The application discloses compositions comprising a xylazine hapten having the Formula (I). The application further discloses xylazine hapten compositions and vaccines against xylazine. The application further discloses methods of preventing xylazine overdose. The application further discloses methods of preventing use disorder of xylazine. The application further discloses methods of generating antibodies against xylazine. The application further discloses methods of treating consumption of a substance laced with xylazine.
The present invention provides methods for treating osteoarthritis. The methods of the invention involve administering to a subject in need of treatment a pharmaceutical composition that contains an effective amount of an KLF4-activating compound, e.g., mocetinostat.
Compositions and methods for control and/or modification of endogenous protein degradation are described. The compositions are directed to heterobifunctional molecules having protein and enzyme system binding moieties linked together by an organic linker group. The compositions are selective for binding to certain endogenous proteins and function to recruit endogenous decomposition systems such as the polyubiquitin system for peptide cleavage and reassimilation.
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
4.
DUAL GIP/GLP-1 PEPTIDE CONJUGATES AND METHODS OF USE
Provided herein are peptides and peptide conjugates comprising a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. The peptides may be used for blood glucose management and treating conditions such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH).
5.
INCORPORATION OF UNNATURAL NUCLEOTIDES AND METHODS THEREOF
The invention novel methods for engrafting or expanding a switchable engineered effector cell (e.g., CAR-T cell) in a subject who has not undergone lymphodepleting (LD) chemotherapy. The methods entail administering to a subject a switchable effector platform (e.g., sCAR-T platform). The platform includes a switch molecule that specifically binds to a target molecule on the surface of a cell in the subject, and a complementary engineered effector cell (e.g., CAR-T cell) containing a CAR extracellular domain that specifically binds to a CAR-interacting domain in the switch molecule. Some methods of the invention are directed to treating or promoting regression of tumors in subjects who have not undergone lymphodepleting (LD) chemotherapy.
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
7.
MOLECULAR EDITING OF MULTIPLE C-H BONDS LEVERAGING RECOGNITION OF DISTANCE, GEOMETRY AND CHIRALITY
This disclosure provides functional templates that direct Pd to functionalize multiple C—H bonds in polycyclic aza-arenes such as quinolines and related heterocycles at locations that are difficult to isolate and reach for substitution. Herein disclosed are two conceptually distinct directing templates (T) that enable site-selective C6 and C7-H activation of polycyclic aza-arenes. These catalytic pyridine-based templates recruit the aza-arene substrate through N-coordination, enabling the directing arm to deliver the catalyst and precisely activate remote and adjacent C6 or C7-H bond (FIG. 1d). In parallel, we discovered that the use of a simple and readily prepared template chaperone (TC) can turn over the directing template, allowing it to be used catalytically for the first time. Notably, chiral recognition is vital in the granular discrimination between competing C3 and C7-H bonds when the differentiation via distance and geometry is insufficient. Thus, precise recognition of a directing template's distance, geometry and chirality now enables the iterative C—H editing of quinoline and related pharmacophores at any desired site and order. The methods disclosed herein can also be used for diverse and late-stage modification of heterocycle-based drug molecules and pharmacophores.
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
Among the various aspects of the present disclosure is the provision of compositions and methods for potent protein synthesis inhibitors for toxoplasmosis treatment. The present disclosure includes a method of treatment or prophylaxis of Toxoplasma gondii infection or infection caused by a parasite closely related to Toxoplasma gondii in a subject in need thereof. Also disclosed are small molecule compositions of bicyclic pyrrolidine inhibitors of Toxoplasma gondii phenylalanine t-RNA synthetase (PheRS).
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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
A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
The present disclosure relates generally to compounds that utilize a tetracycline scaffold, including specifically a minocycline or sancycline scaffold. Provided are also pharmaceutical compositions and methods of using such compounds. Certain compounds provided herein lack significant antibiotic activity.
C07D 413/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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 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 265/30 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings
C07D 309/14 - Nitrogen atoms not forming part of a nitro radical
C07D 405/10 - 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 carbon chain containing aromatic rings
10.
PALLADIUM-CATALYZED METHYLENE C-H LACTAMIZATION AND CYCLOAMINATION OF CARBOXYLIC ACIDS
ββ-amino acids possessing γ- and δ-lactam, pyrrolidine, and tetrahydroquinoline scaffolds pertinent to drug discovery. The disclosed methods establish a general synthetic platform for the synthesis of multiple classes of lactams, pyrrolidines and piperidines under the same catalytic manifold. The synthetic utility of this reaction was demonstrated by formal synthesis of Stemoamide.
C07D 211/68 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
C07D 409/02 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
Aspects of the disclosure relate to novel antibody and antigen binding fragments. Further aspects relate to polypeptides comprising the antigen binding fragment(s) of the disclosure, and compositions comprising the polypeptides, antibodies, and/or antigen binding fragments of the disclosure. Also described are nucleic acids encoding an antibody or antigen binding fragment of the disclosure. In particular embodiments, the disclosure provides immunological compositions that target TdT peptides, including those associated with HLA-A2. Specific embodiments allow for detection, diagnosis, treatment, and prevention of cancer in an individual in need thereof.
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
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
12.
IMMUNOGENIC PROTEINS AND NUCLEIC ACIDS ENCODING THE SAME
The invention relates to proteins and nucleic acids for immunization regimens, modifications thereof, and/or development of nanoparticles, and/or development of membrane-anchored immunogens, and methods of making and using the same. The invention also encompasses cell surface trimers that bind to the broadly neutralizing antibodies and/or nucleic acids encoding the same.
