Abstract: The present application provides a upadacitinib salt compound and a preparation method therefor. The salt involved in the method in the present application has an easy preparation operation, a cheap raw material easy to get, and a good purification effect on upadacitinib, and is beneficial to industrial production.

Abstract: The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis), kits, methods of synthesis, and products-by-process.

Abstract: A benzofuropyrimidine derivative or benzothienopyrimidine derivative that is a novel organic compound is provided. An organic compound represented by General Formula (G1) below. Q represents oxygen or sulfur. Ar1, Ar2, Ar3, and Ar4 each independently represent an aromatic hydrocarbon ring, and the number of carbon atoms included in the aromatic hydrocarbon ring is 6 to 25. m and n are each 0 or 1. A is a group having 12 to 100 carbon atoms in total and includes one or more of a benzene ring, a naphthalene ring, a fluorene ring, a phenanthrene ring, a triphenylene ring, a heteroaromatic ring including a dibenzothiophene ring, a heteroaromatic ring including a dibenzofuran ring, a heteroaromatic ring including a carbazole ring, a benzimidazole ring, and a triphenylamine structure.

Abstract: The subject of the present invention are water-soluble derivatives of camptothecin, their synthesis and use. These compounds exhibit preferable biological properties for use in anti-neoplasm therapy.

Abstract: The present application relates to an anti-tumor compound and a preparation method and use thereof, and in particular to a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, and a preparation method and use thereof.

Abstract: A method for preparing dihydroartemisinin bulk drug in single process comprises: S1. dissolving artemisinin in aprotic solvent; S2. adding phase transfer catalyst and reducing agent in sequence to cause a reduction reaction with artemisinin; S3. adjusting the pH of the reaction system obtained in step S2 to 5-7 with acid solution, adding water and stirring, separating the liquids, extracting the aqueous phase obtained by the separation with the same aprotic solvent as in step S1, combining the organic phase obtained by extraction and separation, washing with water, and drying, obtaining dried organic phase; S4. placing the dried organic phase obtained in step S3 in a crystallization device that has the functions of crystallization-press filtration-drying, and then the crystals are precipitated, concentrated, press-filtered, and dried to obtain the refined dihydroartemisinin.

Abstract: The present disclosure relates to compounds of Formula I: and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, useful in the treatment of treating viral infections, for example, coronaviridae infections.

Abstract: To provide a fused thiophene molecule having further sufficiently high hole mobility. Disclosed is a fused thiophene molecule that has seven aromatic rings containing three thiophene rings in one molecule and in which the seven aromatic rings have one or two naphthalene structures. And, semiconductor devices including a layer using the fused thiophene molecule are disclosed.

Abstract: A system and method for concurrently wagering on multiple past events such as sports events that may include retrieving data about multiple events that occurred in the past that included multiple participants. The data may include information about the participants as well as pre-event rankings, and final or post-event rankings ordering the results with respect to other participants in the same event. A user may adjust the pre-event rankings or accept them as—is. The user's rankings for the participants of the events may be submitted, and a prize calculated based on the difference between the predicted rankings submitted by the user, and the final rankings of the participants based on actual past events. Various terminals, terminal configurations, and user interface aspects are also disclosed.

Abstract: Influenza is an acute infectious respiratory disease caused by the influenza virus. It is part of the group of Acute Respiratory Viral Infections (ARVI). It occasionally spreads in the form of epidemics and pandemics. Currently, more than 2000 variants of the influenza virus differing in the antigen spectrum have been identified. Given that influenza is a serious threat to public health (worldwide, these annual epidemics lead to 3-5 million cases of severe illness, millions of hospitalizations, and up to 650,000 deaths), it seems appropriate to search for new anti-influenza drugs with improved characteristics.

Abstract: The disclosure relates to compounds of formula (I) and pharmaceutically acceptable salts, and compositions thereof, wherein the substituents are as defined herein. Also provided are methods of making compounds of formula (I), and methods involving the compounds or compositions for treating disorders and diseases described herein.

Abstract: Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

Abstract: The present disclosure provides bifunctional compounds as HPK1 degraders via ubiquitin proteasome pathway, and method for treating diseases modulated by HPK1.

Abstract: Metal complexes of formula (I) are described: [M(L1)x(L2)y(hydra)z]n??formula (I) wherein: M=metal atom having an atomic number selected from the ranges a) through c): a) 12, 21 to 34, with the exception of 30, b) 39 to 52, with the exception of 48, c) 71 to 83, with the exception of 80, L1=neutral or anionic ligand, with x=0 or 1, L2=neutral or anionic ligand, with y=0 or 1, (hydra)=acetone dimethylhydrazone monoanion, with z=1, 2, or 3, n=1 or 2, and the total charge of the complex is 0.

