The present invention provides the compound, 3-[(1S,2S)-1-[5-[(4S)-2,2-Dimethyloxan-4-yl]-2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-4-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one, or a pharmaceutically acceptable salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound.
A61K 31/437 - 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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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 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
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
2.
NITROGEN-CONTAINING HETEROCYCLIC COMPOUND HAVING NRF2 ACTIVATION EFFECT
Provided is a low-molecular compound or a salt thereof, or a solvate thereof which has the ability to activate Nrf2.
Provided is a low-molecular compound or a salt thereof, or a solvate thereof which has the ability to activate Nrf2.
The present invention provides a compound represented by the formula (1) or a salt thereof, or a solvate thereof, wherein Xa1 is CRa1 or N, Xa3 is CRa3 or N, Ra1, Ra2 and Ra3 are each independently selected from the group consisting of hydrogen, halogen and C1-C6 alkoxy, Xb1, Xb2 and Xb3 are each independently selected from the group consisting of CH2, O, NH, S and C=O, Y is C6-C10 aryl optionally having a substituent or 5- to 10-membered heteroaryl optionally having a substituent, and Z is C6-C10 aryl optionally having a substituent, 5- to 10-membered heteroaryl optionally having a substituent or C1-C6 alkyl optionally having a substituent.
Provided is a low-molecular compound or a salt thereof, or a solvate thereof which has the ability to activate Nrf2.
The present invention provides a compound represented by the formula (1) or a salt thereof, or a solvate thereof, wherein Xa1 is CRa1 or N, Xa3 is CRa3 or N, Ra1, Ra2 and Ra3 are each independently selected from the group consisting of hydrogen, halogen and C1-C6 alkoxy, Xb1, Xb2 and Xb3 are each independently selected from the group consisting of CH2, O, NH, S and C=O, Y is C6-C10 aryl optionally having a substituent or 5- to 10-membered heteroaryl optionally having a substituent, and Z is C6-C10 aryl optionally having a substituent, 5- to 10-membered heteroaryl optionally having a substituent or C1-C6 alkyl optionally having a substituent.
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
A61K 31/536 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
A61K 31/5365 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/538 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61K 31/541 - Non-condensed thiazines containing further heterocyclic rings
A61K 31/5415 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
C07D 217/06 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 237/32 - Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
C07D 265/16 - 1,3-OxazinesHydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with only hydrogen or carbon atoms directly attached in positions 2 and 4
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 413/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
Provided herein is a method for removing a tert-butoxycarbonyl (Boc) group in a compound having a Boc group on a nitrogen atom, comprising treating the compound with a trifluoromethanesulfonic acid metal salt (metal triflate: M(OTf)n) or rare-earth metal halide (MXn) in the presence of a base to obtain a compound in which the Boc group is converted to H—.
C07B 51/00 - Introduction of protecting groups or activating groups, not provided for in groups
C40B 50/18 - Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creationParticular methods of cleavage from the solid support using a particular method of attachment to the solid support
4.
METHOD FOR PREDICTING IN VIVO PHARMACOKINETICS OF MOLECULE
The present invention provides a method for measuring in vitro pharmacokinetics of a molecule, the method including steps of: (a) contacting a molecule with a cell expressing FcRn in an aqueous medium to allow the cell to take up the molecule to be an uptake amount higher than 0.068 pmol/2×105 cells, in which step (a) has at least one feature selected from the following (i) to (iii): (i) a period of the contact of the molecule with the cell is 5 hours or more; (ii) the cell after the contact with the molecule is not washed under acidic conditions; and (iii) the cell expresses a target of the molecule on a surface of the cell; and (b) measuring in vitro pharmacokinetics of the molecule, in which the molecule contains an FcRn-binding domain, and the like.
The present disclosure relates to CXCR3 ligands having CXCR3-expressing-cell migration-inducing activity, and specifically to amino acid modifications and amino acid sequences that are important for CXCR3-expressing-cell migration-inducing activity.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
6.
ANTI-MYOSTATIN ANTIBODIES, POLYPEPTIDES CONTAINING VARIANT FC REGIONS, AND METHODS OF USE
The disclosure provides anti-myostatin antibodies and methods of making and using the same. Nucleic acids encoding the anti-myostatin antibodies and host cells comprising the nucleic acids are also provided. The anti-myostatin antibodies have uses that include treating a muscle wasting disease, reducing body fat accumulation, and increasing mass and strength of muscle tissue. The disclosure also provides polypeptides containing a variant Fc region and methods of making and using the same. Nucleic acids encoding the polypeptides and host cells comprising the nucleic acids are also provided. The polypeptides have uses that include suppressing the activation of immune cells; treating an immunological inflammatory disease, autoimmune disease, or viral infection; and increasing muscle mass and strength or reducing body fat accumulation.
Provided is a low-molecular compound or a salt thereof, or a solvate thereof which has the ability to activate Nrf2. The present invention provides a compound represented by the formula (1) or a salt thereof, or a solvate thereof, wherein Xa1 is CRa1 or N, Xa3 is CRa3 or N, Ra1, Ra2 and Ra3 are each independently selected from the group consisting of hydrogen, halogen and C1-C6 alkoxy, Xb1, Xb2 and Xb3 are each independently selected from the group consisting of CH2, O, NH, S and C=O, Y is C6-C10 aryl optionally having a substituent or 5- to 10-membered heteroaryl optionally having a substituent, and Z is C6-C10 aryl optionally having a substituent, 5- to 10-membered heteroaryl optionally having a substituent or C1-C6 alkyl optionally having a substituent.
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61K 31/541 - Non-condensed thiazines containing further heterocyclic rings
A61K 31/5415 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
C07D 217/06 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 237/32 - Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
C07D 265/14 - 1,3-OxazinesHydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
C07D 279/08 - 1,3-ThiazinesHydrogenated 1,3-thiazines condensed with carbocyclic rings or ring systems
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 413/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 413/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
The present invention provides anticancer agents comprising as an active ingredient a bispecific antibody that comprises a domain comprising a glypican 3-binding antibody variable region, a domain comprising a T cell receptor complex-binding antibody variable region, and common L chains that can enhance the affinity for the two antigens, as well as pharmaceutical compositions comprising the bispecific antibody as an active ingredient, the compositions being for use in combination with other anticancer agents. The bispecific antibodies are novel molecules which are produced with high efficiency and have strong anti-tumor activity as well as safety and excellent pharmacodynamics. The bispecific antibodies can be expected to be applied to various cancers.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
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
In one non-limiting embodiment, the present disclosure relates to lyophilized formulations containing an IL-31 antagonist (for example, an anti-IL-31RA antibody) as an active ingredient, the lyophilized formulations further containing arginine and/or a salt thereof and sucrose and/or trehalose. In another non-limiting embodiment, the present disclosure relates to solution formulations containing an IL-31 antagonist as an active ingredient, the solution formulations further containing arginine and/or a salt thereof. In other non-limiting embodiments, the present disclosure relates to methods for stabilizing an antibody (for example, an anti-IL-31RA antibody) in an antibody-containing formulation, methods for suppressing antibody aggregation (aggregate formation) in an antibody-containing formulation, and methods for reducing components with charge heterogeneity in an antibody-containing formulation, the methods being characterized in that the formulation is prepared to contain arginine and/or a salt thereof, and/or sucrose and/or trehalose.