The invention provides novel neutralizing antibodies and related antibody compositions against respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). Also provided in the invention are polynucleotides and vectors encoding such antibodies, as well as pharmaceutical compositions containing the antibodies or polynucleotides. Therapeutic uses of the antibodies or pharmaceutical compositions in preventing or treating RAV and hMPV infections are also encompassed by the invention.
Methods and compositions are provided for extending the half-life of a therapeutic agent. A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/20 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid
A61K 31/23 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Herein described is the chemical proteomic discovery of compounds that covalently and stereoselectively bind cysteine-342 in ERCC3 and lead to the degradation of this protein in cancer cells. ERCC3 is part of the TFIIH complex that regulates transcription and DNA repair processes. The covalent compounds rapidly (within 3 h) degrade ERCC3, but not other proteins in the proteome, and this effect is observed at low-μM concentrations of compound. The enantiomers of active compounds do not engage or degrade ERCC3.
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
The present invention provides engineered human metapneumovirus (hMPV) F protein trimer immunogens. These engineered proteins are stabilized via specific modifications introduced into both the F2 subunit and the F1 subunit of a wildtype hMPV soluble F sequence, e.g., shortened F2 subunit C -terminus and interprotomer disulfide bond in the F1 subunit. Also provided in the invention are nanoparticle vaccines that contain the engineered hMPV soluble F immunogens displayed on self-assembling nanoparticles. The invention also provides methods of using such vaccine compositions in various therapeutic applications, e.g., for preventing or treating hMPV infections.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
The application discloses the use of a bifunctional chiral palladium catalyst that enables remote γ- and d-methylene C-H (hetero)arylation of cyclic carbocyclic acids. Specifically, the application discloses methods of enantioselective remote γ-C-H arylation or heteroarylation, δ-C-H arylation or heteroarylation, or sequential γ-methylene C-H arylation or heteroarylation of diverse free cycloalkane carboxylic acids comprising the use of palladium catalysts with chiral oxazoline-pyridone ligands.
The present disclosure provides a compound of Formula (I): or a tautomer or pharmaceutically acceptable salt thereof, wherein Rings A, B, C, and R1 and R2 are defined herein, their pharmaceutical compositions, and methods of use for treating diseases that are vulnerable to inhibition of TEAD family transcription factors and/or inhibition of the pro-growth activity of the transcriptional coactivator YAP.
The present disclosure provides a compound of Formula (I): or a tautomer or pharmaceutically acceptable salt thereof, wherein Rings A, B, C, and R1 and R2 are defined herein, their pharmaceutical compositions, and methods of use for treating diseases that are vulnerable to inhibition of TEAD family transcription factors and/or inhibition of the pro-growth activity of the transcriptional coactivator YAP.
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
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 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/4995 - Pyrazines or piperazines forming part of bridged ring systems
A61K 31/501 - PyridazinesHydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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 295/185 - Radicals derived from carboxylic acids from aliphatic carboxylic acids
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 403/12 - 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
The invention provides chimeric antigen receptor T (CAR-T) cell compositions for targeting tumor cells. The compositions contain (a) a CAR-T cell having in the extracellular domain of its CAR a catalytic antibody (e.g., a scFv molecule derived from catalytic antibody 38C2), and (b) an adapter compound containing a substrate moiety of the catalytic antibody that is linked to a targeting moiety that specifically recognizes a surface molecule of a target tumor cell. The compositions allow formation of a covalent bond between the catalytic antibody in the CAR and the targeting moiety. The targeting moieties employed in the compositions can be obtained via screening DNA-encoded compound library for specific binding to the target tumor surface molecules. Also provided in the invention are therapeutic methods of using the CAR-T cell compositions of the invention to in the treatment of various tumors of interest.
The invention provides novel methods for analyzing (e.g., imaging) drugs in mammalian tissues, and methods for identifying drug targets and analyzing drug-target interactions.
The present invention provides novel ligand compounds that specifically bind to inhibitory Siglecs (e.g., Siglec 7 and Siglec 9). The novel Sig7/9 ligands and related drug conjugates described herein are capable of inhibiting recruitment of Sig7/9 by tumor cells to phagocytic and immunological synapses. By promoting Sig7/9 sequestration and degradation, the compositions and methods of the invention enhance cancer immune therapy via suppressing Sig7/9-mediated inhibition of both innate adaptive immune cell activation and functions.
C07B 43/06 - Formation or introduction of functional groups containing nitrogen of amide groups
C07C 233/01 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
C07C 233/16 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
23.
METHOD FOR THE SITE-SPECIFIC ENZYMATIC LABELLING OF NUCLEIC ACIDS IN VITRO BY INCORPORATION OF UNNATURAL NUCLEOTIDES
Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.
C07H 19/24 - Heterocyclic radicals containing oxygen or sulfur as ring hetero atom
C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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
The invention relates to the use of artificial neural networks, such as autoencoders, in population genomics and individual genome processing to fill-in missing data from genomic assays with significant sparsity, such as low-pass whole genome sequencing or array-based genotyping. An autoencoder-based neural network approach for the simultaneous execution of genetic imputation as well as feature extraction and dimensionality reduction for downstream tasks is provided.
Disclosed are compounds, and corresponding methods of treatment, that activate myocyte-specific enhancer factor 2 (MEF2) transcriptional activity that are therefore useful in treating deficits in MEF2C activity found in autism spectrum disorder (ASD), intellectual disability (ID), attention deficit and hyperactivity disorder (ADHD), and in diseases characterized by cognitive decline such as Alzheimer's disease (AD), Lewy body dementia (LED), Frontotemporal dementia (FTD), and other forms of dementia, as well as movement disorders such as Parkinson's disease (PD) and parkinsonism from other causes.
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
26.
