The present invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides potent inhibitors of Aurora A kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
Antibodies, fragments thereof and fusion proteins that specifically bind to CD19, are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Systems and methods for distributing a filling fluid are discussed. More particularly an exemplary filling system may include a reservoir holding a filling fluid for distribution. The filling system may also include a pump and filling nozzle fluidly coupled to the reservoir. A processor executes a filling module that when executed receives at least one input fluid property of the filling fluid and generates at least one set of operating parameters for controlling operation of the pump during a filling operation based at least in part on the fluid property. The generated set of operating parameters enable control of the pump to distribute the filling fluid through the filling nozzle, such that a fluid interface with a stable resting profile forms in the filling fluid in the filling nozzle adjacent to the nozzle opening after the filling fluid is distributed from the filling nozzle.
B65B 3/12 - Methods of, or means for, filling the material into the containers or receptacles by application of pressure to material mechanically, e.g. by pistons or pumps
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 39/12 - Nozzles, funnels or guides for introducing articles or materials into containers or wrappers movable towards, or away from, container or wrapper during filling or depositing
B65B 57/14 - Automatic control, checking, warning or safety devices responsive to absence, presence, abnormal feed, or misplacement of articles or materials to be packaged and operating to control, or stop, the feed of articles or material to be packaged
The present invention provides compounds useful as inhibitors of PDK1. The present invention also provides compositions thereof, and methods of treating PDK1-mediated diseases.
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 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
C07D 241/26 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
C07D 241/28 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
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 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
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 409/04 - 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 directly linked by a ring-member-to-ring- member bond
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 417/14 - 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 473/34 - Nitrogen atom attached in position 6, e.g. adenine
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
This invention provides novel solid pharmaceutical compositions and processes for the bulk production of said compositions. This invention also provides methods of using the pharmaceutical compositions in the treatment of cancer.
A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
7.
CD38-binding proteins comprising de-immunized Shiga toxin A subunit effectors
The instant invention provides binding proteins (“CD38-binding proteins”) which each comprise (1) a CD38-binding region for cell-targeting and (2) a Shiga toxin A Subunit effector polypeptide (“Shiga toxin effector polypeptide”). The Shiga toxin effector polypeptide components of the CD38-binding proteins may comprise a combination of mutations relative to a wild-type Shiga toxin sequence providing (1) de-immunization and/or (2) a reduction in protease sensitivity; wherein each Shiga toxin effector polypeptide retains one or more Shiga toxin function, such as, e.g., stimulating cellular internalization, directing intracellular routing, catalytic activity, and/or potent cytotoxicity. The CD38-binding proteins may have one or multiple uses, e.g., the selective killing of a specific CD38-expressing cell-type; and more generally, for the diagnosis and treatment of cancers and disorders involving CD38-expressing cells, e.g., in CD38-positive hematopoietic cancers such as multiple myeloma.
This invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides compounds that inhibit Aurora kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH (USA)
MEMORAIL HOSPITAL FOR CANCER AND ALLIED DISEASES (USA)
MILLENNIUM PHARMACEUTICALS, INC. (USA)
Inventor
Feucht, Judith
Mansilla-Soto, Jorge
Riviere, Isabelle
Sadelain, Michel
Vincent, Loic
Shapiro, Gary
Ng, Mei Rosa
Tavares, Dan
He, Xingyue
Abstract
The presently disclosed subject matter provides chimeric antigen receptors (CARs) that specifically target CD19 and cells comprising such CD19-targeted CARs. The presently disclosed subject matter further provides uses of the CD19-targeted CARs for treatment, e.g., for treating blood cancer.
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
Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.
A61K 31/423 - Oxazoles condensed with carbocyclic rings
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 31/437 - 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 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/5025 - Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61K 31/541 - Non-condensed thiazines 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 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/428 - Thiazoles condensed with carbocyclic rings
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 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/04 - 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 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 present invention relates to an implantable cell chamber device capable of retaining cells but permitting diffusion of biomolecules. Also disclosed are methods for delivering a therapeutic biomolecule to a subject in need thereof on a continuous or semi-continuous basis, by administering to the subject a cell chamber device comprising cells that secrete the therapeutic biomolecule.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/436 - 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
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61K 31/4418 - Non-condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic ring directly attached to the heterocyclic ring, e.g. cyproheptadine
The present disclosure provides, among other things, a method of engineering genetically modified cells comprising, maintaining the cells in a collection chamber, contacting the cells with a fluid flow of a composition comprising viral or non-viral particles, thereby engineering genetically modified cells. The present disclosure also provides, among other things, a method of engineering genetically modified cells comprising, subjecting the cells to a centrifugal force, contacting the cells with a fluid flow of a composition comprising viral or non-viral particles, thereby engineering genetically modified cells.
