANTS AND PLANT CELLS
Nucleic acid expression constructs are provided and, more particularly, nucleic acid constructs for expression of human alpha-galactosidase in plant cells, cells expressing the nucleic acid construct, producing the human alpha-galactosidase and uses thereof.
YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD. (Israel)
PROTALIX LTD. (Israel)
Inventor
Soreq, Hermona
Ruderfer, Ilya
Shaaltiel, Yoseph
Abstract
A method of treating or preventing Parkinson's disease in a subject in need thereof is disclosed. The method comprises administering to the subject a therapeutically effective amount of AChE-R, wherein the AChE-R is devoid of an N-terminal extension. An additional method of treating or preventing Parkinson's disease in a subject is disclosed. The method comprises administering to the subject a therapeutically effective amount of AChE-R, wherein the AChE-R comprises a modification for increasing bioavailability.
Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and/or a longer lasting activity under both lysosomal conditions and in a serum environment.
Multimeric protein structures comprising at least two glucocerebrosidase molecules being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and uses thereof in the treatment of Gaucher disease. The multimeric protein structures are characterized by longer-lasting activity as compared to native glucocerebrosidase both in serum and in lysosomes.
Multimeric protein structures are disclosed herein, as well a process for preparing same, and methods employing same for treating various diseases or disorders. The multimeric protein structures comprise at least two monomers of a therapeutic protein, including a TNF-alpha, a luteinizing hormone, an immunoglobin, a TNF-alpha receptor, a CTLA-4, a urate oxidase, a VEGF, a PDGF, a VEGF receptor, a PDGF receptor, an interleukin-17, and/or fragments thereof, the monomers being covalently linked to one another via a linking moiety. The multimeric protein structures exhibit improved performance as compared to the corresponding native proteins, including a longer lasting activity in vivo.
A method of treating Fabry is provided. The method comprises administering to a subject in need thereof a therapeutically effective amount of alkaline alpha galactosidase, thereby treating Fabry disease.
A reusable, disposable device for culturing plant tissues or cells including a non-rigid container having dimensions and gas exchange ports designed for maintaining oxygen saturation and shear forces suitable for culturing plant tissue or cells in 400 liters or more of culture medium is provided. Also provided are methods for producing a catalytically active human recombinant protein in a plant cell, using the disposable device of one of the embodiments of the instant specification.
Conjugates of a saccharide and a biomolecule, covalently linked therebetween via a non-hydrophobic linker and methods of preparing same are disclosed. Also disclosed are medical uses utilizing such conjugates. Glycosylation reagents for use in preparing these conjugates are also disclosed. Glycosylated proteins, characterized by improved performance, are also disclosed.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61P 43/00 - Drugs for specific purposes, not provided for in groups
A reusable, disposable device for culturing plant tissues or cells including a non-rigid container having dimensions and gas exchange ports designed for maintaining oxygen saturation and shear forces suitable for culturing plant tissue or cells in 400 liters or more of culture medium is provided. Also provided are methods for producing a catalytically active human recombinant protein in a plant cell, using the disposable device of one of the embodiments of the instant specification.
A device, system and method for producing glycosylated proteins in plant culture, particularly proteins having a high mannose glycosylation, while targeting such proteins with an ER signal and/or by-passing the Golgi. The invention further relates to vectors and methods for expression and production of enzymatically active high mannose lysosomal enzymes using transgenic plant root, particularly carrot cells. More particularly, the invention relates to host cells, particularly transgenic suspended carrot cells, vectors and methods for high yield expression and production of biologically active high mannose Glucocerebrosidase (GCD). The invention further provides for compositions and methods for the treatment of lysosomal storage diseases.
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
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical, biochemical, biological and biotechnological preparations and substances for producing biopharmaceuticals, namely recombinant proteins; chemical, biochemical and biotechnological preparations and substances for industrial and scientific use, namely, recombinant vectors for cloning and expression of DNA; chemical, biochemical, biological and biotechnological preparations and substances for use in the manufacture of recombinant proteins, namely, recombinant vectors for cellular expression of recombinant DNA; chemical, biochemical, biological and biotechnological preparations and substances for supporting cellular expression of recombinant proteins, namely , cell growth support structures medium and substrates for use in cell cultures; chemical, biochemical, biological and biotechnological preparations and substances for use in the manufacture of recombinant protein based products, namely, medicines, pharmaceuticals, diagnostics, vaccines, antibodies and biological molecules; chemical, biochemical, biological and biotechnological preparations and substances, namely, recombinant vectors for industrial and scientific research use in laboratories, diagnostics and analytics. Chemical, biochemical and biotechnological preparations and substances for medical use, namely, recombinant vectors for cloning and expression of DNA; chemical, biochemical, biological and biotechnological preparations and substances, namely, recombinant vectors for medical research use in laboratories, diagnostics and analytics. Bioreactor for cell culturing; apparatus for culturing and harvesting of plant cells capable of expressing recombinant proteins. Providing a system for culturing plant cells used to produce biopharmaceuticals, namely, recombinant proteins; research and development for others in the field of genetically engineered plants and plant cell for producing biopharmaceuticals, namely recombinant proteins; development of new technology for the others in the field of recombinant biotechnology; product research and development; scientific research and industrial research for others, namely, drug discovery, cell discovery, discovery of recombinant proteins, gene research, enzyme research, molecular research, genomics and gene expression research and development; technical consultation in the field of biotechnology and in the field of recombinant production technology.