SELECTIVE MAMMALIAN STERILE 20-LIKE KINASE 1 (MST1) MODULATOR COMPOUNDS AS THERAPEUTICS FOR DIABETES AND LIVER REGENERATION
Described herein are compounds that are MST1 inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of MST1 activity, such as diabetes and liver regeneration.
C07D 217/22 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 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
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
27.
NUCLEOSIDE TRIPHOSPHATE TRANSPORTER AND USES THEREOF
Disclosed herein are proteins, methods, cells, engineered microorganisms, and kits for generating a modified nucleoside triphosphate transporter from Phaeodactylum tricornutum. Also disclosed herein proteins, methods, cells, engineered microorganisms, and kits for production of a nucleic acid molecule that comprises an unnatural nucleotide utilizing a modified nucleoside triphosphate transporter from Phaeodactylum tricornutum.
Mycobacterium tuberculosisMycobacterium tuberculosis (Mtb). Cell wall inhibitors are a critical component of TB treatment. Uniquely, the Compound 95 series has been shown to form a covalent adduct with serine residue 801 in the acyltransferase (AT) domain of Pks13. The inhibition of the Pks13 AT domain ultimately leads to disruption of mycolic acid synthesis, which is an essential component of the mycobacterial cell wall. While Pks13 is recognized as a high-value drug target, there are no Pks13 inhibitors in development and Compound 95 represents a new class of inhibitors for TB treatment.
The present invention features methods for reducing alcohol intake, intake of drugs of abuse, food intake, or to increase fat breakdown or lipolysis by administering a sphingosine-1-phosphate receptor modulator.
Compositions are provided, of the general formula X1-X2-X3, wherein (a)X2 comprises an antigen; (b) X1 is absent or comprises or consists of the amino acid sequence (C)KKKTG (SEQ ID NO: 1); and (c) X3 is absent or comprises or consists of the amino acid sequence GTKKK(C) (SEQ ID NO:2), wherein (i) only one of X1 and X3 is present, and (ii) the residue m parentheses m SEQ ID NO: 1 and SEQ ID NO: 2 is optional and may be present or may be deleted.
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (>200 fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, non-viral methods for reprogramming human somatic cells.
Disclosed herein are methods for using an antimalarial endoperoxide compound, such as artemisinin, in treating a subject suffering from myelodysplastic syndromes (MDS), and hi slowing or preventing the progression of MDS in the subject to development of acute myeloid leukemia (AML).
A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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 31/438 - 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 being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/541 - Non-condensed thiazines containing further heterocyclic rings
Disclosed herein are compounds, their pharmaceutical compositions, and their methods of use for treating a neurodegenerative disease, such as Alzheimer's disease. Lewy body dementia, or Parkinson' disease. In some embodiments, the compound is one that activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and/or heat-shock factor-1 (HSF-1) transcription-mediated signaling pathway: the compound is administered with at least one antibody that is directed against an aberrant misfolded protein. The compound, illustrated by camosic acid in one example, is unexpectedly effective in reducing the type of neuroinflammation resulting from antibody-protein complexes encountered in antibody therapies of the disease. The compounds also are useful in a method of treating neuroinflammation in a subject who suffers from a neurodegenerative disease and/or has been administered at least one antibody that is directed against an aberrant misfolded protein.
C07C 233/58 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07C 69/757 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
34.
COMPOSITIONS AND METHODS RELATED TO HIV-1 IMMUNOGENS
The present invention provides HIV-1 vaccine immunogens. Some of the immunogens contain a soluble gp140-derived protein that harbors a modified N-terminus of the HR1 region in gp41. Some of the immunogens contain an HIV-1 Env-derived trimer protein that is presented on a nanoparticle platform. The invention also provides methods of using the HIV-1 vaccine immunogens for eliciting an immune response or treating HIV infections.
A61K 39/21 - Retroviridae, e.g. equine infectious anemia virus
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
35.
GENE EXPRESSION PROFILES ASSOCIATED WITH CHRONIC ALLOGRAFT NEPHROPATHY
By a genome-wide gene analysis of expression profiles of over 50,000 known or putative gene sequences in peripheral blood, the present inventors have identified a consensus set of gene expression-based molecular biomarkers associated with chronic allograft nephropathy and/or interstitial fibrosis and tubular atrophy CAN/IFTA and subtypes thereof. These genes sets are useful for diagnosis, prognosis, monitoring and/or subtyping of CAN/IFTA.
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
36.
HIGH THROUGHPUT PARALLEL SYNTHESIS OF SMALL MOLECULE DEGRADERS
Disclosed herein are high throughput synthetic methods for the deliberate and prospective discovery of molecular glues which can be used to form composite protein-ligand surfaces that facilitate interfacial binding to other proteins over dispersed surfaces. In particular, this application discloses a high throughput approach using sulfur(VI) fluoride exchange (SuFEx) transformations and N-hydroxysuccinimide (NHS)-ester derived amide couplings to prospectively repurpose known ligands for a prolein-of-interest into degraders and compounds capable of inducing proximity to other proteins. Disclosed herein are methods of developing known ligands of a target protein into degraders of the target proteins. Further disclosed are methods of developing novel small molecule chromatin-competitive inhibitors of the eleven nineteen leukemia (ENL) YEATS domain into effective degraders of ENL.
The invention provides fusion molecules for inducing proximity between integral membrane proteins and integral membrane proteases (sheddases), thereby promoting targeted proteolysis (shedding) of the target membrane protein ectodomain. These fusion molecules, Sheddase-Targeting Chimera (SHEDTACs), contain a protease-targeting domain and a substrate-targeting domain that respectively bind to a sheddase and a target protein of interest (e.g., a cell surface receptor). Also provided in the invention are polynucleotides encoding the fusion molecules, related expression vectors and host cells, as well as methods using the fusion molecules to accelerate integral membrane proteolysis by local sheddases.
