A system for visual inspection of a manufacturing line comprising a plurality of segments includes a program memory storing instructions that, when executed by one or more processing units, cause the system to receive, from a plurality of imaging devices each assigned to a segment of the plurality of segments, image data of assigned segments of the manufacturing line. The system analyzes the image data to identify an operational state of the plurality of segments by applying a machine learning algorithm to a model trained with a plurality of training data comprising a set of training images representing an assigned segment of a respective imaging device during run-time operation of the manufacturing line or during line clearance of the manufacturing line. The model is configured to receive image data of the respective imaging device as input and to output an image classification associated with detection of an anomaly in the assigned segment. Responsive to identifying at least one anomaly in the plurality of segments, the system causes a display to present a notification regarding the at least one anomaly.
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
G06V 20/52 - Surveillance or monitoring of activities, e.g. for recognising suspicious objects
Devices for storing a drug, placebo, and/or other substance(s) and related assemblies are disclosed. The device may include a container having a wall with an inner surface and an outer surface. The inner surface may at least partially define a reservoir for storing the drug, placebo, and/or other substance(s). The device may further include a film which is at least partially transparent. The film may include an adhesive layer configured to couple the film with the outer surface of the wall of the container. The film may further include a tinted layer configured to prevent or substantially inhibit a viewer from visually distinguishing whether at least one substance disposed in the reservoir corresponds to the drug or placebo. Additionally, the device may include a label coupled with the film and comprising readable information and/or instructions relating to the drug, placebo, and/or other substance(s).
Disclosed herein are compounds useful for the inhibition of IGF-1R. The compounds have a general Formula (I) or a pharmaceutically acceptable salt thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, an IGF-1R mediated disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).
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
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
A61P 37/00 - Drugs for immunological or allergic disorders
A61K 31/5365 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
The present disclosure relates to an automated method for plating cells in a patch with different spot volumes in order to obtain at least one single, well spaced cell colony. There are multiple different spot volumes within each patch, and each spot is separated by a fixed distance. The disclosure further provides picking colonies by an automated method.
Systems for inspecting one or more products on a production line and related methods are disclosed. The system (10) may include an optical scanner (22) and a frame (20). The optical scanner may be configured to scan at least one product of the product(s) (12a, 12b, 12c) on the production line (14) at a predetermined inspection location. The frame may be separate from the production line and configured to support the optical scanner adjacent to the at least one predetermined inspection. The frame may include a base (24) and vertical support (26) extending upwardly from the base. A top end of the vertical support may be configured to support the optical scanner adjacent to the predetermined inspection location. In some embodiments, the system may include a processing subsystem (32) configured to analyze output from the optical scanner to determine at least one characteristic of the at least one product on the production line, including, for example, the presence of label(s) (13a, 13b, 13c).
G01N 21/88 - Investigating the presence of flaws, defects or contamination
B65B 57/02 - Automatic control, checking, warning or safety devices responsive to absence, presence, abnormal feed, or misplacement of binding or wrapping material, containers, or packages
B65B 57/10 - Automatic control, checking, warning or safety devices responsive to absence, presence, abnormal feed, or misplacement of articles or materials to be packaged
G01N 21/90 - Investigating the presence of flaws, defects or contamination in a container or its contents
G01N 21/95 - Investigating the presence of flaws, defects or contamination characterised by the material or shape of the object to be examined
6.
HETEROCYCLIC INHIBITORS OF IGF-1R AND USES THEREOF
Disclosed herein are compounds useful for the inhibition of insulin-like growth factor 1 receptor (IGF-1R). The compounds have a general Formula (I): or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, thyroid-associated ophthalmopathy, Graves' opthalmopathy or Graves' orbitopathy. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon 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 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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
Convergent pathways for the preparation of a peptide by solid phase peptide synthesis or liquid phase peptide synthesis, as well as peptide fragments suitable for use in such pathways, are provided. The convergent pathways may be utilized for the synthesis of agonists of the glucagon-like peptide 1 receptor (GLP-1R) such as the peptide component of maridebart cafraglutide.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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
8.
BIOLOGICAL DETECTION SYSTEMS AND METHODS FOR SETTING MEDICALLY SUITABLE TARGET RANGES OF ATTRIBUTES USING PRINCIPAL COMPONENT ANALYSIS (PCA)
Biological detection systems and methods are disclosed for defining medically suitable target ranges of molecular attributes. A trial session dataset is received defining a set of subjects and biological experiment data of a test molecule provided to the set of subjects during a trial session. A principal component analysis (PCA) algorithm inputs such data and outputs principal component(s) defining a biological response to the test molecule and correlated with the test molecular attribute. A machine learning classifier inputs the principal component(s)and classifies a plurality of clusters based thereon. First and second positions of respective first and second clusters are selected to define control and sample datasets, respectively. A difference in direction and/or distance from an origin for the first and second positions is detected, and an effective target range is determined therefrom defining a range of attribute exposure values of the test molecule that has a medically suitable biological response correlated with the test molecular attribute.
G16C 20/70 - Machine learning, data mining or chemometrics
G16H 20/10 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
9.
T CELL ENGAGER MASKING MOLECULES WITH REDUCED ISOMERIZATION TENDENCIES
The present invention relates to T cell engager masking molecules, and methods related thereto, that contribute to reduce the severity of cytokine release syndrome, wherein said molecules comprise (i.) a binding peptide which is deprived of an isomerization site and which binds to a T-cell engaging paratope of a bispecific T cell engager molecule (TCE), (ii.) a linker, and (iii.) a half-life extending polymer.