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
C07K 14/715 - ReceptorsCell surface antigensCell surface determinants for cytokinesReceptorsCell surface antigensCell surface determinants for lymphokinesReceptorsCell surface antigensCell surface determinants for interferons
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
10.
CYCLIC COMPOUND HAVING SELECTIVE KRAS INHIBITORY EFFECT ON HRAS AND NRAS
Cyclic compounds that selectively inhibit KRAS were found. Moreover, cyclic compounds were found to interact with an amino acid residue specific to KRAS.
The present invention provides modified arninoacyl-tRNA synthetases (ARSs) having increased reactivity with N-methyl amino acids compared to natural aminoacyl-tRNA synthetases. The modified aminoacyI-tRNA synthetases according to the present invention can aminoacylate tRNAs with their corresponding N-methyl-substituted amino acids such as N-methyl-phenylalanine, N-methyl-valine, N-methyl-serine, N-methyl-threonine, N-methyl-tryptophan, and N-methyl-leucine more efficiently than natural aminoacyl-tRNA synthetases. The present invention enables a more efficient production of polypeptides containing N-methyl amino acids.
This information processing system for identifying molecules that are suitable for a drug candidate comprises: a characteristic prediction unit that, for molecules constituting elements of a sequence information set that is a set of sequence information for a plurality of different molecules, calculates a characteristic prediction value for each molecule using a prediction model for predicting the characteristics of the molecules from the sequence information for the molecules, and estimates the uncertainty of the prediction; and a candidate molecule identification unit that searches for candidates for molecules having desired characteristics on the basis of the characteristic prediction value and an estimated value of the uncertainty of the prediction.
The invention provides a means for a treatment for a demyelinating disease of the central nervous system (CNS) characterized by the presence of an anti-myelin oligodendrocyte glycoprotein (MOG) antibody, and also for reducing the risk of relapse in the demyelinating disease, comprising an anti-IL-6 receptor antibody or antigen binding fragment 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
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
14.
MEDICINE CONTAINER, MEDICINE SUCTION METHOD, MEDICINE DISCHARGE METHOD, AND GASKET RELEASE TOOL
The present invention comprises: a cylindrical container body for storing a medicine, said container body including a tip part in which a dispensing port for dispensing medicine stored inside the container body is formed, a base end part that is open in the axial direction; a gasket that is in close contact with the inner peripheral surface of the container body along the entire circumferential perimeter thereof when inserted into the opening of the base end part in the container body; and a release part that causes the gasket to move slightly. The release part includes: a mounting part that is mounted on the base end part of the container body; and a movable part that is configured so as to move while being guided by the mounting part and thereby cause the gasket to move slightly.
A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
A61J 1/05 - Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids
15.
POLYPEPTIDE INCLUDING ANTIGEN-BINDING DOMAIN AND CARRYING SECTION
The present invention relates to polypeptides containing an antigen-binding domain and a carrying moiety having an inhibiting domain that inhibits the antigen-binding activity of the antigen-binding domain, and having a longer half-life than that of the antigen-binding domain existing alone; methods for producing and screening for the polypeptides; pharmaceutical compositions containing the polypeptide; methods for producing and screening for a single-domain antibody whose antigen-binding activity is inhibited by its association with particular VL, VH or VHH; and fusion polypeptide libraries including a single-domain antibody whose antigen-binding activity is inhibited by its association with particular VL, VH or VHH.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
16.
ANTIBODY SUBSTITUTING FOR FUNCTION OF BLOOD COAGULATION FACTOR VIII
The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.
F. HOFFMANN-LA ROCHE AKTIENGESELLSCHAFT (Switzerland)
Inventor
Sase Hitoshi
Susumu Ai
Abstract
Provided is a medicine for treating or preventing cancer that contains a first active ingredient and that is used in combination with a second active ingredient, wherein: the first active ingredient is a compound represented by formula (1), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof; and the second active ingredient is GDC-6036 or a pharmaceutically acceptable salt thereof.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61P 35/02 - Antineoplastic agents specific for leukemia
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07K 7/54 - Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
18.
METHOD FOR TREATING AND/OR PREVENTING REGNASE-1-RELATED DISEASE
The present invention found that, for example, inhibiting phosphorylation of a Ser residue in Regnase-1 is effective in treating and/or preventing diseases. The invention also found that, for example, inhibiting the binding of Regnase-1 with at least one factor selected from the group consisting of TBK1, IKKi, Act-1, IKK, and IRAK is effective in treating and/or preventing diseases.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07K 7/64 - Cyclic peptides containing only normal peptide links
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/573 - ImmunoassayBiospecific binding assayMaterials therefor for enzymes or isoenzymes
19.
METHOD OF MODIFYING ISOELECTRIC POINT OF ANTIBODY VIA AMINO ACID SUBSTITUTION IN CDR
The present inventors provide methods for modifying the isoelectric point of an antibody while retaining its antigen-binding activity, comprising modifying the charge of at least one exposable amino acid residue on the surface of the complementarity determining region (CDR). The present invention also provides methods for purifying multispecific antibodies, comprising modifying isoelectric point, and methods for improving the plasma pharmacokinetics of antibodies, comprising modifying isoelectric point. The present invention further provides antibodies with a modified isoelectric point, pharmaceutical compositions comprising the antibodies as an active ingredient, and methods for producing the antibodies and compositions.
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 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
20.
CYTOTOXICITY-INDUCING THERAPEUTIC AGENT FOR USE IN TREATMENT OF CANCER
The present disclosure provides anticancer agents containing a multispecific antigen-binding molecule that can efficiently and specifically recruit T cells to the target cancer cells, particularly CLDN6-expressing cancer cells and such, and can treat cancer through the cytotoxic activity of T cells against target cancer tissues containing CLDN6-expressing cells; combination therapies using the anticancer agent and at least one other anticancer agent; and pharmaceutical compositions for use in the combination therapies.