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
C12N 15/79 - Vectors or expression systems specially adapted for eukaryotic hosts
A61K 39/395 - AntibodiesImmunoglobulinsImmune 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
38.
HIGH-CONTENT AND HIGH-RESOLUTION IN VIVO SCREEN FOR ANALYZING GENE FUNCTIONS
The present invention provides high-content and high-resolution in vivo screens for analyzing functions of a plurality of genes. In the functional screens of the invention, genetic perturbations are delivered to a CRISPR-expressing transgenic system by specific AAV vectors that are fully compatible with Perturb-seq platforms. The screens enable functional genomics analyses across diverse tissues, cell types, and model organisms in vivo, with high-throughput single-cell readout.
Provided are Hepatitis Virus C (HCV) soluble fusion immunogens (SE1E2) that are derived from engineered or redesigned HCV sE1 and sE2 polypeptides and are configured to form native-like E1E2 interface that may be used in vaccine formulations. Also provided are related vaccine compositions that display the engineered SE1E2 immunogens after cleavage into an SE1E2 protein with native E1E2 conformation on a self-assembling nanoparticle scaffold. Also provided are methods of using the immunogens and vaccine compositions in methods for prophylaxis or therapy for HCV infections.
The United States Government As Represented By The Department Of Veterans Affairs (USA)
Icahn School of Medicine at Mount Sinai (USA)
Molsoft (USA)
The Scripps Research Institute (USA)
Inventor
Hioe, Catarina E.
Totrov, Maxim
Zhu, Jiang
Abstract
Disclosed are trimeric complexes comprising an uncleaved prefusion optimized gp140 env trimer. Disclosed are compositions comprising a trimeric complex, wherein the trimeric complex comprises an uncleaved prefusion optimized gp140 env trimer. Disclosed are methods of inducing an immune response against HIV in a subject comprising administering one or more of the disclosed compositions to a subject in need thereof. Disclosed are methods of generating neutralizing antibodies (nAbs) to HIV in a subject comprising administering one or more of the disclosed compositions to a subject in need thereof. Disclosed are method of treating a subject infected with HIV comprising administering one or more of the disclosed compositions to a subject in need thereof. Disclosed are methods of inducing an immune response against HIV in a subject comprise administering a composition or vaccine comprising a trimeric complex, wherein the trimeric complex comprises an uncleaved prefusion optimized gp140 env trimer, as disclosed herein, in combination with administering a composition or vaccine comprising a nucleic acid construct, wherein the nucleic acid construct comprises a nucleic acid sequence that encodes for a polypeptide comprising an HIV-1 derived V1V2 domain and a trimer-forming scaffold.
BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (USA)
THE SCRIPPS RESEARCH INSTITUTE (USA)
Inventor
Shim, Hong Seok
Depinho, Ronald A.
Boutin, Adam T.
Schultz, Peter G.
Lairson, Luke L.
Bollong, Michael J.
Abstract
The present disclosure provides compositions for activating TERT expression and methods of using the same for treating or ameliorating aging, aging-related diseases, and neurodegenerative conditions.
A61K 31/145 - Amines, e.g. amantadine having sulfur atoms, e.g. thiurams (N—C(S)—S—C(S)—N or N—C(S)—S—S—C(S)—N)Sulfinylamines (—N=SO)Sulfonylamines (—N=SO2)
42.
UNNATURAL BASE PAIR COMPOSITIONS AND METHODS OF USE
Disclosed herein are methods, cells, engineered microorganisms, and kits for increasing the production of polypeptides comprising one or more unnatural amino acids. Further provided are cells, engineered microorganisms, and kits for increasing the retention of unnatural nucleic acids encoding the unnatural amino acids in an engineered cell, or semi-synthetic organism.
Disclosed herein are kappa-opioid receptor (KOR) antagonist compounds of Formula (I) and their pharmaceutically acceptable salts, and pharmaceutical compositions thereof: (I) The compounds are useful in methods of treatment of various diseases and disorders for which KOR antagonism is indicated, including substance abuse disorders, depression, anxiety, and other psychiatric conditions.
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 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
The invention provides novel ligands of Kappa (κ) opioid receptors, such as can be used to modulate a Kappa opioid receptor. Methods of synthesis and methods of use are also provided. Compounds of the invention can be used therapeutically in the treatment of dissociative disorders or pain, or to provide neuroprotection, or to induce diuresis, or to modulate the immune system, or for treatment of one or more of an affective disorders comprising depression or stress/anxiety; an addictive disorder; alcoholism, epilepsy; a cognition deficiency; schizophrenia; Alzheimer's disease; or pain.
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 211/58 - Nitrogen atoms attached in position 4
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 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
This disclosure provides methods of detecting sub-acute rejection and other categories of rejection in kidney transplant recipients using unique sets of gene expression markers.
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
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
Seattle Children’s Hospital d/b/a Seattle Children’s Research Institute (USA)
The Scripps Research Institute (USA)
Inventor
Gallardo Garcia Freire, Christian Matias
Torbett, Bruce E.
Abstract
Methods and systems to functionally ablate 3′ end of RNA are described. The functional ablation renders polymerases unable to initiate reverse transcription in the absence of an annealing primer. The methods and systems can be used to enhance the specificity and selectivity of cDNA generation from RNA.