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
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
Disclosed herein are compounds useful for the inhibition of STAT6. The compounds have a general Formula (I) or (II) or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) and (II) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, diseases/disorders related to the activity of STAT6, such as an allergic disease or an inflammatory disease, including but not limited to atopic dermatitis or bronchial asthma. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I) and (II).
A61P 37/00 - Drugs for immunological or allergic disorders
C07D 207/263 - 2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
C07D 249/06 - 1,2,3-TriazolesHydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 401/12 - 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 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 405/14 - 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 413/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
A61K 31/435 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
A61K 31/4353 - 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
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
11.
DRUG DELIVERY DEVICES AND FLANGE EXTENSION MEMBERS
Drug delivery devices and flange extension members for syringes are disclosed. A drug delivery device may include a syringe and a flange extension member. The syringe may include a barrel having a proximal end, a distal end, and a longitudinal axis. The syringe may additionally include a flange disposed at the proximal end of the barrel and extending radially outwardly or substantially radially outwardly with respect to the longitudinal axis. The flange extension member may be coupled with at least the flange of the syringe. The flange extension member may comprise at least one anti-rotation member engaging at least one of the barrel of the syringe and the flange of the syringe to inhibit or prevent the flange extension member from rotating with respect to the longitudinal axis.
Provided herein are methods of determining the concentration of diethylenetriamene pentaacetate (DTPA) in a pharmaceutical formulation. In exemplary embodiments, the method comprises providing (i) a reference standard comprising, citrate and a known concentration of DTPA and (ii) a sample of a pharmaceutical formulation comprising DTPA, citrate and a protein; wherein the citrate concentration of the reference standard is the same as the citrate concentration of the sample of the pharmaceutical formulation; wherein each of the reference standard and the sample of the pharmaceutical formulation further comprise iron and the iron concentration of the reference standard is the same as the iron concentration of the sample of the pharmaceutical formulation and the iron present in each of the reference standard and sample is in excess of the citrate present in each of the reference standard and sample, and applying each of the reference standard and sample to an RPLC column.
A load vessel draining system for use with a drug purification system. The system includes a load vessel, a liquid handling module coupled to the load vessel and configured to draw fluid from the load vessel, and a chase solution vessel coupled to the load vessel. A backflow mechanism is coupled to each of the chase solution vessel and the load vessel, and the backflow mechanism is configured to at least selectively prevent fluid from the load vessel from prematurely backflowing into the chase solution vessel. So configured, the chase solution from the chase solution vessel is added to the load vessel upon one or more of: (1) the load vessel reaching an empty state; or (2) pressure within the load vessel exceeding a predetermined threshold.
This disclosure relates to methods of treating KRAS G12C mutant non-small cell lung cancer (NSCLC) by administering a triple combination therapy including defactinib, avutometinib, and sotorasib in a subject such as humans.
The present disclosure is directed to bispecific binding proteins and their utility for treating cancer. The disclosed bispecific binding proteins comprises a LTβR binding domain that binds to one or more amino acid residues of human LTβR cysteine-rich domain 4 (CRD4), where the human LTβR CRD4 comprises amino acid residues 169-211 of human LTβR (SEQ ID NO: 1). The disclosed bispecific binding proteins further comprises a fibroblast activation protein alpha (FAP) binding domain. The bispecific binding proteins (i) agonize LTβR, (i) do not inhibit LIGHT binding to LTβR, and (ii) do not inhibit LT1α2β binding to LTβR.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
16.
NEXT-GENERATION SEQUENCING PLATFORM FOR SEQUENCE VARIANT ANALYSIS OF MANUFACTURING CELL LINES
Methods for monitoring cell aging of manufacturing cell lines based on next generation sequencing (NGS) are provided. The methods can predict stability risks in a biologic-producing cell line.
The present invention relates to methods of treating obesity and obesity-related conditions. The claimed methods can be used to reduce gastrointestinal side-effects associated with administration of GLP-1R agonists. Included also are titrations of maridebart cafraglutide doses.
Drive assemblies for a drug delivery device and related methods are disclosed. A drive assembly comprises a casing having a proximal end, a distal end, and a longitudinal axis extending between the proximal end and the distal end, a plunger rod guide operably coupled to the casing, a spring at least partially disposed within the casing and wound around at least a portion of the plunger rod guide, and a lock component selectively coupled with the casing and configured to receive at least a portion of the plunger rod guide therein. The spring is configured to exert a force on the plunger rod guide that causes the plunger rod guide to rotate. The lock component is configured to prevent rotational movement of the plunger rod guide relative to the casing when the lock component is coupled with the casing.
The present invention relates to methods of reducing weight, HbA1c levels, high-sensitivity C-reactive protein, and systolic blood pressure in human patients comprising administering to the patient maridebart cafraglutide with the result being treatment of obesity, type II diabetes, and other obesity related conditions such as atherosclerotic cardiovascular disease and heart failure.
Systems and methods for inspecting one or more drug containers (10) disposed in a processing tray (11) are disclosed. A system (100) includes an imaging system (112) and a processing system (114). The imaging system (112) can include an image sensor (140) and a telecentric lens (146) and be configured to generate one or more images of the one or more drug containers (10) disposed in the processing tray (11). The processing system (114) can be configured to analyze the one or more images to determine a count of the one or more drug containers (10) disposed in the processing tray (11). A method includes generating (1103), by an imaging system (112) comprising an image sensor (140) and a telecentric lens (146), one or more images of one or more drug containers (10) disposed in a processing tray (11); and analyzing (1104), by one or more processors (114), the one or more images to determine a count (1006, 1105) of the one or more drug containers (10) disposed in the processing tray (11).