01 - Chemical and biological materials for industrial, scientific and agricultural use
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
[ Chemical, biochemical, biological and biotechnological preparations and substances for scientific and medical research use, namely, recombinant vectors for cloning; proteins and reagents for scientific and medical research use, namely, for use in recombinant protein expression in cells; recombinant vectors and reagents for expressing recombinant DNA for industrial, scientific, and medical research use; chemical, biochemical, biological and biotechnological preparations and substances, namely, recombinant vectors for industrial, scientific, and medical research use in laboratories, diagnostics and analytics; chemical, biochemical, biological and biotechnological preparations and substances, namely, cell growth support structures medium and substrates for use in cell cultures for industrial, scientific and medical research; chemical, biochemical, biological and biotechnological preparations and substances for use in the manufacture of medicines, pharmaceuticals, diagnostics, vaccines, antibodies and biological molecules from recombinant proteins or peptides expressed in cell cultures, namely, cell growth support structures and substrates for use in cell cultures, recombinant vectors for cloning and reagents for expression of recombinant proteins; none of the foregoing being diagnostic assays for scientific, research, clinical, or medical laboratory use ] [ Bioreactor for cell culturing ] Providing medical and scientific research equipment to others for culturing cells used to produce biopharmaceuticals, namely, recombinant proteins; research and development for others in the field of genetically engineered plants and plant cells for producing biopharmaceuticals, namely, recombinant proteins; development of new technology for others in the field of recombinant biotechnology; product research and development; scientific research and industrial research for others, namely, drug discovery, cell discovery, discovery of recombinant proteins, gene research, enzyme research, molecular research, genomics and gene expression research and development; technical consultation in the field of biotechnology and in the field of recombinant production technology
A reusable, disposable device for culturing plant tissues or cells including a non-rigid container having dimensions and gas exchange ports designed for maintaining oxygen saturation and shear forces suitable for culturing plant tissue or cells in 400 liters or more of culture medium is provided. Also provided are methods for producing a catalytically active human recombinant protein in a plant cell, using the disposable device of one of the embodiments of the instant specification.
Modified DNase I protein in which one or more amino acids of a DNase I protein are modified non-cellularly, are provided. The modified DNase I protein exhibits a DNA hydrolytic activity in the presence of actin and an improved DNA hydrolytic activity compared to a homologous non-modified DNase I protein. Processes of preparing the modified DNase I protein and uses thereof in, for example, reducing a DNA content in sputum and/or in treating a disease or condition associated with excess extracellular DNA in a fluid, secretion or tissue of a subject, are also provided.
Methods of treating Fabry disease via administration of stabilized plant recombinant human alpha galactosidase protein comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety, and unit dosages of protein are disclosed herein. The disclosed protocols are safe, have greater than 2 week intervals between administrations and exhibit important improvement in patient's disease parameters, in terms of reduced Gb3 accumulation, pain and GI parameters, kidney and cardiac stabilization in the clinical setting.
Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and/or a longer lasting activity under both lysosomal conditions and in a serum environment.
A modified DNase protein is described herein as well as pharmaceutical compositions comprising same, the modified DNase protein comprising a DNase polypeptide attached to at least two poly(alkylene glycol) moieties. Further described herein is a process of preparing a modified DNase protein, the process comprising: contacting the polypeptide with an agent that comprises a poly(alkylene glycol) attached to an aldehyde group, to obtain a conjugate of the polypeptide and the agent; and contacting the conjugate with a reducing agent.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 47/60 - 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A modified uricase is described herein, as well as a method of reducing a level of uric acid by contacting a medium with the modified uricase. The modified uricase comprises a uricase polypeptide crosslinked by at least one bifunctional linking moiety that comprises a poly(alkylene glycol) moiety. A molecular weight of the bifunctional linking moiety is from about 1.5 kDa to about 4 kDa, and/or the modified uricase comprises a plurality of polypeptides having the amino acid sequence SEQ ID NO: 2. Further described is a polypeptide having the amino acid sequence SEQ ID NO: 2. A process of preparing the modified uricase is also described, comprising contacting the polypeptide with a crosslinking agent that comprises a poly(alkylene glycol) moiety and at least two aldehyde groups, to obtain a conjugate; and contacting the conjugate with a reducing agent.
A61K 47/60 - 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61P 13/04 - Drugs for disorders of the urinary system for urolithiasis
A61P 19/06 - Antigout agents, e.g. antihyperuricemic or uricosuric agents
C12N 9/06 - Oxidoreductases (1.), e.g. luciferase acting on nitrogen containing compounds as donors (1.4, 1.5, 1.7)
C12N 9/96 - Stabilising an enzyme by forming an adduct or a compositionForming enzyme conjugates