Systems and methods for distributing a filling fluid are discussed. More particularly an exemplary filling system may include a reservoir holding a filling fluid for distribution. The filling system may also include a pump and filling nozzle fluidly coupled to the reservoir. A processor executes a filling module that when executed receives at least one input fluid property of the filling fluid and generates at least one set of operating parameters for controlling operation of the pump during a filling operation based at least in part on the fluid property. The generated set of operating parameters enable control of the pump to distribute the filling fluid through the filling nozzle, such that a fluid interface with a stable resting profile forms in the filling fluid in the filling nozzle adjacent to the nozzle opening after the filling fluid is distributed from the filling nozzle.
B65B 3/12 - Methods of, or means for, filling the material into the containers or receptacles by application of pressure to material mechanically, e.g. by pistons or pumps
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 39/12 - Nozzles, funnels or guides for introducing articles or materials into containers or wrappers movable towards, or away from, container or wrapper during filling or depositing
B65B 57/14 - Automatic control, checking, warning or safety devices responsive to absence, presence, abnormal feed, or misplacement of articles or materials to be packaged and operating to control, or stop, the feed of articles or material to be packaged
15.
LIPID COMPOSITIONS FOR DELIVERY OF STING AGONIST COMPOUNDS AND USES THEREOF
The present disclosure provides lipid compositions comprising lipid particles (e.g., lipid nanodiscs), wherein the lipid particles (e.g., lipid nanodiscs) comprise a STING agonist amphiphile conjugate, a phospholipid and a PEG-lipid. The compositions are used in methods to induce or promote immune responses, such as immune responses useful for the treatment of cancer or infectious disease.
A61K 47/69 - 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 47/54 - 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 compound
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 31/7084 - Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
Antibodies, fragments thereof and fusion proteins that specifically bind to Clec12A, are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various autoimmune diseases and cancers, including leukemia, lymphoma, or myeloma, including, for example, acute myeloid leukemia.
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
Antibodies, fragments thereof and fusion proteins that specifically bind to ADGRE2, are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various autoimmune diseases and cancers, including, for example, acute myeloid leukemia.
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
19.
CHIMERIC RECEPTORS TARGETING ADGRE2 AND/OR CLEC12A AND USES THEREOF
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH (USA)
MEMORIAL HOSPITAL FOR CANCER AND ALLIED DISEASES (USA)
Inventor
Sadelain, Michel
Haubner, Sascha P.
Mansilla-Soto, Jorge
He, Xingyue
Shapiro, Gary
Abstract
The presently disclosed subject matter provides for chimeric receptors that target ADGRE2 and chimeric receptors that target CLEC12A. The presently disclosed subject matter also provides for cells comprising the ADGRE2-targeted chimeric receptors, cells comprising the CLEC12A-targeted chimeric receptors, and cells comprising the ADGRE2-targeted chimeric receptors and the CLEC12A-targeted chimeric receptors. The presently disclosed subject matter further provides uses of such cells for treating tumors, e.g., AML.
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
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH (USA)
MEMORIAL HOSPITAL FOR CANCER AND ALLIED DISEASES (USA)
MILLENNIUM PHARMACEUTICALS, INC. (USA)
Inventor
Sadelain, Michel
Haubner, Sascha P.
Mansilla-Soto, Jorge
Shapiro, Gary
He, Xingyue
Abstract
The presently disclosed subject matter provides for chimeric receptors that target ADGRE2 and chimeric receptors that target CLEC12A. The presently disclosed subject matter also provides for cells comprising the ADGRE2 -targeted chimeric receptors, cells comprising the CLEC12A-targeted chimeric receptors, and cells comprising the ADGRE2-targeted chimeric receptors and the CLEC12A-targeted chimeric receptors. The presently disclosed subject matter further provides uses of such cells for treating tumors, e.g., AML.
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
Antibodies, fragments thereof and fusion proteins that specifically bind to ADGRE2, are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various autoimmune diseases and cancers, including, for example, acute myeloid leukemia.
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
22.
