Provided herein are compounds of Formula (I):
Provided herein are compounds of Formula (I):
and forms thereof, including compositions thereof and uses therewith for treating spinal muscular atrophy.
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
METHODS OF USING A BISPECIFIC ANTIBODY THAT RECOGNIZES COAGULATION FACTOR IX AND/OR ACTIVATED COAGULATION FACTOR IX AND COAGULATION FACTOR X AND/OR ACTIVATED COAGULATION FACTOR X
An objective of the present invention is to provide an effective pharmaceutical composition or a dosage regimen for preventing and/or treating bleeding, a disease accompanying bleeding, or a disease caused by bleeding. The inventors discovered that by administering a pharmaceutical composition comprising a bispecific antigen-binding molecule that recognizes (a) blood coagulation factor IX and/or activated blood coagulation factor IX and (b) blood coagulation factor X and/or activated blood coagulation factor X according to a given dosage regimen, bleeding, a disease accompanying bleeding, or a disease caused by bleeding can be prevented and/or treated more effectively.
The present disclosure relates to methods of treating cancer comprising administering to a subject an anti-IL-27 antibody, atezolizumab, and bevacizumab.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
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
A method of preparing a prefilled syringe (1), comprises (i) obtaining a syringe barrel (11) having an open end (111) and a tip (112) with an orifice (113) essentially opposite to the open end (111), and a needle adaptor cap (12) assembled on the tip (112) of the syringe barrel, wherein the needle adaptor cap (12) has a rubber element (121) tightly sealing the orifice (113) of the tip (112) of the syringe barrel (11) and the syringe barrel (11) together with the needle adaptor cap (12) assembled on the tip (112) of the syringe barrel (11) is sterilized by a first sterilizing comprising a main step of exposing the syringe barrel (11) together with the needle adaptor cap (12) assembled on the tip (112) of the syringe barrel (11) to ethylene oxide for about 5 hours to about 60 hours at a relative humidity of about 40% to about 100% and at a temperature of about 30° C. to about 60° C.; (ii) filling a drug substance (14) through the open end (111) of the syringe barrel (11) into an interior of the syringe barrel; (iii) sealing the interior of the syringe barrel (11) by advancing a rubber stopper (13) through the open end (111) of the syringe barrel (11); (iv) packaging the syringe barrel (11) together with the rubber stopper (13) sealing the interior of the syringe barrel (11) and the needle adaptor cap (12) assembled on the tip (112) of the syringe barrel (11); and (v) second external surface sterilizing the packaged syringe barrel (11) together with the rubber stopper (13) sealing the interior of the syringe barrel (11) and the needle adaptor cap (12) assembled on the tip (112) of the syringe barrel (11). The rubber element (121) of the needle adaptor cap (12) and the rubber stopper (13) are made of a rubber material having a comparably low oxygen transmission rate such as, at 1 atmosphere, of not more than 64 cubic centimeter per square meter and day. The second external surface sterilizing comprises a main step of exposing the packaged syringe barrel (11) together with the rubber stopper (13) sealing the interior of the syringe barrel (11) and the needle adaptor cap (12) assembled on the tip (112) of the syringe barrel (11) to ethylene oxide for about 3 hours to about 30 hours at a relative humidity of about 40% to about 100% and at a temperature of about 25° C. to about 45° C. At least one of the duration, the relative humidity and the temperature of the second external surface sterilizing is essentially lower than the respective duration, relative humidity or temperature of the first sterilization.
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm rests
A61M 5/315 - Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod; Appliances on the rod for facilitating dosing
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
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 7/28 - Closing semi-rigid or rigid containers or receptacles not deformed by, or not taking-up shape of, contents, e.g. boxes or cartons by applying separate preformed closures, e.g. lids, covers
B65B 55/10 - Sterilising wrappers or receptacles prior to, or during, packaging by liquids or gases
7.
PHARMACEUTICAL COMPOSITION FOR USE IN THE TREATMENT OR PREVENTION OF A C5-RELATED DISEASE AND A METHOD FOR TREATING OR PREVENTING A C5-RELATED DISEASE
The present invention relates to pharmaceutical compositions for use in the treatment or prevention of a C5-related disease and methods for treating or preventing a C5-related disease. The present invention further relates to dosages and administrations of anti-C5 antibody or pharmaceutical compositions containing the anti-C5 antibody.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
8.
TREATING INFLUENZA USING SUBSTITUTED POLYCYCLIC PYRIDONE DERIVATIVES AND PRODRUGS THEREOF IN A SUBJECT HAVING INFLUENZA AND A SEVERE INFLUENZA CONDITION
A method for treating an influenza virus infection is described. The disclosed method generally involves administering an effective amount of a compound (A), for example baloxavir marboxil, and a compound (B), for example a neuraminidase inhibor, to a subject that (1) has an influenza virus infection, (2) has been symptomatic of the influenza virus infection for no more than 96 hours, and (3) further has at least one severe influenza condition selected from the following: (a) being hospitalized due to severe influenza virus infection, (b) requiring an extension of hospitalization because of the influenza virus infection during the hospitalization, (c) having a National Early Warning Score 2 of four or more, (d) being on support for respiration, and (e) having at least one complication attributable to the influenza virus infection that necessitates hospitalization.