Provided herein is a therapy of Compound G, or pharmaceutically acceptable salt thereof, and Compound A, or pharmaceutically acceptable salt thereof, for treating an MTAP-null cancer in a subject in need of treatment.
A61K 31/4353 - 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
A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61K 9/00 - Medicinal preparations characterised by special physical form
C07D 211/60 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07C 51/15 - Preparation of carboxylic acids or their salts, halides, or anhydrides by reaction of organic compounds with carbon dioxide, e.g. Kolbe-Schmitt synthesis
C07C 51/60 - Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides into halides with the same carboxylic acid part
A drug delivery device (10, 100, 200) which includes a housing (12, 112, 212) having a distal end, a proximal end, and an opening adjacent to the distal end, a drug storage container (20) including a delivery member (16) having an insertion end configured to extend at least partially through the opening, a plunger moveable (26) in a distal direction to expel a drug from the drug storage container through the delivery member, a guard member (32, 132, 232) moveable relative to the housing, and a guard extension (37, 137, 237) positioned proximal to the guard member and operably coupled to the guard member. The guard extension may have a first engagement component on an inner surface thereof, and the guard member may have a second engagement component. The first and second engagement components are configured to limit axial movement of the guard extension in a proximal direction when the guard member is in the extended position.
A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
24.
5,6-FUSED BICYCLIC ALCOHOL COMPOUNDS AS 15-PROSTAGLANDIN DEHYDROGENASE MODULATORS
Disclosed herein are compounds useful for the inhibition of 15-PGDH. The compounds have a general Formula (I): (I) or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a 15-PGDH-mediated disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).
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 9/00 - Drugs for disorders of the cardiovascular system
A61P 19/08 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
25.
LOCI WITH INCREASED TRANSGENE EXPRESSION AND USES THEREOF
Methods of determining glycan pairing content of a protein composition are provided. In exemplary embodiments, the method comprises (a) treating a sample of the protein composition with (i) a mannosidase and (ii) a β1-4 endoglycosidase, to produce a mixture of components of the protein, wherein at least some of the components comprises one or more digested glycan structures; and (b) separating the components of the mixture based on molecular weight; and (c) quantifying the abundance of glycan pairs, optionally, quantifying (i) paired afucosylated glycans, (ii) unpaired afucosylated glycans, (iii) paired high mannose glycans, and/or (iv) unpaired high mannose glycans, of the mixture. In exemplary aspects, the method comprises quantifying the relative unpaired afucosylated (AF) glycan content and/or relative unpaired high mannose (HM) glycan content of the mixture.
A drug delivery device may include a housing having a distal end, a proximal end, and an opening adjacent to the distal end, a flange protruding radially inward from an inner surface of the housing, a drug storage container including a delivery member having an insertion end configured to extend at least partially through the opening, a plunger moveable in a distal direction to expel a drug from the drug storage container through the delivery member, a guard moveably positioned adjacent to the opening, a guard extension positioned proximal to the guard and operably coupled to the guard, a releaser member operably coupled to the guard extension, the releaser member having a distally facing contact surface, and a first biasing member disposed between the flange of the housing and the distally facing contact surface of the releaser member. The first biasing member may be configured to bias the releaser member in a proximal direction in at least a pre-delivery state.
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
28.
DAMPER OVERFILL CHAMBER TO INCREASE FUNCTIONAL ROBUSTNESS REGARDING VARIANCE IN PARTS AND PROCESSES
A damper mechanism for a drug delivery device comprising a frame member, a damper member operably coupled to a drive assembly of the drug delivery device, a damper fluid chamber formed between at least a portion of the frame member and the damper member, and a damper fluid disposed within the damper fluid chamber. The frame member and the damper member rotate relative to each other, and the damper fluid exerts an opposing force on at least one of the frame member and the damper member. The damper fluid chamber includes a main section and an overfill section. The overfill section receives excess damper fluid from the main section to reduce an effect a variation in fill level in the damper fluid chamber has on the opposing force exerted on at least one of the frame member or the damper member.
Systems for measuring a drug container closure member such as a syringe stopper and related methods and devices are disclosed. A system for measuring a drug container closure member may include a measurement device configured to measure at least one characteristic of the drug container closure member. The system may further include a positioning device or fixture having a base and an arm configured to extend from the base. Furthermore, the arm may be configured to hold the drug container closure member in at least one position allowing the measurement device to measure the at least one characteristic of the drug container closure member.
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
G01B 5/00 - Measuring arrangements characterised by the use of mechanical techniques
G01B 11/02 - Measuring arrangements characterised by the use of optical techniques for measuring length, width, or thickness
G01B 21/04 - Measuring arrangements or details thereof, where the measuring technique is not covered by the other groups of this subclass, unspecified or not relevant for measuring length, width, or thickness by measuring coordinates of points
The disclosure relates to compositions and methods for treating DLL3-expressing cancers by administration of an anti-DLL3 antigen-binding agent (e.g., tarlatamab) to a subject once every four weeks (Q4W).
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
Provided herein are FLT1 binding proteins, as well as related nucleic acids, vectors, host cells, pharmaceutical compositions and kits. The present disclosure additionally provides methods of treating a subject in need thereof, including subjects in need of treatment for PAD, CLI, ANOCA, or heart failure (HF). Further provided are methods of increasing VEGF-mediated and/or PlGF-mediated signal transduction in a subject, which, in turn, increases blood flow, capillary density, capillary or coronary growth, and/or cardiac perfusion in the subject. The present disclosure further provides methods of reducing blood pressure and risk of heart failure in a subject. In exemplary embodiments, each of the methods comprise administering to the subject a pharmaceutical composition of the present disclosure. In various embodiments, the pharmaceutical composition comprises a FLT1 binding protein of the present disclosure.