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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present invention provides a crystal of a low molecular weight compound which has Nrf2 activation effect, a crystal of a salt of the compound, or a crystal of a solvate of the compound or the salt. The present invention specifically provides a crystal of a compound represented by any one of formulae (1) to (5), a crystal of a salt of the compound, or a crystal of a solvate of the compound or the salt.
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 25/00 - Drugs for disorders of the nervous system
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The present invention relates to pharmaceutical compositions containing a combination of a first antigen-binding molecule and a second antigen-binding molecule, wherein the first antigen-binding molecule and the second antigen-binding molecule are not linked by a covalent bond, and they are more likely to form a heterodimer than homodimers when mixed in solution. Furthermore, the present invention relates to antigen-binding molecules, therapeutic methods, and screening methods that are associated with the combination.
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
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
The present invention provides a pharmaceutical composition for treating IL-6-related diseases containing an IL-6 inhibitor as an active ingredient, wherein the pharmaceutical composition is routinely administered after a short-interval dosing period where the same dose as the routine dose is administered at a shorter interval than the routine dosing interval.
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
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
24.
COMPOUND HAVING PHOTOCLEAVABLE MOIETY, CONJUGATE, AND SCREENING METHOD USING SAME
The present invention relates to a compound having (i) a photocleavable moiety, and (ii) at least one selected from the group consisting of a target substance binding site and an anchor binding site.
C07D 311/18 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted otherwise than in position 3 or 7
C07K 1/16 - ExtractionSeparationPurification by chromatography
The present invention relates to anti-HLA-DQ2.5 antibodies and formulations containing the same. The present invention provides anti-HLA-DQ2.5 antibodies that have been modified. The anti-HLA-DQ2.5 antibodies of the invention have binding activity to complexes formed by HLA-DQ2.5 and a gluten peptide, but have substantially no binding activity to complexes formed by HLA-DQ2.5 and an irrelevant peptide. Furthermore, the antibodies of the invention are shown to have inhibitory effects on T cell activation by gluten peptides. The present invention also relates to formulations, in particular, formulations for injection, containing an anti-HLA-DQ2.5 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
In a cell culture plan creation device (40), an input unit (142) receives input of a cell culture end time and a target cell amount at the culture end time, and a plan creation unit (144) creates a cell culture plan including a first execution designation for one or more passage processes sequentially executed so as to obtain the target cell amount at the culture end time and a second execution designation for a culture process executed following each passage process. The first execution designation includes information for identifying the type of passage process and information for identifying the timing for executing passage processes.
The present invention provides cross-species anti-latent TGF-beta 1 antibodies. The present inventors have conducted diligent studies and consequently created cross-species anti-latent TGF-beta 1 antibodies which inhibit a protease mediated activation of TGF-beta 1 but do not inhibit integrin mediated activation of latent TGF-beta 1. It has been reported that latent TGF-beta is cleaved to release active TGF-beta by proteases. However, surprisingly, the present inventors have found that the anti-TGF-beta 1 antibodies inhibit a protease mediated activation of latent TGF-beta 1 without inhibiting protease mediated cleavage of the LAP region of latent TGF-beta 1, and have in vivo anti-fibrotic effects as well. Further, antibodies of the invention are useful for the diagnosis or treatment of cancer, and can also be used in combination with immune check point inhibitors.
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
29.
METHOD FOR PREPARING PREFILLED SYRINGE FORMULATION
An object of the present invention is to reduce formation of visually detectable particles in a formulation for injection in which a solution containing a protein is filled in a container. The present invention provides a method for determining a protein having a high risk of forming particles.
A61M 5/36 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests with means for eliminating or preventing injection or infusion of air into body
The present inventors found cyclic peptide compounds that interact with Ras, and non-natural amino acids useful for the production of the cyclic peptide compounds. The inventors also found that the cyclic peptide compounds inhibit the binding between Ras and SOS. In addition, the inventors found specific non-natural amino acids contained in the cyclic peptide compounds and methods for production thereof.
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07C 317/04 - SulfonesSulfoxides having sulfone or sulfoxide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
C07C 323/09 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton having sulfur atoms of thio groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 213/64 - One oxygen atom attached in position 2 or 6
C07D 213/65 - One oxygen atom attached in position 3 or 5
C07D 295/15 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
C07D 309/12 - Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
The problem to be solved is to provide a humanized anti-IL-6 receptor antibody MRA-containing formulation which is suitable for subcutaneous administration, wherein dimerization or deamidation is prevented during long-term storage. The present application is directed to a stable antibody-containing liquid formulation characterized by containing arginine and histidine buffer. A method of inhibiting deamidation or dimerization of such an antibody in a concentrated liquid formulation includes histidine buffer in the liquid formulation.
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 9/00 - Medicinal preparations characterised by special physical form
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
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 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
The present invention provides efficient methods based on alteration of the protein A-binding ability, for producing or purifying multispecific antibodies having the activity of binding to two or more types of antigens to high purity through a protein A-based purification step alone. The methods of the present invention for producing or purifying multispecific antibodies which feature altering amino acid residues of antibody heavy chain constant region and/or variable region. Multispecific antibodies with an altered protein A-binding ability, which exhibit plasma retention comparable or longer than that of human IgG1, can be efficiently prepared in high purity by introducing amino acid alterations of the present invention into 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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/36 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
An object of the present disclosure is to provide a staked-in needle prefilled syringe formulation containing an antibody engineered by a mutation to histidine, which reduces the difficulty in pushing out a drug and the risk of causing clogging in a needle. The staked-in needle prefilled syringe formulation can be produced by a simple method on an industrial scale. The present prefilled syringe formulation is characterized by having an elastomeric needle shield having a low zinc leaching capacity.
A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
34.
MULTI-SPECIFIC ANTIGEN-BINDING MOLECULE HAVING ALTERNATIVE FUNCTION TO FUNCTION OF BLOOD COAGULATION FACTOR VIII
Various bispecific antibodies that specifically bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.
The present invention provides methods of efficiently producing various optically active aromatic amino acid derivatives by reacting, using an additive, a specific ester compound with an aromatic halide and zinc in the presence of a catalyst. The present invention also provides amino acid derivatives that can be produced by the methods.
C07C 269/06 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
C07D 239/26 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
An objective of the invention is to provide anti-latent TGF-beta 1 antibodies and methods of using such antibodies. The present invention provides anti-latent TGF-beta 1 antibodies which inhibit a protease mediated activation of latent TGF-beta 1 without inhibiting integrin mediated activation of latent TGF-beta 1 or with partially inhibiting integrin mediated activation of latent TGF-beta 1, or which inhibit a protease mediated activation of latent TGF-beta 1 but have less impact on inhibiting integrin mediated activation of latent TGF-beta 1. The invention also provides optimized anti-latent TGF-beta 1 antibodies in which pH-dependent binding property is improved. The anti-latent TGF-beta 1 antibodies may be used for treating fibrosis or cancer. For example, renal fibrosis, liver fibrosis, and lung fibrosis may be treated using the anti-latent TGF-beta 1 antibodies.
