Abstract: The present invention pertains to methods of producing polypeptide of interest in cell cultures lacking glutamine. The present invention further pertains to a method of producing a protein of interest in a large scale cell culture, comprising supplementing the cell culture with nucleic acid synthesis precursors and/or corticosteroids.

Abstract: Provided herein is a method of monitoring the change of the alpha-4 integrin activities in an individual by correlating with the soluble vascular cell adhesion molecule (sVCAM) and/or soluble mucosal addressin cell adhesion molecule (sMAdCAM) levels. Particularly, this method can be used, for example, to evaluate the pharmacokinetics and pharmacodynamics (PK/PD) of an alpha-4 integrin inhibitor used to treat a disease associated with pathological or chronic inflammation.

Abstract: This disclosure relates to compounds of formula (I?), or pharmaceutically acceptable salts thereof, in which all of the variables are as defined in the application. The compounds of the present disclosure are capable of inhibiting the activity of tyrosine kinase 2 (TYK2). The disclosure further provides methods of preparing the compounds of the disclosure, and methods for their therapeutic use.

Abstract: Disclosed herein are methods for preparing compositions containing oligonucleotides. Methods of this disclosure involve subjecting an aqueous solution of a oligonucleotide to ultrafiltration/diafiltration (UF/DF) in order to form a retentate containing the oligonucleotide, where the ultrafiltration/diafiltration (UF/DF) is carried out using an aqueous buffer solution containing one or more salts. Also disclosed herein are oligonucleotide-containing compositions obtained by these methods.

Abstract: A device or system for delivering fluid to or removing fluid from a CSF-containing space of a brain and for recording electrical activity from white or grey matter in the brain includes a catheter including a proximal end, a distal end portion, a first lumen extending from the proximal end to the distal end portion, and one or more electrodes positioned relative to the catheter a distance from a distal end of the catheter, such that the one or more electrodes would be placed in contact with white or grey matter of the brain if the distal end of the catheter were positioned in the CSF-containing space. The catheter may include the electrodes or a lead adjacent the catheter may include the electrodes.

Abstract: A burr hole device is configured to receive a catheter and a cable of a sheath. The sheath is configured to receive a portion of the catheter and has an electrode. When the catheter and sheath are implanted with the burr hole device, the catheter and electrode of the sheath are implanted in a brain. Systems and apparatuses may include the burr hole device and/or a cranial port device, the catheter, and the sheath.

Abstract: Featured are biomarkers for progressive multifocal leukoencephalopathy (PML). Also provided are methods for reducing the occurrence or severity of PML during immunomodulator therapy or identification of PML in an immunocompromised subject.

Abstract: Natalizumab is a safe and efficacious treatment for inflammatory and autoimmune diseases, such as multiple sclerosis, Crohn's Disease, and rheumatoid arthritis. Chain swapping between natalizumab and IgG4 molecules acts to reduce the level of bivalent natalizumab present following administration of natalizumab, and thus to lower the activity of natalizumab in the patient. Differences in IgG4 levels across patients or within a single patient across time may change the pharmacokinetic profile of natalizumab. Patients with lower levels of IgG4 may experience higher nadir levels of natalizumab during a dosing period. Monitoring IgG4 and/or bivalent natalizumab levels, and determining a dose or dosage period based on the monitoring may improve the safety and/or efficacy of natalizumab therapy.

Abstract: A burr hole device is configured to receive a catheter and a cable of a sheath. The sheath is configured to receive a portion of the catheter and has an electrode. When the catheter and sheath are implanted with the burr hole device, the catheter and electrode of the sheath are implanted in a brain. Systems and apparatuses may include the burr hole device and/or a cranial port device, the catheter, and the sheath.

Abstract: The present disclosure provides compounds of Formula I, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof. The provided compounds may be glycogen synthase kinase 3 (GSK3) inhibitors. The present disclosure also provides pharmaceutical compositions, combination therapies, and kits comprising the compounds, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, or prodrugs thereof, and methods of treating or preventing diseases and disorders associated with GSK3.