Provided herein are systems and methods for screening and analyzing compounds based upon the elucidation of the interaction among cereblon, its substrates and certain compounds or agents. As an example, a system and method can include a computational model that mimics in silico the cereblon protein. Also provided herein are systems and methods for identifying a compound that induces a conformational change in Cereblon, and in particular P98A mutant cereblon.
Disclosed herein are methods for using an antimalarial endoperoxide compound, such as artemisinin, in treating a subject suffering from myelodysplastic syndromes (MDS), and in slowing or preventing the progression of MDS in the subject to development of acute myeloid leukemia (AML).
A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
51.
SMALL MOLECULES FOR REPROGRAMING ANTI-TUMOR IMMUNITY OF T CELLS
Provided herein are methods for expanding activated T cells to produce T cells with less differentiated status and enhanced in vivo persistence after adoptive transfer. Activated T cells suitable for the methods include, e.g., progenitor exhausted (Tim3−TCF-1+), stem memory, and central memory T cells. The invention also provides methods for identifying progenitor exhausted T cells specific to an antigen. Further, the invention provides progenitor exhausted T cells, pharmaceutical compositions, and kits as well as methods for the treatment of cancer or infection using the same.
Provided herein are methods of forming immune complexes for analyzing immunity against a specific antigen or pathogen in an immunized or infected subject. The methods entail isolating polyclonal immunoglobulin (Ig) molecules from a blood or serum sample from an immunized or infected subject, enzymatically digesting the polyclonal Ig molecules to generate Fab molecules, and contacting the Fab molecules with a soluble pathogen and/or antigen of interest, and identifying one or more immune complexes formed between the pathogen and/or antigen and the Fab molecules.
G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
G01N 33/564 - ImmunoassayBiospecific binding assayMaterials therefor for pre-existing immune complex or autoimmune disease
NNAr macrocyclizations that establish the tricyclic skeleton of Compound I. In addition to the antimicrobial evaluation of tetrachlorovancomycin (Compound I), the preparation of key binding pocket and peripherally-modi fied derivatives, which overcome vancomycin resistance and introduce independent and synergistic mechanisms of action, revealed their exceptional antimicrobial potency and provide the foundation for use of this new class of synthetic glycopeptide analogues. Also disclosed are a pharmaceutical composition containing bactericidal amount of tetrachlorovancomycin, a derivative thereof or a salt of either dissolved or dispersed in a pharmaceutically acceptable diluent.
By a genome-wide gene analysis of expression profiles of over 50,000 known or putative gene sequences in peripheral blood, the present inventors have identified a consensus set of gene expression-based molecular biomarkers associated with subclinical acute rejection (subAR). These genes sets are useful for diagnosis, prognosis, monitoring of subAR.
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
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
G16H 20/40 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
The present invention relates to influenza immunogens and a vaccine platform for influenza viruses. In particular, the invention relates to a non-naturally occurring polypeptides comprising an engineered hemagglutinin lateral patch sequence and a secretion signal sequence, nucleic acids encoding the same, vectors containing the nucleic acids, nanoparticles containing the polypeptides, nucleic acids or vectors, cells containing the nanoparticles, polypeptides, nucleic acids or vectors, pharmaceutical compositions comprising the cells, nanoparticles, polypeptides, nucleic acids or vectors, vaccines comprising the pharmaceutical compositions and methods for immunization with the vaccines.
Drug discovery methodologies are enhanced through the use of variant capture maps that provide visualizations of functional covariance between different amino acids of a protein. These variant capture maps can be filtered with 3D distance data and overlapped to provide a rich source of information regarding sequence, structure, and function of a protein to assist development of treatment compounds and protocols.
The present invention relates to influenza immunogens and a vaccine platform for influenza viruses. In particular, the invention relates to a non-naturally occurring polypeptides comprising an engineered hemagglutinin stem sequence and a secretion signal sequence, nucleic acids encoding the same, vectors containing the nucleic acids, nanoparticles containing the polypeptides, nucleic acids or vectors, cells containing the nanoparticles, polypeptides, nucleic acids or vectors, pharmaceutical compositions comprising the cells, nanoparticles, polypeptides, nucleic acids or vectors, vaccines comprising the pharmaceutical compositions and methods for immunization with the vaccines.
The present invention relates to coronavirus immunogens and a vaccine platform for coronaviruses. In particular, the invention relates to a non-naturally occurring polypeptides comprising an engineered pathogen S2 subunit and a secretion signal sequence, nucleic acids encoding the same, vectors containing the nucleic acids, nanoparticles containing the polypeptides, nucleic acids or vectors, cells containing the nanoparticles, polypeptides, nucleic acids or vectors, pharmaceutical compositions comprising the cells, nanoparticles, polypeptides, nucleic acids or vectors, vaccines comprising the pharmaceutical compositions and methods for immunization with the vaccines.
The present invention provides novel engineered influenza hemagglutinin (HA) proteins, related polynucleotide sequences, and vaccine compositions including nanoparticle compositions. Relative to a wildtype HA protein, the engineered HA proteins are stabilized via substitutions of one or more conserved residues in the HA2 ectodomain with hydrophobic residues. The invention also provides methods of using such vaccine compositions in various therapeutic applications, e.g., for preventing or treating influenza viral infections.
The invention relates to PGT121-germline-targeting designs, trimer stabilization designs, combinations of those two, trimers designed with modified surfaces helpful for immunization regimens, other trimer modifications and on development of trimer nanoparticles and methods of making and using the same.