Provided are CD8 binding agents comprising a VHH domain that specifically binds human CD8. Also provided are nucleic acids encoding such CD8 binding agents, vectors comprising such nucleic acids, host cells comprising same, and methods of making such CD8 binding agents. Also provided are CD8 binding agents having the VHH domain conjugated to a detectable label. Provided are methods of using such CD8 binding agents to detect CD8+ T cells, monitor disease progress, and monitor treatment progress in a subject having cancer, autoimmune disease or condition, transplant rejection or graft-versus-host disease.
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 51/10 - Antibodies or immunoglobulins; Fragments thereof
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
10.
METHODS AND COMPOSITIONS FOR TREATING TRIPLE-NEGATIVE BREAST CANCER
The invention provides methods and compositions (e.g., pharmaceutical compositions) for treating breast cancer (e.g., TNBC (e.g., eTNBC)) in a subject. In some aspects, the methods include administering a treatment regimen including a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antibody (e.g., atezolizumab) or an anti-PD-1 antibody), a taxane (e.g., nab-paclitaxel or paclitaxel), an anthracycline (e.g., doxorubicin or epirubicin), and an alkylating agent (e.g., a nitrogen mustard derivative (e.g., cyclophosphamide)) to the subject. In some aspects, the treatment regimen increases the subject's likelihood of having a pathologic complete response (pCR) as compared to treatment with the taxane, the anthracycline, and the alkylating agent without the PD-1 axis binding antagonist. Also provided are pharmaceutical compositions for use in treating breast cancer (e.g., TNBC (e.g., eTNBC)) in a subject.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/196 - Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
A61K 31/513 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/198 - Alpha-amino acids, e.g. alanine, edetic acid (EDTA)
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 9/00 - Medicinal preparations characterised by special physical form
This application relates to anti-D-Dimer recombinant antibodies that specifically bind to fibrin and fibrinogen degradation products (FDP) such as D-Dimer, fragment DD and fragment D with high binding affinity and do not bind to fragment E and fibrinogen. The present invention also refers to methods and assays for detection of D-Dimer and FDP fragments in samples using said recombinant antibodies.
Provided are fused ring compounds of Formula (I), Formula (II), or Formula (III), as further detailed herein, which are used for the inhibition of Ras proteins, as well as compositions comprising these compounds and methods treatment by their administration.
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 403/04 - 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 directly linked by a ring-member-to-ring- member bond
C07D 403/12 - 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 chain containing hetero atoms as chain links
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/04 - 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 directly linked by a ring-member-to-ring- member bond
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
Disclosed herein are diagnostic and therapeutic methods for the treatment of hematologic cancers, including multiple myeloma (MM), as well as related compositions. In particular, the invention relates to diagnostic and therapeutic methods for treatments involving a PD-L1 axis binding antagonist (e.g., an anti-PD-L1 antibody, e.g., atezolizumab) and an anti-CD38 antibody (e.g., an anti-CD38 antagonist antibody, e.g., daratumumab) for use in treating hematologic cancer (e.g., a multiple myeloma (MM), e.g., a relapsed or refractory MM).
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
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
Pharmaceutical compositions of metabotropic glutamate 5 receptor (mGlu5) antagonists or a pharmacologically acceptable salt thereof are disclosed. The compositions contain the therapeutic active compound with non-ionic polymer and ionic polymer, binder and fillers in either matrix pellet, matrix tablet or coated pellets. The compositions provide a pH-independent in vitro release profile with NMT 70% in one hour, NMT 85% in 4 hour, and NLT 80% in 8 hours. The compositions are useful for the treatment of CNS disorders, such as Treatment-Resistant Depression (TRD) and Fragile X Syndrome.
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
The present invention relates to oligomer compounds (oligomers), which target Tau mRNA in a cell, leading to reduced expression of Tau protein. Reduction of Tau protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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
A slide imaging apparatus that includes a copy holder moving system and an imaging system. The copy holder moving system includes a movable stage configured to move along first and second slide movement axes relative to the imaging system, wherein the imaging system is configured to form an image of a sample mounted on a slide located in the/each imaging location on the movable stage during an image forming process that includes the movable stage moving relative to the imaging system along the first and second slide movement axes. The copy holder moving system also includes a copy holder configured to be mounted to the movable stage, wherein the copy holder is configured to be mounted to the movable stage in each of a plurality of indexing positions.
The present invention relates to antisense oligonucleotides (oligomers) that are complementary to HTRA1, leading to modulation of the expression of HTRA1. Modulation of HTRA1 expression is beneficial for a range of medical disorders, such as macular degeneration, e.g. age-related macular degeneration.
The present invention relates to antisense oligonucleotides which are complementary to conserved TDP-43 binding sites on pre-mRNA transcripts, which are capable of restoring RNA binding protein function in the processing of multiple independent mRNAs in TDP-43 depleted cells.
Various aspects of the invention relate to recombinant polypeptides that specifically bind human von Willebrand Factor. Such recombinant polypeptides typically include a modified extracellular domain of platelet glycoprotein Ibα that typically comprises at least one mutation selected from G233T, D235V, and K237V, and such recombinant polypeptides optionally include an oligomerization domain.
Provided herein are compounds of Formula (I):
7 are as defined herein, including compositions thereof and uses therewith for treating spinal muscular atrophy.
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07D 239/70 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
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
This invention pertains to fused ring compounds of Formula (I), as further detailed herein, which are used for the inhibition of Ras proteins, as well as compositions comprising these compounds and methods of treatment by their administration.