Abstract: A 4,4?-divinylazoarylene-bridged diruthenium complex bearing two Ru(CO)(L-?2[N,O]?)(PiPr3)2 entities, its synthesis, and its use as an catalyst in inorganic processes.

Abstract: Porphyrins and porphyrin derivatives of General Formulas I-V are suitable for use as donor-type materials for photovoltaic cells, absorbers for dye-sensitized solar cells, emitters for red and near infra-red organic light-emitting diodes (OLEDs), absorbers and re-emitters for organic concentrators (e.g., large area organic film for collection of sunlight) for small-size and high efficiency inorganic photovoltaics, and absorbers for hydrogeneration.

Abstract: The present invention provides a surface treatment liquid for metal having a sufficiently high film-forming property. The present invention relates to a surface treatment liquid for metal comprising an azole silane coupling agent, the surface treatment liquid further comprises (A) an organic acid ion having one to three acidic groups in one molecule; (B) an inorganic acid (or mineral acid) ion; (C) an alkali metal ion and/or an ammonium ion; and (D) a copper ion.

Abstract: Provided are crystals of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate, compositions comprising the same, and methods of making and using such crystals.

Abstract: The present disclosure is concerned with compounds, compositions, and methods for synthesizing sphingosines and glycolipids including glycosphingolipids, such as but not limited to lactosyl sphingosine.

Abstract: In various aspects, the present disclosure pertains to sorbents for isolating at least one target protein from a liquid sample, the sorbents comprising a solid support comprising attached at least one attached high affinity reagent with an affinity for the at least one target protein. Other aspects of the present disclosure include kit that contain such sorbents and methods of treating samples using the same.

Abstract: The invention relates to an isolated non-naturally occurring protein comprising the amino acid sequence as set forth in SEQ ID NO: 1, and wherein the amino acid in position 8, 47, 209 and/or 354 is substituted by any amino acid different from the amino acid indicated at that position in said sequence SEQ ID NO: 1.

Abstract: The present disclosure provides AAV capsid proteins comprising a modification in the amino acid sequence and virus vectors comprising the modified AAV capsid protein. The disclosure also provides methods of administering the virus vectors and virus capsids of the disclosure to a cell or to a subject in vivo.

Abstract: The disclosure provides a recombinant cell capable of producing a steviol glycoside, wherein the cell comprises a nucleic acid coding for a variant of a parent polypeptide, wherein the variant has steviol glycoside transport mediating activity, wherein the variant comprises an amino acid sequence which, when aligned with the amino acid sequence of the parent polypeptide, comprises at least one modification of the amino acid residue corresponding to any of the amino acids in the amino acid sequence of the parent polypeptide, wherein the variant has an improved ability to produce rebaudioside M and optionally other steviol glycosides extracellularly if compared with the parent polypeptide when measured under the same conditions.

Abstract: The present disclosure provides a fusion protein useful for treating a non-nuclear organelle associated disorder, such as a genetic disorder, e.g., Friedrich's Ataxia. The fusion protein may comprise a protein of interest to be delivered to a non-nuclear organelle; an organelle targeting sequence (OTS); a cell penetrating peptide (CPP); and a target enhancing sequence (TES); wherein the CPP is capable of interference with delivery of the protein of interest to the non-nuclear organelle; and wherein the TES prevents said interference by the CPP. The fusion protein may also comprise a protein of interest to be delivered to a non-nuclear organelle; a CPP and a TES. The present disclosure also provides methods for treating a non-nuclear organelle associated disorder by administering the fusion protein to a subject in need thereof.

Abstract: The present application relates to anti-mesothelin constructs (such as antimesothelin antibodies, cytokine fusion proteins that comprise the anti-mesothelin constructs), methods of preparing the anti-mesothelin constructs and methods of using the constructs (e.g., methods of treating a disease or condition). The present application also relates to a combination therapy for treating cancer that comprises administering anti-mesothelin agent and a cytokine (such as IL-21 or IL-15). Combination therapy may further comprises administration of an anti-Her2 agent.

Abstract: Provided are various embodiments relating to compositions and methods for treating vascular disease, including core NOX1 promoters and variants thereof for regulating expression of transgenes in response to vascular pathology and allowing for increased transgene loading capacity. Also provided are variant FOXP polypeptides having a zinc finger and leucine zipper region of a different FOXP polypeptide. Further provided are vectors comprising the core NOX1 promoters and/or a coding sequence for variant FOXP polypeptides described herein and optionally coding sequence(s) for one or more additional therapeutic polypeptide(s), such as IL10, for treating inflammation-associated diseases, such as vascular disease. Also provided is a screening model for testing therapeutic agents capable of treating established and ongoing atherosclerotic pathology.