The invention provides chimeric antigen receptor T (CAR-T) cell compositions for targeting tumor cells. The compositions contain (a) a CAR-T cell comprising in the extracellular domain of its CAR a barstar moiety, and a switch molecule comprising a cognate barnase moiety fused to a targeting moiety, or (b) a CAR-T cell comprising in the extracellular domain of its CAR a barnase moiety, and a switch molecule comprising a cognate barstar moiety fused to a targeting moiety. The targeting moiety specifically recognizes a surface molecule of a tumor cell. The compositions allow tight binding between the CAR and the switch molecule. The targeting moieties employed in the compositions can be any agent or compound that specifically recognizes a target molecule (e.g., a cell surface receptor or antigen) on a target cell (e.g., a tumor cell). Also provided are therapeutic methods of using the CAR-T cell compositions.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
THE UNIVERSITY OF FLORIDA RESEARCH FOUNDATION (USA)
Inventor
Hill, Sarah
Dai, Nathan
Shenvi, Ryan
Bohn, Laura
Abstract
Described herein are short asymmetric syntheses that serve as routes that allow divergent access to focused libraries of salvinorins that include multiple analogs that exceed the potency, selectivity, stability and functional bias of salvinorin A itself.
A61K 31/335 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
A61K 31/352 - 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 condensed with carbocyclic rings, e.g. cannabinols, methantheline
The present application provides nucleoside analogue compounds of Formulae I-V for the treatment of Dengue Fever (DF). The present application further provides compositions and combinations thereof as well as methods of treatment of Dengue Fever using the nucleoside compounds of Formula I-V and compositions and combinations thereof.
A61K 31/7064 - 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
C07D 473/34 - Nitrogen atom attached in position 6, e.g. adenine
The Administrators of the Tulane Educational Fund (USA)
The Boad of Regents of the University of Texas System (USA)
The Scripps Resesrch Institute (USA)
Zalgen Labs, LLC (USA)
Inventor
Branco, Luis M.
Garry, Robert F.
Robinson, James E.
Saphire, Erica O.
Hastie, Kathryn M.
Geisbert, Thomas W.
Abstract
Disclosed herein are compositions comprising recombinant arenavirus monoclonal antibodies and antigen-binding fragments thereof, as well as therapeutic methods using the antibodies. In some embodiments, the antibodies provide pan-arenavirus protection against a number of arenavirus types and strains.
Simek-Lemos, Melissa Danielle De Jean De St. Marcel
Kaminsky, Stephen
Abstract
The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies are characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/21 - Retroviridae, e.g. equine infectious anemia virus
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
Compounds are provided that antagonize the kappa-opioid receptor (KOR) and products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope or salt thereof:
Compounds are provided that antagonize the kappa-opioid receptor (KOR) and products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope or salt thereof:
Compounds are provided that antagonize the kappa-opioid receptor (KOR) and products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope or salt thereof:
wherein X, Y, R1, R2, R4, R5 R6, R7, R8 and R11 are as defined herein.
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
A61P 25/00 - Drugs for disorders of the nervous system
Provided herein are compounds of Formula (I), their pharmaceutically acceptable salts, and their pharmaceutical compositions: (I) wherein R1, R2, R3, L, X, and Ar are defined in the present disclosure. The compounds are inhibitors of cyclic gmp-amp synthase (cGAS) or CGAS-related cGAMP production, and they are useful in treating or preventing inflammatory diseases or conditions in a subject.
Provided herein are compounds of Formula (I), their pharmaceutically acceptable salts, and their pharmaceutical compositions: (I) wherein R1, R2, R3, L, X, and Ar are defined in the present disclosure. The compounds are inhibitors of cyclic gmp-amp synthase (cGAS) or CGAS-related cGAMP production, and they are useful in treating or preventing inflammatory diseases or conditions in a subject.
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/422 - Oxazoles not condensed and containing further heterocyclic rings
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 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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 413/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 413/14 - 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
69.
Stabilized hemagglutinin (HA) trimers as influenza vaccine antigens
The present invention provides novel engineered influenza hemagglutinin (HA) proteins, related polynucleotide sequences, and vaccine compositions including nanoparticle compositions. Relative to a wildtype HA protein, the engineered HA proteins are stabilized via substitutions of one or more conserved residues in the HA2 ectodomain with hydrophobic residues. The invention also provides methods of using such vaccine compositions in various therapeutic applications, e.g., for preventing or treating influenza viral infections.
The present invention provides assay systems and related methods for monitoring RuBISCO catalyzed carbon fixation in a manner that is insulated from host metabolism. The invention also provides methods for evolving specific RuBISCO enzymes to identify variants with improved activities.
Disclosed herein are palladium-catalyzed dehydrogenation processes of carboxylic acids to make α, β-unsaturated carboxylic acids or γ-alkylidene butenolides. The processes allow the chemoselective dehydrogenation of carboxylic acids in the presence of other enolizable functionalities such as ketones, providing reactivity that is inaccessible with existing carbonyl desaturation protocols.
C07C 51/377 - Preparation of carboxylic acids or their salts, halides, or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groupsPreparation of carboxylic acids or their salts, halides, or anhydrides by reactions not involving formation of carboxyl groups by hydrogenolysis of functional groups
C07C 67/317 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groupsPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenolysis of functional groups
72.
REGIO-CONTROLLABLE [2+2] BENZANNULATION WITH TWO ADJACENT C(SP3)-H BONDS
This application discloses methods of twofold β,γ-methylene C(sp3)-H activation/C-C bond formation using a Pd(II) catalyst bound to amide-pyridone ligands, resulting in regio-controllable [2+2] annulation between aliphatic acids and dihaloarenes.
C07C 29/36 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy groups, e.g. O-metal
C07C 29/44 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by addition reactions, i.e. reactions involving at least one carbon-to-carbon double or triple bond
C07D 213/02 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
C07D 213/24 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
73.