CHIMERIC RECEPTORS TARGETING ADGRE2 AND/OR CLEC12A AND USES THEREOF
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH (USA)
MEMORIAL HOSPITAL FOR CANCER AND ALLIED DISEASES (USA)
MILLENNIUM PHARMACEUTICALS, INC. (USA)
Inventor
Sadelain, Michel
Haubner, Sascha P.
Mansilla-Soto, Jorge
Shapiro, Gary
He, Xingyue
Abstract
The presently disclosed subject matter provides for chimeric receptors that target ADGRE2 and chimeric receptors that target CLEC12A. The presently disclosed subject matter also provides for cells comprising the ADGRE2 -targeted chimeric receptors, cells comprising the CLEC12A-targeted chimeric receptors, and cells comprising the ADGRE2-targeted chimeric receptors and the CLEC12A-targeted chimeric receptors. The presently disclosed subject matter further provides uses of such cells for treating tumors, e.g., AML.
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
Antibodies, fragments thereof and fusion proteins that specifically bind to Clec12A, are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various autoimmune diseases and cancers, including leukemia, lymphoma, or myeloma, including, for example, acute myeloid leukemia.
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
Antibodies, fragments thereof and fusion proteins that specifically bind to ADGRE2, are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various autoimmune diseases and cancers, including, for example, acute myeloid leukemia.
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
Antibodies, fragments thereof and fusion proteins that specifically bind to Clec12A, are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various autoimmune diseases and cancers, including leukemia, lymphoma, or myeloma, including, for example, acute myeloid leukemia.
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
26.
METHODS AND PRODUCTS FOR TREATMENT OF GASTROINTESTINAL DISORDERS
Described herein are compositions and methods for the delivery of microbial therapeutics useful for the treatment of disorders related to intestinal dysbiosis.
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
27.
METHODS AND COMPOSITIONS FOR CRYOPRESERVATION OF IMMUNE CELLS
The present disclosure provides, among other things, a cryopreservation medium comprising a cryoprotectant, an albumin, a disaccharide and a non-pyrogenic and isotonic crystalloid solution. The disclosure also provides, among other things, a cryopreservation medium for cryopreserving immune cells, the medium comprising: human serum albumin (HSA), sodium chloride, sodium gluconate, sodium acetate trihydrate, potassium chloride, magnesium chloride, dimethyl sulfoxide (DMSO), and a trehalose. The present disclosure also provides, a method of cryopreserving immune cells, transporting and subsequently administering such immune cells to a patient in need thereof.
The present disclosure provides, among other things, a method of cryopreserving and thawing cells that results in the thawed cells having high cellular viability and functionality post- thawing. In some embodiments, a large-scale method of cryopreserving cells is provided, the method comprising : (a) contacting the cells with a cryopreservation medium; (b) cooling the cells to -80°C at a controlled rate to minimize latent heat of fusion; and (c) storing the cells in liquid nitrogen vapor phase, thereby cryopreserving the immune cells.
The present disclosure provides, among other things, a cryopreservation medium comprising a cryoprotectant, an albumin, a disaccharide and a non-pyrogenic and isotonic crystalloid solution. The disclosure also provides, among other things, a cryopreservation medium for cryopreserving immune cells, the medium comprising: human serum albumin (HSA), sodium chloride, sodium gluconate, sodium acetate trihydrate, potassium chloride, magnesium chloride, dimethyl sulfoxide (DMSO), and a trehalose. The present disclosure also provides, a method of cryopreserving immune cells, transporting and subsequently administering such immune cells to a patient in need thereof.
The present disclosure provides, among other things, a method of cryopreserving and thawing cells that results in the thawed cells having high cellular viability and functionality post-thawing. In some embodiments, a large-scale method of cryopreserving cells is provided, the method comprising: (a) contacting the cells with a cryopreservation medium; (b) cooling the cells to -80°C at a controlled rate to minimize latent heat of fusion; and (c) storing the cells in liquid nitrogen vapor phase, thereby cryopreserving the immune cells.
The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer in patients in need thereof. The methods comprise administering to a patient in need a small ubiquitin-like modifier (SUMO) activating enzyme (SAE) inhibitor, such as [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate or a pharmaceutically acceptable salt, in combination with one or more checkpoint inhibitors. Also provided are medicaments for use in treating cancer.