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 9/00 - Drugs for disorders of the cardiovascular system
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal 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
33.
SUBCUTANEOUS ADMINISTRATION OF ANTI-DLL3 AGENT FOR TREATMENT OF CANCER
Provided herein is a method for treating DLL3-expressing cancers using an anti-DLL3 antigen-binding protein administered subcutaneously. The anti-DLL3 antigen-binding protein comprises the amino acid sequence of SEQ ID NO: 13 and the amino acid sequence of SEQ ID NO: 22, and may be administered to a subject once every two weeks (Q2W), once every three weeks (Q3W), or once every four weeks (Q4W).
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Methods of producing Minute Mouse Virus (MMV) stock are described herein. Methods of producing xenotropic murine leukemia virus (xMuLV) stock are described herein.
Disclosed herein are compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C. The compounds have a general Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C disorder.
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
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
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
36.
A CELL-BASED PLATFORM FOR IDENTIFYING NATIVE PROTEIN-PROTEIN INTERACTIONS IN MAMMALIAN DISPLAY LIBRARIES
The present disclosure is directed to methods of identifying a binding protein from a library of cell surface expressed binding proteins having a target protein binding specificity. These methods comprise providing a first cell population, where the first cell population comprises a library of cell surface expressed binding proteins; and providing a second cell population, where cells of the second population express the target protein. The first and second cell populations are contacted under conditions suitable for the target protein to bind to a corresponding surface expressed binding protein, if the binding protein is present in the library. A binding interaction between a target protein and surface expressed binding protein induces trogocytosis between cells of the binding interaction. Trogocytosis is assessed between cells after the contacting step, and a surface expressed binding protein of the library having the target protein binding specificity is identified if trogocytosis is detected.
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
G01N 33/554 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals the carrier being a biological cell or cell fragment, e.g. bacteria, yeast cells
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
37.
SYNTHETIC PROCESSES FOR PHARMACEUTICALLY ACTIVE COMPOUNDS
A process for making a compound of Compound 1 having the following structure: or a salt thereof, said method comprising contacting 2-fluorobenzoic acid (compound 1) with an iron catalyst and a phosphine ligand in the presence of a methylaluminum reagent and 1,2-dichloropropane.
C07C 51/60 - Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides into halides with the same carboxylic acid part
C07C 51/353 - Preparation of carboxylic acids or their salts, halides, or anhydrides by reactions not involving formation of carboxyl groups by isomerisationPreparation of carboxylic acids or their salts, halides, or anhydrides by reactions not involving formation of carboxyl groups by change of size of the carbon skeleton
The present invention relates to methods and cell lines for increasing yield of proteins such as antibodies, and also methods of producing proteins in modified mammalian cells.
A bubble trap system configured for use with a single use centrifuge system includes a bubble trap configured to be disposed on a suction side of a centrifuge feed pump. The bubble trap includes a body having a first end with an inlet, a second end with an outlet, a fluid flow path disposed between the inlet and the outlet, a first area within the body, a second area within the body, and an opening between the first and second ends of the body. A chamber is coupled to and in fluid communication with the opening of the body. A first eccentric reducer is coupled to the inlet and has an inlet tube in fluid communication with the first area of the body, and a second eccentric reducer is coupled to the outlet and has an outlet tube in fluid communication with the second area of the body.
The present disclosure relates to the treatment of (a) biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormone-sensitive prostate cancer with an anti-STEAP1 antigen binding protein.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A method for assessing transferability of a fill recipe includes collecting acceleration data of a needle of an off-line filler using an accelerometer, and collecting acceleration data of a needle of an online filler using another accelerometer. The method further includes calculating at least one of velocity, speed, or displacement data of the needle of each of the off-line filler and the online filler. The method also includes generating a graphical representation of at least one of the calculated velocity, speed, or displacement data of the needle of the off-line filler relative to the at least one of the calculated velocity, speed, or displacement data of the needle of the online filler by overlaying the at least one of the calculated velocity, speed, and displacement data to identify any data discrepancy. The method still further includes adjusting at least one parameter of the fill recipe for transferring.
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
The present invention relates to mammalian cells modified to have reduced AEP protease activity. Such cells can be used for producing recombinant proteins.
A61K 31/451 - Non-condensed piperidines, e.g. piperocaine having a carbocyclic ring directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
45.
METHODS FOR REDUCING FILTER FOULING IN PERFUSION CELL CULTURES WITH RECIRCULATING TANGENTIAL FLOW FILTRATION
The present disclosure provides methods for producing recombinant proteins (e.g., antibodies) in mammalian cell culture under conditions that limit filter fouling and enable robust recirculating tangential flow (RTF) filtration operation in perfusion processes in which the working volume is increased to a final working volume during the cell culture.
The invention provides a method for treating prurigo nodularis by administering an anti-OX40 or anti- OX40L inhibitor, and an article of manufacture with instructions for such use. In particular the invention relates to a dosage regiment wherein an anti-OX40 antibody is administered at a dose of between about 150 mg and 300 mg once every 4 weeks, with an additional loading dose of anti-OX40 antibody between about 150 mg and 300 mg at week 2.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Disclosed herein are engineered polypeptides having improved imine reductase (IRED) activity, the nucleotides that encode said engineered polypeptides, and methods for using said engineered polypeptides in a reduction of an imine to a chiral amine.
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
C12N 9/04 - Oxidoreductases (1.), e.g. luciferase acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
48.