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic 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 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 407/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61K 9/00 - Medicinal preparations characterised by special physical form
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
23.
THYMIDINE KINASE (TK-1) IN PROGNOSTIC INDICES FOR DLBCL
The present disclosure relates to the finding that thymidine kinase 1 (TK-1) represents a valuable biomarker in a method for determining a Prognostic Index (PI) for risk stratification of a patient with aggressive B-cell lymphoma, especially diffuse large B-cell lymphoma (DLBCL), to the use of TK-1 in such PI and to a PI comprising the marker TK-1.
A machine-learning model (e.g., a clustering model) may be used to predict a phenotype of a tumor based on expression levels of a set of genes. The set of genes may have been identified using a same or different machine-learning model. The phenotype may include an immune-excluded, immune-desert or an inflamed/infiltrated phenotype. A treatment strategy and/or treatment recommendation may be identified based on the predicted phenotype.
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
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
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The invention provides dosage regimes for treatment of synucleinopathies. In one regime, a subject receives 3000-5000 mg of an antibody intravenously every 3-5 weeks. In another regime, a subject receives 1300-1700 mg of an antibody intravenously every 3-5 weeks.
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 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
A process for the manufacture N-(5-((5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)thiazole-4-carboxamide (I) wherein the vicinal amino fluoro substituents are introduced by treating 5 with sodium chloro((4-nitrophenyl)sulfonyl)amide and N-bromosucinimide and unraveling the resulting substituted aziridine (6) with trimethylamine trihydrofluoride to afford 7 which is further processed to afford 1.
C07D 417/14 - 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 three or more hetero rings
28.
DOSAGE OF BALOXAVIR MARBOXIL FOR PEDIATRIC PATIENTS
The present invention relates to a method for treating an influenza virus infection, wherein said method comprises administering an effective amount of a compound to a patient having an influenza virus infection, wherein the compound has one of the formulae (I) and (II), as set forth herein, or is a pharmaceutically acceptable salt thereof, and wherein dosages set forth herein are used.
A prefilled syringe is disclosed that includes a barrel, a stopper displaceable within and defining a sealed chamber in an interior of the barrel, a liquid filled in the chamber of the barrel, and a plunger extending within the barrel. The stopper expels the liquid out of the barrel via an orifice when being forwarded towards the orifice by the plunger such that a volume of the chamber is reduced. The plunger includes a proximal portion, a distal portion and a rod portion extending between the proximal portion and the distal portion. The plunger is shaped to form a pathway between an opening of the barrel and a segment where the proximal portion of the plunger is neighboring the stopper such that a sterilizing agent can be provided through the opening of the barrel to the segment where the proximal portion of the plunger is neighboring the stopper.
Provided herein are combination therapies comprising an ATP competitive AKT inhibitor, fulvestrant, and CDK4/6 inhibitor for use in treating hormone receptor positive and HER2 negative locally advanced unresectable or metastatic breast cancer.
A61K 31/566 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. oestrane, oestradiol having an oxo group in position 17, e.g. oestrone
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
A61K 9/00 - Medicinal preparations characterised by special physical form
31.
Pyrazolopyrimidine inhibitors of JAK kinases and uses thereof
Compounds of formula (I)
6 are as defined herein, and salts thereof that are useful as JAK kinse inhibitors are described herein. Also provided are pharmaceutical compositions that include such a JAK inhibitor and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a Janus kinase activity in a patient.
The invention provides methods of dosing for the treatment of cancers. In particular, provided are methods for treating human patients having lung cancer, such as non-small cell lung cancer (NSCLC), by administering a combination of an anti-TIGIT antagonist antibody and an anti-PD-L1 antagonist 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
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
F. HOFFMANN-LA ROCHE AG (EX-US TERRITORIES) (Switzerland)
Inventor
Koehler, Michael F. T.
Smith, Peter Andrew
Winter, Dana
Sow, Boubacar
Sturino, Claudio
Pelletier, Guillaume
Boudreault, Jonathan
Abstract
Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidases SpsB and/or LepB, an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.
A61K 31/505 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
C07D 239/28 - 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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
A61K 31/351 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/545 - Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula , e.g. cephalosporins, cefaclor, cephalexine
34.
Regio-selective synthesis of imidazo[1,2-a]pyrimidines
A method of regio-selectively synthesizing an imidazo-pyrimidine compound of formulae (XXa) or (XXb)
comprising a step of coupling a first compound of formula XX-P1a or XX-P1b with a second compound of formula XX-P2
4 together with the imidazole ring atoms to which they are bonded form a phenyl ring and the products are substituted benzimidazopyrimidines. The reaction can be generalized to form imidazo[1,2-a]pyrimidines substituted at either of their 2- and 4-positions by alkoxy or thioalkyl groups.
A method of synthesizing
comprising a step of making an imidazo-pyrimidine compound by coupling a first compound of formula (II) with a second compound of formula (III)
Followed by a deprotection and tosylation step. The methods are able to produce an isotopically substituted molecule having upwards of 95% purity relative to non-isotopically substituted molecules.