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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
Systems and methods for distributing a filling fluid are discussed. More particularly an exemplary filling system may include a reservoir holding a filling fluid for distribution. The filling system may also include a pump and filling nozzle fluidly coupled to the reservoir. A processor executes a filling module that when executed receives at least one input fluid property of the filling fluid and generates at least one set of operating parameters for controlling operation of the pump during a filling operation based at least in part on the fluid property. The generated set of operating parameters enable control of the pump to distribute the filling fluid through the filling nozzle, such that a fluid interface with a stable resting profile forms in the filling fluid in the filling nozzle adjacent to the nozzle opening after the filling fluid is distributed from the filling nozzle.
B65B 3/12 - Methods of, or means for, filling the material into the containers or receptacles by application of pressure to material mechanically, e.g. by pistons or pumps
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 39/12 - Nozzles, funnels or guides for introducing articles or materials into containers or wrappers movable towards, or away from, container or wrapper during filling or depositing
B65B 57/14 - Automatic control, checking, warning or safety devices responsive to absence, presence, abnormal feed, or misplacement of articles or materials to be packaged and operating to control, or stop, the feed of articles or material to be packaged
Disclosed is a method for treating a subject having primary sclerosing cholangitis, comprising administering to said subject an effective amount of a humanized antibody or antigen-binding fragment thereof having binding specificity for α4β7 integrin.
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
34.
ADMINISTRATION OF SUMO-ACTIVATING ENZYME INHIBITOR AND ANTI-CD38 ANTIBODIES
The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer or autoimmune disease in patients in need thereof. The methods comprise administering to a patient in need a small ubiquitin-like modifier (SUMO) activating enzyme (SAE) inhibitor, such as [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1- yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxy-cyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt, in combination with one or more anti-CD38 antibodies. Also provided are medicaments for use in treating cancer or autoimmune disease.
A61K 31/34 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
A61K 31/505 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
Antibodies, fragments thereof and fusion proteins that specifically bind to CD19, are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Antibodies, fragments thereof and fusion proteins that specifically bind to CD19, are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 35/02 - Antineoplastic agents specific for leukemia
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
37.
CHIMERIC ANTIGEN RECEPTORS TARGETING CD19 AND USE THEREOF
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH (USA)
MEMORIAL HOSPITAL FOR CANCER AND ALLIED DISEASES (USA)
Inventor
Feucht, Judith
Mansilla-Soto, Jorge
Riviere, Isabelle
Sadelain, Michel
Vincent, Loic
Shapiro, Gary
Ng, Mei Rosa
Tavares, Dan
He, Xingyue
Abstract
The presently disclosed subject matter provides chimeric antigen receptors (CARs) that specifically target CD 19 and cells comprising such CD19-targeted CARs. The presently disclosed subject matter further provides uses of the CD19-targeted CARs for treatment, e.g., for treating blood cancer.
Antibodies, fragments thereof and fusion proteins that specifically bind to CD19, are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 35/02 - Antineoplastic agents specific for leukemia
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
39.
CHIMERIC ANTIGEN RECEPTORS TARGETING CD19 AND USE THEREOF
The presently disclosed subject matter provides chimeric antigen receptors (CARs) that specifically target CD 19 and cells comprising such CD19-targeted CARs. The presently disclosed subject matter further provides uses of the CD19-targeted CARs for treatment, e.g., for treating blood cancer.
The present disclosure provides lipid compositions comprising lipid particles (e.g., lipid nanodiscs), wherein the lipid particles (e.g., lipid nanodiscs) comprise a STING agonist amphiphile conjugate, a phospholipid and a PEG-lipid. The compositions are used in methods to induce or promote immune responses, such as immune responses useful for the treatment of cancer or infectious disease.
A61K 47/54 - 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 compound
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 47/69 - 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
The present disclosure provides, among other things, a method of engineering genetically modified cells comprising, maintaining the cells in a collection chamber, contacting the cells with a fluid flow of a composition comprising viral or non-viral particles, thereby engineering genetically modified cells. The present disclosure also provides, among other things, a method of engineering genetically modified cells comprising, subjecting the cells to a centrifugal force, contacting the cells with a fluid flow of a composition comprising viral or non-viral particles, thereby engineering genetically modified cells.
The present disclosure provides methods, pharmaceutical compositions, and kits for therapeutically or prophylactically treating a subject suffering from a viral infection. The method comprises administering to the subject a therapeutically effective amount of I-263a or a pharmaceutically acceptable salt thereof.