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
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 19/04 - Drugs for skeletal disorders for non-specific disorders of the connective tissue
37.
HIGH CONCENTRATION ANTIBODY-CONTAINING LIQUID FORMULATION
The problem to be solved is to provide a humanized anti-IL-6 receptor antibody MRA-containing formulation which is suitable for subcutaneous administration, wherein dimerization or deamidation is prevented during long-term storage. The present application is directed to a stable antibody-containing liquid formulation characterized by containing arginine and histidine buffer. A method of inhibiting deamidation or dimerization of such an antibody in a concentrated liquid formulation includes histidine buffer in the liquid formulation.
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 9/00 - Medicinal preparations characterised by special physical form
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
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 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
The invention provides methods and compositions for treating cancer (e.g., a locally advanced, recurrent, or metastatic solid tumor) in a subject, for example, by administering an anti-cancer therapy that includes an anti-latent TGF-beta 1 antibody to the subject. Also provided are compositions (e.g., an anti-latent TGF-beta 1 antibody, pharmaceutical compositions thereof, kits thereof, and articles of manufacture thereof) for use in treating cancer in a subject.
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
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
39.
PREPARATION CONTAINING CYCLIC PEPTIDE COMPOUND AND METHOD FOR PRODUCING SAME
The present invention relates to a composition containing: a compound represented by the following Formula (1):
The present invention relates to a composition containing: a compound represented by the following Formula (1):
The present invention relates to a composition containing: a compound represented by the following Formula (1):
or, a salt thereof, or a solvate thereof; a liquid additive; and optionally an oily component.
All currently available treatment options for thyroid eye disease (TED) carry substantial potential safety risks. The present disclosure provides a means for treating or preventing TED comprising an IL-6 inhibitor such as anti-IL-6 receptor antibody or antigen binding fragment thereof such as satralizumab.
This method for producing an amide group-containing compound comprises a step A for reacting NCA with an amino group of an amino group-containing compound in the presence of a Lewis acid in a first solvent.
As a method for cyclization when producing a cyclic peptide compound having a double bond that forms a crosslink between amino acids, the present invention provides a method for cyclization by means of a cyclization position at which it is possible to reduce the produced amount of a cyclic dimer, which is a by-product. In addition, as a method for producing a cyclized precursor peptide compound, the present invention provides an efficient production method in which three fragment peptides are synthesized by means of liquid phase fragment coupling. Also provided are: a crystal of a cyclic peptide compound; and a method for producing said crystal by means of crystallization.
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
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
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07K 7/54 - Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
44.
METHOD FOR SCREENING MOLECULES OF INTEREST CAPABLE OF FORMING COMPLEXES WITH PLURALITY OF TARGET MOLECULES, AND METHOD FOR PRODUCING MOLECULES OF INTEREST INCLUDING SCREENING METHOD
The present invention relates to a method for screening molecules of interest, which are molecules capable of forming complexes with a plurality of types of target molecules, the method including a step for bringing a candidate molecule-nucleic acid conjugate library into contact with a plurality of types of target molecules in close proximity to each other.
METHOD FOR SCREENING FOR MOLECULES OF INTEREST CAPABLE OF FORMING COMPLEXES WITH PLURALITY OF TARGET MOLECULES, AND METHOD FOR PRODUCING MOLECULES OF INTEREST INCLUDING SCREENING METHOD
The present invention pertains to a method for screening molecules of interest, said method including: (1) a step (linking step) for linking a plurality of types of target molecules to each other or linking one or more types of target molecules with a candidate molecule-nucleic acid conjugate to prepare a conjugate; and (2) a step (contact step) for bringing a candidate molecule-nucleic acid conjugate into contact with a conjugate in which the plurality of types of target molecules are linked, or bringing a target molecule not used in the linking step in contact with a conjugate in which the one or more types of target molecules are linked with a candidate molecule-nucleic acid conjugate.
The present invention relates to fusion proteins comprising a ligand binding domain, a protease cleavage site, and a ligand moiety. The fusion proteins of the invention comprise a ligand binding domain, a ligand moiety, and a protease cleavage site that, when activated by cleavage by a protease, restores biological activity of the ligand. The invention also relates to methods of producing the fusion proteins, their uses and pharmaceutical compositions comprising said fusion proteins. The present invention also relates to a method of reducing the association between heavy chain variable domain (VH) and light chain variable domain (VL) within the ligand binding domain that promotes dissociation of one from the other. The present disclosure provides fusion proteins in which the ligand is fused to the C-terminus of the constant region, or the N-terminus of the ligand binding domain.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
47.
METHOD FOR STABILIZING PROTEIN-CONTAINING PHARMACEUTICAL PREPARATION
The present invention provides, pertaining to a pharmaceutical preparation that is a solution containing a protein as an active ingredient, a method for reducing protein adsorption by a container and particle generation in the solution, wherein: the container material is glass; the inner surface of the container is coated; the angle of contact with water of at least a part of this inner surface is 90° or greater; and the particles have a particle diameter of 40 μm or larger.
METHOD FOR SCREENING MOLECULES OF INTEREST CAPABLE OF FORMING COMPLEXES WITH PLURALITY OF TYPES OF TARGET MOLECULES, AND METHOD FOR PRODUCING MOLECULES OF INTEREST INCLUDING SCREENING METHOD
The present invention relates to a method for screening molecules of interest, said method including: (1) a step (binding step) in which a plurality of types of target molecules are bound to each other, or one or more types of target molecules are bound with a candidate molecule-nucleic acid complex to prepare a conjugate; and (2) a step (contact step) in which a candidate molecule-nucleic acid complex is brought into contact with a conjugate formed by binding the plurality of types of target molecules, or a target molecule that was not used in the binding step is brought into contact with a conjugate formed by binding the one or more types of target molecules with a candidate molecule-nucleic acid complex.
The present disclosure provides, for example, a method for producing 2-(4-cyclopropyl-2-fluoroanilino)-3,4-difluoro-5-[[3-fluoro-2-(methylsulfamoylamino)pyridin-4-yl]methyl]benzamide or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt, the method comprising reacting (2-amino-3-fluoropyridin-4-yl)methanol with methyl chloroformate and N,N-dimethylaminopyridine in acetonitrile to give (2-amino-3-fluoropyridin-4-yl)methyl methyl carbonate. According to the present disclosure, there is provided a method for producing a specific aryl amide derivative that has RAF/MEK complex-stabilizing activity and/or MEK-inhibiting activity and is useful for the treatment or prevention of a cell proliferative disorder, particularly a cancer, the method enabling the aryl amide derivative to be produced with a small number of steps.
