The present disclosure provides a method for producing recombinant adeno-associated virus particles having a ligand on surfaces thereof, virus-like particles, host cells, and virus virions (VP) having low hepatotoxicity, the method comprising: (A) a step for introducing, into host cells via gene delivery, a nucleic acid molecule containing a nucleotide sequence that encodes a desired protein, and one or more types of nucleic acid molecules containing a nucleotide sequence that allows the expression of VP1, VP2, VP3, and VP3 modified with the ligand upon gene delivery; and (B) a step for subjecting the host cells to conditions that allow the generation of the recombinant adeno-associated virus particles.
The present invention relates to a lyophilized preparation containing, as an active ingredient, a fusion protein of an antibody and heparan N-sulfatase (SGSH), the lyophilized preparation further comprising an isotonic agent, a nonionic surfactant, and a buffering agent, wherein the nonionic surfactant contains polysorbate and poloxamer, and the buffering agent contains histidine.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61P 25/00 - Drugs for disorders of the nervous system
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
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
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
According to one embodiment of the present invention, it is possible to efficiently produce a highly-active recombinant protein by expressing, in the form of a fusion protein with serum albumin (SA), a physiologically-active protein having a low expression level and/or low activity when the physiologically-active protein is expressed as a recombinant protein by generally using host cells, such as CHO cells. The fusion protein may be one obtained by binding the physiologically-active protein either to the amino terminal side of the SA or to the carboxyl terminal. Also, the fusion protein may be a conjugate with a ligand or an antibody.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
Problem
Problem
To provide a method for producing a glycoprotein having N-linked sugar chains containing M6Ps in a wild type as a protein (M6P low-modified protein) in which the M6Ps originally contained in the glycoprotein are deleted or the number thereof is reduced, the M6P low-modified protein, and a method for utilizing the M6P low-modified protein.
Problem
To provide a method for producing a glycoprotein having N-linked sugar chains containing M6Ps in a wild type as a protein (M6P low-modified protein) in which the M6Ps originally contained in the glycoprotein are deleted or the number thereof is reduced, the M6P low-modified protein, and a method for utilizing the M6P low-modified protein.
Resolution Means
Problem
To provide a method for producing a glycoprotein having N-linked sugar chains containing M6Ps in a wild type as a protein (M6P low-modified protein) in which the M6Ps originally contained in the glycoprotein are deleted or the number thereof is reduced, the M6P low-modified protein, and a method for utilizing the M6P low-modified protein.
Resolution Means
A protein in which at least one of one or more N-linked sugar chains that is linked to Asn is deleted by adding a mutation to at least one amino acid sequence represented by Asn-Xaa-Yaa (where Xaa represents an amino acid other than proline, and Yaa represents threonine or serine) contained in an amino acid sequence of a glycoprotein having, in a wild type, one or more N-linked sugar chains binding thereto, the one or more N-linked sugar chains each containing one or more mannose-6-phosphate (M6Ps).
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
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
NATIONAL UNIVERSITY CORPORATION TOKAI NATIONAL HIGHER EDUCATION AND RESEARCH SYSTEM (Japan)
JCR PHARMACEUTICALS CO., LTD. (Japan)
Inventor
Nishiguchi, Koji
Fujita, Kosuke
Ashida, Yuhei
Abstract
The present disclosure provides a medicine for treating or preventing a hereditary disease, etc. The present disclosure provides a medicine for altering, preventing, or treating a condition, disease, disorder or symptom, which is caused by a frame-shift mutation due to the insertion or deletion of one or more bases, by cleaving at least one a target nucleic acid sequence in a nucleic acid within a cell, said medicine comprising a vector. This vector contains a construct that contains a promoter specific to the cell, a sequence encoding a Cas nuclease, a promoter enabling the expression of a gRNA in the cell after the introduction of the vector, and a sequence encoding a gRNA that binds to a target nucleic acid sequence having the insertion or deletion. This construct is configured so as to form a cleavage site, by the Cas nuclease, in proximity to the target nucleic acid sequence having the insertion or deletion.
An object of the present invention is to provide a nucleic acid molecule or a viral virion containing the nucleic acid molecule, the nucleic acid molecule having integrated therein a gene encoding a fusion protein of an anti-transferrin receptor antibody and a physiologically active protein, the fusion protein having an adjusted binding activity to TfR, and being capable of reducing a side reaction such as an anemia symptom caused by binding of the anti-TfR antibody to the transferrin receptor, for example, when the gene encoding the fusion protein of the anti-TfR antibody and the physiologically active protein is used in gene therapy.
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 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
Provided is an anti-human transferrin receptor antibody or an analog thereof, wherein in the heavy chain variable region of the antibody, (a) CDR1 comprises the amino acid sequence set forth as SEQ ID NO: 62 or SEQ ID NO: 63, (b) CDR2 comprises the amino acid sequence set forth as SEQ ID NO: 13 or SEQ ID NO: 14, and (c) CDR3 comprises the amino acid sequence set forth as SEQ ID NO: 15 or SEQ ID NO: 16, and an analogue thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 25/00 - Drugs for disorders of the nervous system
Provided is an anti-human transferrin receptor antibody or an analog thereof, wherein in the heavy chain variable region of the antibody, (a) CDR1 comprises the amino acid sequence set forth as SEQ ID NO: 62 or SEQ ID NO: 63, (b) CDR2 comprises the amino acid sequence set forth as SEQ ID NO: 13 or SEQ ID NO: 14, and (c) CDR3 comprises the amino acid sequence set forth as SEQ ID NO: 15 or SEQ ID NO: 16, and an analogue thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
The present invention provides gene therapy transgenes encoding a fusion protein comprising at least one anti-hTfR1 VHH and a human SGSH protein. Provided herein includes a recombinant AAV (rAAV) comprising a AAV9 capsid and a transgene encoding a fusion protein comprising at least one anti-hTfR1 VHH and a human SGSH protein. The present invention also provides methods for treating MPS IIIA in a patient using such rAAV vectors and compositions thereof.
The technic to pass through the blood-brain barrier is provided. A conjugate comprising:
(1) a peptide that binds to a transferrin receptor, wherein the peptide is:
(i) a peptide comprising 1st to 15th amino acid sequence (Ala-Val-Phe-Val-Trp-Asn-Tyr-Tyr-Ile-Ile-Arg-Arg-Tyr-MeY-Cys) of an amino acid sequence described in SEQ ID NO: 1;
(ii) a peptide comprising an amino acid sequence having substitution, deletion, addition and/or insertion of 1 to 11 amino acid residues in the 1st to 15th amino acid sequence of the amino acid sequence described in SEQ ID NO: 1;
(iii) a peptide comprising 1st to 12th amino acid sequence (Ala-Val-Phe-Val-Trp-Asn-Tyr-Tyr-Ile-Ile-Ser-Cys) of an amino acid sequence described in SEQ ID NO: 14; or
(iv) a peptide comprising an amino acid sequence having substitution, deletion, addition and/or insertion of 1 to 8 amino acid residues in the 1st to 10th amino acid sequence of the amino acid sequence described in SEQ ID NO: 14, and
(2) a compound comprising an antibody or an antigen-binding fragment thereof.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
11.
