Abstract: The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.

Abstract: The invention provides a composition of glucocerebrosidase, such as velaglucerase alfa, and isofagomine, in a molar ratio of at least about 1:2.5. Also provided is a use of the composition for treatment of a disorder related to a dysfunction in a GCase pathway. The disorder could be a lysosomal storage disease, such as Gaucher disease, Fabry disease, Pompe disease, a mucopolysaccharidoses, or multiple system atrophy. The disorder could also be a neurodegenerative disorder, such as Parkinson disease, Alzheimer's disease, or Lewy body dementia. The composition can have 0.5 to 5.0 mg/kg of glucocerebrosidase and isofagomine in at least about a 3-fold molar excess to the glucocerebrosidase. The composition can be administered intravenously or subcutaneously.

Abstract: The present invention provides means for producing a parathyroid gland organoid. A culture method of the present invention includes a cell population containing a parathyroid gland cell in a ratio of 50% or more, and a mesenchymal cell in a ratio of 10% or more; and a step of culturing the cell population.

Abstract: Disclosed herein are evacuated blood collection tubes comprising protease inhibitor cocktails in liquid form and uses thereof for assessing features associated with the contact system in a subject, including the endogenous level of contact system activation, the endogenous level of a drug that targets a component of contact system during treatment, and/or the immunogenicity of such a drug.

Abstract: A compound of formula (I), or a salt thereof that may have an antagonistic action against an NMDA receptor that includes an NR2B subunit and may be useful as a prophylactic or therapeutic agent for depression, bipolar disorder, migraine, pain, a symptom peripheral to dementia, or the like.

Abstract: The present invention provides a therapeutic agent for an immune/inflammatory disease comprising an anti-human TIGIT antibody, which activates a suppressive immune checkpoint molecule (TIGIT), as an active ingredient. Also, provided is an antibody having the following characteristics a) and b): a) the third CDR of heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 4 b) the third CDR of light chain variable region comprises the amino acid sequence of SEQ ID NO: 6.

Abstract: The invention relates to an affinity resin functionalized with small molecule inhibitors of glycoside-cleaving enzymes, e.g., ?-galactosidase A (?-Gal A), glucocerebrosidase (GCB), ?-galactosidase, and acid alpha-glucosidase (GAA), and a method for purifying glycoside-cleaving enzymes produced in a cell line using the small molecule inhibitor-functionalized affinity resin.

Abstract: Provided herein are methods and kits for analyzing a biological sample obtained from a subject having, suspected of having, or being at risk for a disease associated with the contact activation system.

Abstract: Systems and methods providing a clotting factor VIII dosing regimen are disclosed. The systems and methods include determining an estimated pharmacokinetic profile of a patient using a Bayesian model of pharmacokinetic profiles of sampled patients. The systems and methods can determine a first dosing regimen for a first dosing interval including (i) a first dosage and (ii) a first therapeutic plasma protein level in the patient varying over time based at least upon the estimated pharmacokinetic profile. The systems and methods can determine a second dosing regimen for a second dosing interval including (i) a second dosage and (ii) a second therapeutic plasma protein level in the patient varying over time. The estimated pharmacokinetic profile can be adjusted based on previous patient treatments. Further, a user can select which days a dosage is to be applied such that the protein level does not fall below a target trough.

Abstract: A device is provided for pooling a fluid from a container unit having at least one container, and includes an inlet port having at least one inlet channel configured for receiving the fluid or ambient air, and an outlet port having at least one outlet channel configured for delivering the fluid to an attachment. Both inlet and outlet ports are disposed on the device. A cavity is provided for accommodating insertion of the container unit for pooling the fluid from the at least one container. At least one spike is disposed in the cavity and configured for puncturing a stopper of the at least one container when the container unit transitions from an upper position to a lower position.

Abstract: Plunger rod stops attach to existing syringes to limit the range of motion of the plunger, thereby to precisely control the amount of liquid that can be expelled from the syringe when the plunger rod stop is in place. In some embodiments, plunger rod stop devices generally include a body configured to attach to the plunger, and a stand-off extending from the body, configured to contact the finger flange when the plunger is depressed. In other embodiments, the plunger rod stop attaches to the finger flange or other fixed component of the syringe and the stand-off is configured to contact the plunger or plunger rod. Methods of the invention involve using the devices to interfere with the range of motion of the plunger, then reconfiguring or removing the device to allow the plunger to be moved a predetermined length, which corresponds to a precise dosage amount.

Abstract: The present application provides a semi-permeable hydrogel composition comprising an alginate matrix that is covalently crosslinked in its periphery to a multi-armed water soluble polymer, along with related methods and uses thereof.

Abstract: The invention relates to parathyroid hormone (PTH) variants and pharmaceutical compositions comprising same. The invention further relates to PTH compositions with improved serum half-life and peak-trough ratios, and methods of controlling serum calcium levels with the PTH variants and compositions of the invention. The invention further relates to methods of treating hypoparathyroidism and/or hypocalcemia due to hypoparathyroidism with the PTH variants and compositions of the invention.

Abstract: The invention relates to COnditional Bispecific Redirected Activation constructs, or COBRAs, that are administered in an active pro-drug format. Upon exposure to tumor proteases, the constructs are cleaved and activated, such that they can bind one or more tumor target antigens (TTAs) as well as CD3, thus recruiting T cells expressing CD3 to the tumor, resulting in treatment. In some embodiments, the tumor target antigen includes B7H3, CA9 (CAIX), EGFR, EpCAM, FOLR1, HER2, LyPD3, and/or Trop2.

Abstract: Provided are compositions and methods for preparing and identifying antibodies having CDR3s that vary in sequence and in length from very short to very long which in certain embodiments may bind to a carbohydrate moiety or the active site of an enzyme. Libraries coding for antibodies with the CDR3s are also provided. The libraries can be provided by modifying a pre-existing nucleic acid library.

Abstract: The present invention provides, among other things, compositions and methods for prophylaxis and treatment of autoimmune disease. The present invention is based, in part, on the surprising discovery that a human interleukin-2 mutein activates proliferation of regulatory T cells. In one aspect, the present invention provides compositions and methods for proliferation of regulatory T cells. In another aspect, a human interleukin-2 (IL-2) mutein comprising an amino acid sequence that is at least 90% identical to the wild type IL-2 protein is described, wherein the IL-2 mutein has at least one amino acid substitution selected from a group consisting of T111H, T37Y, E15T, M23L, P34F, E68F and E62A.

Abstract: Plasma kallikrein binding proteins and methods of using such proteins are described.

Abstract: Methods for treating uterine fibroids, endometriosis, adenomyosis, or heavy menstrual bleeding in a subject, which include administering to the subject from 10 mg to 60 mg per day of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N?-methoxyurea, and from 0.01 mg to 5 mg per day of a hormone replacement medicament. The present disclosure has methods for reducing menstrual bleeding in a subject, reducing bone mineral density loss in a subject caused by administering a GnRH antagonist to the subject, suppressing sex hormones in a subject, reducing vasomotor symptoms or hot flashes in a subject, and reducing symptoms of decreased libido in a subject having uterine fibroids, endometriosis, or adenomyosis.