The present invention provides a biomarker for predicting prognosis in a sepsis patient, the biomarker comprising IL-1β and TNF-α. The index for predicting the prognosis in a sepsis patient is the blood concentration ratio of IL-1β with respect to TNF-α.
PHARMACEUTICAL COMPOSITION FOR USE IN PREVENTION AND/OR TREATMENT OF DISEASE THAT DEVELOPS OR PROGRESSES AS A RESULT OF DECREASE OR LOSS OF ACTIVITY OF BLOOD COAGULATION FACTOR VIII AND/OR ACTIVATED BLOOD COAGULATION FACTOR VIII
The inventors discovered that by administering a pharmaceutical composition comprising a bispecific antigen-binding molecule that recognizes blood coagulation factor IX and/or activated blood coagulation factor IX and blood coagulation factor X and/or activated blood coagulation factor X according to a given dosage regimen, diseases that develop and/or progress due to a decrease or deficiency in the activity of blood coagulation factor VIII and/or activated blood coagulation factor VIII can be prevented and/or treated more effectively.
The problem to be solved is to provide a humanized anti-IL-6 receptor antibody MRA-containing formulation which is suitable for subcutaneous administration, wherein dimerization or deamidation is prevented during long-term storage. The present application is directed to a stable antibody-containing liquid formulation characterized by containing arginine and histidine buffer. A method of inhibiting deamidation or dimerization of such an antibody in a concentrated liquid formulation includes histidine buffer in the liquid formulation.
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 9/00 - Medicinal preparations characterised by special physical form
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
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 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
This method for producing a eutectic containing a cyclic peptide and a compound having a melting point of 20°C or greater comprises a step for bringing the cyclic peptide into contact with the compound and a solvent.
The present invention provides a filling nozzle obtained by using a resin selected from a cycloolefin polymer and a cycloolefin copolymer, or a filling nozzle including a tubular passage for supplying a pharmaceutical solution, and a filling port disposed at a lower end of the tubular passage, in which the tubular passage and the filling port have a circular peripheral cross-section, and an inner diameter of the passage of the filling port is larger than an inner diameter of the tubular passage disposed on an upstream side.
B65B 39/00 - Nozzles, funnels or guides for introducing articles or materials into containers or wrappers
B05B 15/525 - Arrangements for cleaningArrangements for preventing deposits, drying-out or blockageArrangements for detecting improper discharge caused by the presence of foreign matter for removal of clogging particles by increasing the cross section of the discharge openings
B05B 15/65 - Mounting arrangements for fluid connection of the spraying apparatus or its outlets to flow conduits
B65B 3/00 - Packaging plastic material, semiliquids, liquids or mixed solids and liquids, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans or jars
B65B 3/04 - Methods of, or means for, filling the material into the containers or receptacles
In the present invention, a robot system (100) includes: mobile manipulators (10) each including a local controller (11); workbench robots (20) each including a local controller (21); a general controller (30); and a work instruction device (40) that performs work instructions for causing a cell experiment to be executed. The work instruction device (40): accesses experiment definition data including preparation transport information and workbench experiment specific information; and creates, on the basis of the preparation transport information, a preparation transport instruction for extracting cells that are the subject of the experiment from a first storage location and transporting the cells to the workbench, and, on the basis of the workbench experiment specific information, a workbench experiment instruction for executing an experiment on the transported cells.
B25J 5/00 - Manipulators mounted on wheels or on carriages
C12M 1/00 - Apparatus for enzymology or microbiology
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor
G01N 35/02 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions.
The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions.
The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.
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
The present invention relates to a pharmaceutical composition comprising poorly soluble compounds such as BSC class II or IV kinase inhibitors, a process for the preparation thereof and its use in the treatment of diseases, in particular cancer. further particularly in non-small lung cancer.
The present invention relates to one or more binding molecules that are capable of inducing receptor signaling of a receptor complex, conditioned upon non-competitive and/or biparatopic binding to a scaffold protein. The present invention also relates to the therapeutic use of the one or more binding molecules in cancer and autoimmune disease.
A61K 31/473 - QuinolinesIsoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/4743 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having sulfur as a 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
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
60.
THERAPEUTIC AGENT FOR CANCER OF PATIENT WITH DECREASE IN RB1 FUNCTION USING MYT1 INHIBITOR AND CHEMOTHERAPEUTIC AGENT IN COMBINATION, AND TREATMENT METHOD THEREOF
The present invention provides a pharmaceutical composition comprising, in combination with a chemotherapeutic agent, an MYT1 inhibitor as an active ingredient for treatment or prevention of cancer of a patient with a decrease in RB1 function.
A61K 31/437 - 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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present inventors successfully obtained anti-NR10 antibodies having an effective neutralizing activity against NR10. The anti-NR10 antibodies provided by the present invention are useful as, for example, pharmaceuticals for treating or preventing inflammatory diseases.
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
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
62.
NOVEL THERAPEUTIC AGENT FOR SEPTICEMIA, AND A METHOD FOR SCREENING FOR SAME
The present invention provides a therapeutic agent for sepsis and/or septic shock and a method for screening for the therapeutic agent. The present invention relates to a therapeutic agent for sepsis and/or septic shock comprising an Arid5A inhibitor as an active ingredient. The present invention also relates to a method for screening for a candidate substance useful for the treatment of sepsis and/or septic shock, the method comprising: (a) determining an effect of test agents on the expression and/or function of Arid5A and (b) selecting the agents that decrease the expression and/or function of Arid5A as compared to the absence of the test agents.
C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
The present invention provides a pharmaceutical composition having excellent dissolution property and content uniformity and a production method thereof by mixing a p-toluenesulfonate of 7-[[2,3-difluoro-4-[2-[2-methoxyethyl(methyl)amino]ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4,5]deca-9-ene-9-carboxamide with specific additives, and formulating the mixture.
Disclosed are bispecific antibodies with heavy chain constant regions having the sequence of an IgG1 constant region with one or more mutations including one or more substitutions that reduce the ability of the heavy chain constant regions to bind to a human Fcγ receptor.
A61K 39/00 - Medicinal preparations containing antigens or 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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
65.