THERAPEUTIC COMPOUND FOR NEURONAL CEROID LIPOFUSCINOSIS
[Problem to be solved] To provide a therapeutic compound for neuronal ceroid lipofuscinosis. [Solution] Provided is a compound for treatment and/or prevention of neuronal ceroid lipofuscinosis represented by the following general formula [I]. In the general formula [I]. R1 is a methyl group or a hydroxymethyl group, R2 is a methyl group or a hydroxymethyl group, R3 is one of a hydroxy group, a methoxy group, an ethoxy group, an isopropoxy group, a methoxyethoxy group, a methoxypropoxy group, or an ethoxypolopoxy group, and R4 is one of a hydroxy group. a methoxy group, an ethoxy group, an isopropoxy group, a methoxyethoxy group, a methoxypropoxy group, or an ethoxypolopoxy group, In particular, provided is a compound represented by the general formula [I] with R1 being a methyl group, R2 being a methyl group, R3 being a hydroxy group, and R4 being a methoxyethoxy group.
[Problem to be solved] To provide a therapeutic compound for neuronal ceroid lipofuscinosis. [Solution] Provided is a compound for treatment and/or prevention of neuronal ceroid lipofuscinosis represented by the following general formula [I]. In the general formula [I]. R1 is a methyl group or a hydroxymethyl group, R2 is a methyl group or a hydroxymethyl group, R3 is one of a hydroxy group, a methoxy group, an ethoxy group, an isopropoxy group, a methoxyethoxy group, a methoxypropoxy group, or an ethoxypolopoxy group, and R4 is one of a hydroxy group. a methoxy group, an ethoxy group, an isopropoxy group, a methoxyethoxy group, a methoxypropoxy group, or an ethoxypolopoxy group, In particular, provided is a compound represented by the general formula [I] with R1 being a methyl group, R2 being a methyl group, R3 being a hydroxy group, and R4 being a methoxyethoxy group.
A61K 31/4375 - 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 nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
[Problem] To provide: a novel peptide that binds to a human transferrin receptor (hTfR); and various uses of the novel peptide. [Solution] A peptide consisting of an amino acid sequence disclosed in Ala-Val-MeF3C-Val-W7N-Asn-3Py6NH2-F4OMe-Ile-Ile-Arg-Arg-4Py-MeTyr-Cys (SEQ ID NO: 1) or a pharmaceutically acceptable salt thereof; a complex comprising said peptide or pharmaceutically acceptable salt thereof, and a material bound to a linker; a composition comprising said peptide or said complex; and a method for producing a pharmaceutical or diagnostic composition.
A61K 47/51 - 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
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 25/00 - Drugs for disorders of the nervous system
13.
Pharmaceutical Composition for Treatment of Mucopolysaccharidosis Type 1
The present disclosure relates to methods for treatment of mucopolysaccharidosis type I in a subject in need thereof by administering a pharmaceutical composition containing a fusion protein of an anti-human transferrin receptor antibody and human α-L-iduronidase.
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 25/00 - Drugs for disorders of the nervous system
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
Provided are: a peptide which has affinity for a human transferrin receptor and can be bound to one of compounds (e.g., a protein, a nucleic acid, a low-molecular-weight compound) to be allowed to function in the central nerve system (CNS) for the purpose of allowing the compound to pass through the blood-brain barrier; and a use of the peptide. The peptide is, for example: a peptide comprising an amino acid sequence selected from the group consisting of amino acid sequences represented by SEQ ID Nos: 4 to 6; or a mutant thereof.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 25/00 - Drugs for disorders of the nervous system
Disclosed is a fusion protein containing a brain-derived neurotrophic factor (BDNF). The fusion protein is a fusion protein of BDNF and a specific range of human anti-transferrin receptor antibody, which makes BDNF administered into the blood able to pass through the blood-brain barrier.
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 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
[Problems] To provide a technique for efficiently incorporating an agent having to function in muscle tissue, which is not sufficiently incorporated into muscle tissue when administered in body, into muscle tissue, particularly muscle tissue composed of skeletal muscle or cardiac muscle. [Solution] A conjugate of an anti-human transferrin receptor antibody and an agent, wherein the agent is a biologically active agent that should function in muscle tissue, e.g., a lysosomal enzyme such as acid α-glucosidase, α-galactosidase A.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
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.
METHOD FOR PRODUCING FUSION PROTEIN OF SERUM ALBUMIN AND GROWTH HORMONE
Disclosed is a method for producing a fusion protein of human serum albumin and human growth hormone. The method comprises (a) a step of culturing a mammalian cell capable of producing the protein in a serum-free medium and causing the protein to be secreted into the culture fluid, (b) a step of collecting a culture supernatant by removing the mammalian cell from the culture fluid, and (c) a step of purifying the protein from the culture supernatant by using column chromatography using a material to which an antibody having an affinity for the protein is bound as a stationary phase, column chromatography using a material having an affinity for phosphate group as a stationary phase, cation exchange column chromatography, and size exclusion column chromatography.
Disclosed are a software for analyzing images of a fertilized egg, the software providing a means for executing a process including: (a) a step of measuring the difference in area between the female pronucleus and the male pronucleus from images of a fertilized egg obtained in a period of 1 to 10 hours before the time of occurrence of male and female pronuclear membrane breakdown as a reference; (b) a step of measuring the difference in are between the female pronucleus and the male pronucleus from images of the fertilized egg obtained immediately before the time of occurrence of male and female pronuclear membrane breakdown as the reference; and (c) a step of storing the measured values of the area difference obtained in the step (a) and the area difference obtained in the step (b), to be readable at any time as needed, and an apparatus incorporating this software.
A61B 90/00 - Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups , e.g. for luxation treatment or for protecting wound edges
A61B 90/20 - Surgical microscopes characterised by non-optical aspects
A method for decomposing dermatan sulfate and heparan sulfate contained in a sample into a disaccharide, respectively, represented by formula [XI] for the dermatan sulfate and by formula [XII] for the heparan sulfate,
A method for decomposing dermatan sulfate and heparan sulfate contained in a sample into a disaccharide, respectively, represented by formula [XI] for the dermatan sulfate and by formula [XII] for the heparan sulfate,
the method including:
dividing the sample into two portions, where each portion is dispensed in a sealed container for separately decomposing the dermatan sulfate and the heparan sulfate;
heating one portion for decomposing the dermatan sulfate in hydrogen chloride methanol solution comprising 2,2-dimethoxypropane, at a temperature of 60 to 80° C., and for 20 to 100 minutes, and
heating the other portion for decomposing the heparan sulfate in hydrogen chloride methanol solution comprising 2,2-dimethoxypropane, at a temperature of 65 to 85° C., and for 80 to 180 minutes.
The present invention addresses the problem of providing cells that accumulate in a cancer tissue, have secured safety for humans, and can be prepared stably. Further, the present invention addresses the problem of providing a cancer diagnosis method and a cancer therapy method using the aforesaid cells that express sodium iodide symporter (NIS), and providing a composition to be used in the diagnosis and therapy methods. More specifically, the present invention relates to: cells that are dental pulp-derived pluripotent stem cells expressing NIS; a composition for cancer therapy or diagnosis, characterized by comprising a combination of the aforesaid cells with a radionuclide; and a cancer therapy method and a cancer diagnosis method using the composition.
Disclosed is a stable aqueous pharmaceutical composition or lyophilized pharmaceutical composition comprising a protein as the active ingredient. The pharmaceutical composition comprises a protein having physiological activity and two different nonionic surfactants, including polysorbate 80 and polyoxyethylene(160) polyoxypropylene(30) glycol as the nonionic surfactants, for example, and as optional components, sodium chloride as a neutral salt, sucrose as a disaccharide and citrate buffer as a buffering agent.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61J 1/14 - Containers specially adapted for medical or pharmaceutical purposes DetailsAccessories therefor
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
The present invention discloses gene therapy vectors for treatment of Hunter Syndrome. The gene therapy vector expresses a fusion protein comprising at least one anti-hTfR1 VHH antibody fused to a human iduronate -2-sulfatase.