REAGENTS AND METHODS FOR REPLICATION, TRANSCRIPTION, AND TRANSLATION IN SEMI-SYNTHETIC ORGANISMS
Disclosed herein are compositions, methods, cells, engineered microorganisms, and kits for increasing the production of proteins or polypeptides comprising one or more unnatural amino acids. Further provided are compositions, cells, engineered microorganisms, and kits for increasing the retention of unnatural nucleic acids encoding the unnatural amino acids in an engineered cell, or semi-synthetic organism.
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C07H 19/24 - Heterocyclic radicals containing oxygen or sulfur as ring hetero atom
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
74.
QUINOLINE DERIVATIVES WHICH ACT AS KAPPA-OPIOID RECEPTOR ANTAGONISTS
Disclosed herein are kappa-opioid receptor (KOR) antagonist compounds of Formula (I), Formula (II), and their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds are useful in methods of treatment of various diseases and disorders for which KOR antagonism is indicated, including substance abuse disorders, depression, anxiety, and other psychiatric conditions.
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 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 471/02 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups in which the condensed system contains two hetero rings
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
75.
LIGAND-ENABLED TRANSANNULAR C-H FUNCTIONALIZATION OF CYCLOALKANE CARBOXYLIC ACIDS
The present invention relates to glycan-masked and membrane-tethered SARS-CoV-2 RBD vaccine constructs and methods for making and administering the same. The present invention also encompasses a general vaccine platform for coronaviruses.
The present invention provides engineered soluble F proteins of paramyxoviruses such as respiratory syncytial viruses (RSVs), human metapneumoviruses (hMPVs), and human parainfluenza viruses (hPIVs). These engineered proteins are stabilized via specific modifications in the wildtype soluble F sequences, e.g., substitutions in the 023 strand and/or introducing an engineered disulfide bond in a 0 hairpin in the Fl subunit. Also provided in the invention are nanoparticle vaccines that contain the engineered soluble F immunogens displayed on self-assembling nanoparticles. The invention also provides methods of using such vaccine compositions in various therapeutic applications, e.g., for preventing or treating viral infections such as RSV, MPV and PIV infections.
Disclosed herein are enantioselective synthetic methods of making known cyclic imine (CI) toxins and analogues thereof as small molecule inhibitors of NMD3 with selective and potent anti -cancer activity.
C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
Compositions and methods for control and/or modification of endogenous protein acetylation are described. The compositions are directed to heterobifunctional molecules having protein and enzyme binding moieties linked together by an organic linker group. The compositions are selective for binding to certain endogenous proteins and function to recruit acety lation enzymes to acetylate or deacety late the proteins.
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
80.
SEQUENCING POLYCLONAL ANTIBODIES DIRECTLY FROM SINGLE PARTICLE CRYOEM DATA
Provided herein are methods for discovery of epitope specific monoclonal antibodies to pathogens directly from immune sera for immunotherapeutic use. Further provided herein are methods to determine molecular structure of antibodies targeting an antigen from convalescent or vaccinated individuals for the purpose of rational vaccine design.
Provided herein are glycan engineered SARS-CoV-2 RBD polypeptides, fusion polypeptides comprising thereof, and immunogenic compositions comprising thereof. Also provided are methods of administering the RBD polypeptide, fusion polypeptide or immunogenic composition to a subject to elicit an immune response. Also provided are polynucleotides encoding the fusion polypeptide, and methods of administering a composition comprising the polynucleotide to a subject to elicit an immune response. In some embodiments, the polynucleotide is an RNA comprising modified ribonucleotides.
Disclosed herein are proteins, methods, cells, engineered microorganisms, and kits for generating a modified nucleoside triphosphate transporter from Phaeodactylum tricornutum. Also disclosed herein proteins, methods, cells, engineered microorganisms, and kits for production of a nucleic acid molecule that comprises an unnatural nucleotide utilizing a modified nucleoside triphosphate transporter from Phaeodactylum tricornutum.
Methods and compositions are provided for extending the half-life of a therapeutic agent. A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/20 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid
A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/30 - Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
Provided herein are compounds, compositions, and their methods of use for treatment and/or prevention of infections of HBV in a subject by administering a compound of structural formula (I) or a pharmaceutically acceptable salt thereof: wherein R1 and R2 are defined herein.
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
There are disclosed imidazolinopyrimidinone compounds that have activity to induce TRAIL gene expression in macrophages. There is further disclosed a method for treating various cancers comprising administering effective amounts of an imidazolinopyrimidinone having the structure of Formula I herein.
Described herein are methods, compositions, and systems useful for detecting transplant rejection and associated abnormal conditions in solid organ transplant recipients, such as kidney transplant recipients. Methods described herein may involve combined assessment of blood gene expression profiles from an assessment of particular, related mRNA transcript levels and donor-derived cell-free nucleic acids (dd-cfDNA).
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
87.
ENGINEERED LASSA VIRAL IMMUNOGENS AND VACCINE COMPOSITIONS
The present invention provides engineered immunogenic proteins that are derived from Lassa virus (LASV) glycoprotein complex (GPC), and related vaccine compositions.
Pharmaceutical compositions comprising a peptidic inhibitor of cathepsin B, such as Z-Arg-Lys-AOMK (Z-R-K-AOMK). Methods for inhibiting neutral pH cathepsin B activity, comprising administering to a subject in need an effective amount of a peptidic inhibitor of cathepsin B. Methods for treatment or prevention of a disease comprising administering to a subject in need an effective amount of a peptidic inhibitor of cathepsin B. Methods of producing pH-selective peptide-AMC substrates and novel peptidic-AOMK inhibitors of cathepsin B.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61P 43/00 - Drugs for specific purposes, not provided for in groups
89.