The invention further comprises compounds of formula:
A method of preparing a prefilled syringe is disclosed that includes obtaining a syringe barrel and a needle adaptor cap assembled on the tip of the syringe barrel, wherein the needle adaptor cap has a rubber element tightly sealing the orifice of the tip of the syringe barrel and the syringe barrel together with the needle adaptor cap assembled on the tip of the syringe barrel is sterilized by a first sterilizing. Filling a drug substance into an interior of the syringe barrel and sealing the interior of the syringe barrel. Packaging the syringe barrel with a rubber stopper sealing the interior thereof and the needle adaptor cap assembled on the tip of the syringe barrel. Providing a second external surface sterilizing of the packaged syringe barrel with the rubber stopper sealing the interior thereof and the needle adaptor cap assembled on the tip of the syringe barrel.
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm rests
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
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 55/02 - Sterilising, e.g. of complete packages
38.
TREATMENT OF CD20-POSITIVE B-CELL LYMPHOMA WITH OBITUZUMAB
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
A method of preparing a prefilled syringe is disclosed that includes obtaining a syringe barrel and a needle adaptor cap assembled on the tip of the syringe barrel, wherein the needle adaptor cap has a rubber element tightly sealing the orifice of the tip of the syringe barrel and the syringe barrel together with the needle adaptor cap assembled on the tip of the syringe barrel is sterilized by a first sterilizing. Filling a drug substance into an interior of the syringe barrel and sealing the interior of the syringe barrel. Packaging the syringe barrel with a rubber stopper sealing the interior thereof and the needle adaptor cap assembled on the tip of the syringe barrel. Providing a second external surface sterilizing of the packaged syringe barrel with the rubber stopper sealing the interior thereof and the needle adaptor cap assembled on the tip of the syringe barrel.
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm rests
A61M 5/315 - Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod; Appliances on the rod for facilitating dosing
A61M 5/32 - Syringes - Details - Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
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 7/28 - Closing semi-rigid or rigid containers or receptacles not deformed by, or not taking-up shape of, contents, e.g. boxes or cartons by applying separate preformed closures, e.g. lids, covers
B65B 55/10 - Sterilising wrappers or receptacles prior to, or during, packaging by liquids or gases
B65B 55/02 - Sterilising, e.g. of complete packages
40.
DOSAGE REGIMEN FOR COMBINATION THERAPY USING PD-1 AXIS BINDING ANTAGONISTS AND GPC3 TARGETING AGENT
Provided are dosage regimens for combination therapy using PD-1 axis binding antagonists and GPC3 targeting agent. For example, the dosage regimens comprise (i) a loading period within which the GPC3 targeting agent is administered, followed by (ii) a maintenance period within which the PD-1 axis binding antagonist and the GPC3 targeting agent are administered.
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
A glass vial illumination and inspection system may be provided with a light source and a stand. The stand may have an internal cavity configured to receive at least a portion of the light source. A recess may be located in the stand and configured to receive at least a portion of a glass vial. The stand may be configured to aim the light output from the light source toward the glass vial to illuminate the vial. The stand may be configured to position the vial such that an inspector can manually inspect the illuminated vial for defects. Methods of use are also disclosed.
COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES (France)
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) (France)
Inventor
Lafaye, Pierre
Bay, Sylvie
Delatour, Benoit
Dhenain, Marc
Duyckaerts, Charles
Li, Tengfei
Vandesquille, Matthias
Czech, Christian
Grueninger, Fiona
Abstract
The present invention relates to variable domains of a camelid heavy-chain antibodies directed against a phosphorylated tau protein and conjugates thereof. The present invention also relates to the use of these domains or conjugates for treating or diagnosing disorders mediated by neurofibrillary tangles, neuropil threads or dystrophic neurites, such as tauopathies.
In one embodiment, a method includes receiving one or more querying images associated with a container of a pharmaceutical product, each of the one or more querying images being based on a particular angle of the container of the pharmaceutical product, calculating one or more confidence scores associated with one or more defect indications, respectively for the container of the pharmaceutical product, by processing the one or more querying images using a target machine-learning model, and determining a defect indication for the container of the pharmaceutical product from the one or more defect indications based on a comparison between the one or more confidence scores and one or more predefined threshold scores, respectively.
3-Carbonylamino-8-aminoisoquinoline compounds of formula (I):
variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the 3-carbonylamino-8-aminoisoquinoline compounds.
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
C07D 491/052 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
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
A61K 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
45.
METHODS AND SYSTEMS FOR DETERMINING SYNAPSE FORMATION
The presently disclosed subject matter relates to methods and compositions for determining synapse formation, e.g., synapse formation associated with the activity of multispecific antibodies such as T cell-dependent bispecific 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
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
46.
Diagnostic and therapeutic methods for the treatment of breast cancer
Provided herein, inter alia, are predictive diagnostic, pharmacodynamic, and therapeutic methods for the treatment of breast cancer. In embodiments, the methods and compositions are based, at least in part, on the discovery that the estradiol (E2)-induced score or estrogen receptor (ER) pathway activity score determined from a sample (e.g., a tissue sample, e.g., a tumor tissue sample, e.g., a FFPE, a FF, an archival, a fresh, or a frozen tumor tissue sample) from an individual can be used in methods of determining whether the individual having breast cancer is likely to respond to a treatment including an endocrine therapy, selecting a therapy for an individual having breast cancer; treating an individual having breast cancer; and monitoring therapeutic efficacy of an endocrine therapy, as well as related kits.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 80/00 - ICT specially adapted for facilitating communication between medical practitioners or patients, e.g. for collaborative diagnosis, therapy or health monitoring
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
Methods for preparing the Bruton's Tyrosine Kinase (“BTK”) inhibitor compound 2-{3′-hydroxymethyl-1-methyl-5-[5-((S)-2-methyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-[3,4′]bipyridinyl-2′-yl}-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one are provided. Methods for preparing tricyclic lactam compounds are also provided.