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
23.
Method for Producing Antibody-Lysosomal Enzyme Fusion Protein
Disclosed is a method for producing a fusion protein in which an antibody and a lysosomal enzyme are fused. The method is a method for producing a fusion protein in which an antibody and a human lysosomal enzyme are fused, the method including: (a) culturing mammalian cells producing the fusion protein in a serum-free medium to secrete the fusion protein in a culture medium; (b) collecting a culture supernatant by removing the mammalian cells from the culture medium; and (c) purifying the fusion protein from the culture supernatant by using a column chromatography using a material to which a substance having affinity for the antibody is bound as a solid phase, an anion exchange column chromatography, a cation exchange column chromatography, and a size exclusion column chromatography.
C07K 1/16 - ExtractionSeparationPurification by chromatography
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 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
A production method of recombinant adeno-associated virus particles (rAAV virions) having less empty viral contamination is disclosed. The production method includes: (a) culturing mammalian cells containing an introduced AAV vector in a medium to release rAAV virions into the medium; (b) recovering a culture supernatant from the medium; and (c) purifying the rAAV virions from the recovered culture supernatant by affinity column chromatography using a material having an affinity for an AAV capsid protein as a stationary phase and anion column chromatography.
One embodiment of the present invention makes it possible to express, in the form of a fusion protein with a serum albumin (SA), a physiologically active protein that is expressed in a low amount and/or is less active when a host cell such as a CHO cell is normally used to express the physiologically active protein as a recombinant protein, thereby efficiently producing the physiologically active protein as a highly active recombinant protein. The fusion protein may be obtained by bonding the physiologically active protein to the amino-terminal side of the SA, or may be obtained by bonding the physiologically active protein to a carboxyl terminal. Further, said fusion protein can be a body coupled with a ligand or an antibody.
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
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
According to one embodiment of the present invention, a bioactive protein that usually has a low expression level and/or low activity when expressed as a recombinant protein using a host cell such as a CHO cell can be expressed in the form of a fusion protein with serum albumin (SA) to allow efficient production as a highly active recombinant protein. The fusion protein may be one in which the bioactive protein is bonded to either the amino terminal side or the carboxyl terminal side of the SA. The fusion protein can also form a conjugate with a ligand or an antibody.
According to one embodiment of the present invention, it is possible to efficiently produce a highly-active recombinant protein by expressing, in the form of a fusion protein with serum albumin (SA), a physiologically-active protein having a low expression level and/or low activity when the physiologically-active protein is expressed as a recombinant protein by generally using host cells, such as CHO cells. The fusion protein may be one obtained by binding the physiologically-active protein either to the amino terminal side of the SA or to the carboxyl terminal. Also, the fusion protein may be a conjugate with a ligand or an antibody.
Disclosed are cell culture vessels capable of preventing the deformation of the culture vessels in a manipulation of taking in/out a cell or replacing a culture medium and preventing over-time increase in the concentration of carbon dioxide or and temporal decrease of pH of the culture medium and over-time temporal decrease of pH of the culture medium in cell culture as advantageous effects, and further parallel filter connectors for configuring such cell culture vessels. The cell culture vessels have two types of filters in parallel so as to partition a gas phase inside the cell culture vessel and the outer air, and the parallel filter connectors for configuring the cell culture vessels have an opening to be connected to the body of the cell culture vessel, and two openings capable to be installed with each one of the two types of different filters.
The invention provides a nucleic acid molecule comprising a gene encoding a fusion protein of a ligand and a protein having physiological activity, to be used for expressing the fusion protein in cells, tissue or the body. The invention further provides a nucleic acid molecule comprising the fusion protein-encoding gene, which is in the form of a plasmid, in a form encapsulated in a recombinant virus virion, or a form encapsulated in liposomes or lipid nanoparticles. The invention further relates to the use of a medicine which is a nucleic acid molecule comprising the fusion protein-encoding gene.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
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 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
C12N 9/42 - Hydrolases (3.) acting on glycosyl compounds (3.2) acting on beta-1, 4-glucosidic bonds, e.g. cellulase
The purpose of the present invention is to provide a nucleic acid molecule, a vector, recombinant cells, and a drug for treating a central nervous system disease which is likely to migrate into the central nervous system. The nucleic acid molecule according to the present invention comprises a base sequence encoding a fusion protein of: an anti-transferrin receptor (TfR) antibody or an antigen-binding fragment thereof; and a protein which functions in the central nervous system.
[Problem] To provide a method for manufacturing, as a protein (mannose-6-phosphate (M6P) low-modification protein) lacking or having a reduced number of M6P that should be originally contained in the glycoprotein, a glycoprotein having, as a wild type, N-linked glycans including M6P, and to provide the M6P low-modification protein and a method for using the M6P low-modification protein. [Solution] A wild type glycoprotein to which N-linked glycans including one or a plurality of mannose 6-phosphates (M6P) are bonded, wherein at least one amino acid sequence represented by Asn-Xaa-Yaa (Xaa represents an amino acid other than proline, and Yaa represents threonine or serine) and included in the amino acid sequence of the glycoprotein and in which the N-linked glycans have been bonded to the Asn is mutated such that at least one of the N-linked glycans is deleted.
The present invention relates to a mutant of human α-N-acetylglucosaminidase (hNAGLU), more specifically a hNAGLU mutant produced by adding a mutation to an amino acid sequence for hNAGLU such that an expression level of hNAGLU in a host cell in which a gene encoding hNAGLU is introduced can be increased compared with the case where a gene encoding wild-type hNAGLU is introduced. For example, the hNAGLU mutant has an amino acid sequence represented by SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 15, or SEQ ID NO: 19, or has an amino acid sequence introduced a mutation to the amino acid sequence of any one of the hNAGLU mutants.
C12N 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
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 15/52 - Genes encoding for enzymes or proenzymes
C12N 15/62 - DNA sequences coding for fusion proteins
33.
MEDICINE FOR DISEASE CAUSED BY FRAME-SHIFT MUTATION
NATIONAL UNIVERSITY CORPORATION TOKAI NATIONAL HIGHER EDUCATION AND RESEARCH SYSTEM (Japan)
JCR PHARMACEUTICALS CO., LTD. (Japan)
Inventor
Nishiguchi, Koji
Fujita, Kosuke
Ashida, Yuhei
Abstract
The present disclosure provides a medicine for treating or preventing a genetic disease, etc. The present disclosure provides a medicine for altering, preventing, or treating a condition, disease, disorder or symptom, which is caused by a frame-shift mutation due to the insertion or deletion of one or more bases, by cleaving at least one target nucleic acid sequence in a nucleic acid within a cell, said medicine comprising a vector. This vector contains a construct that contains a promoter specific to the cell, a sequence encoding a Cas nuclease, a promoter enabling the expression of a gRNA in the cell after the introduction of the vector, and a sequence encoding a gRNA that binds to the target nucleic acid sequence having the insertion or deletion. This construct is configured so as to form a cleavage site, by the Cas nuclease, in proximity to the target nucleic acid sequence having the insertion or deletion.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A chromatography column for the use of separation of acidic sugar chains, wherein the column comprises a first column and a second column, the second column connected by a flow path downstream of an outlet of the first column, and selected from the following (1) or (2): (1) the carrier of the first column is hydrophobically modified silica having a group containing a primary amine, a secondary amine or/and a tertiary amine, and the carrier of the second column is a resin having a group containing a primary amine, a secondary amine or/and a tertiary amine; (2) the carrier of the first column is a resin having a group containing a primary amine, a secondary amine or/and a tertiary amine, and the carrier of the second column is hydrophobically modified silica having a group containing a primary amine, a secondary amine, or/and a tertiary amine.
