Abstract: Highly efficient methods are provided for preparing key intermediates in the synthesis of Compound (I), which are broadly applicable and can provide selected components having a variety of substituents groups.

Abstract: This disclosure provides protein separation techniques using detergents that have alkyl chains longer than 12 carbon atoms, which improves protein separation during electrophoresis.

Abstract: The present invention provides antibodies, or antigen-binding fragment thereof, which specifically bind to tumor necrosis factor (TNF)-like ligand (TL1A). The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and therapeutic methods for use of these antibodies for the treatment and/or prevention of TL1A mediated diseases, disorders or conditions.

Abstract: Provided are novel antibodies and antigen-binding fragments thereof that bind interleukin-18 receptor beta (IL-18R?), along with conjugates thereof, nucleic acids encoding the same, compositions comprising the same, and methods of producing and using the same, including in the treatment of various diseases and conditions, such as inflammatory bowel disease, and other immune-mediated diseases, autoimmune diseases, inflammatory diseases, cancers, and infectious diseases.

Abstract: The present invention provide novel immunofiber compositions for protein or peptide purification and simple and cost-efficient methods and systems using these compositions. In some embodiments, the immunofibers comprise a customized Z-33 peptide derived from Staphylococcus aureus Protein A which is used to construct immuno-amphiphile molecules that assemble into immunofibers in aqueous solution with bioactive epitopes on the surface and have peptide or protein binding ability.

Abstract: Provided herein are system, apparatus, device, method, and/or computer program product embodiments, and/or combinations and sub-combinations thereof, for classifying a document using CNN and BiLSTM.

Abstract: In some aspects, the present disclosure is directed to a method of treating a tumor in a subject in need thereof comprising administering a KRAS inhibitor and a regulatory T cell (Treg)-depleting agent to the subject. In some aspects, the present disclosure is further directed to methods of reducing the number of Treg cells (Tregs) in a tumor environment (TME) in a subject who receives a therapy with a KRAS inhibitor comprising administering a Treg-depleting agent to the subject. In some aspects, the present disclosure is further directed to methods of treating a tumor in a subject who is identified as having an increased number of Tregs in a TME, or as having a spatial cellular community comprising Tregs in a TME.

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 disclosure provides pharmaceutical compositions comprising an antibody and at least two antioxidants. In some aspects, pharmaceutical composition is formulated for subcutaneous delivery. In some aspects, the pharmaceutical composition further comprises an endoglycosidase hydrolase enzyme. Other aspects of the present disclosure are directed to methods of subcutaneously delivering the pharmaceutical composition.

Abstract: A method includes receiving natural language input text characterizing clinical data for a patient. The method also includes receiving a prompt composition that includes adjudication rules for performing lines of therapy adjudication and an instruction parameter that specifies a task for a LLM to synthesize a group of multiple synthetic experts that each use the adjudication rules to perform chain-of-thought reasoning for making lines of therapy (LoT) adjudication decisions. The method also includes structuring an adjudication prompt by concatenating the prompt composition to the natural language input text, processing, using the LLM, the adjudication prompt to cause the LLM to synthesize the group of multiple synthetic experts and generate a respective group answer. The method also includes determining a final answer based on the respective group answer generated from the group of multiple synthetic experts.

Abstract: Disclosed are compounds of Formula (I): or stereoisomers, tautomers, or salts thereof, wherein each R is independently H or D. Also disclosed are methods of using such compounds to decrease the levels of IKZF1-4 proteins; and pharmaceutical compositions comprising the compound. The compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.

Abstract: The present disclosure provide novel methods of large-scale production of recombinant proteins, e.g., therapeutic proteins such as antibodies, comprising concentrating an eukaryotic cell culture to a high density and transiently transfecting the eukaryotic cells with a polynucleotide encoding the recombinant protein using electroporation, e.g., flow electroporation. In some aspects, the culture is performed under perfusion conditions using, e.g., a tangential flow filtration method such as alternating tangential flow filtration. The proteins obtained using the disclosed methods are comparable to those produced using stable transfection. The methods disclosed herein can be used, for example, to accelerate therapeutic agent development, to reduce host cell toxicity, or for individualized therapeutics such as small scale manufacturing of treatments for rare or orphan diseases.