Abstract: The present disclosure relates to IL2 agonists with improved therapeutic profiles.

Abstract: Provided herein, inter alia, are human interleukin-2 (IL-2) muteins or variants thereof. In particular, provided herein are IL-2 muteins that have a decreased binding capacity for IL-2R?. Such IL-2 muteins are useful, for example, as IL-2 partial agonist in applications where reduction or inhibition of one or more IL-2 and/or IL-15 functions is useful (e.g., in the treatment of autoimmune diseases or conditions). Also provided are nucleic acids encoding such IL-2 muteins, methods of making such IL-2 muteins, pharmaceutical compositions that include such IL-2 muteins and methods of treatment using such pharmaceutical compositions.

Abstract: Provided herein are activatable cytokine constructs that include: (a) a first monomer construct comprising a first mature cytokine protein (CP1), a first cleavable moiety (CM1), and a first dimerization domain (DD1), wherein the CM1 is positioned between the CP1 and the DD1; and (b) a second monomer construct comprising a second mature cytokine protein (CP2), a second cleavable moiety (CM2), and a second dimerization domain (DD2), where the CM2 is positioned between the CP2 and the DD2, where: the CM1 and the CM2 function as a substrate for a protease; the DD1 and the DD2 bind each other; and where the ACC is characterized by a reduction in at least one activity of the CP1 and/or CP2 as compared to a control level of the at least one activity of the CP1 and/or CP2.

Abstract: A system for selecting an immunogenic peptide composition comprising a processor and a memory storing processor-executable instructions that, when executed by the processor, cause the processor to create a first peptide set by selecting a plurality of base peptides, wherein at least one peptide of the plurality of base peptides is associated with a disease, create a second peptide set by adding to the first peptide set a modified peptide, wherein the modified peptide comprises a substitution of at least one residue of a base peptide selected from the plurality of base peptides, and create a third peptide set by selecting a subset of the second peptide set, wherein the selected subset of the second peptide set has a predicted vaccine performance, wherein the predicted vaccine performance has a population coverage above a predetermined threshold, and wherein the subset comprises at least one peptide of the second peptide set.

Abstract: A method for administration of an IgG preparation by an intradermal (ID) route to a subject includes loading with a volume of the IgG preparation an ID delivery device including needles, applying the device to a skin delivery site, using the device to allow dermal penetration of the needles, delivering the volume of the IgG preparation at the skin delivery site, and removing the injection delivery device. The method can be used in the treatment of a disease, such as an immunodeficiency.

Abstract: A method of isolating an antibody is disclosed. The method comprises contacting a hydrophobic chelator, a non-ionic detergent and metal ions so as to generate an aggregate comprising the hydrophobic chelator, the detergent and the metal ions; and contacting the aggregate with a medium comprising the antibody under conditions that allow partitioning of the antibody into the aggregate. Kits for isolating the antibody are also disclosed.

Abstract: A large and highly diverse nanobody library was constructed and screened against multiple variants of SARS-COV-2 to find nanobodies with high sensitivity and specificity for the variants. Four rounds of positive selection against a panel of six diverse SARS-COV-2 variant RBDs was performed with our high-diversity. At least 59 of these nanobodies were found to work well against Alpha, Beta, Gamma, Delta, Kappa, Lambda and Mu with some overlap efficacy against other variants. These nanobodies have efficacy as stand-alone nanobodies and as a construct comprising nanobodies linked to the human IgG1 constant fragment (Fc) (nanobody-hFc constructions or nb-hFcs) to make enhanced humanized sdAbs with all the attributes of nanobodies with improved half-life and optimized effector functions. Several promising nanobodies that neutralize the original SARS-COV-2 and several of its variants have been identified, including Delta, with high efficacy. In particular, a subset of these nanobodies bind to the Omicron RBD.

Abstract: The present disclosure relates to a PROX1 (Prospero homeobox protein 1) protein binding molecule. More specifically, the binding molecule of the present disclosure relates to a binding molecule having excellent binding ability to the PROX1 protein and having an excellent neutralizing effect on the PROX1 protein, and it is very useful for diagnosis, prevention or treatment of retinal neurodegenerative diseases.

Abstract: The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to Plasmodium falciparum reticulocyte binding protein homologue 5 (PfRH5), compositions thereof and methods of making such antibodies, fragments and compositions. Method and compositions for treating, preventing or diagnosing Plasmodium falciparum infection and malaria are also part of the present invention.

Abstract: The present invention provides an antibody of the class IgG4 comprising at least one heavy chain which comprises a CH1 domain and a hinge region, wherein in each heavy chain: a. the inter-chain cysteine at position 127, numbered according to the Kabat numbering system, in the CH1 domain is substituted with another amino acid; and b. one or more of the amino acids positioned in the upper hinge region is substituted with cysteine.