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
The purpose of the present invention is to provide a nucleic acid molecule into which a gene for encoding a fusion protein of an anti-transferrin receptor (TfR) antibody and a bioactive protein has been incorporated, with which it is possible to reduce side effects such as anemia occurring due to the anti-TfR antibody binding to a transferrin receptor when the gene for encoding the fusion protein of the anti-TfR antibody and the bioactive protein is used in gene therapy, for example, and in which the TfR-binding activity is regulated. Another purpose of the present invention is to provide a virus virion including said nucleic acid molecule.
To provide a peptide, etc., capable of passing through the blood-brain barrier (BBB) by binding to a human transferrin receptor (hTfR). A peptide, etc., having the amino acid sequence shown in SEQ ID NO: 1 (Ala-Val-Phe-Val-Trp-Asn-Tyr-Tyr-Ile-Ile-Ser-Cys) or an amino acid sequence having substitutions, deletions, additions, and/or insertions of 1 to 10 amino acid residues (inclusive) in the amino acid sequence shown in SEQ ID NO: 1.
C07K 7/64 - Cyclic peptides containing only normal peptide links
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active 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
37.
PEPTIDE HAVING AFFINITY FOR HUMAN TRANSFERRIN RECEPTOR
In one embodiment, the present invention pertains to a peptide having affinity for the human transferrin receptor, and to applications of the same, wherein in order to pass through the blood-brain barrier, the peptide can be used by binding to any compound (such as proteins, nucleic acids, and low-molecular weight compounds) that should function in the central nervous system (CNS). The peptide includes, for example, an amino acid sequence selected from the group consisting of amino acid sequences expressed by SEQ ID NOs: 3-7 and SEQ ID NO: 55, or a mutant of the same.
A61P 3/08 - Drugs for disorders of the metabolism for glucose homeostasis
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
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
A61P 21/04 - Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
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 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
A61K 47/62 - 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
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C12N 1/15 - Fungi Culture media therefor modified by introduction of foreign genetic material
C12N 1/19 - YeastsCulture media therefor modified by introduction of foreign genetic material
C12N 1/21 - BacteriaCulture media therefor modified by introduction of foreign genetic material
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
To provide a pharmaceutical composition having a novel use comprising a dental pulp-derived multipotent stem cell preparation that can be administered to humans. A pharmaceutical composition comprising dental pulp-derived stem cells as an active ingredient for suppressing infiltration into a tissue of at lease neutrophils, monocytes, or lymphocytes.
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
A61P 11/00 - Drugs for disorders of the respiratory system
41.
THERAPEUTIC COMPOUND FOR NEURONAL CEROID LIPOFUSCINOSIS
[Problem to be solved] To provide a therapeutic compound for neuronal ceroid lipofuscinosis. [Solution] Provided is a compound for treatment and/or prevention of neuronal ceroid lipofuscinosis represented by the following general formula [I]. In the general formula [I], R1 is a methyl group or a hydroxymethyl group, R2 is a methyl group or a hydroxymethyl group, R3 is one of a hydroxy group, a methoxy group, an ethoxy group, an isopropoxy group, a methoxyethoxy group, a methoxypropoxy group, or an ethoxypolopoxy group, and R4 is one of a hydroxy group, a methoxy group, an ethoxy group, an isopropoxy group, a methoxyethoxy group, a methoxypropoxy group, or an ethoxypolopoxy group. In particular, provided is a compound represented by the general formula [I] with R1 being a methyl group, R2 being a methyl group, R3 being a hydroxy group, and R4 being a methoxyethoxy group.
A61K 31/435 - 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
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
42.
HUMAN TRANSFERRIN RECEPTOR-BINDING ANTIBODY-PEPTIDE CONJUGATE
[Problem] To provide an art for crossing the blood-brain barrier. [Solution] A conjugate comprising the following: (1) a transferrin receptor-binding peptide, wherein (i) the peptide contains the amino acid sequence from the 1st to the 15th (Ala-Val-Phe-Val-Trp-Asn-Tyr-Tyr-Ile-Ile-Arg-Arg-Tyr-MeY-Cys) of the amino acid sequence given by SEQ ID NO: 1; (ii) the peptide has an amino acid sequence exhibiting a substitution, deletion, addition, and/or insertion of from 1 to 11 amino acid residues in the amino acid sequence from the 1st to the 15th of the amino acid sequence given by SEQ ID NO: 1; (iii) the peptide contains the amino acid sequence from the 1st to the 12th (Ala-Val-Phe-Val-Trp-Asn-Tyr-Tyr-Ile-Ile-Ser-Cys) of the amino acid sequence given by SEQ ID NO: 14; or (iv) the peptide has an amino acid sequence exhibiting a substitution, deletion, addition, and/or insertion of from 1 to 8 amino acid residues in the amino acid sequence from the 1st to the 10th of the amino acid sequence given by SEQ ID NO: 14, and (2) a compound containing an antibody or an antigen-binding fragment thereof.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
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
A61P 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/14 - Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
[Problem] To provide a novel peptide that binds to the human transferrin receptor (hTfR). [Solution] A peptide having the amino acid sequence indicated in SEQ ID NO: 1, namely, Ala-Val-MePhe-Val-Trp-Asn-Tyr-Tyr-Ile-Ile-K(MePEG4c)-Arg-Phe-MeTyr-Cys, or a peptide including an amino acid sequence in which the amino acid sequence indicated in SEQ ID NO: 1 has one or more predetermined substitutions.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
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
The present invention discloses an aqueous pharmaceutical composition containing a protein in which serum albumin and growth hormone are linked. The aqueous pharmaceutical composition contains, as an active ingredient, a fusion protein of human serum albumin and human growth hormone; the concentration of the fusion protein is 10-100 mg/mL; the concentration of sucrose is 10-150 mg/mL; the concentration of a nonionic surfactant is 0.15-10 mg/mL; the concentration of a preservative is 0.5-12 mg/mL; the concentration of a buffer is 1-30 mM; and the pH is 5.0-8.0.
Provided is a pharmaceutical composition for the treatment of mucopolysaccharidosis type 1 patients. The patient here is in particular a patient having a disorder of the central nervous system. A pharmaceutical composition containing a fusion protein of anti-human transferrin receptor antibody and human α-L-iduronidase as an active ingredient is administered to the mucopolysaccharidosis type 1 patient by intravenous drip at a dose of 0.1-10 mg/kg body weight. The administration is carried out continuously for at least 3 months on a 5-21 day interval. This results in particular in the degradation of dermatan sulfate and heparan sulfate that have accumulated in the tissues of the patient and particularly in the central nervous system.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
Disclosed is a stable aqueous pharmaceutical composition or freeze-dried pharmaceutical composition that comprises a protein as an active ingredient. This pharmaceutical composition comprises a protein having a physiological activity and two kinds of nonionic surfactants and includes, for example, a composition in which the nonionic surfactants are Polysorbate 80 and polyoxyethylene (160) polyoxypropylene (30) glycol and which further contains, as optional ingredients, sodium chloride as a neutral salt, sucrose as a disaccharide and a citrate buffer as a buffer.