ARTIFICIAL INTELLIGENCE (AI) VALIDATION DATASET GENERATION SYSTEMS AND METHODS FOR GENERATING AI VALIDATION DATASETS FOR VALIDATING AI-BASED PROTEIN SEQUENCE MODELS
Artificial intelligence (Al) validation dataset generation systems and methods are described for generating Al validation datasets for validating Al-based protein sequence models. Such systems and methods include filtering a reference proteome dataset to generate a high completeness proteome data subset comprising reference proteomes. The high completeness proteome data subset is filtered to generate a protein confidence-based proteome data subset with reference proteomes above a protein confidence threshold. The plurality of protein sequences is clustered to generate a set of protein sequence clusters and a validation cluster subset is randomly allocated therefrom for creation of a protein sequence validation dataset. Validation metrics may then be generated by comparing (a) a set of predetermined values of the protein sequence validation dataset; and (b) the one or more predicted protein sequences as output by an Al-based protein sequence model.
Disclosed herein are compounds having activity as inhibitors of Werner Syndrome RecQ DNA helicase (WRN), pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to colorectal, endometrial, gastric and ovarian cancer. In particular, the disclosure provides compounds of Formula (A-I): (I), and pharmaceutically acceptable salts thereof, wherein the substituents are as described herein.
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
C07D 207/09 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
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 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
INHBEINHBE gene. Methods of using such RNAi constructs to treat or prevent visceral obesity and diseases associated with visceral obesity, such as cardiovascular disease, are also described.
Disclosed herein are compounds having activity as inhibitors of Werner Syndrome RecQ DNA helicase (WRN), pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to colorectal, endometrial, gastric and ovarian cancer. In particular, the disclosure provides compounds of Formula (I):, and pharmaceutically acceptable salts thereof, wherein the substituents are as described herein.
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 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
Compositions comprising a monomer and a dimer of an anti-PCSK9 antibody such as evolocumab are described herein. Methods of determining the presence, absence, or amount of a dimer in a composition comprising evolocumab are described herein.
Provided herein are pharmaceutical compositions comprising Compound A, such as 1-40 wt% Compound A, wherein the pharmaceutical compositions are suitable for oral administration. In some embodiments, the disclosed compositions are suitable for high drug loading. The disclosed compositions are suitable for treating diseases or disorders responsive to inhibiting protein arginine methyltransferase 5 (PRMT5) (e.g., cancer).
The present invention relates treating cancer, such as treating a solid tumor, by combining a bispecific molecule that simultaneously targets PD-L1 and 4-1BB, and a multispecific T cell engager molecule that targets CD3 and a Tumor Antigen.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
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
Systems and methods for inspecting pharmaceutical product are disclosed. A controller connected to a multi-axis robotic arm may be used to automatically perform a process that includes agitating liquid in a vial using a multi-axis robotic arm, pausing agitation of the vial for inspection of the liquid, and releasing the vial from the multi-axis robotic arm. The liquid may be agitated by moving the vial through an agitation motion profile that includes at least two-dimensional motion of the vial around an axis according to programmed motion parameters used to control movement of one or more axes of the multi-axis robotic arm. The motion of the vial includes at least two nonparallel vectors to move the vial around an axis. Such motion may induce a swirling motion of the fluid that mimics the motion that may be used in a manual visual inspection process.
Provided herein are methods of separating diastereomers of a double-stranded oligonucleotide. In exemplary embodiments, the method comprises: (a) applying a sample comprising diastereomers of a double-stranded oligonucleotide to an anion exchange (AEX) chromatographic matrix, wherein each strand of the double-stranded oligonucleotide comprises at least one phosphorothioate internucleotide linkage; and (B) applying a mobile phase to the AEX chromatographic matrix to elute the diastereomers of the double-stranded oligonucleotide from the matrix, wherein the mobile phase comprises a buffer and an elution salt and has a pH of greater than 10.
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
CNR1CNR1 gene. Methods of using such RNAi constructs to reduce visceral adiposity and treat or prevent obesity and obesity-related conditions, such as type 2 diabetes, fatty liver disease, steatohepatitis, and cardiovascular disease, are also described.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
Provided herein are methods of separating peptides of an enzyme digestion which may be useful in analyzing a protein for post-translational modifications. In exemplary embodiments, the method comprises (a) applying a sample comprising enzyme-digested peptides of a protein to a multi-column liquid chromatography (MCLC) system comprising a first RPLC column in tandem with a second RPLC column, whereby digested peptides of the sample bind to the first and/or second RPLC column and (b) applying a mobile phase to the MCLC system to obtain eluted peptides, wherein the first RPLC column is (i) different from the second RPLC column, (ii) joined to the second RPLC column through a connector, and (iii) in fluid communication with the second RPLC column. Fluids applied flow from the first RPLC column to the second RPLC column through the connector without flowing through any intervening valves or diverters.
Disclosed herein are methods for mitigating viscous fingering during cation exchange chromatography and reducing the number of peaks in a cation exchange chromatography isocratic elution profile.
B01D 15/16 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
B01D 15/20 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the sorbent material
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
B01D 15/42 - Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
Described herein are methods of treating a MTAP-null cancer in a patient in need thereof comprising administering (a) Compound A, or pharmaceutically acceptable salt thereof, at a total daily dose of 120 mg, 240 mg, 300 mg, 480 mg, 600 mg, 800 mg, 900 mg, 1200 mg, or 1600 mg; and (b) Compound B, or pharmaceutically acceptable salt thereof, at a total daily dose of 10 mg, 15 mg, 30 mg, or 60 mg.
The present application relates to recombinant expression of proteins within cells, including expression of therapeutic molecules. In some aspects, the present application relates to an intein-based split biomarker selection system allows using a single selection pressure for the incorporation of multiple transgenic fragments simultaneously.