ANTI-HLA-DQ2.5/8 ANTIBODY AND ITS USE FOR THE TREATMENT OF CELIAC DISEASE
The invention provides anti-HLA-DQ2.5/8 antibodies and methods of using the same. The antibodies of the present invention have binding activity to human HLA-DQ2.5/8 and monkey MHC-DQ, but substantially no binding activity to HLA-DR, HLA-DP, or a complex of the invariant chain (CD74) and HLA-DQ2.5/8. The antibodies bind to HLA-DQ2.5/8 in the presence of a gluten peptide such as gliadin, i.e., bind to HLA-DQ2.5/8 forming a complex with the gluten peptide. The antibodies have neutralizing activity against the binding between HLA-DQ2.5/8 and TCR, and thus block the interaction between HLA-DQ2.5/8 and an HLA-DQ2.5/8-restricted CD4+ T cell. The antibodies do not undergo rapid internalization mediated by the invariant chain. These characteristics are particularly useful for treating celiac disease. Thus, the present invention also provides a method of treating celiac disease using the antibodies of the present invention.
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
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
The present invention provides antibodies that comprises an antigen-binding region and an antibody constant region and binds to C1s in a pH-dependent manner. The present invention provides pharmaceutical compositions comprising any one of the antibodies, and methods of treating an individual having a complement-mediated disease or disorder, or preventing an individual potentially having a complement-mediated disease or disorder, the method comprising administering any one of the antibodies to the individual.
The present inventors newly discovered that even if an antigen-binding molecule inhibits in vitro some of the physiological activities of an antigen having two or more physiological activities without inhibiting the remaining physiological activities, the molecule can promote elimination of the antigen from blood (from serum or plasma) and as a result reduce the physiological activities in vivo, when the antigen-binding molecule is conferred with the properties: (i) of binding to human FcRn under an acidic pH range condition; (ii) of binding under a neutral pH range condition to human Fc receptor stronger than native human IgG, and (iii) that its antigen-binding activity alters according to the ion concentration.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
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 relates to fusion proteins or protein complexes comprising a ligand binding moiety fused to a ligand moiety, wherein the ligand binding moiety comprises an IL-12 binding domain and a protease cleavage site that, when activated by cleavage by a protease, restores biological activity of the ligand moiety, wherein the ligand moiety is an IL-12 fusion protein. The invention also relates to a polypeptide representing a mutated p40 subunit of IL-12, and to an IL-12 fusion protein or a protein complex comprising the mutated p40 subunit. The invention also relates to anti-IL-12 binding molecule or anti-IL-12 binding molecule complex defined by its variable light and heavy chains. The invention also relates to polynucleotides encoding the fusion proteins or fusion protein complexes or polypeptides or binding molecules, to methods of producing same, to their uses and pharmaceutical compositions comprising same.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
69.
ANTI-LATENT TGF-BETA 1 ANTIBODIES AND METHODS OF USE
An objective of the invention is to provide anti-latent TGF-beta 1 antibodies and methods of using such antibodies. The present invention provides anti-latent TGF-beta 1 antibodies which inhibit a protease mediated activation of latent TGF-beta 1 without inhibiting integrin mediated activation of latent TGF-beta 1 or with partially inhibiting integrin mediated activation of latent TGF-beta 1, or which inhibit a protease mediated activation of latent TGF-beta 1 but have less impact on inhibiting integrin mediated activation of latent TGF-beta 1. The invention also provides optimized anti-latent TGF-beta 1 antibodies in which pH-dependent binding property is improved. The anti-latent TGF-beta 1 antibodies may be used for treating fibrosis or cancer. For example, renal fibrosis, liver fibrosis, and lung fibrosis may be treated using the anti-latent TGF-beta 1 antibodies.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
The invention provides anti-DDR2 antibodies that binds to DDR2, and methods of using the same. The invention further provides isolated nucleic acids encoding the anti-DDR2 antibodies, host cells comprising the same, and methods of producing the anti-DDR2 antibodies. The invention further provides use of the anti-DDR2 antibodies in the manufacture of a medicament.
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
A61P 11/00 - Drugs for disorders of the respiratory system
71.
ANTIGEN-BINDING MOLECULE COMPRISING ALTERED ANTIBODY VARIABLE REGION BINDING CD3 AND CD137
Antigen-binding domains that are capable of binding to CD3 and CD137 but do not bind to CD3 and CD137 at the same time and methods of using the same are provided. Methods to obtain antigen binding domains which bind to two or more different antigens more efficiently are also provided.
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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
72.
PYRAZOLOPYRIDINE DERIVATIVE HAVING GLP-1 RECEPTOR AGONIST EFFECT
The present invention provides a compound having the basic structure shown by Formula (I) in which the indole ring and the pyrazolopyridine structure is bound through a substituent, a salt thereof or a solvate of either the compound or a salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound, salt or solvate as an active ingredient.
A61K 31/437 - 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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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 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
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
Disclosed are bispecific antibodies with heavy chain constant regions having the sequence of an IgG1 constant region with one or more mutations including one or more substitutions that reduce the ability of the heavy chain constant regions to bind to a human Fcγ receptor.
A61K 39/00 - Medicinal preparations containing antigens or 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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
The present disclosure provides, for example, a method of stabilizing the RAF/MEK complex in a subject, the method comprising administering to the subject an effective amount of a compound represented by the general formula below or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt:
The present disclosure provides, for example, a method of stabilizing the RAF/MEK complex in a subject, the method comprising administering to the subject an effective amount of a compound represented by the general formula below or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt:
The present disclosure provides, for example, a method of stabilizing the RAF/MEK complex in a subject, the method comprising administering to the subject an effective amount of a compound represented by the general formula below or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt:
wherein X1, X2, X3 and X4 are each independently —CR2═ or —N═, R2 is, for example, a halogen atom, R1 is, for example, —S(═O)2—NH—R8, R8 is, for example, a C1-6 alkyl group, R3 is, for example, a hydrogen atom, R5 is, for example, a halogen atom, R6 is, for example, a hydrogen atom, and R4 is, for example, a cyclopropyl group.
C07C 307/02 - Monoamides of sulfuric acids or esters thereof, e.g. sulfamic acids
C07C 317/50 - SulfonesSulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the nitrogen atoms being part of any of the groups X being a hetero atom, Y being any atom
C07C 333/20 - Esters of dithiocarbamic acids having nitrogen atoms of dithiocarbamate groups bound to hydrogen atoms or to acyclic carbon atoms
C07D 213/73 - Unsubstituted amino or imino radicals
C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
C07D 305/06 - Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring atoms
C07D 307/14 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
C07D 307/93 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
C07D 309/08 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
C07D 309/14 - Nitrogen atoms not forming part of a nitro radical
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
The present invention provides a compound having the basic structure shown by Formula (I) in which the indole ring and the pyrazolopyridine structure is bound through a substituent, a salt thereof or a solvate of either the compound or a salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound, salt or solvate as an active ingredient.