The present disclosure relates to processes for preparing (cyclopentyl[d]pyrimidin-4-yl)piperazine compounds, and more particularly relates to processes for preparing (R)-4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d] pyrimidin-4-yl)piperazine and N-protected derivatives thereof, which may be used as an intermediate in the synthesis of Ipatasertib (i.e., (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)-propan-1-one). The present disclosure additionally relates to various compounds that are intermediates employed in these processes.
C07C 255/22 - Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and carboxyl groups, other than cyano groups, bound to the same saturated acyclic carbon skeleton containing cyano groups and at least two carboxyl groups bound to the carbon skeleton
Methods of treating joint damage in a subject eligible for treatment are provided involving administering an antagonist that binds to a B-cell surface marker, such as CD20 antibody, to the subject in an amount effective to slow progression of the joint damage as measured by radiography. Further provided are articles of manufacture useful for such methods.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 39/00 - Medicinal preparations containing antigens or antibodies
Provided herein are compounds of Formula (I):
and forms thereof, including compositions thereof and uses therewith for treating spinal muscular atrophy.
C07D 239/70 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
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 are compounds, compositions thereof and uses therewith for treating spinal muscular atrophy. In a specific embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN2 into mRNA that is transcribed from the SMN2 gene. In another specific embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN1 into mRNA that is transcribed from the SMN1 gene. In yet another embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN1 and SMN2 into mRNA that is transcribed from the SMN1 and SMN2 genes, respectively.
A01N 43/00 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
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 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 311/16 - 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 in position 7
C07D 405/04 - 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 directly linked by a ring-member-to-ring- member bond
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 413/04 - 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 directly linked by a ring-member-to-ring- member bond
C07D 417/04 - 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 directly linked by a ring-member-to-ring- member bond
C07D 417/14 - 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 three or more hetero rings
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
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
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
The invention provides a compound of formula (I):
7 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.
The invention relates to compounds of formula I:
4 and n are as defined herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
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
Methods of treating joint damage in a subject eligible for treatment are provided involving administering an antagonist that binds to a B-cell surface marker, such as CD20 antibody, to the subject in an amount effective to slow progression of the joint damage as measured by radiography. Further provided are articles of manufacture useful for such methods.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 39/00 - Medicinal preparations containing antigens or antibodies
55.
Bispecific antigen-binding molecules and methods of use
The present invention provides bispecific antigen-binding molecules having a monovalent arm specific to a first target antigen (e.g., a T cell antigen, such as CD3) and a bivalent arm specific for a second target antigen (e.g., a tumor antigen, such as HER2). Bispecific antigen-binding molecules are useful in the treatment of disorders, such as cancer (e.g., HER2-positive cancer). The invention also features methods of producing bispecific antigen-binding molecules, methods of treating disorders using bispecific antigen-binding molecules, and compositions including bispecific antigen-binding molecules.
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
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 9/00 - Medicinal preparations characterised by special physical form
Methods of using a bispecific antibody that recognizes coagulation factor IX and/or activated coagulation factor IX and coagulation factor X and/or activated coagulation factor X
An objective of the present invention is to provide an effective pharmaceutical composition or a dosage regimen for preventing and/or treating bleeding, a disease accompanying bleeding, or a disease caused by bleeding. The inventors discovered that by administering a pharmaceutical composition comprising a bispecific antigen-binding molecule that recognizes (a) blood coagulation factor IX and/or activated blood coagulation factor IX and (b) blood coagulation factor X and/or activated blood coagulation factor X according to a given dosage regimen, bleeding, a disease accompanying bleeding, or a disease caused by bleeding can be prevented and/or treated more effectively.
The invention provides novel compounds having the general formula I:
B2, n, p, q, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.
C07D 231/54 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
C07D 249/16 - Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
A61P 25/00 - Drugs for disorders of the nervous system
59.
Bicyclic ketone compounds and methods of use thereof
The invention provides novel compounds having the general formula I:
1, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.
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 235/12 - Radicals substituted by oxygen atoms
COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES (France)
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) (France)
Inventor
Lafaye, Pierre
Bay, Sylvie
Delatour, Benoit
Dhenain, Marc
Duyckaerts, Charles
Li, Tengfei
Vandesquille, Matthias
Czech, Christian
Grueninger, Fiona
Abstract
The present invention relates to variable domains of a camelid heavy-chain antibodies directed against a phosphorylated tau protein and conjugates thereof. The present invention also relates to the use of these domains or conjugates for treating or diagnosing disorders mediated by neurofibrillary tangles, neuropil threads or dystrophic neurites, such as tauopathies.
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
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
C07D 403/06 - 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 only aliphatic carbon atoms
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
The invention provides formulations comprising a protein in combination with a compound that prevents oxidation of the protein. The invention also provides methods for making such formulations and methods of using such formulations. The invention further provides methods of screening for compounds that prevent oxidation of a protein in a protein composition and methods of preventing oxidation of a protein in a formulation.
