Abstract: Provided herein are methods for mapping antibody binding to an immunogen, comprising: immunizing a subject with an immunogen and obtaining sera from the immunized subject at multiple time intervals following immunization, wherein the sera comprises antibodies that are used to form one or more immune complexes with the immunogen; isolating the one or more immune complexes formed by the serum derived antibodies bound to the immunogen; imaging, by electron microscopy, the one or more immune complexes in each of the time intervals, to obtain structural images formed between the immunogen and serum antibodies; determining, from the plurality of structural images, immunogen-antibody binding site for each of the immune complexes obtained at the plurality of time intervals; mapping immunogen-antibody binding by measuring differences in structural images obtained at different time intervals to determine immunogen-antibody binding over multiple time intervals.

Abstract: Described are methods for providing personalized medicine for the treatment of B cell malignancies including lymphoma. The methods make use of Chimeric Antigen Receptor (CAR) technology.

Abstract: In various embodiments, disclosed herein are methods of assessing therapeutic efficacy of an anticoagulant. Preferably, the method comprising providing a blood sample; perfusing the blood sample over a surface coated with collagen or immobilized rTF; measuring platelet aggregation and fibrin deposition on the surface coated with collagen or immobilized rTF; and assessing therapeutic efficacy of the anticoagulant based on the volume of platelet aggregates and/or deposited fibrin.

Abstract: The invention relates to PGT121-germline-targeting designs, trimer stabilization designs, combinations of those two, trimers designed with modified surfaces helpful for immunization regimens, other trimer modifications and on development of trimer nanoparticles and methods of making and using the same.

Abstract: Dual variable domain (DVD) immunoconjugates and uses thereof are provided. Aspects of the subject immunoconjugates include a DVD immunoglobulin molecule having a first and a second variable domain, and a cargo moiety (e.g., a drug moiety) that is covalently conjugated to the second variable domain via a linker. Methods of making and using the subject immunoconjugates in the prevention and/or treatment of cancer and other diseases are also provided.

Abstract: Chiral acetyl-protected aminoethyl quinoline (APAQ), pyridine and imazoline ligands are disclosed that enable Pd (II)-catalyzed enantioselective arylation or heteroarylation of ubiquitous prochiral ?-methylene C—H bonds of aliphatic amides offers an alternative disconnection for constructing ?-chiral centers. Systematic tuning of the ligand structure reveals that a six-membered instead of a five-membered chelation of these types of ligands with the Pd(II) is important for accelerating the C(sp3)-H activation thereby achieving enantioselectivity for quinoline and pyridine ligands.

Abstract: The present disclosure provides compositions, methods, kits, and platforms for selectively activating and deactivating chimeric receptor effector cells using humanized chimeric receptor effector cell switches that comprise a humanized targeting moiety that binds CD19 on a target cell and a chimeric receptor interacting domain that binds to a chimeric receptor effector cell and/or chimeric receptor effector cell switches comprising optimized chimeric receptor interacting domains. Also disclosed are methods of treating disease and conditions with such chimeric receptor effector cells and chimeric receptor effector cell switches.

Abstract: The present invention provides methods for modulating opioid receptor mediated analgesic effect, e.g., promoting or enhancing analgesia in subjects in need of pain relief. Also provided in the invention are methods for ameliorating or suppressing withdrawal symptoms in subjects with chronic opioid use. These methods of the invention entail administering to the subjects in need of treatment a therapeutically effective amount of a GPR139 antagonist compound. The invention further provides methods for identifying novel compounds that can be useful for modulating opioid receptor mediated analgesic effect.

Abstract: The invention is directed to methods of converting a carboxylic acid group in a compound, via a redox active ester, to a corresponding boronic ester by treatment with bis(pinacolato)diboron-alkyllithium complex in the presence of a ligand, a Ni(ll) salt or a copper salt, and an Mg(ll) salt, in the presence of an alkyllithium or a lithium hydroxide or alkoxide salt. The product pinacolato boronate ester can be cleaved to provide a boronic acid. The invention is also directed to methods of preparing various compounds of medical value comprising boronic acid groups, and to novel boronic-acid containing compounds of medicinal value, including an atorvastatin boronic acid analog, a vancomycin aglycone boronic acid analog, and boronic acid containing elastase inhibitors mCBK319, mCBK320, mCBK323, and RPX-7009.