A61K 31/437 - 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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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 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
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The present invention relates to fusion proteins or protein complexes comprising a ligand binding moiety fused to a ligand moiety, wherein the ligand binding moiety comprises an IL-12 binding domain and a protease cleavage site that, when activated by cleavage by a protease, restores biological activity of the ligand moiety, wherein the ligand moiety is an IL-12 fusion protein. The invention also relates to a polypeptide representing a mutated p40 subunit of IL-12, and to an IL-12 fusion protein or a protein complex comprising the mutated p40 subunit. The invention also relates to anti-IL-12 binding molecule or anti-IL-12 binding molecule complex defined by its variable light and heavy chains. The invention also relates to polynucleotides encoding the fusion proteins or fusion protein complexes or polypeptides or binding molecules, to methods of producing same, to their uses and pharmaceutical compositions comprising same.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
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
C12N 15/62 - DNA sequences coding for fusion proteins
C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
The present invention provides multispecific antigen-binding molecules that comprise a first antigen-binding domain having RNF43-binding activity and a second antigen-binding domain having T cell receptor complex-binding activity, uses of such multispecific antigen-binding molecules, etc. The present inventors discovered novel multispecific antigen-binding molecules with excellent cellular cytotoxicity and high stability, which comprise a first antigen-binding domain having RNF43-binding activity and a second antigen-binding domain having T cell receptor complex-binding activity. Since the molecules of the present invention show a strong cytotoxicity against cells and tissues expressing RNF43, it is possible to produce novel pharmaceutical compositions comprising the multispecific antigen-binding molecules for treating or preventing various cancers.
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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
79.
BINDING MOLECULE EXHIBITING SELECTIVE BINDING FOR RAS(G12D) MUTANT
It was found that a binding molecule having features (i) of directly interacting with Asp12 of mutant RAS (G12D), and (ii) of interacting with a Switch 2 region of the mutant RAS (G12D), and having the Switch 2 region of the mutant RAS (G12D) intramolecularly interacting with Asp12 of the mutant RAS (G12D) has high binding selectivity for the mutant RAS (G12D). Such a molecule can be a promising candidate compound for treating and/or preventing a disease related to expression of the mutant RAS (G12D).
The present inventors provide methods for modifying the isoelectric point of an antibody while retaining its antigen-binding activity, comprising modifying the charge of at least one exposable amino acid residue on the surface of the complementarity determining region (CDR). The present invention also provides methods for purifying multispecific antibodies, comprising modifying isoelectric point, and methods for improving the plasma pharmacokinetics of antibodies, comprising modifying isoelectric point. The present invention further provides antibodies with a modified isoelectric point, pharmaceutical compositions comprising the antibodies as an active ingredient, and methods for producing the antibodies and compositions.
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 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
Provided is a syringe including: a barrel; and a partitioning device, the partitioning device including: a cylindrical housing; and an inner plug, the housing including an engaging part configured to engage with the inner plug in an out-of-communication state, the inner plug including an engaged part configured to engage with the engaging part from a proximal side in the out-of-communication state, and the partitioning device being configured so that, when a pressing force is applied from the proximal side, one of the engaging part and the engaged part rides over an other one thereof and release engagement between the engaging part and the engaged part, thereby allowing the inner plug to have the proximal side space inside the housing and the distal side space inside the housing communicating with each other to achieve communication between the proximal side space inside the barrel and the distal side space inside the barrel.
The purpose of the present invention is to provide a pre-filled syringe formulation with staked needle, which contains an antibody at a high concentration and can be produced on an industrial scale in a simple manner without causing clogging. A pre-filled syringe formulation with staked needle, in which a protein solution is packed. The pre-filled syringe formulation is characterized in that a cap formed with a material having low water vapor permeability is provided at the needle.
A61L 31/16 - Biologically active materials, e.g. therapeutic substances
A61M 5/28 - Syringe ampoules or cartridges, i.e. ampoules or cartridges provided with a needle
A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
83.
PURIFICATION METHOD AND PRODUCTION METHOD OF CYCLIC PEPTIDE
Disclosed is a purification method of a cyclic peptide, the purification method comprising a separation step (i) or (ii) described below. (i) A cyclic peptide, which is a purification target substance, is separated in the form of a composite body with a metal atom or a metal ion from a mixture that contains the cyclic peptide as the purification target substance. (ii) A cyclic peptide, which is a purification target substance, or a peptide, which is an impurity, is separated in the form of a composite body with a metal atom or a metal ion from a mixture that contains the cyclic peptide as the purification target substance and the peptide as the impurity. With respect to this purification method, the metal atom and the metal ion are at least one kind of atom and ion selected from the group consisting of an atom and an ion of an alkali metal, an atom and an ion of an alkaline earth metal, an atom and an ion of a transition metal, an atom and an ion of a poor metal, and an atom and an ion of a rare earth metal.
The present disclosure relates to: a polypeptide with controlled association between polypeptides; in one aspect, a polypeptide with controlled association between Fcs; a method for producing a polypeptide with controlled association between Fcs (CH3s in one aspect); a method for controlling association between Fcs; a composition containing the Fc region; and a composition containing a nucleic acid encoding the polypeptide, etc.
The present invention pertains to a solid dispersion comprising: (1) an amorphous substance to be dispersed having a molecular weight of 1,000-5,000 g/mol; and (2) a polymer, wherein the ratio of the total mass of the polymer to the total mass of the substance to be dispersed is less than 1.0, and the following (I) or (II) is satisfied. (I) The glass transition temperature of the substance to be dispersed is different by at least 1ºC from the glass transition temperature of the solid dispersion. (II) The glass transition temperature of the solid dispersion is 94.5-105.5% of the value of Tga expressed by expression (A). [In expression (A), Tgc represents the glass transition temperature of the substance to be dispersed, Tgp represents the glass transition temperature of the polymer, Wa represents the total mass of the solid dispersion, Wc represents the total mass of the substance to be dispersed contained in the solid dispersion, and Wp represents the total mass of the polymer contained in the solid dispersion.]
The present invention relates to a polypeptide complex comprising a first antigen-binding portion capable of specifically binding to a plasma protein and a second antigen-binding portion capable of binding to a target antigen other than a plasma protein, wherein the first antigen-binding portion and the second antigen-binding portion are directly linked without the mediation of a linker, or are linked via a non-cleavable linker consisting of not more than four amino acid residues. The polypeptide of the present invention does not bind to the target antigen in the presence of the plasma protein but binds to the target antigen in the absence of the plasma protein.
A robot system (100) includes a workbench robot (20) which is fixed to a workbench and which has a mechanism for gripping an object on the workbench, and an integrated controller (30) for controlling operations of the workbench robot (20), wherein the integrated controller (30) performs weighing-out processing for: causing the workbench robot (20) to grip a medicine spoon, perform an operation to use the medicine spoon to scoop a powdered, granular or viscous substance that is to be weighed out and that is contained in a source container, into a transfer destination container, and use weighing scales to measure the weight of the substance in the transfer destination container; and for acquiring the measurement result.