Abstract: Antibody molecules that specifically bind to APRIL are disclosed. The antibody molecules can be used to treat, prevent, and/or diagnose disorders, such as IgA nephropathy.

Abstract: A method of treating active Systemic Lupus Erythematosus (SLE) in a patient by administering a clinically proven safe and clinically proven effective amount of an anti-IL-12/IL-23p40 antibody or an anti-IL-23 antibody, e.g., the anti-IL-12/IL-23p40 antibody ustekinumab, wherein the patient achieves a significant improvement in disease activity.

Abstract: The present invention identifies the influence of the TGF?/Smad3/SMO molecular mechanism in cancer cells and elucidates that a high expression level of SMO is associated with the overall survival rate of cancer patients, demonstrating that SMO is a potential prognostic marker for cancer. The present invention relates to a specific epitope of SMO as an antigen and an antibody or a fragment thereof recognizing and binding specifically to the epitope. Therefore, the antibody of the present invention is expected to be useful as a therapeutic agent for SMO-related cancers.

Abstract: A humanized anti-neurotensin receptor 1 (NTSR1) antibody or an antigen-binding fragment thereof. Also, a method for treating, prophylactic treating and/or preventing diseases and/or disorders caused by or related to NTSR1 activity and/or signaling, and a method or kit for detecting NTSR1 in a sample.

Abstract: The present invention provides compositions and methods for reducing inflammation. In one aspect, the present invention provides a protein inhibitor comprising an ectodomain of at least one TREM or TREML protein. The invention also relates to inhibiting the interaction between a TREM or TREML protein and mitochondria released or derived from necroptotic cells; or between a TREM or TREML protein and cardiolipin.

Abstract: In the methods of the invention, an agent that increases phagocytosis and/or efferocytosis of cellular components of coronary plaque is administered to the subject in a dose and for a period of time effective to stabilize, prevent or reduce aneurysm disease in the individual.

Abstract: The present invention relates to an antibody or an antigen-binding fragment thereof specifically binding to CD66c which is expressed in myeloid-derived suppressor cell (MDSC) and a use thereof, and specifically to an antibody or an antigen-binding fragment thereof specifically binding to CD66c, a pharmaceutical composition or a diagnosing composition including the same. The anti-CD66c antibody of the present invention can be used usefully for the treatment of various diseases by targeting MDSC which can induce the immunosuppression.

Abstract: The invention provides antibodies specifically binding to c-Kit and methods of using such antibodies in stem cell replacement and treatment of cancer.

Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Abstract: Provided herein are method of treating cancer using bispecific antigen-binding molecules that bind to Mucin 16 (MUC16) and CD3. According to certain embodiments, the antibodies useful herein bind human MUC16 with high affinity and bind CD3 to induce human T cell proliferation. According to certain embodiments, bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human MUC16 are particularly useful herein. In certain embodiments, the bispecific antigen-binding molecules in combination with an anti-4-1BB agonist are capable of inhibiting the growth of tumors expressing MUC16, for example, ovarian tumors.

Abstract: A bispecific antibody which is capable of specifically binding to PD-1 and CD3 is disclosed. The bispecific antibody is suitable for preventing, suppressing symptom progression or recurrence of, and/or treating autoimmune diseases. Also disclosed is a formulation which can reduce occurrence of adverse infusion reactions or adverse reaction called cytokine release syndrome. The bispecific antibody has the feature to allow interaction between PD-1 and PD-L1 as its ligand, contributes enhancement or duration of its effects.

Abstract: The present application relates to antibodies specifically binding to the V-domain immunoglobulin-containing suppressor of T-cell activation (VISTA) at acidic pH and their use in cancer treatment. In some embodiments, the antibodies bind specifically to human VISTA at acidic pH, but do not significantly bind to human VISTA at neutral or physiological pH.

Abstract: The present invention relates, in part, to agents that bind Clec9A and their use as diagnostic and therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the Clec9A binding agents and their use in the treatment of various diseases.

Abstract: The present invention relates to methods for promoting T cells response. The inventors examined the expression and function of CLEC-1 in human DCs and demonstrated for the first time a cell-surface expression. They investigated its functional role following triggering on orchestration of T-cell responses. The inventors showed in vitro and in vivo with CLEC-1 deficient rats and rat CLEC-1 Fc fusion protein that disruption of CLEC-1 signalling enhances in vitro Th17 activation and in vivo enhances T cell priming and Th17 and Th1 activation. In particular, the present invention relates to CLEC-1 antagonists for promoting T cells response in a subject in need thereof.