Abstract: Disclosed herein are relaxin immunoglobulin fusion proteins useful for the treatment or prevention of a disease or condition in a subject.

Abstract: Described are methods for providing personalized medicine for the treatment of B cell malignancies including lymphoma. The methods make use of Chimeric Antigen Receptor (CAR) technology.

Abstract: This application describes a compound represented by Formula (I): wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

Abstract: The invention provides compounds for activating the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR), or activating the transcriptional targets of ATF6, in the endoplasmic reticulum of a cell, the compounds being of any of formulas (I) through (IX) as described herein. The compounds can be used for treatment of conditions involving gain-of-toxic-function and loss-of-function folding disorders including lysosomal storage diseases, antitrypsin-associated emphysema and similar diseases. These molecules are also expected to have disease-ameliorating effects in Alzheimer's disease and diabetes.

Abstract: In various embodiments, disclosed herein are assays for measuring thrombin generated (TG) in a blood sample, comprising: incubating the blood sample with TF, FIXa, and CaCl2; and measuring TG in the blood sample. Also disclosed herein are assays for determining a bleeding risk in a subject, comprising obtaining a blood sample from the subject; adding to the blood sample TF and/or FIXa; determining the amount of coagulation factor VIII (FVIII:C) in the blood sample; and determining (a) a mild bleeding risk in the subject if the amount of FVIII:C in the sample is >5 IU/dL, (b) a moderate bleeding risk in the subject if the amount of FVIII:C in the sample is 1-5 IU/dL, and (c) a severe bleeding risk in the subject if the amount of FVIII:C in the subject is <1 IU/dL.

Abstract: Compounds are provided that antagonize the kappa-opioid receptor (KOR) and products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope or salt thereof: wherein X, Y, R1, R2, R4, R5 R6, R7, R8 and R11 are as defined herein.

Abstract: Coronavirus S ectodomain trimers stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the coronavirus S ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to coronavirus in a subject. In additional embodiments, the therapeutically effective amount of the coronavirus S ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing coronavirus infection.

Abstract: By a genome-wide gene analysis of expression profiles of known or putative gene sequences in peripheral blood and biopsy samples, the present inventors have identified a consensus set of gene expression-based molecular biomarkers for distinguishing liver transplantation patients who have Acute Rejection (AR), Hepatitis C Virus Recurrence (HCV-R), both AR/HCV-R, or Acute Dysfunction No Rejection (ADNR). These molecular biomarkers are useful for diagnosis, prognosis and monitoring of liver transplantation patients.

Abstract: The present invention provides novel nanoparticle presented vaccine compositions that are stabilized with a locking domain. Various immunogens can be employed in the preparation of the vaccine compositions, including viral immunogens such as HIV-1 and Ebola viral immunogens, and non-viral immunogens such as immunogens derived from bacteria, parasites and mammalian species. The invention also provides methods of using such vaccine compositions in various therapeutic applications, e.g., for preventing or treating viral infections.

Abstract: Disclosed herein are chimeric antigen receptor effector cells (CAR-ECs) and CAR-EC switches. The switchable CAR-ECs are generally T cells. The one or more chimeric antigen receptors may recognize a peptidic antigen on the CAR-EC switch. The CAR-ECs and switches may be used for the treatment of a condition in a subject in need thereof.

Abstract: The disclosure provides antibodies, antibody fragments or antigen-binding fragments, as well as related antibody drug conjugates (ADCs) and chimeric antigen receptors (CARs), that specifically recognize human ROR2, Also provided in the disclosure are methods of using such antibodies in various diagnostic and therapeutic applications.