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
C07D 409/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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
The present disclosure provides, among other things, a method for efficiently producing natural killer cells from induced pluripotent cells. The method includes the steps of: (I) culturing pluripotent stem cells in a culture medium to produce CD56+/CD3− immune 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
The present invention relates to an implantable cell chamber device capable of retaining cells but permitting diffusion of biomolecules. Also disclosed are methods for delivering a therapeutic biomolecule to a subject in need thereof on a continuous or semi-continuous basis, by administering to the subject a cell chamber device comprising cells that secrete the therapeutic biomolecule.
A61B 17/12 - Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels or umbilical cord
A61B 17/50 - Instruments, other than pincettes or toothpicks, for removing foreign bodies from the human body
This invention provides novel solid pharmaceutical compositions and processes for the bulk production of said compositions. This invention also provides methods of using the pharmaceutical compositions in the treatment of cancer.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
The present disclosure provides, among other things, a method for efficiently producing natural killer cells from induced pluripotent cells. The method includes the steps of: (I) culturing pluripotent stem cells in a culture medium to produce CD56+/CD3- immune cells.
The invention features new a method for treating inflammatory bowel disease, including Crohn's Disease (CD) or ulcerative colitis in a human patient, comprising administering to a patient a combination therapy comprising an anti-α4β7 antibody, a TNFα antagonist, and an immunomodulator.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 31/58 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
The present disclosure provides, among other things, a cryopreservation medium for cryopreserving mammalian cells, the medium comprising: dimethyl sulfoxide (DMSO), disaccharide, human serum, and IL-7 and/or IL-15. The present disclosure also provides, among other things, a cryopreservation medium for cryopreserving mammalian cells, the medium comprising: between about 1 w/v % and 10 w/v % dimethyl sulfoxide (DMSO), between about 0.25 w/v % and 5 w/v % disaccharide, and between about 10 w/v % and 90 w/v % human serum. The present disclosure also provides, among other things, a cryopreservation medium for cryopreserving mammalian cells, the medium comprising: between about 1 w/v % and 10 w/v % dimethyl sulfoxide (DMSO), between about 0.25 w/v % and 5 w/v % disaccharide, and between about 0.5w/v % and 30 w/v % human serum albumin.
The present invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides potent inhibitors of Aurora A kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A computing device-implemented method for automated tracking and optimization of global manufacturing and supply based on impacts of post-approval changes (PACs) is discussed. An exemplary method includes retrieving data from data sources including at least an inventory database, a regulatory database, and a PAC information database. The method further includes analyzing the retrieved data to identify one or more impacts of at least one PAC on one or more drug products or drug substances using a predefined ruleset for determining which changes were implemented for each lot. The method also includes generating a list of the identified one or more impacts on the one or more drug products or drug substances.
Described herein are compositions and methods for the delivery of microbial therapeutics useful for the treatment of disorders related to intestinal dysbiosis. In various aspects, the present invention provides compositions and methods that are useful treating or preventing inflammatory bowel disease (IBD) in a subject in need thereof. For instance, the present invention, in part, relates to a plurality of bacterial isolates, wherein at least two of the plurality of bacterial isolates are isolated from a stool of different human donors.
Described herein are compositions and methods for the delivery of microbial therapeutics useful for the treatment of disorders related to intestinal dysbiosis. In various aspects, the present invention provides compositions and methods that are useful treating or preventing inflammatory bowel disease (IBD) in a subject in need thereof. For instance, the present invention, in part, relates to a plurality of bacterial isolates, wherein at least two of the plurality of bacterial isolates are isolated from a stool of different human donors.
Disclosed are methods for the treatment of cancer in patients in need of such treatment. The methods comprise administering to such a patient an Aurora kinase inhibitor such as 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid or a pharmaceutically acceptable salt in combination with a platin. Also disclosed are medicaments for use in the treatment of cancer.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/18 - Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
61.
ANTIBODY PURIFICATION METHODS AND COMPOSITIONS THEREOF
Methods of purifying a humanized α4β7 antibody, such as vedolizumab, produced in a mammalian cell culture are described herein, as are compositions resulting from said purification processes.
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
A61P 37/00 - Drugs for immunological or allergic disorders
A61P 43/00 - Drugs for specific purposes, not provided for in groups
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
G01N 33/00 - Investigating or analysing materials by specific methods not covered by groups
62.