An equipment mover includes a base and an attachment. The base has a transport mechanism, a base platform connected to the transport mechanism, and a mount extending from the base platform. The attachment has an attachment platform, a linkage, a linkage actuator, a clamping arm, a clamp actuator, one or more power sources, and a controller. The attachment platform is rotatably secured to the mount of the base to allow relative rotation between the attachment platform and the base platform. The linkage is connected to the attachment platform at a proximal end and further includes a distal end. The linkage actuator includes a linkage motor operably connected to the linkage to move the distal end of the linkage vertically. A clamping arm is connected to the distal end of the linkage and includes a clamp.
B66F 9/06 - Devices for lifting or lowering bulky or heavy goods for loading or unloading purposes movable, with their loads, on wheels or the like, e.g. fork-lift trucks
Systems and methods for inspecting and quality control of manufacturing and packaging of pharmaceutical product are disclosed. An exemplary? system comprises sensor circuitry/ and a controller circuit. The sensor circuitry comprises an embedded sensor platform, including an embedded accelerometer in an interior of the container empty of pharmaceutical product. The embedded accelerometer can measure container motion or position, orientation and movement information during experimental agitation of the container. The controller circuit generates an agitation protocol using the container motion or position information, which can be used to assist in subsequent agitation and inspection of containers filled with pharmaceutical products. The controller circuit can detect anomalies or defects associated with the container or the pharmaceutical product using data, collected by the embedded sensors.
G05B 19/423 - Teaching successive positions by walk-through, i.e. the tool head or end effector being grasped and guided directly, with or without servo-assistance, to follow a path
A61J 3/00 - Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
B01F 35/00 - Accessories for mixersAuxiliary operations or auxiliary devicesParts or details of general application
The disclosure provides processes for preparing Compound C-5, A-5, and Compound B-5, or salts thereof, as described herein. The disclosure also provides Compounds B-5a, B‑4a, and B-3a, or salts thereof, as described herein.
A module may receive or generate a mask that defines a shape of a feature depicted in a first image. The mask includes first boundary pixels that define an outer perimeter of the feature. The module may identify a transfer area in a second image to which the feature will be transferred and overlay the mask on the transfer area to align the first boundary pixels with second boundary pixels of the second image that define an outer perimeter of the transfer area. The module may define respective gradient values for pixels of the first image within the first boundary pixels of the mask and generate a set of replacement values for pixels of the transfer area based on the second boundary pixels and the respective gradient values. The module may generate the synthetic image by replacing pixel values of the transfer area with the set of replacement values
Disclosed herein are compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C. The compounds have a general Formula (I): or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C disorder
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
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
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
68.
SOLID FORMS OF MACROCYCLIC COMPOUNDS AND USES THEREOF
The disclosure provides solid forms of Compound A, as described herein. The disclosure also provides pharmaceutical compositions comprising the disclosed solid forms and methods of using the disclosed solid forms and pharmaceutical compositions (e.g., to treat cancer).
Disclosed herein are compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G12R, G13D. Q61H, Q61L. Q61R or G12C. The compounds have a general Formula (I): or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compormds, and compositions for treatment of, for example, a KRAS G12D, G12V, G12A, G12S, G12R. G13D, Q61H. Q61L, Q61R or G12C disorder.
Disclosed herein are compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C. The compounds have a general Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C disorder.
The present disclosure relates to methods for purifying proteins of interest using ultrafiltration and/or diafiltration. Specifically, the present disclosure utilizes a more accurate means for estimating the osmolality of the protein solution that has undergone an ultrafiltration and/or diafiltration operation. The method involves a mathematical model, which employs estimation of the osmolarity of the protein mixture based on the activity of water and Norrish constants for each excipient present in the protein mixture.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G16B 99/00 - Subject matter not provided for in other groups of this subclass
72.
SOLID STATE FORMS OF (2R,3S)-2-(4-(CYCLOPENTYLAMINO)PHENYL)-1-(2-FLUORO-6-METHYLBENZOYL)-N-(4-METHYL-3-(TRIFLUOROMETHYL)PHENYL)PIPERIDINE-3-CARBOXAMIDE
The present disclosure provides crystalline and amorphous HCl and HBr salt forms of (2R,3S)-2-(4-(cyclopentylamino)phenyl)-1-(2-fluoro-6-methylbenzoyl)-N-(4-methyl-3-(trifluoromethyl)phenyl)piperidine-3-carboxamide, pharmaceutical compositions, and methods of treating a disease mediated by C5aR inhibition.
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
A61P 37/00 - Drugs for immunological or allergic disorders
C07D 211/60 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
A61K 31/451 - Non-condensed piperidines, e.g. piperocaine having a carbocyclic ring directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
Described herein are techniques for predicting one or more properties of a multi-chain protein, the multi-chain protein including at least a first chain and a second chain. In some embodiments, the techniques include: obtaining sequence data for the multi-chain protein, the sequence data indicating a first amino acid sequence specifying at least a portion of the first chain and a second amino acid sequence specifying at least a portion of the second chain; generating a concatenated amino acid sequence by concatenating the first amino acid sequence, a linker, and the second amino acid sequence; encoding the concatenated amino acid sequence to obtain a numeric representation of the concatenated amino acid sequence; and processing the numeric representation of the concatenated amino acid sequence using a trained machine learning model to obtain an output indicative of the one or more properties of the multi-chain protein.
The present disclosure, relates, in general, to methods of treating eosinophilic esophagitis (EOE) using an antibody specific for thymic stromal lymphopoietin (TSLP).
