Abstract: The present disclosure relates to crystalline forms of 2-[(2S)-1-azabicyclo[2.2.2]oct-2-yl]-6-(3-methyl-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4(3H)-one hemihydrate (Compound 1) and/or tautomers thereof, wherein Compound 1 has the structure: (I)·0.5H2O; processes for preparing crystalline forms of Compound 1 and/or tautomers thereof; pharmaceutical compositions comprising the crystalline forms; methods of inhibiting a cell division cycle 7 in a mammal comprising administering the crystalline forms; and methods of treating a cell division cycle 7 mediated cancer in a mammal comprising administering the crystalline forms or a pharmaceutical composition comprising the crystalline forms.

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 both tumor target antigens (TTAs) as well as CD3, thus recruiting T cells expressing CD3 to the tumor, resulting in treatment.

Abstract: The present disclosure provides isolated, engineered, non-naturally occurring CB1 binding proteins, including anti-CB1 antibodies or antigen-binding fragment thereof. The CB1 binding proteins find utility in the treatment and diagnosis of CB1 mediated conditions, diseases and disorders.

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 both tumor target antigens (TTAs) as well as CD3, thus recruiting T cells expressing CD3 to the tumor, resulting in treatment.

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: The disclosure relates to antibodies that bind FcRn and methods of using these antibodies.

Abstract: The present invention provides a production method of a thienopyrimidine derivative or a salt thereof which has a gonadotropin releasing hormone (GnRH) antagonistic action with high quality in high yield. The present invention provides a method of producing a thienopyrimidine derivative, which comprises reacting 6-(4-aminophenyl)-1-(2,6-difluorobenzyl)-5-dimethylaminomethyl-3-(6-methoxypyridazin-3-yl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione or salt thereof, 1,1?-carbonyldiimidazole or a salt thereof and methoxyamine or a salt thereof, and the like.

Abstract: The present disclosure provides antibody drug conjugates comprising STING modulators. Also provided are compositions comprising the antibody drug conjugates. The compounds and compositions are useful for stimulating an immune response in a subject in need thereof.

Abstract: Provided herein are methods for purifying recombinant A Disintegrin-like and Metallopeptidase with Thrombospondin Type 1 Motif 13 (ADAMTS13) protein from a sample. The method comprises enriching for ADAMTS13 protein by chromatographically contacting the sample with hydroxyapatite under conditions that allow ADAMTS13 protein to appear in the eluate or supernatant from the hydroxylapatite. The methods may further comprise tandem chromatography with a mixed mode cation exchange/hydrophobic interaction resin that binds ADAMTS13 protein. Additional optional steps involve ultrafiltration/diafiltration, anion exchange chromatography, cation exchange chromatography, and viral inactivation. Also provided herein are methods for inactivating virus contaminants in protein samples, where the protein is immobilized on a support. Also provided herein are compositions of ADAMTS13 prepared according to said methods.

Abstract: Adeno-associated liquid and lyophilized pharmaceutical compositions are provided herein. In exemplary aspects, the pharmaceutical compositions comprise about 5 mM to about 25 mM L-histidine, about 0 mM to about 150 mM sodium chloride, about 0.001% (w/v) to about 0.01% (w/v) polysorbate 80 (PS80), and about 1% to about 10% (w/v) sucrose, trehalose, or combination thereof to AAV. In exemplary aspects, the pharmaceutical compositions further comprise glycine or mannitol. Methods of preparing a pharmaceutical composition comprising AAV, methods of treating a bleeding disorder in a subject, and methods of storing AAV compositions are also provided.

Abstract: Provided is a heterocyclic compound that can have an antagonistic action on an NMDA receptor containing the NR2B subunit, and is expected to be useful as a prophylactic or therapeutic agent for major depression, bipolar disorder, migraine, pain, peripheral symptoms of dementia and the like. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof.

Abstract: The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.

Abstract: Compounds that are mammalian metabolites of an agonist of G-protein-coupled receptor 1.39 (GPR139), intermediates used in the synthesis of such metabolites, pharmaceutical compositions comprising such metabolites, and the use of such metabolites as biomarkers and agents in the treatment of schizophrenia, for example, negative and/or cognitive symptoms of schizophrenia, disorders associated with social and cognitive dysfunction, as well as several other disorders related to modulated of GPR139.

Abstract: The present invention provides a heterocyclic compound having an antagonistic action on an NMDA receptor containing the NR2B subunit, and expected to be useful as an agent for the prophylaxis or treatment of major depression, bipolar disorder, migraine, pain, behavioral and psychological symptoms of dementia and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as described in the description, or a salt thereof.

Abstract: The present invention aims to provide a preparation expected to improve the bitter taste of an organic acid salt of vonoprazan and permit rapid dissolution of the organic acid salt of vonoprazan after administration. The present invention provides a preparation containing fine granules or granules containing (1) a core granule containing an organic acid salt of vonoprazan, (2) an intermediate layer containing the same organic acid as the organic acid forming the salt of vonoprazan in (1), or a salt thereof, and (3) a coating layer containing a water-insoluble polymer.

Abstract: The present invention provides a culture method capable of maturing an organoid through long-term culture, and suitable for producing a conformational organ. The culture method of the present invention is a method for culturing an organoid and/or cells constituting an organ immobilized in a chamber with a culture fluid perfused, and the culture fluid is perfused in such a manner as to generate a turbulent flow in the chamber.

Abstract: Provided herein are methods and compositions for treating a coronavirus disease, and particularly its complications, in a subject infected with a pathogenic coronavirus, such as a subject infected with a SARS-CoV-2 or suffering from one or more signs or symptoms of COVID-19. The composition comprises a therapeutically effective amount of an isolated or recombinant disintegrin and metalloproteinase with a thrombospondin type 1 motif (ADAMTS13) protein. The present disclosure further relates to methods for diagnosing a coagulopathy in subject infected with a coronavirus disease, particularly SARS-CoV-2, or suffering from one or more signs or symptoms of COVID-19. The method comprises testing for elevated levels of VWF, depressed levels of ADAMTS13, and the presence of UHMW VWF multimers. These factors, in combination, indicate the presence of a coagulopathy.

Abstract: This invention relates to ADAMTS13 variants and methods of administering ADAMTS13 variants to a treat a disease or condition associated with ADAMTS13 and VWF dysfunction.

Abstract: Provided in this disclosure are anti-CD38 binding domains, a composition comprising the anti-CD38 binding domains, nucleic acids encoding the anti-CD38 binding domains, and a method of using the anti-CD38 binding domains or the composition for treating multiple myeloma.

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 both 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 is B7H3.