ALPHA4BETA7 INHIBITOR AND IL-23 INHIBITOR COMBINATION THERAPY
Provided herein are combination therapies comprising an alpha4beta7 inhibitor, e.g., an anti-alpha4beta7 antibody, e.g., vedolizumab, and an IL-23 inhibitor, e.g., an anti-IL-23 antibody.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present disclosure provides heteroaryl compounds and pharmaceutically acceptable salts thereof useful as adjuvants and their use in pharmaceutical compositions such as vaccines. Further disclosed is the use of heteroaryl compounds and pharmaceutically acceptable salts thereof for stimulating an immune response in a subject.
A61K 31/505 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
C07D 405/06 - 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 only aliphatic carbon atoms
C07D 409/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
64.
ADMINISTRATION OF SUMO-ACTIVATING ENZYME INHIBITOR AND CHECKPOINT INHIBITORS
The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer in patients in need thereof. The methods comprise administering to a patient in need a small ubiquitin-like modifier (SUMO) activating enzyme (SAE) inhibitor, such as [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-y1]-5-methy1-2- thieny1}carbony1)pyrimidin-4-y1]amino}-2-hydroxycyclopenty1]methyl sulfamate or a pharmaceutically acceptable salt, in combination with one or more checkpoint inhibitors. Also provided are medicaments for use in treating cancer.
This invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides compounds that inhibit Aurora kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.
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 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 409/04 - 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 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
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 relates to anti-CD38 binding domains, characterized by their CDRs sequences. Some experimental data are provided with antibodies having the sequences claimed in claims 1-9. See Affinity values in Table 4. CD38-TM1, CD38-TM2 and CD38-TM5 bind non-overlapping epitope residues on human CD38 compared with daratumumab. CD38-TM3 and CD38-TM4 bind an epitope partially overlapping daratumumab on human CD38.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The instant invention provides binding proteins ("CD38-binding proteins") which each comprise (1) a CD38-binding region for cell-targeting and (2) a Shiga toxin A Subunit effector polypeptide ("Shiga toxin effector polypeptide"). The Shiga toxin effector polypeptide components of the CD38-binding proteins may comprise a combination of mutations relative to a wild-type Shiga toxin sequence providing (1) de-immunization and/or (2) a reduction in protease sensitivity; wherein each Shiga toxin effector polypeptide retains one or more Shiga toxin function, such as, e.g., stimulating cellular internalization, directing intracellular routing, catalytic activity, and/or potent cytotoxicity. The CD38- binding proteins may have one or multiple uses, e.g., the selective killing of a specific CD38- expressing cell-type; and more generally, for the diagnosis and treatment of cancers and disorders involving CD38-expressing cells, e.g., in CD38-positive hematopoietic cancers such as multiple myeloma.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
The present disclosure relates to anti-CD38 binding domains, characterized by their CDRs sequences. Some experimental data are provided with antibodies having the sequences claimed in claims 1-9. See Affinity values in Table 4. CD38-TM1, CD38-TM2 and CD38-TM5 bind non-overlapping epitope residues on human CD38 compared with daratumumab. CD38-TM3 and CD38-TM4 bind an epitope partially overlapping daratumumab on human CD38.
A61P 35/02 - Antineoplastic agents specific for leukemia
A61P 35/04 - Antineoplastic agents specific for metastasis
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
70.
CD38-BINDING PROTEINS COMPRISING DE-IMMUNIZED SHIGA TOXIN A SUBUNIT EFFECTORS
The instant invention provides binding proteins ("CD38-binding proteins") which each comprise (1) a CD38-binding region for cell-targeting and (2) a Shiga toxin A Subunit effector polypeptide ("Shiga toxin effector polypeptide"). The Shiga toxin effector polypeptide components of the CD38-binding proteins may comprise a combination of mutations relative to a wild-type Shiga toxin sequence providing (1) de-immunization and/or (2) a reduction in protease sensitivity; wherein each Shiga toxin effector polypeptide retains one or more Shiga toxin function, such as, e.g., stimulating cellular internalization, directing intracellular routing, catalytic activity, and/or potent cytotoxicity. The CD38- binding proteins may have one or multiple uses, e.g., the selective killing of a specific CD38- expressing cell-type; and more generally, for the diagnosis and treatment of cancers and disorders involving CD38-expressing cells, e.g., in CD38-positive hematopoietic cancers such as multiple myeloma.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
71.