A61K 31/405 - Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
C12Q 1/28 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase involving peroxidase
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The invention provides stable aqueous pharmaceutical formulations comprising a therapeutic antibody, trehalose, a buffer, and optional surfactant, and having a pH in the range of about 5.5 to about 7.0. The invention also provides methods for making such formulations and methods of using such formulations.
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
Methods for preparing the Bruton's Tyrosine Kinase (“BTK”) inhibitor compound 2-{3′-hydroxymethyl-1-methyl-5-[5-((S)-2-methyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-[3,4′]bipyridinyl-2′-yl}-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one are provided. Methods for preparing tricyclic lactam compounds are also provided.
The invention relates to methods of treating a patient suffering from an IL-33-mediated disorder, such as asthma, comprising administering to the patient an IL-33 axis binding antagonist based on the genotype of the /L1RL1gene, the genotype of a polymorphism in genomic vicinity to the IL-33 gene, the expression level of periostin or the expression level of soluble ST2. The invention further relates to methods of determining whether a patient is at increased risk of an IL-33-mediated disorder, as well as methods of determining whether a patient suffering from such a disorder is likely to respond to a treatment comprising an IL-33 axis binding antagonist, based on the genotype of the /L1RL1gene the genotype of a polymorphism in genomic vicinity to the IL-33 gene, the expression level of periostin or the expression level of soluble ST2.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes 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 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
The present invention relates to oligomer compounds (oligomers), which target Tau mRNA in a cell, leading to reduced expression of Tau protein. Reduction of Tau protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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
68.
Multivalent and multiepitopic antibodies having agonistic activity and methods of use
Provided herein are tetravalent antigen binding complexes having agonist activity for a cell surface receptor. In some embodiments, the complexes comprise binding specificities for multiple epitopes of the same cell surface receptor. Further provided herein are nucleic acids, vectors, host cells, pharmaceutical compositions, and methods of production related thereto.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The subject disclosure presents systems and methods for automatically selecting meaningful regions on a whole-slide image and performing quality control on the resulting collection of FOVs. Density maps may be generated quantifying the local density of detection results. The heat maps as well as combinations of maps (such as a local sum, ratio, etc.) may be provided as input into an automated FOV selection operation. The selection operation may select regions of each heat map that represent extreme and average representative regions, based on one or more rules. One or more rules may be defined in order to generate the list of candidate FOVs. The rules may generally be formulated such that FOVs chosen for quality control are the ones that require the most scrutiny and will benefit the most from an assessment by an expert observer.
G06K 9/62 - Methods or arrangements for recognition using electronic means
G02B 21/36 - Microscopes arranged for photographic purposes or projection purposes
G06F 3/0354 - Pointing devices displaced or positioned by the user; Accessories therefor with detection of 2D relative movements between the device, or an operating part thereof, and a plane or surface, e.g. 2D mice, trackballs, pens or pucks
70.
Method for the determination of anti-drug antibodies against an effector function suppressed human or humanized drug antibody
Herein is reported an anti-drug antibody immunoassay for the determination of the presence of an anti-drug antibody against an effector function suppressed human or humanized drug antibody in a sample comprising the incubation of a sample comprising mammalian blood serum with full length human Fcgamma receptor I or an Fc-region binding fragment thereof so that a complex between the anti-drug antibody against the effector function suppressed human or humanized drug antibody present in the sample and the human Fcgamma receptor I or the Fc-region binding fragment thereof forms, whereby the full length human Fcgamma receptor I or the Fc-region binding fragment thereof is conjugated to a detectable label, and the determination of the formed complex by the detectable label.
G01N 31/00 - Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroups; Apparatus specially adapted for such methods
The present disclosure relates to processes for preparing (cyclopentyl[d]pyrimidin-4-yl)piperazine compounds, and more particularly relates to processes for preparing (R)-4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d] pyrimidin-4-yl)piperazine and N-protected derivatives thereof, which may be used as an intermediate in the synthesis of Ipatasertib (i.e., (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)-propan-1-one). The present disclosure additionally relates to various compounds that are intermediates employed in these processes.
C07C 253/30 - Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
C07C 255/22 - Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and carboxyl groups, other than cyano groups, bound to the same saturated acyclic carbon skeleton containing cyano groups and at least two carboxyl groups bound to the carbon skeleton
C07B 57/00 - Separation of optically-active organic compounds
C12P 41/00 - Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
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 are compounds of Formula (I):
and forms thereof, including compositions thereof and uses therewith for treating spinal muscular atrophy.
A01N 43/90 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07D 239/70 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
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
74.
Optimized variants of anti-VEGF antibodies and methods of treatment thereof by reducing or inhibiting angiogenesis
The present invention provides anti-VEGF antibodies and compositions that include anti-VEGF antibodies (e.g., antibody conjugates, fusion proteins, and polymeric formulations), and uses thereof, for example for treatment of disorders associated with pathological angiogenesis. The present invention also provides methods of identifying antibody variants with improved properties, for example, enhanced binding affinity, stability, pharmacokinetics, and/or expression.
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61K 47/61 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
A61K 39/00 - Medicinal preparations containing antigens or antibodies
75.