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A drug delivery device may include a housing defining a longitudinal axis and having an opening, a drug storage container including a delivery member having an insertion end configured to extend at least partially through the opening during a delivery state, a plunger moveable toward a distal end of the drug storage container to expel a drug from the drug storage container, a drive mechanism operably coupled to the plunger, at least one cavity formed in a wall of the housing to permit a user to view the drug storage container through the at least one cavity, and a window disposed over the at least one cavity and configured to protect the drug in the drug storage container from wavelengths of light in an ultraviolet (UV) range, a visible range, and/or an infrared range.
The present disclosure, relates, in general, to methods of treating eosinophilic esophagitis (EOE) using an antibody specific for thymic stromal lymphopoietin (TSLP).
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61K 39/00 - Medicinal preparations containing antigens or antibodies
78.
TETHERED SPIRO-HETEROCYCLIC INHIBITORS OF KRAS G12C MUTANT PROTEINS AND USES THEREOF
The present disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung cancer, pancreatic cancer, colorectal cancer, and solid tumors. In particular, the disclosure provides compounds of Formula (I):, and pharmaceutically acceptable salts thereof, wherein the substituents are as described.
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
C07D 498/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
Disclosed herein are heavy-chain antibodies having activity as agonists of the dimeric interleukin‑2 receptor, pharmaceutical compositions comprising the heavy-chain antibodies, and methods of treating certain disorders, such as cancer, including but not limited to, small cell lung cancer. Also disclosed herein are methods of treating DLL3-expressing cancers comprising the administration of a T-cell engaging molecule that binds to DLL3 and an IL-2-based therapy.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The invention is directed to a method of treating pediatric osteogenesis imperfecta comprising administering an anti-sclerostin antibody to the subject in an amount ranging from 1 mg/kg to 10 mg/kg.
A method of assessing stopper movement in a syringe is provided, the syringe comprising a syringe barrel and a stopper movably disposed within the syringe barrel. The method comprises inoculating a biological particulate through an open proximal end of the syringe barrel such that the biological particulate covers at least a portion of an interface between a proximal face of the stopper and an inner wall of the syringe barrel. A cavity of the syringe contains a fill volume of liquid. Afterwards, the method comprises subjecting the syringe to one or more conditions, extracting the fill volume of liquid from the cavity of the syringe, performing a sterility test on the extracted fill volume of liquid, and determining stopper movement in the syringe based on the sterility test.
Described herein are methods of treating MTAP-null gastrointestinal cancer in a patient comprising administering to the patient a PRMT5 inhibitor, gemcitabine, and paclitaxel (e.g., nab-paclitaxel), or a PRMT5 inhibitor and mFOLFIRINOX. Also described herein are methods of treating MTAP-null gastrointestinal cancer in a patient comprising administering to the patient a PRMT5 inhibitor, gemcitabine, cisplatin, and an anti-PD 1 antibody or an anti-PDL1 antibody.
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
Described herein are methods of treating a MTAP-null lung cancer in a patient comprising administering to the patient a PRMT5 inhibitor and an anti-PD1 antibody, optionally in combination with carboplatin and either paclitaxel or pemetrexed. Further described herein are methods of treating a MTAP-null cancer in a patient also suffering from brain metastases comprising administering to the patient a PRMT5 inhibitor.
The present disclosure relates to improved GLP-1 receptor agonist polypeptides and molecules comprising these improved GLP-1 receptor agonist polypeptides, such as molecules comprising one or more GLP-1 receptor agonist polypeptides conjugated to an anti- gastric inhibitory peptide receptor (GIPR) antibody. The present disclosure is also directed to the use of these improved GLP-1 receptor agonist polypeptides and conjugate molecules comprising these polypeptides for treating or preventing obesity, an obesity related condition, type 2 diabetes, and/or a type 2 diabetes related condition.
Disclosed herein are ultrafiltration/diafiltration (UF/DF) methods comprising the use of diafiltration buffer concentrates, as well as UF/DF methods in which a composition comprising a recombinant protein is concentrated by an ultrafiltration step to a recombinant protein concentration above an intended concentration following a subsequent diafiltration step.
Disclosed herein are compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C. The compounds have a general Formula (I): or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C disorder.
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
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The disclosure provides a method of treating brain metastases in a human subject with a DLL3-positive cancer. The method comprises administering to the subject an anti-DLL3 agent comprising a first binding domain that binds to human DLL3 on the surface of a target cell and a second binding domain that binds to human CD3 on the surface of a T cell, wherein the anti-DLL3 agent is administered at a dose of from 3 mg to 200 mg once a week, once every two weeks, or once every three weeks.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Disclosed herein are compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C. The compounds have a general Formula (I): (I) or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C disorder.
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
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
Systems for packaging container(s) is disclosed. The system comprises a carton having a storage configuration where the carton is substantially flat and an assembled configuration. The carton comprises a bottom box, a lid coupled to the bottom box, a first flap extending from the first sidewall of the bottom box, and a second flap extending from the second sidewall of the bottom box. The first and second flaps define a set of cavities. The system also comprises an insert configured to be disposed within the bottom box of the carton. The insert has a storage configuration where the insert is substantially flat and an assembled configuration. The insert defines at least one cavity dimensioned to house at least one container.