CD38-binding proteins comprising de-immunized Shiga toxin A subunit effectors
The instant invention provides binding proteins (“CD38-binding proteins”) which each comprise (1) a CD38-binding region for cell-targeting and (2) a Shiga toxin A Subunit effector polypeptide (“Shiga toxin effector polypeptide”). The Shiga toxin effector polypeptide components of the CD38-binding proteins may comprise a combination of mutations relative to a wild-type Shiga toxin sequence providing (1) de-immunization and/or (2) a reduction in protease sensitivity; wherein each Shiga toxin effector polypeptide retains one or more Shiga toxin function, such as, e.g., stimulating cellular internalization, directing intracellular routing, catalytic activity, and/or potent cytotoxicity. The CD38-binding proteins may have one or multiple uses, e.g., the selective killing of a specific CD38-expressing cell-type; and more generally, for the diagnosis and treatment of cancers and disorders involving CD38-expressing cells, e.g., in CD38-positive hematopoietic cancers such as multiple myeloma.
The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer or autoimmune disease in patients in need thereof. The methods comprise administering to a patient in need a small ubiquitin-like modifier (SUMO) activating enzyme (SAE) inhibitor, such as [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxy-cyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt, in combination with one or more anti-CD20 antibodies. Also provided are medicaments for use in treating cancer or autoimmune disease.
A computing device-implemented method for automated tracking and optimization of global manufacturing and supply based on impacts of post-approval changes (PACs) is discussed. An exemplary method includes retrieving data from data sources including at least an inventory database, a regulatory database, and a PAC information database. The method further includes analyzing the retrieved data to identify one or more impacts of at least one PAC on one or more drug products or drug substances using a pre-defined ruleset for determining which changes were implemented for each lot. The method also includes generating a list of the identified one or more impacts on the one or more drug products or drug substances.
Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.
A61K 31/423 - Oxazoles condensed with carbocyclic rings
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 31/437 - 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 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/5025 - Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61K 31/541 - Non-condensed thiazines 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 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/428 - Thiazoles condensed with carbocyclic rings
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 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/04 - 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 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
This invention provides novel solid pharmaceutical compositions and processes for the bulk production of said compositions. This invention also provides methods of using the pharmaceutical compositions in the treatment of cancer.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
Systems and methods for distributing a filling fluid are discussed. More particularly an exemplary filling system may include a reservoir holding a filling fluid for distribution. The filling system may also include a pump and filling nozzle fluidly coupled to the reservoir. A processor executes a filling module that when executed receives at least one input fluid property of the filling fluid and generates at least one set of operating parameters for controlling operation of the pump during a filling operation based at least in part on the fluid property. The generated set of operating parameters enable control of the pump to distribute the filling fluid through the filling nozzle, such that a fluid interface with a stable resting profile forms in the filling fluid in the filling nozzle adjacent to the nozzle opening after the filling fluid is distributed from the filling nozzle.
B65B 3/04 - Methods of, or means for, filling the material into the containers or receptacles
B65B 3/12 - Methods of, or means for, filling the material into the containers or receptacles by application of pressure to material mechanically, e.g. by pistons or pumps
B65B 3/26 - Methods or devices for controlling the quantity of the material fed or filled
B67C 3/00 - Bottling liquids or semiliquids; Filling jars or cans with liquids or semiliquids using bottling or like apparatus; Filling casks or barrels with liquids or semiliquids
Systems and methods for distributing a filling fluid are discussed. More particularly an exemplary filling system may include a reservoir holding a filling fluid for distribution. The filling system may also include a pump and filling nozzle fluidly coupled to the reservoir. A processor executes a filling module that when executed receives at least one input fluid property of the filling fluid and generates at least one set of operating parameters for controlling operation of the pump during a filling operation based at least in part on the fluid property. The generated set of operating parameters enable control of the pump to distribute the filling fluid through the filling nozzle, such that a fluid interface with a stable resting profile forms in the filling fluid in the filling nozzle adjacent to the nozzle opening after the filling fluid is distributed from the filling nozzle.