GPC3-targeting drug which is administered to patient responsive to GPC3-targeting drug therapy
A method is provided for determining the efficacy of GPC3-targeting drug therapy for cancer in a patient before the start of GPC3-targeting drug therapy or for determining the continuation of GPC3-targeting drug therapy for a patient treated with GPC3-targeting therapy. The method includes determining the number of an immunocyte or an expression level of a molecule expressed on the immunocyte in a biological sample isolated from the patient before the start of GPC3-targeting drug therapy and/or the patient treated with the GPC3-targeting drug therapy, wherein when the number of the immunocyte or the expression level of the molecule expressed on the immunocyte is a predetermined value, the efficacy of the GPC3-targeting drug therapy is determined or the continuation of the GPC3-targeting drug therapy is determined. GPC3-targeting drugs and drug preparations for use according to the disclosed methods are also provided.
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
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
G01N 33/569 - Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A61K 39/00 - Medicinal preparations containing antigens or antibodies
76.
Isoform enriched antibody preparation and method for obtaining it
Herein is reported a method for producing an antibody preparation comprising the steps of a) applying a buffered solution comprising different isoforms of an antibody to a cation exchange chromatography material, b) applying a first solution with a first conductivity to the cation exchange chromatography material, whereby the antibody isoforms remain bound to the cation exchange chromatography material, and c) applying a second solution with a second conductivity to the cation exchange chromatography material and thereby obtaining the antibody preparation, whereby the conductivity of the second solution exceeds the conductivity of the first solution by not more than 10%.
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 16/30 - 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
77.
Camelid single-domain antibody directed against phosphorylated tau proteins and methods for producing conjugates thereof
COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES (France)
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) (France)
Inventor
Lafaye, Pierre
Bay, Sylvie
Delatour, Benoit
Dhenain, Marc
Duyckaerts, Charles
Li, Tengfei
Vandesquille, Matthias
Czech, Christian
Grueninger, Fiona
Abstract
The present invention relates to variable domains of a camelid heavy-chain antibodies directed against a phosphorylated tau protein and conjugates thereof. The present invention also relates to the use of these domains or conjugates for treating or diagnosing disorders mediated by neurofibrillary tangles, neuropil threads or dystrophic neurites, such as tauopathies.
The present invention relates to anti-FcRH5 antibodies, including anti-FcRH5 antibodies comprising an FcRH5 binding domain and a CD3 binding domain (e.g., FcRH5 T cell-dependent bispecific (TDB) antibodies), and methods of using the same.
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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 39/00 - Medicinal preparations containing antigens or antibodies
79.
Oligopeptide and methods for producing conjugates thereof
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) (France)
COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES (France)
Inventor
Lafaye, Pierre
Bay, Sylvie
Delatour, Benoit
Dhenain, Marc
Duyckaerts, Charles
Li, Tengfei
Vandesquille, Matthias
Czech, Christian
Grueninger, Fiona
Abstract
The present invention relates to an oligopeptide and conjugates thereof. The present invention also relates to the use of these oligopeptide conjugates for treating or diagnosing disorders mediated by amyloid β deposits. Finally, the present invention also relates to a coupling method for obtaining oligopeptide coupled with a substance of interest (functional conjugates).
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
A61K 49/08 - Nuclear magnetic resonance (NMR) contrast preparations; Magnetic resonance imaging (MRI) contrast preparations characterised by the carrier
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CRNS) (France)
INSTITUT PASTEUR (France)
COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES (France)
Inventor
Lafaye, Pierre
Bay, Sylvie
Delatour, Benoit
Dhenain, Marc
Duyckaerts, Charles
Li, Tengfei
Vandesquille, Matthias
Czech, Christian
Grueninger, Fiona
Abstract
The present invention relates to variable domain of a camelid heavy-chain antibodies directed to amyloid β and conjugates thereof. The present invention also relates to the use of these antibody conjugates for treating or diagnosing disorders mediated by amyloid β deposits.
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
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61K 51/10 - Antibodies or immunoglobulins; Fragments thereof
The invention is concerned with the compounds of formula I:
and salts thereof and other compounds of formulas II-IX as disclosed herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formulas I-IX as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain or asthma.
C07D 417/14 - 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 three or more hetero rings
C07D 403/12 - 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 chain containing hetero atoms as chain links
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
C07D 401/12 - 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 chain containing hetero atoms as chain links
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/12 - 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 chain containing hetero atoms as chain links
C07F 9/6512 - Six-membered rings having the nitrogen atoms in positions 1 and 3
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
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
The present invention relates to oligomer compounds (oligomers), which target Tau mRNA in a cell, leading to reduced expression of Tau protein. Reduction of Tau protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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
Compounds of Formulae Ia, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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
A61K 31/535 - 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
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
Cysteine engineered antibodies comprising a free cysteine amino acid in the heavy chain or light chain are prepared by mutagenizing a nucleic acid sequence of a parent antibody and replacing one or more amino acid residues by cysteine to encode the cysteine engineered antibody; expressing the cysteine engineered antibody; and isolating the cysteine engineered antibody.
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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 51/10 - Antibodies or immunoglobulins; Fragments thereof
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 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
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
87.