A61J 1/05 - Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 43/00 - Drugs for specific purposes, not provided for in groups
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
[Problem] To disclose a method for producing recombinant adeno-associated virus particles (rAAV virions) having less empty viral contamination. The production method (a) cultures mammalian cells into which an AAV vector has been introduced in medium to release rAAV virions into the medium, (b) recovers a culture supernatant from the medium, and (c) purifies rAAV virions from the recovered culture supernatant using anion column chromatography and affinity column chromatography that uses a material having an affinity for an AAV capsid protein as the stationary phase.
Disclosed is a method for producing a fusion protein in which an antibody is fused with a lysosomal enzyme. This method for producing a fusion protein in which an antibody is fused with a human lysosomal enzyme comprises: (a) culturing mammalian cells that produce the fusion protein in serum-free culture medium and bringing about secretion of the fusion protein into the culture medium, (b) recovering the culture supernatant by removing the mammalian cells from the culture medium, and (c) purifying the fusion protein from the culture supernatant using: column chromatography that uses as the stationary phase a material to which a substance exhibiting affinity for the antibody is bonded, anion-exchange column chromatography, cation-exchange column chromatography, and size-exclusion column chromatography.
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
C07K 1/16 - ExtractionSeparationPurification by chromatography
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
The present invention provides a nucleic acid molecule that contains a gene encoding a fused protein of a ligand and a protein having a physiological activity, said nucleic acid molecule being to be used for expressing the fused protein in a cell, a tissue or in vivo. The present invention also provides the nucleic acid molecule containing a gene encoding the aforesaid fused protein, said nucleic acid molecule being in the form of a plasmid, encapsulated in a recombinant viral virion, or encapsulated in a liposome or a lipid nanoparticle. Further, the present invention pertains to the use of the nucleic acid molecule, which contains a gene encoding the aforesaid fused protein, as a medicine.
Disclosed is a cell culture device that has advantages of preventing deformation of the culture device during operations for taking-in/out of cells and changing a medium and preventing an increase in the carbon dioxide concentration and a decrease in the medium pH over time during cell culture. Also disclosed is a parallel filter connector for assembling the cell culture device. This cell culture device is provided with two different kinds of filters which are disposed in parallel and each demarcate between the inner gas phase of the cell culture device and the outside air. The parallel filter connector for assembling the cell culture device has an opening connected to the main body of the cell culture device and two openings to which the two different types of filters can be respectively provided.
A method for quantifying Hex4, lyso-GM1, Fuc-GlcNAc-Asn, or lyso-sulfatide included in cerebrospinal fluid, the method including adding an internal standard substance to a solution including the cerebrospinal fluid, submitting the solution including the cerebrospinal fluid, to which the internal standard substance has been added, to liquid chromatography to obtain an eluate, and subjecting the eluate to mass analysis.
Disclosed are a means to convert compounds having physiological or pharmacological activity and unable to pass through the blood-brain barrier into a form that allows them to pass through the blood-brain barrier, and compounds converted thereby. The means is an anti-human transferrin receptor antibody and the converted compounds are molecular conjugates between physiologically active protein or pharmacologically active low-molecular-weight compounds and an anti-human transferrin receptor antibody.
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 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
The present invention relates to a mutant of human α-N-acetylglucosaminidase (hNAGLU), more specifically a hNAGLU mutant produced by adding a mutation to the amino acid sequence for hNAGLU so that the amount of expression of hNAGLU in a host cell in which a gene encoding hNAGLU is introduced can be increased compared with the case where a gene encoding wild-type hNAGLU is introduced. For example, the hNAGLU mutant has an amino acid sequence represented by SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 15 or SEQ ID NO: 19, or has an amino acid sequence having a structure that a mutation is added to any one of these amino acid sequences.
Disclosed is a fusion protein containing a brain-derived neurotrophic factor (BDNF). The fusion protein is a fusion protein of BDNF and a specific range of human anti-transferrin receptor antibody, which makes BDNF administered into the blood able to pass through the blood-brain barrier.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
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 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
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
The present disclosure relates to a method for producing dental pulp-derived cells enriched with pluripotent stem cells including: (a) digesting dental pulp with a protease to prepare a dental pulp suspension; (b) culturing the suspension to proliferate pluripotent stem cells contained in the suspension; (c) freezing the proliferated pluripotent stem cells in a state in which the pluripotent stem cells are suspended in a first cryopreservation liquid; (d) thawing the frozen pluripotent stem cells; (e) culturing the thawed pluripotent stem cells in a state in which the pluripotent stem cells are adhered to surfaces of particles to proliferate the pluripotent stem cells on the surfaces of the particles; and (f) bringing the particles into contact with a protease to separate the pluripotent stem cells adhered to the surfaces of the particles from the particles.
Disclosed are a human serum albumin mutant that can be linked to a physiologically active protein to increase the stability of the protein in the blood, as well as a resulting protein produced by linking with the mutant. The protein produced by linking with the mutant consists of a human serum albumin mutant comprising the amino acid sequence set forth as SEQ ID NO:3 or an amino acid sequence that, in comparison with it, lacks not more than 10 amino acid residues and/or has not more than 10 amino acid residues replaced, with the proviso that the asparagine residue occurring at position 318 and the threonine at position 320 from the N-terminus of the amino acid sequence set forth as SEQ ID NO:3 are preserved and linked by peptide bonds via a single amino acid residue (X) except proline placed between those two amino acid residues, and a physiologically active protein linked to the mutant.
Provided is an anti-human transferrin receptor antibody or an analog thereof, wherein in the heavy chain variable region of the antibody, (a) CDR1 comprises the amino acid sequence set forth as SEQ ID NO: 62 or SEQ ID NO: 63, (b) CDR2 comprises the amino acid sequence set forth as SEQ ID NO: 13 or SEQ ID NO: 14, and (c) CDR3 comprises the amino acid sequence set forth as SEQ ID NO: 15 or SEQ ID NO: 16, and an analogue thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
[Problem] To provide a peptide, etc., capable of passing through the blood-brain barrier (BBB) by binding to a human transferrin receptor (hTfR). [Solution] A peptide, etc., having the amino acid sequence shown in SEQ ID NO: 1 (Ala-Val-Phe-Val-Trp-Asn-Tyr-Tyr-Ile-Ile-Ser-Cys) or an amino acid sequence having substitutions, deletions, additions, and/or insertions of 1 to 10 amino acid residues (inclusive) in the amino acid sequence shown in SEQ ID NO: 1.
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
An aqueous preparation containing a protein as an active ingredient which is stable in storage in solution and makes an injection pain reduced is provided. More specifically an aqueous preparation containing a phosphate buffer at a concentration of 1 to 20 mM and a protein as an active ingredient is provided. Further more specifically provided is an aqueous preparation containing a phosphate buffer at a concentration of 1 to 20 mM, human growth hormone as an active ingredient, a poloxamer as a non-ionic surfactant; and phenol as a isotonic agent.
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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
[Problem] To provide a medicinal composition having a novel use that comprises a dental pulp-derived pluripotent stem cell preparation available for humans. [Solution] A medicinal composition that comprises dental pulp-derived stem cells as an active ingredient and that is for inhibiting infiltration into a tissue of at least any of neutrophils, monocytes and lymphocytes. Composition.