B65B 3/04 - Methods of, or means for, filling the material into the containers or receptacles
B65B 3/12 - Methods of, or means for, filling the material into the containers or receptacles by application of pressure to material mechanically, e.g. by pistons or pumps
B65B 3/26 - Methods or devices for controlling the quantity of the material fed or filled
B67C 3/22 - Bottling liquids or semiliquids; Filling jars or cans with liquids or semiliquids using bottling or like apparatus - Details
Disclosed herein are WNT and Hippo pathway markers associated with sensitivity to treatment with Aurora A kinase inhibitors. Claimed genes include LEF1, MAP3K7, APC, FZD2, PRKCA, RORA, CAMK2G, JUN, XP01, ROR2, CCND1 & CTNNB1 (WNT pathway) and AMOT, DVL2, LATS1, LATS2, MOB1 B, NPHP4, TJP1, TJP2, WCC1, WWTR1 & YAP1 (Hippo pathway). Sensitivity to treatment with an Aurora A kinase inhibitor is observed when the aforementioned markers have mutations in tumor cells. Compositions and methods are provided to assess marker genes to predict response to Aurora Kinase A inhibition treatment and for patient selection.
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
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
Disclosed herein are markers whose mutational status is associated with sensitivity to treatment with NAE inhibitors. Mutational status is determined by measurement of characteristics of markers corresponding to the marker genes. Compositions and methods are provided to assess markers of marker genes to predict response to NAE inhibition treatment.
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
86.
Triple combination therapy for treating Crohn's disease
The invention features new a method for treating inflammatory bowel disease, including Crohn's Disease (CD) or ulcerative colitis in a human patient, comprising administering to a patient a combination therapy comprising an anti-α4β7 antibody, a TNFα antagonist, and an immunomodulator.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 31/58 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
42 - Scientific, technological and industrial services, research and design
Goods & Services
Providing medical and scientific research information in the field of pharmaceuticals and clinical trials; Scientific investigations for medical purposes; Clinical research in the field of gastro-intestinal diseases and disorders
42 - Scientific, technological and industrial services, research and design
Goods & Services
Clinical trials; clinical research; providing medical and scientific research information in the field of pharmaceuticals and clinical trials; scientific investigations for medical purposes.
89.
COCRYSTAL FORMS OF ((1S,2S,4R)-4-{4-[(1S)-2,3-DIHYDRO-1H-INDEN-1-YLAMINO]-7H-PYRROLO[2,3-D]PYRIMIDIN-7-YL}-2-HYDROXYCYCLOPENTYL) METHYL SULFAMATE, FORMULATIONS AND USES THEREOF
A61K 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A method for treating or preventing GvHD in a human patient, comprising administering to a patient suffering from GvHD or at risk for GvHD, a humanized antibody having binding specificity for human α4β7 integrin.
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 37/06 - Immunosuppressants, e.g. drugs for graft rejection
A61K 9/00 - Medicinal preparations characterised by special physical form
The present invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides potent inhibitors of Aurora A kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.
Provided is a method for producing an optically active pyrimidine amide derivative that can be produced on an industrial scale. Compound (I), (V) or a salt thereof is subjected to an asymmetric reduction reaction, the obtained compound (II) or a salt thereof is subjected to a deprotection reaction, the obtained compound (III) or a salt thereof is reacted with compound (IV) or a salt thereof, and compound (V) or a salt thereof is obtained. (In the formulas, the symbols are as defined in the description.)
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
The invention provides methods for the treatment of chronic pouchitis comprising administering an anti-a4ß7 antibody, e.g., vedolizumab, to a human subject in need thereof.
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
The invention provides methods for the treatment of chronic pouchitis comprising administering an anti-α4β7 antibody, e.g., vedolizumab, to a human subject in need thereof.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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
97.
TREATMENT OF MERLIN-DEFICIENT TUMORS USING NAE INHIBITORS
The present disclosure provides a method of treating a Merlin-deficient tumor using particular sulfamate inhibitors of Nedd8-activating enzyme. The present disclosure also provides a method of treating Merlin-deficient tumors using particular sulfamate inhibitors of Nedd8-activating enzyme in combination with a KSR1 inhibitor. The present disclosure further provides a method of treating Merlin-deficient tumors using a prodrug of particular sulfamate inhibitors of Nedd8-activating enzyme.
Provided herein is a method of treating or alleviating one or more symptoms of a disorder, disease, or condition mediated by a dopamine D2 or D3 receptor with 3-((1- cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof. Also provided herein is a method of increasing the serum prolactin level with 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)- 1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof.
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 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
100.
METHOD OF TREATING PEDIATRIC DISORDERS WITH ANTIBODIES SPECIFIC FOR ALPHA 4 BETA 7 INTEGRIN (VEDOLIZUMAB)
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
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61K 39/00 - Medicinal preparations containing antigens or antibodies