Compositions and methods for inhibiting hypdxia induced damage
Provided are compositions and methods for inhibiting hypoxia-induced damage. The compositions and methods involve the use of one or more agents that can inhibit one or any combination of the genes BCL2L14, BLOC1S2, C20RF42, CPT1A, FBP1, GCNT3, RHOB, SCIN, TACR1 and TNFAIP6. Polynucleotide and non-polynucleotide agents which can be used for inhibiting one or more of the genes are included. The method involves introducing one or more gene inhibiting agents to a cell, tissue, organ, or individual such that formation of hypoxia related damage is inhibited. Kits which contain the agents and printed information about using them for inhibiting hypoxia induced damage are also included.
The present invention discloses a method for determining the efficacy of GPC3-targeting drug therapy for cancer in a patient before the start of GPC3-targeting drug therapy or a patient or determining the continuation of GPC3-targeting drug therapy for a patient, including monitoring a concentration of free GPC3 in a biological sample isolated from the patient before the start of GPC3-targeting drug therapy and/or the patient treated with the GPC3-targeting drug therapy, wherein when the concentration of free GPC3 is a predetermined value, the efficacy of the GPC3-targeting drug therapy is determined or the continuation of the GPC3-targeting drug therapy is determined. The present invention also discloses a GPC3-targeting drug or a preparation which is to be further administered to a patient for which the efficacy of the GPC3-targeting drug therapy has been determined or the continuation of the GPC3-targeting drug therapy has been determined.
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
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
A61K 39/00 - Medicinal preparations containing antigens or antibodies
89.
Composition for use as an abnormal coagulation control plasma in in vitro assays
A composition, which relates to the field of the clinical analysis of blood, comprises human plasma, buffered isotonic solution and ferulic acid. The composition can be used as an abnormal coagulation control in haemostasis, coagulation and fibrinolysis assays. Ferulic acid can be used in the preparation of abnormal control plasma in haemostasis assays.
G01N 33/96 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61K 39/00 - Medicinal preparations containing antigens or antibodies
91.
System for dispensing a sample into a buffer liquid
A system for dispensing a sample into a buffer liquid includes a pressure chamber having pressure supply means for generating an overpressure within the pressure chamber. An inlet capillary supplies a buffer liquid to an outlet end arranged in the pressure chamber, and an outlet capillary discharges the buffer liquid from the pressure chamber. The outlet capillary has an inlet end in the pressure chamber facing the outlet end of the inlet capillary to form a capillary gap. A dispenser having a dispensing end is in the pressure chamber at the capillary gap to allow the sample at the dispensing end to be dispensed into the buffer liquid entering the outlet capillary inlet end. The pressure chamber includes a sample port that allows the dispenser to be moved into and out of the pressure chamber.
11 are as defined in the description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds of formula I are useful in differentiating stem cells into more mature or adult-like hepatocytes for use as drug screening platforms and in disease modeling applications.
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
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 491/052 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
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
94.
Combination treatment for acute myeloid leukemia (AML)
The present invention relates to a pharmaceutical product comprising a) as a first component an inhibitor of the MDM2-p53 interaction such as, for example:
and b) as a second component cytarabine; as a combined preparation for the sequential or simultaneous use in the treatment of cancer.
A01N 43/04 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atom with one hetero atom
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 9/00 - Medicinal preparations characterised by special physical form
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/77 - Polymers containing oxygen of oxiranes
Provided herein are compounds, compositions thereof and uses therewith for treating spinal muscular atrophy. In a specific embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN2 into mRNA that is transcribed from the SMN2 gene. In another specific embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN1 into mRNA that is transcribed from the SMN1 gene. In yet another embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN1 and SMN2 into mRNA that is transcribed from the SMN1 and SMN2 genes, respectively.
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 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 311/16 - 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 in position 7
C07D 405/04 - 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 directly linked by a ring-member-to-ring- member bond
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 413/04 - 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 directly linked by a ring-member-to-ring- member bond
C07D 417/04 - 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 directly linked by a ring-member-to-ring- member bond
C07D 417/14 - 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 three or more hetero rings
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
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
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
96.
Anti-transferrin receptor antibodies and methods of use
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
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 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61K 39/00 - Medicinal preparations containing antigens or antibodies
97.
Integrin antagonist conjugates for targeted delivery to cells expressing VLA-4
The invention relates to compounds of formula I: wherein R1, R2, and n are defined in the detailed description and claims. In particular, the present invention relates to the compounds of formula I for use in the manufacture and delivery of conjugated moieties such as small molecules, peptides, nucleic acids, fluorescent moieties, and polymers which are linked to VLA-4 integrin antagonists to target cells expressing VLA-4.
C07D 207/452 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
C07C 327/28 - Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
C07D 403/12 - 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 chain containing hetero atoms as chain links
C07D 239/54 - Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
The invention provides stable aqueous pharmaceutical formulations comprising a therapeutic antibody, trehalose, a buffer, and optional surfactant, and having a pH in the range of about 5.5 to about 7.0. The invention also provides methods for making such formulations and methods of using such formulations.
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 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
99.
Methods of treating inflammatory bowel disease using IL-22 Fc fusion proteins
The invention relates to IL-22 polypeptides, IL-22 Fc fusion proteins and IL-22 agonists, composition comprising the same, methods of making and methods of using the composition for the treatment of diseases. The invention also relates to IL-22 receptor associated reagents and methods of use 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 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
C07F 7/08 - Compounds having one or more C—Si linkages
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 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/501 - Pyridazines; Hydrogenated pyridazines 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
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 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group 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
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 491/056 - Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
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
patents