B65D 5/02 - Rigid or semi-rigid containers of polygonal cross-section, e.g. boxes, cartons or trays, formed by folding or erecting one or more blanks made of paper by folding or erecting a single blank to form a tubular body with or without subsequent folding operations, or the addition of separate elements, to close the ends of the body
B65D 5/50 - Internal supporting or protecting elements for contents
A drug delivery device may include a housing having an opening, a drug storage container including a delivery member having an insertion end configured to extend at least partially through the opening during a delivery state, a plunger moveable toward a distal end of the drug storage container to expel a drug from the drug storage container, a guard moveably positioned adjacent to the opening, and a drive mechanism including a releaser member, a plunger guide, and a guard extension. The device may also include a container holder configured to support the drug storage container. The container holder may have a substantially tubular body portion and a pair of arms extending axially from a proximal end of the body portion, and the arms may be configured to abut a distal end surface of the guard extension to at least partially support the guard extension in at least a pre-delivery state.
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
91.
GLUCAGON RECEPTOR AGONISTS, CONJUGATED TO GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE ANTIBODIES
Disclosed herein are polypeptides having activity as agonists of a glucagon receptor ("GCGR"), molecules comprising such polypeptides and molecules comprising an antibody that specifically binds to a glucose-dependent insulinotropic polypeptide receptor ("GIPR"), pharmaceutical compositions comprising such polypeptides and molecules, and methods of using such polypeptides, molecules, and pharmaceutical compositions in weight management and the treatment of certain disorders such as obesity.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 3/08 - Drugs for disorders of the metabolism for glucose homeostasis
A61P 5/48 - Drugs for disorders of the endocrine system of the pancreatic hormones
92.
DUAL SELECTION EXPRESSION VECTOR SYSTEMS FOR MULTI-CHAIN BIOLOGICS
Dual selection expression vector systems in which one vector employs a metabolic selectable marker and the other employs an antibiotic resistance selectable marker, compositions and mammalian host cells comprising such expression vector systems, and methods of using the foregoing in the expression of recombinant proteins, including polypeptides comprising three or four unique polypeptide chains, are provided.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C12N 15/64 - General methods for preparing the vector, for introducing it into the cell or for selecting the vector-containing host
C12N 15/65 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression using markers
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
93.
REAL-TIME SAVING OF HIGH-RESOLUTION IMAGES ON COMMERCIAL AUTOMATED VISUAL INSPECTION (AVI) SYSTEMS
An automated visual inspection (AVI)-based method may include: generating, using an imaging unit, image data of a product; receiving, at a first image analysis hardware unit, the image data from a hardware image splitter; analyzing, using the first image analysis hardware unit, the image data for product defects using a first visual inspection analysis; generating, using the first image analysis hardware unit, first image processing metadata based on the first visual inspection analysis; receiving, at an image storage hardware unit, the image data from the hardware image splitter; storing, using the image storage hardware unit, the image data into a buffer; receiving, at an image storage hardware unit, the first image processing metadata; and/or associating, using the image storage hardware unit, the inspection metadata that includes the first image processing metadata with the image data.
The present invention relates to methods of modulating the charge variant profile of a recombinantly produced monoclonal antibody by altering bioreactor media hold durations. Methods of increasing product yield and titer by manipulating media hold durations are also described.
Disclosed herein are expression cassettes, expression vectors, dual vector systems, and mammalian host cells, including but not limited to Chinese hamster ovary (CHO) cells, comprising the foregoing, for the expression of certain antibody modalities, wherein each expression vector employs a promoter set optimized for the antibody modality. Also disclosed herein are methods of producing certain antibody modalities using these mammalian host cells.
Disclosed herein are expression systems for producing multi-specific antibodies having only one Fab or having two Fabs that are identical, host cells comprising such expression systems, including but not limited to Chinese hamster ovary (CHO) cells, and methods for producing multi- specific antibodies utilizing such expression systems.
The disclosure provides methods for analyzing two or more different therapeutic proteins co-formulated in a sample mixture. The methods involve intact mass analysis, peptide mapping, and a multi-attribute method (MAM) to detect, quantify, and monitor critical quality attributes (CQAs) of co-formulated therapeutic proteins, such as monoclonal antibodies.
A computer-implemented method for generating one or more modified amino acid sequences comprises obtaining, via one or more processors, one or more candidate amino acid sequences and characteristic data associated with the one or more candidate amino acid sequences; classifying, via the one or more processors, the one or more candidate amino acid sequences into a first set of high-viscous amino acid sequences and a second set of low-viscous amino acid sequences using a predictive model, the classifying comprising: calculating one or more viscosity predictions based on the one or more candidate amino acid sequences and the obtained characteristic data; and determining the first set of high-viscous amino acid sequences and the second set of low-viscous amino acid sequences based on the one or more viscosity predictions and a predetermined viscosity threshold, wherein the first set of high-viscous amino acid sequences comprises at least one candidate amino acid sequence; and generating, via the one or more processors, the one or more modified amino acid sequences based on the first set of high-viscous amino acid sequences using a generative model, wherein at least one of the one or more modified amino acid sequences has a viscosity prediction lower than the predetermined viscosity threshold.
An integrated bubble trap device for a working heart system includes a body having an internal cavity configured to be partially filled with a liquid, an inlet configured to be in fluid communication with a liquid reservoir, an outlet configured to connect to a left atrium of an excised heart of a test specimen, and a syringe port configured to connect the internal cavity of the body with a syringe. An aperture at the bottom of the body is configured to connect to a pressure sensor. The integrated bubble trap device may further include a catheter extension configured to connect the liquid reservoir to the inlet adapter of the integrated bubble trap device and an adjustable clamp to hold the liquid reservoir in a position. In a method of use, the integrated bubble trap device removes bubbles from a perfusion buffer.
The present disclosure, relates, in general, to methods of treating chronic obstructive pulmonary disease (COPD) using an antibody specific for thymic stromal lymphopoietin (TSLP).
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61P 11/00 - Drugs for disorders of the respiratory system
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