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contractionDrugs for heart failure
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
A61P 9/14 - VasoprotectivesAntihaemorrhoidalsDrugs for varicose therapyCapillary stabilisers
A61P 11/00 - Drugs for disorders of the respiratory system
[Problem] To provide a pharmaceutical composition containing a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, which is stable enough to permit its distribution to the market.
[Solution] A lyophilized formulation containing; a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, and further containing a neutral salt, a disaccharide, a nonionic surfactant, and a buffer. Such a lyophilized formulation includes, for example, as an active ingredient, a fusion protein comprising an anti-transferrin receptor antibody and human iduronate-2-sulfatase, and further containing sodium chloride as the neutral salt, sucrose as the disaccharide, poloxamer as the nonionic surfactant, and phosphate buffer as the buffer.
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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
Disclosed is a method for decomposing chondroitin sulfate contained in a sample into disaccharide. In particular disclosed is a method for decomposing chondroitin sulfate contained in a sample into disaccharide by heating the chondroitin sulfate in HCl-methanol containing 2,2-dimethoxypropane at a temperature of 60° C. to 90° C. for 50 minutes to 180 minutes, optionally in the method, the sample is selected from body fluid, a cell, a tissue, an organ, a cell culture solution, a tissue culture solution, a food, and a feed, or a derived therefrom.
The present invention discloses an aqueous pharmaceutical composition containing a protein in which serum albumin and growth hormone are linked. The aqueous pharmaceutical composition contains, as an active ingredient, a fusion protein of human serum albumin and human growth hormone; the concentration of the fusion protein is 10-100 mg/mL; the concentration of sucrose is 10-150 mg/mL; the concentration of a nonionic surfactant is 0.15-10 mg/mL; the concentration of a preservative is 0.5-12 mg/mL; the concentration of a buffer is 1-30 mM; and the pH is 5.0-8.0.
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61P 5/06 - Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
C07K 14/61 - Growth hormone [GH], i.e. somatotropin
Disclosed is a method for producing a fusion protein of human serum albumin and human growth hormone. The method includes: (a) a step for culturing, in a serum-free medium, mammalian cells which produce the fusion protein, and dispersing the fusion protein in a culture solution; (b) a step for removing the mammalian cells from the culture solution to recover a culture supernatant; and (c) a step for purifying the fusion protein from the culture supernatant by using a column chromatography in which a material to which an antibody having affinity for the fusion protein binds is used as a stationary phase, a chromatography in which a material having affinity for a phosphate group is used as a stationary phase, a cation exchange column chromatography, or a size exclusion column chromatography.
Disclosed are a software for analyzing images of a fertilized egg, the software providing a means for executing a process including: (a) a step of measuring the difference in area between the female pronucleus and the male pronucleus from images of a fertilized egg obtained in a period of 1 to 10 hours before the time of occurrence of male and female pronuclear membrane breakdown as a reference; (b) a step of measuring the difference in are between the female pronucleus and the male pronucleus from images of the fertilized egg obtained immediately before the time of occurrence of male and female pronuclear membrane breakdown as the reference; and (c) a step of storing the measured values of the area difference obtained in the step (a) and the area difference obtained in the step (b), to be readable at any time as needed, and an apparatus incorporating this software.
G06K 9/00 - Methods or arrangements for reading or recognising printed or written characters or for recognising patterns, e.g. fingerprints
A61B 90/00 - Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups , e.g. for luxation treatment or for protecting wound edges
A61B 90/20 - Surgical microscopes characterised by non-optical aspects
Aqueous pharmaceutical compositions containing a fusion protein of an antibody and a lysosomal enzyme as an active ingredient, which are stable enough to be marketed, are disclosed. The aqueous pharmaceutical composition, for example, comprises the fusion protein of the antibody and the lysosomal enzyme at a concentration of 0.5 to 20 mg/mL, sodium chloride at a concentration of 0.3 to 1.2 mg/mL, sucrose at a concentration of 50 to 100 mg/mL, a nonionic surfactant at a concentration of 0.15 to 3 mg/mL, a buffer at a concentration of 3 to 30 mM, and is adjusted to pH 5.0 to 7.5.
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 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
A61K 39/00 - Medicinal preparations containing antigens or antibodies
67.
QUANTIFICATION METHOD OF Hex4, lyso-GM1, Fuc-GlcNAc-Asn, AND lyso-sulfataide INCLUDED IN CEREBROSPINAL FLUID
The present invention addresses the problem of providing a method for quantifying Hex4, lyso-GM1, Fuc-GlcNAc-Asn, or lyso-sulfataide in a brain. The present invention relates to a method for quantifying Hex4, lyso-GM1, Fuc-GlcNAc-Asn, or lyso-sulfataide included in a cerebrospinal fluid, the method comprising: a step for adding an internal standard substance to a solution containing the cerebrospinal fluid; a step for subjecting the solution, which contains the cerebrospinal fluid and to which the internal standard substance is added, to liquid chromatography to obtain an effluent; and a step for providing the effluent for mass spectrometry.
G01N 27/62 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosolsInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electric discharges, e.g. emission of cathode
G01N 33/66 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving blood sugars, e.g. galactose
G01N 30/04 - Preparation or injection of sample to be analysed
The present invention provides a fusion protein of BDNF and an anti-human transferrin receptor antibody, in which in a heavy chain variable region of the antibody, (a) CDR1 includes an amino acid sequence of SEQ ID NO: 66 or SEQ ID NO: 67, (b) CDR2 includes an amino acid sequence of SEQ ID NO: 13 or SEQ ID NO: 14, and (c) CDR3 includes an amino acid sequence of SEQ ID NO: 15 or SEQ ID NO: 16.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligationUse of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
(1) Pharmaceutical preparations for the treatment of central nervous system disorders; pharmaceutical preparations for the treatment of peripheral nervous system disorders; pharmaceutical preparations for the treatment of growth deficiencies; pharmaceutical preparations for the treatment of enzyme deficiencies; pharmaceutical preparations for the treatment of lysosomal storage diseases; pharmaceutical preparations for the treatment of Fabry disease, Gaucher disease, GM1 Gangliosidosis, GM2 Gangliosidosis, Krabbe disease, Niemann-Pick disease, Metachromatic leukodystrophy, Hurler syndrome, Hunter disease, Sanfilippo syndrome, Morquio syndrome, Sly syndrome, Pompe disease, Alfa-mannosidosis disease, Fucosidosis disease, and Neuronal ceroid lipofuscinosis
70.
NUCLEIC ACID MOLECULE USED FOR PRODUCTION OF RECOMBINANT AAV VIRION
The purpose of the present invention is to provide a method for increased efficiency in production of recombinant AAV particles. This nucleic acid molecule includes: (a) a base sequence coding for Rep protein of AAV or a functional equivalent thereof; (b) a base sequence coding for Cap protein of AAV or a functional equivalent thereof; (c) a base sequence including a first AAV inverse terminal repetition (ITR) or a functional equivalent thereof; (d) a base sequence including a second AAV inverse terminal repetition (ITR) or a functional equivalent thereof; (e) a base sequence, located between the first ITR and the second ITR, for inserting a base sequence coding for a foreign protein, and/or a base sequence coding for a foreign protein; (f) a base sequence including an adenovirus E2A region or a functional equivalent thereof; (g) a base sequence including an adenovirus E4 region or a functional equivalent thereof; and (h) a base sequence including an adenovirus VA1 RNA region or a functional equivalent thereof.