CROSS-REACTIVE MONOCLONAL ANTIBODIES AGAINST CORONAVIRUSES
The invention provides antibodies and related antibody agents that are cross-reactive with the spike proteins of multiple human coronaviruses. Also provided in the invention are methods and kits of using such antibodies in various diagnostic and therapeutic applications. In one aspect, the invention provides novel antibodies or antigen-binding fragments thereof that specifically bind to a human coronavirus spike protein.
The present invention provides novel engineered nanoparticle scaffold sequences that are derived from the 13-01 protein. Relative to the known 13-01 protein or variants thereof, the novel 13-01 derived scaffold sequences of the invention contain an extended N-terminal helix. Also provided in the invention are vaccine constructs that contain various immunogenic proteins displayed on the novel nanoparticle scaffold sequences described herein. The vaccine constructs of the invention include, e.g., nanoparticles displaying tandem repeats of influenza M2e proteins or HCV E2 core proteins.
The present disclosure relates to compounds, and to their pharmaceutical compositions, that inhibit dipeptidyl peptidase IV (DPP4). The compounds selectively promote the proliferation of alveolar type 2 cells (AEC2s) and are useful in therapeutic methods of treating diseases whose etiology, for example, derives from epithelial degeneration and maladaptive remodeling, such as pulmonary diseases like idiopathic pulmonary fibrosis (IPF), acute respiratory distress syndrome (ARDS), and infant respiratory distress syndromes (IRDS).
A61P 11/00 - Drugs for disorders of the respiratory system
C07D 207/16 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 209/52 - Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
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 473/06 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
92.
NOVEL PHOSPHOROUS (V)-BASED REAGENTS, PROCESSES FOR THE PREPARATION THEREOF, AND THEIR USE IN MAKING STEREO-DEFINED ORGANOPHOSHOROUS (V) COMPOUNDS
The present invention relates to novel phosphorous (V) (P(V)) reagents
The present invention relates to novel phosphorous (V) (P(V)) reagents
methods for preparing thereof, and methods for preparing nucleoside phosphorothioate compounds by using the novel reagents.
C07F 9/6578 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and sulfur atoms with or without oxygen atoms, as ring hetero atoms
93.
SMALL MOLECULE MYRISTATE INHIBITORS OF BCR-ABL AND METHODS OF USE
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 9/00 - Drugs for disorders of the cardiovascular system
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 403/06 - 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 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 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
The present disclosure provides methods, compositions, and kits for methods that can improve techniques nucleic acid analysis, and can allow for more reliable and accurate targeted, multiplexed, high throughput sequencing. The methods, compositions, and kits can be used for sequencing target loci of nucleic acid. The methods, compositions, and kits disclosed herein can be used for assisted de novo targeted sequencing. The methods, compositions, and kits disclosed herein can also be used for library labeling for de novo sequencing and phasing.
The disclosure provides the development of enantiomer-specific 7V-arylpyrazole dipeptides as novel N0D2 agonists which are effective at promoting immune checkpoint inhibitor therapy requiring N0D2 for activity. Given the significant functions of N0D2 in innate and adaptive immunity, these novel agonists afford new therapeutic compounds for a variety of NOD2-responsive diseases.
Provided herein are peptides and peptide conjugates comprising a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. The peptides may be used for blood glucose management and treating conditions such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH).
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/59 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
The present disclosure provides compounds, or their tautomers or pharmaceutically acceptable salts thereof, and their pharmaceutical compositions that can selectively activate Yes-associated protein 1 (YAP). YAP activators of the present disclosure are useful in therapies such as wound and organ repair including, for example, treatment of chronic ulcers.
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 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/422 - Oxazoles not condensed and containing further heterocyclic rings
A61K 31/423 - Oxazoles condensed with carbocyclic rings
A61K 31/424 - Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
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 31/4427 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61P 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
98.
PROTEASE INHIBITORS FOR TREATMENT OF CORONAVIRUS INFECTIONS
Provided herein are compounds of Formula (I), their pharmaceutically acceptable salts, and their pharmaceutical compositions:
Provided herein are compounds of Formula (I), their pharmaceutically acceptable salts, and their pharmaceutical compositions:
Provided herein are compounds of Formula (I), their pharmaceutically acceptable salts, and their pharmaceutical compositions:
wherein R1, R2, R3a, R3b, R4, R5, and A are defined in the present disclosure. The compounds are potent inhibitors of the main protease (Mpro) of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), and they are useful in treating or preventing COVID-19 in a subject.
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 207/267 - 2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
C07D 211/76 - Oxygen atoms attached in position 2 or 6
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 405/10 - 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 carbon chain containing aromatic rings
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 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
The present invention provides redesigned soluble coronavirus S protein derived immunogens that are stabilized via specific modifications in the wildtype soluble S sequences. Also provided in the invention are nanoparticle vaccines that contain the redesigned soluble S immunogens displayed on self-assembling nanoparticles. Polynucleotide sequences encoding the redesigned immunogens and the nanoparticle vaccines are also provided in the invention. The invention further provides methods of using the vaccine compositions in various therapeutic applications, e.g., for preventing or treating coronaviral infections.
Dielectric polymer films and electronic energy storage devices (e.g., thin film capacitors) comprising the dielectric polymer films are described herein. The polymer films comprise aromatic polysulfates and polysulfonates of Formula I, as described herein: [‒O‒A122‒X1‒A2‒X12nn (I). Preferred polymers have glass transition temperatures of at least about 120 °C (e.g., 150 to 330 °C), and are useful as dielectric materials in electrostatic energy storage devices such as polymer film capacitors, which can operate under harsh electrification conditions, e.g., high electric field and elevated temperatures.