Abstract: Provided are compounds of Formula (I?) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R8, R9, R11A, R11B, R12, Ri, Rii, A1, A2, Q1, Q2, Q3, X, W, and n are as defined herein; pharmaceutical compositions comprising said compounds or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable excipients; and methods of treating a disorder responsive to inhibition of Bruton's tyrosine kinase using said compounds, or pharmaceutically acceptable salts thereof, or said pharmaceutical compositions.

Abstract: Provided are compounds of Formula (I) or pharmaceutically acceptable salts thereof, wherein ring A, R3, R4, R5, R6, A1, B1, B2, Q1 and Q2 are as defined herein; and methods for their use and production.

Abstract: Described herein are compounds represented by formula (I) or formula (Ia) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising the same and methods of preparing and using the same. The variables R1, R2, R3, R4, R5, R6, Y1, Y2, D, E, G1, G2, n and p are as defined herein.

Abstract: A system includes a first port comprising a first inlet, a first outlet, a first fluid pathway extending from the first inlet to the first outlet, a second inlet, a second outlet, and a second fluid pathway extending from the second inlet to the second outlet. The system further includes one or more CSF catheters having a first lumen, a first distal opening in fluid communication with the first lumen, a second lumen, and a second distal opening in fluid communication with the second lumen. The one or more CSF catheters are, or are configured to be, operatively coupled with the first implantable device such that the first lumen is in fluid communication with the first fluid pathway and the second lumen is in fluid communication with the second fluid pathway. At least the first distal opening is configured to be placed in the CSF-containing space. The system further includes a second port having a third inlet, a third outlet, and a third fluid pathway extending from the third inlet to the third outlet.

Abstract: The invention provides a composition comprising an anti-tumor necrosis factor (TNF)-alpha polypeptide, wherein the composition produces a reduced level of immunogenicity when administered to a subject, as well as a treatment method involving the administration of the composition.

Abstract: Described herein are compounds represented by formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising the same and methods of preparing and using the same. The variables Ar, X, R1, R3, R4, Y1, Y2, n and p are as defined herein.

Abstract: Aspect of the disclosure relate to methods of assessing a bioreactor culture that involve determining a culture parameter of the manufacturing-scale bioreactor culture using a model that relates a Raman spectrum to the culture parameter. Related bioreactor system are also provided.

Abstract: Methods of improving the efficiency of production of a protein product of interest in mammalian cell culture are presented. In particular, the methods result in an increase in the quantity of a protein product produced, or decreases protein product production time in a manufacturing-scale bioreactor cell culture. The disclosed methods comprise: (a) culturing the N-1 bioreactor culture to high viable cell densities; and (b) seeding the production bioreactor culture at high viable cell seeding densities.

Abstract: The present disclosure provides compounds of Formula (I), and salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be useful for inhibiting kinases, e.g., glycogen synthase kinase 3 (GSK3). The provided compounds may be able to selectively inhibit GSK3a, as compared to GSK3P and/or other kinases. The present disclosure further provides pharmaceutical compositions, kits, and methods of use, each of which involve the compounds. The compounds, pharmaceutical compositions, and kits may be useful for treating diseases associated with aberrant activity of GSK3a (e.g., Fragile X syndrome, attention deficit hyperactivity disorder (ADHD), childhood seizure, intellectual disability, diabetes, acute myeloid leukemia (AML), autism, and psychiatric disorder).

Abstract: In some embodiments, a device may include an intraventricular access device and an infusion device. The intraventricular access device may include more than one catheter and a container. In some embodiments, the catheter may include an aspiration lumen and an infusion lumen. A distal end of the intraventricular portion of the catheter may be positionable, during use, in a subject's brain fluid. In some embodiments, the container may be coupled to a proximal end of the aspiration lumen. The proximal end of the aspiration lumen may be in fluid communication with the container. The proximal end of the infusion lumen may be in communication with an infusion pump. In some embodiments, the device inhibits cross contamination between a first fluid in the aspiration lumen and a second fluid in the infusion lumen.