Abstract: The present disclosure relates to the use of host cell protein biomarkers to assess disulfide bond reduction in compositions comprising a protein of interest. In some embodiments, the disclosure relates to methods of predicting the occurrence of disulfide bond reduction or low molecular weight protein species in compositions comprising a protein of interest, wherein the expression or activity level of at least one host cell protein is measured and provides a benchmark value associated with the occurrence of disulfide bond reduction or low molecular weight species of said protein of interest. In some embodiments, the disclosure relates to methods of producing a protein of interest, wherein host cells capable of producing the protein of interest are cultured, the expression or activity level of at least one host cell protein is measured, and downstream isolation of the protein of interest is informed by the host cell protein measurements.

Abstract: Disclosed herein are fusion proteins comprising: (a) a first polypeptide comprising Interleukin-2 (IL2); and (b) a second polypeptide, fused in frame to the first polypeptide, wherein the second polypeptide comprises an extracellular domain of Interleukin-2 Receptor alpha (IL2R?), wherein IL2 or IL2R? comprises at least one fewer glycosylation site compared to native IL2 or native IL2R?. Methods of production and methods of therapeutic use of the fusion proteins are also disclosed.

Abstract: Disclosed are compounds of Formulas (I): (Formulas (I)) or a salt thereof, wherein X, Y, Q, G, R1, and R5a are defined herein. Also disclosed are methods of using such compounds as inhibitors of TLR9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing fibrotic diseases.

Abstract: Disclosed are compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, when Q is: (i) halo, cyano, hydroxyl, NRxRx, C(O)OH, C(O)NH2, C1-6 alkyl substituted with zero to 6 R1a, or P(O)R1cR1c, or (ii) L R1; and A, X1, X2, X3, X4, Z1, Z2, R1, R1a, R1c, R2, R3a, R3b, Rx, L, a, b, and d are defined herein. Also disclosed are methods of using these compounds to modulate the activity of farnesoid X receptor (FXR); pharmaceutical compositions comprising these compounds; and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

Abstract: In certain embodiments, this disclosure provides novel methods of increasing the viable cell density of an N-1 large-scale bioreactor cell culture, comprising culturing a host cell expressing a recombinant poly peptide of interest in a non-perfusion-based culture system, and wherein the viable cell density is increased to at least 5×106 cells/mL. In certain embodiments, the disclosure provides novel methods for large-scale production of a recombinant polypeptide of interest, comprising: (1) culturing a host cell expressing a recombinant polypeptide of interest in an N-1 stage in a non-perfusion-based culture system, wherein the viable cell density is increased to at least 5×106 cells/mL: and (2) culturing N fed-batch production cells in an enriched media with high-seed density at least 1.5×106 cells/mL, wherein the N fed-batch production cells are inoculated from the N-1 stage in a non-perfusion-based culture system.

Abstract: Provided herein are antibodies, or antigen-binding portions thereof, that bind to T-cell immunoglobulin and mucin-domain containing-3 (TIM3) protein. Also provided are uses of these antibodies, or antigen-binding portions thereof, in therapeutic applications, such as treatment of cancer. Further provided are cells that produce the antibodies, or antigen-binding portions thereof, polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof, and vectors comprising the polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof.

Abstract: This disclosure provides methods for identifying a subject suitable for an adeno associated vims (AAV) therapy. In some embodiments, the method comprises measuring a titer of an antibody or antigen-binding portion thereof that specifically binds to an AAV (“anti-AAV antibody”) in a biological sample obtained from the subject using an enzyme-linked immunosorbent assay (ELISA).

Abstract: Disclosed herein are compounds and methods for the prevention and/or treatment of hemoglobinopathies. Also provided herein are such compounds for use in such methods. Also disclosed herein are pharmaceutical compositions comprising such compounds for use in such methods of preventing or treating hemoglobinopathies.