Provided is an anti-human transferrin receptor antibody or an analog thereof, wherein in the heavy chain variable region of the antibody, (a) CDR1 comprises the amino acid sequence set forth as SEQ ID NO: 62 or SEQ ID NO: 63, (b) CDR2 comprises the amino acid sequence set forth as SEQ ID NO: 13 or SEQ ID NO: 14, and (c) CDR3 comprises the amino acid sequence set forth as SEQ ID NO: 15 or SEQ ID NO: 16, and an analogue thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
Disclosed are a human serum albumin mutant that can be linked to a physiologically active protein to increase the stability of the protein in the blood, as well as a resulting protein produced by linking with the mutant. The protein produced by linking with the mutant consists of a human serum albumin mutant comprising the amino acid sequence set forth as SEQ ID NO:3 or an amino acid sequence that, in comparison with it, lacks not more than 10 amino acid residues and/or has not more than 10 amino acid residues replaced, with the proviso that the asparagine residue occurring at position 318 and the threonine at position 320 from the N-terminus of the amino acid sequence set forth as SEQ ID NO:3 are preserved and linked by peptide bonds via a single amino acid residue (X) except proline placed between those two amino acid residues, and a physiologically active protein linked to the mutant.
This filter for filtering comprises a first welding frame, a second welding frame, and a filter sandwiched between and welded to the first welding frame and the second welding frame. The first welding frame and the second welding frame are formed of a flexible film at least 120 µm thick. Moreover, the filter is formed from a substance with a melting point higher than that of the first welding frame and the second welding frame and has a porosity of 10–80%. Furthermore, the first welding frame is formed from high-density polyethylene with a melting point of 120–140°C, linear low-density polyethylene with a melting point of 105–125°C, or a mixture that includes at least the high-density polyethylene or the linear low-density polyethylene.
[Problem] To provide a method for decomposing chondroitin sulfate contained in a sample into disaccharides. [Solution] A method which comprises heating chondroitin sulfate contained in a sample at a temperature of 60-90°C for 50-180 minutes in a hydrochloric acid/methanol mixture containing 2,2-dimethoxypropane, thereby decomposing the chondroitin sulfate contained in a sample into disaccharides. In particular, the sample is one selected from among body fluids, cells, tissues, organs, cell culture media, tissue culture media, foods, and feeds or one derived from any of these.
G01N 27/62 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosolsInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electric discharges, e.g. emission of cathode
Disclosed are pluripotent stem cell-enriched dental pulp-derived cells that can be administered to a human as a drug, and a method for producing the same. A method for producing dental pulp-derived cells enriched with pluripotent stem cells, wherein the production method includes (a) a step for digesting dental pulp by a protease to prepare a dental pulp suspension, (b) a step for culturing the suspension to cause the pluripotent stem cells contained in the suspension to proliferate, (c) a step for freezing the proliferated pluripotent stem cells in a state suspended in a first cryopreservation solution, (d) a step for thawing the frozen pluripotent stem cells, (e) a step for culturing the thawed pluripotent stem cells in a state adhered to the surface of particles to cause the pluripotent stem cells to proliferate on the surface of the particles, and (f) a step for bringing the particles into contact with a protease to separate the pluripotent stem cells adhered to the surface of the particles from the particles and prepare a pluripotent stem cell suspension.
[Problem] To provide software and a device that can be used as a means for increasing the success rate of in vitro fertilization. [Solution] Software for analyzing zygote images, said software providing a means for executing a process including: (a) a step for measuring the difference in area between the female pronucleus and the male pronucleus in images of a zygote obtained 1–10 hours before the dissolution of the membranes of the female and male pronuclei; (b) a step for measuring the difference in area between the female pronucleus and the male pronucleus in an image of the zygote obtained immediately before the dissolution of the membranes of the female and male pronuclei; and (c) a step for readably saving, as needed, the measured values for the difference in area obtained at step (a) and the difference in area obtained at step (b). A device incorporating said software.
[Problem] To provide an aqueous liquid formulation that contains a protein active ingredient, is storage stable as a solution, and causes less pain when injected. [Solution] An aqueous liquid formulation that contains a phosphate buffer that has a concentration of 1–20 mM and a protein active ingredient. For example, an aqueous liquid formulation that contains a phosphate buffer that has a concentration of 1–20 mM as a buffer and human growth hormone as an active ingredient and that also contains a poloxamer as a non-ionic surfactant and phenol as a tonicity agent.
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 5/06 - Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
(1) Pharmaceutical preparations for the treatment and prevention of lysosomal diseases; pharmaceutical preparations for the treatment and prevention of Hunter syndrome
05 - Pharmaceutical, veterinary and sanitary products
10 - Medical apparatus and instruments
40 - Treatment of materials; recycling, air and water treatment,
42 - Scientific, technological and industrial services, research and design
Goods & Services
pharmaceutical preparations; preparations for destroying vermin; fungicides, herbicides; reagents for medical purposes or veterinary purposes. Medical apparatus and instruments. Custom manufacture of pharmaceuticals or chemicals; custom manufacture of reagents for scientific, laboratory, analysis, research, testing, inspection, detecting or verification use. Medical research; chemical research; chemistry services; testing, inspection or research of pharmaceuticals, cosmetics or foodstuffs; chemical analysis; clinical trials; testing the functionality of machines, apparatus and instruments; research relating to industrial machinery; designing of machines, apparatus and instruments for medical purposes [including their parts] or systems composed of such machines, apparatus and instruments.
05 - Pharmaceutical, veterinary and sanitary products
10 - Medical apparatus and instruments
40 - Treatment of materials; recycling, air and water treatment,
42 - Scientific, technological and industrial services, research and design
Goods & Services
pharmaceutical preparations; preparations for destroying vermin; fungicides, herbicides; reagents for medical purposes or veterinary purposes. Medical apparatus and instruments. Custom manufacture of pharmaceuticals or chemicals; custom manufacture of reagents for scientific, laboratory, analysis, research, testing, inspection, detecting or verification use. Medical research; chemical research; chemistry services; testing, inspection or research of pharmaceuticals, cosmetics or foodstuffs; chemical analysis; clinical trials; testing the functionality of machines, apparatus and instruments; research relating to industrial machinery; designing of machines, apparatus and instruments for medical purposes [including their parts] or systems composed of such machines, apparatus and instruments.
05 - Pharmaceutical, veterinary and sanitary products
10 - Medical apparatus and instruments
Goods & Services
(1) Pharmaceutical preparations for the treatment of diseases and disorders affecting the central nervous system, peripheral nervous system, cardiovascular system, endocrine system, excretory system, digestive system, respiratory system, lymphatic system, integumentary system, muscular system, reproductive system, skeletal system, immune system, urinary system, and sensory organs; pharmaceutical preparations for the treatment and prevention of inflammation, inflammatory diseases, auto-immune diseases, neurological disorders, metabolic disorders, dermatological disorders, renal and urological disorders, genetic disorders, tumors, lysosomal diseases, and graft-versus-host disease and preparations for destroying vermin, fungicides, herbicides; diagnostic chemical reagents for medical purposes and veterinary purposes
(2) Medical instruments for use in the treatment of inflammation, inflammatory diseases, auto-immune diseases, neurological disorders, metabolic disorders, dermatological disorders, renal and urological disorders, genetic disorders, tumors, lysosomal diseases, and graft-versus-host disease
05 - Pharmaceutical, veterinary and sanitary products
10 - Medical apparatus and instruments
Goods & Services
(1) Pharmaceutical preparations for the treatment of diseases and disorders affecting the central nervous system, peripheral nervous system, cardiovascular system, endocrine system, excretory system, digestive system, respiratory system, lymphatic system, integumentary system, muscular system, reproductive system, skeletal system, immune system, urinary system, and sensory organs; pharmaceutical preparations for the treatment and prevention of inflammation, inflammatory diseases, auto-immune diseases, neurological disorders, metabolic disorders, dermatological disorders, renal and urological disorders, genetic disorders, tumors, lysosomal diseases, and graft-versus-host disease and preparations for destroying vermin, fungicides, herbicides; diagnostic chemical reagents for medical purposes and veterinary purposes
(2) Medical instruments for use in the treatment of inflammation, inflammatory diseases, auto-immune diseases, neurological disorders, metabolic disorders, dermatological disorders, renal and urological disorders, genetic disorders, tumors, lysosomal diseases, and graft-versus-host disease
83.