The present invention relates to a first antigen-binding molecule, a second antigen-binding molecule, and a combination thereof. The second antigen-binding molecule binds to an antigen/antigen-binding molecule complex containing a first antigen and the first antigen-binding molecule, and enhances the binding activity of the first antigen-binding molecule to the first antigen.
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 5/078 - Cells from blood or from the immune system
90.
ANTI-DENGUE VIRUS ANTIBODIES HAVING CROSS-REACTIVITY TO ZIKA VIRUS AND METHODS OF USE
Agency for Science, Technology & Research (Singapore)
Inventor
Fink, Katja
Wang, Cheng-I
Ng, Lisa Fong Poh
Renia, Laurent
Sampei, Zenjiro
Koo, Xing'Er Christine
Abstract
The disclosure provides anti-DENV antibodies having a cross-reactivity to ZIKV and methods of making and using the same. The anti-DENV antibodies have uses that include treating or preventing ZIKV infection.
The present inventors provide methods for modifying the isoelectric point of an antibody while retaining its antigen-binding activity, comprising modifying the charge of at least one exposable amino acid residue on the surface of the complementarity determining region (CDR). The present invention also provides methods for purifying multispecific antibodies, comprising modifying isoelectric point, and methods for improving the plasma pharmacokinetics of antibodies, comprising modifying isoelectric point. The present invention further provides antibodies with a modified isoelectric point, pharmaceutical compositions comprising the antibodies as an active ingredient, and methods for producing the antibodies and compositions.
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 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
92.
ANTIBODY SUBSTITUTING FOR FUNCTION OF BLOOD COAGULATION FACTOR VIII
The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.
The present disclosure provides an analysis method for measuring the content of light chain-exchanged molecules in a composition containing a multi-specific antigen-binding molecule. The analysis method of the present disclosure includes the steps of: treating a composition comprising a multi-specific antigen-binding molecule and preparing a plurality of types of F(ab) fragments; and measuring the F(ab) fragments by a separation method based on electric charge or hydrophobic interactions and determining the content (content ratio) of each fragment.
In one embodiment of the present invention, it was discovered that a preparation containing an antigen-binding molecule having at least one disulfide bond formed between amino acid residues in a region other than a hinge region can be more efficiently produced with high reproducibility by causing, in chromatography, contact between a reducing agent-containing solution and a mixture containing an antigen-binding molecule having at least one disulfide bond formed between amino acid residues in a region other than a hinge region and a mismatched body and/or incompletely formed body of the disulfide bond of the antigen-binding molecule, and subsequently removing the reducing agent therefrom.
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
An object of the present invention is to provide methods of discovering drugs effective for tough targets, which have conventionally been discovered only with difficulty. The present invention relates to novel methods for cyclizing peptide compounds, and novel peptide compounds and libraries comprising the same, to achieve the above object.
C07K 7/64 - Cyclic peptides containing only normal peptide links
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C07K 1/113 - General processes for the preparation of peptides by chemical modification of precursor peptides without change of the primary structure
C07K 5/087 - Tripeptides the side chain of the first amino acid containing carbocyclic rings, e.g. Phe, Tyr
C07K 5/103 - Tetrapeptides the side chain of the first amino acid being acyclic, e.g. Gly, Ala
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C07K 11/00 - Depsipeptides having up to 20 amino acids in a fully defined sequenceDerivatives thereof
C07K 11/02 - Depsipeptides having up to 20 amino acids in a fully defined sequenceDerivatives thereof cyclic, e.g. valinomycins
An objective of the present invention is to provide target tissue-specific antigen-binding molecules, antigen-binding molecules whose antigen-binding activity varies depending on the concentration of an unnatural compound, libraries comprising a plurality of the antigen-binding molecules which are different from one another, pharmaceutical compositions comprising the antigen-binding molecules, methods of screening for the antigen-binding molecules, and methods for producing the antigen-binding molecules. The present inventors created antigen-binding domains whose antigen-binding activity varies depending on the concentration of a small molecule compound or antigen-binding molecules containing an antigen-binding domain, and libraries comprising a plurality of the antigen-binding domains which are different from one another or antigen-binding domains, and demonstrated that the above-noted objective could be achieved by using the libraries. Various diseases originating from target tissues can be treated in a target tissue-specific manner by using the antigen-binding molecules of the present invention.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/42 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against immunoglobulins (anti-idiotypic antibodies)
C07K 16/44 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere
C40B 50/06 - Biochemical methods, e.g. using enzymes or whole viable microorganisms
The present application concerns methods for treating an IL-6-mediated disorder such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic JIA (sJIA), polyarticular course JIA (pcJIA), systemic sclerosis, or giant cell arteritis (GCA), with subcutaneously administered antibody that binds interleukin-6 receptor (anti-IL-6R antibody). In particular, it relates to identification of a fixed dose of anti-IL-6R antibody, e.g. tocilizumab, which is safe and effective for subcutaneous administration in patients with IL-6-mediated disorders. In addition, formulations and devices useful for subcutaneous administration of an anti-IL-6R antibody are disclosed.
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 9/00 - Medicinal preparations characterised by special physical form
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
98.
CYCLIC COMPOUND HAVING SELECTIVE KRAS INHIBITORY EFFECT ON HRAS AND NRAS
The present inventors found a cyclic compound that selectively inhibits KRAS. The present inventors also found that the cyclic compound interacts with a KRAS-specific amino acid residue.
A robot (100) includes: a workbench robot (20) comprising a manipulator that implements an operation on an object on a workbench; and a controller (30) that controls movement of the workbench robot (20). The manipulator includes an articulated arm and a hand positioned at a leading end of the arm and comprising a plurality of articulated fingers. The hand has a structure by which an object is gripped between a first group of fingers including a first finger and a second group of fingers including a second finger and a third finger, the first and second groups of fingers being mutually opposing. The controller (30) causes the workbench robot (20) to execute at least two types of processes selected from processes of gripping an aspirator in the hand to aspirate a liquid, gripping an electric powered pipettor in the hand to aspirate and discharge a liquid, gripping an electric powered micropipette in the hand to aspirate and discharge a liquid, and gripping a medicine spoon in the hand to scoop out a powder.
Cyclic compounds and oligopeptide compounds that selectively inhibit KRAS were found. Oligopeptide compounds and non-natural amino acids useful for producing a cyclic compound were also found. Moreover, cyclic compounds and oligopeptide compounds were found to interact with an amino acid residue specific to KRAS.