Medium containing uridine and N-acetyl-D-mannosamine
Provided are a novel medium for expressing glycoproteins by culturing cells and a method for producing glycoproteins by culturing cells in the medium. Further provided are a medium comprising uridine and N-acetyl-D-mannosamine for the use of expression of a glycoprotein by culturing cells and a method for producing glycoproteins by culturing cells in for medium.
Provided is an anti-human transferrin receptor antibody or an analog thereof, wherein in the heavy chain variable region of the antibody, (a) CDR1 comprises the amino acid sequence set forth as SEQ ID NO: 62 or SEQ ID NO: 63, (b) CDR2 comprises the amino acid sequence set forth as SEQ ID NO: 13 or SEQ ID NO: 14, and (c) CDR3 comprises the amino acid sequence set forth as SEQ ID NO: 15 or SEQ ID NO: 16, and an analogue thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
[Problem] To provide a pharmaceutical composition containing a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, which is stable enough to permit its distribution to the market.
[Solution] A lyophilized formulation containing; a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, and further containing a neutral salt, a disaccharide, a nonionic surfactant, and a buffer. Such a lyophilized formulation includes, for example, as an active ingredient, a fusion protein comprising an anti-transferrin receptor antibody and human iduronate-2-sulfatase, and further containing sodium chloride as the neutral salt, sucrose as the disaccharide, poloxamer as the nonionic surfactant, and phosphate buffer as the buffer.
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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
Disclosed is a method for producing a glycoprotein using mammalian cells, wherein all or part of the non-reducing ends of N-glycoside binding sugar chains are mannose residues. The method is a method for producing glycoproteins using transformant mammalian cells which are prepared by introducing thereinto a β-N-acetylglucosaminidase gene and inducing its expression.
[Problem] To provide a method for efficiently incorporating a drug that is to function in muscle tissue, but when administered to an organism is itself not adequately incorporated into muscle tissue, into muscle tissue, particularly into muscle tissue constituted of skeletal muscle or heart muscle. [Solution] A complex of a drug and an anti-human transferrin receptor antibody, wherein the drug is a drug having a physiological activity that is to exhibit functionality in muscle tissue, for example, a lysosomal enzyme such as acidic α-glucosidase or α-galactosidase A.
A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
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
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for the treatment of central nervous system disorders; pharmaceutical preparations for the treatment of peripheral nervous system disorders; pharmaceutical preparations for the treatment of growth deficiencies; pharmaceutical preparations for the treatment of enzyme deficiencies; pharmaceutical preparations for the treatment of lysosomal storage diseases; pharmaceutical preparations for the treatment of Fabry disease, Gaucher disease, GM1 Gangliosidosis, GM2 Gangliosidosis, Krabbe disease, Niemann-Pick disease, Metachromatic leukodystrophy, Hurier syndrome, Hunter disease, Sanfilippo syndrome, Morquio syndrome, Sly syndrome, Pompe disease, Alfa-mannosidosis disease, Fucosidosis disease, and Neuronal ceroid lipofuscinosis
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for the treatment of central nervous system disorders; pharmaceutical preparations for the treatment of peripheral nervous system disorders; pharmaceutical preparations for the treatment of growth deficiencies; pharmaceutical preparations for the treatment of enzyme deficiencies; pharmaceutical preparations for the treatment of lysosomal storage diseases; pharmaceutical preparations for the treatment of Fabry disease, Gaucher disease, GM1 Gangliosidosis, GM2 Gangliosidosis, Krabbe disease, Niemann-Pick disease, Metachromatic leukodystrophy, Hurier syndrome, Hunter disease, Sanfilippo syndrome, Morquio syndrome, Sly syndrome, Pompe disease, Alfa-mannosidosis disease, Fucosidosis disease, and Neuronal ceroid lipofuscinosis
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for the treatment of central nervous system disorders; pharmaceutical preparations for the treatment of peripheral nervous system disorders; pharmaceutical preparations for the treatment of growth deficiencies; pharmaceutical preparations for the treatment of enzyme deficiencies; pharmaceutical preparations for the treatment of lysosomal storage diseases; pharmaceutical preparations for the treatment of Fabry disease, Gaucher disease, GM1 Gangliosidosis, GM2 Gangliosidosis, Krabbe disease, Niemann-Pick disease, Metachromatic leukodystrophy, Hurier syndrome, Hunter disease, Sanfilippo syndrome, Morquio syndrome, Sly syndrome, Pompe disease, Alfa-mannosidosis disease, Fucosidosis disease, and Neuronal ceroid lipofuscinosis
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for the treatment and prevention of lysosomal diseases; pharmaceutical preparations for the treatment and prevention of Hunter syndrome
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for the treatment of central nervous system disorders; pharmaceutical preparations for the treatment of peripheral nervous system disorders; pharmaceutical preparations for the treatment of growth deficiencies; pharmaceutical preparations for the treatment of enzyme deficiencies; pharmaceutical preparations for the treatment of lysosomal storage diseases; pharmaceutical preparations for the treatment of Fabry disease, Gaucher disease, GM1 Gangliosidosis, GM2 Gangliosidosis, Krabbe disease, Niemann-Pick disease, Metachromatic leukodystrophy, Hurier syndrome, Hunter disease, Sanfilippo syndrome, Morquio syndrome, Sly syndrome, Pompe disease, Alfa-mannosidosis disease, Fucosidosis disease, and Neuronal ceroid lipofuscinosis
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for the treatment of central nervous system disorders; pharmaceutical preparations for the treatment of peripheral nervous system disorders; pharmaceutical preparations for the treatment of growth deficiencies; pharmaceutical preparations for the treatment of enzyme deficiencies; pharmaceutical preparations for the treatment of lysosomal storage diseases; pharmaceutical preparations for the treatment of Fabry disease, Gaucher disease, GM1 Gangliosidosis, GM2 Gangliosidosis, Krabbe disease, Niemann-Pick disease, Metachromatic leukodystrophy, Hurier syndrome, Hunter disease, Sanfilippo syndrome, Morquio syndrome, Sly syndrome, Pompe disease, Alfa-mannosidosis disease, Fucosidosis disease, and Neuronal ceroid lipofuscinosis
Disclosed is a method for production of a fusion protein in which an antibody and a lysosomal enzyme are fused. The method comprises; (a) a step of culturing mammalian cells producing the fusion protein in a serum-free medium to let the mammalian cells secrete the fusion protein in the culture medium, (b) a step of collecting culture supernatant by removing the mammalian cells from the culture medium, and (c) a step of purifying the fusion protein from the culture supernatant by using a column chromatography employing as a solid phase a material to which a substance having affinity for the fusion protein has been bound, a column chromatography employing as a solid phase a material having affinity for the phosphate group, and a size exclusion column chromatography.
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 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
