Abstract: The present invention is directed to methods of identifying and treating a human subject harboring a tumor or other disease comprising assessing HRG gene expression at a protein level in the human subject and administering a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at a protein level is assessed as high. The present invention is also directed to methods of identifying a human subject harboring a tumor or other disease comprising assessing HRG gene expression at a protein level in the human subject and withholding a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at a protein level is assessed as low.

Abstract: Methods and compositions for treating ovarian cancer in a human patient with ascites by administering a therapeutically effective amount of an Ang2 inhibitor in combination with a taxane.

Abstract: There are disclosed TIMP-3 muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them.

Abstract: The present disclosure provides compositions and methods relating to antigen binding proteins, in particular, antibodies and bispecific antibodies which specifically bind to mesothelin. The disclosure provides nucleic acids encoding such antigen binding proteins and antibodies and methods of making and using such antibodies, including methods of treating and preventing cancer or other hypoproliferative disorders and related disorders by administering such antigen binding proteins and antibodies to a subject in need of such treatment.

Abstract: The ability to generate a single antibody-based construct that can recognize multiple targets simultaneously, is paramount to advance many therapeutics candidates to clinic. Often, this implies extensive protein design with vary degrees of success. In the case of multispecific antibodies, the driving of the HC/LC pairing in the Fab region represents one of the most difficult challenges yet in the field of multispecific engineering. Described here is the discovery of a new single chain Fab module that utilizes a novel linker between VL-CL and VH-CH1 domains which will further enable the production of multispecifics.

Abstract: Provided herein are processes for synthesizing intermediates useful in preparing Mcl-1 inhibitors. In particular, provided herein are processes for synthesizing compound IA, wherein R1 is described herein. Compound IA can be useful in synthesizing compound A1, or a salt or solvate thereof, and compound A2, or a salt of solvate thereof.

Abstract: The present invention relates to IL-17 Receptor A (IL-17RA or IL-17R) antigen binding proteins, such as antibodies, polynucleotide sequences encoding said antigen binding proteins, and compositions and methods for diagnosing and treating diseases mediated by IL-17 Receptor A activation by one or more IL-17 ligands. The present invention relates to the identification of neutralizing determinants on IL-17 Receptor A (IL-17RA or IL-17R) and antibodies that bind thereto. Aspects of the invention also include antibodies that compete for binding with the IL-17RA neutralizing antibodies described herein.

Abstract: The invention generally relates to anti-sclerostin antibodies having C-terminal modifications, and compositions comprising such antibodies.

Abstract: Systems and methods are described for reducing lab-to-lab and/or instrument-to-instrument variability of Multi-Attribute Methods (MAM) analyses via run-time signal intensity calibration. In various aspects, multiple MAM-based instruments each have detectors and different instrument conditions defined by different instrument models or sets of settings. Each MAM-based instrument receives respective samples and a reference standard as a calibrant. Each MAM-based instrument detects, via its detector, sample isoforms of its respective sample and reference standard isoforms of the reference standard. The MAM-based instruments are associated with processor(s) that determine, via respective MAM iterations, correction factors and sample abundance values corresponding to the sample isoforms. The correction factors are based on the reference standard, and the sample abundance values are based on the correction factors.

Abstract: The invention relates to the treatment of bone disorders. In particular, the invention provides an approach involving administration of a high initial dose or doses of an sclerostin antibody to bring about a rapid increase in bone formation, followed by administration of lowers doses of the antibody to give a sustained lower rate of bone formation after the initial burst of bone formation. The invention also provides an approach involving decreasing dosing frequency with such an antibody to control bone formation. The approaches may be used in particular in those subjects who would benefit most from such an initial rapid burst of bone formation. Examples of such subjects include subjects who have been recently diagnosed or are experiencing severe symptoms of the disorder, as well as those subjects who have been administered a different treatment for the bone disorder which is proving ineffective. The approaches may be used in combination with each other.

Abstract: The invention generally relates to electrophoretic mass spectrometry probes and systems and methods of uses thereof. In certain aspects, the invention provides a mass spectrometry probe having a hollow body with a distal tip, an electrically conductive hollow conduit, and an electrode. The electrically conductive hollow conduit may be operably coupled to a reservoir and a power source, and the electrically conductive hollow conduit may be configured to transport a liquid sample into the hollow body and polarize the liquid sample as it flows through the electrically conductive hollow conduit and into in the hollow body. The electrode and the electrically conductive hollow conduit are disposed within the hollow body (e.g., at different heights within the hollow body).

Abstract: The present invention relates to methods for treating or preventing atherosclerotic cardiovascular disease and other conditions associated with elevated levels of lipoprotein (a) (Lp(a)) using RNAi constructs targeting the LPA gene, which encodes apolipoprotein(a), a component of Lp(a) particles. In particular, the present invention relates to methods for reducing serum Lp(a) levels and reducing the risk of cardiovascular events in patients with elevated levels of Lp(a) comprising administering an LPA-targeted RNAi construct according to specific dosage regimens. Pharmaceutical compositions comprising the LPA-targeted RNAi constructs for use in the methods are also disclosed.

Abstract: Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders.

Abstract: The present invention relates to methods for administering therapeutic doses of bispecific T-cell engaging molecules for the treatment of cancer in a patient. The administration methods reduce the incidence and/or severity of adverse events, such as cytokine release syndrome, and entail administering to a patient a priming dose of the bispecific T-cell engaging molecule by continuous intravenous infusion over a period of days followed by administration of a therapeutic dose of the bispecific T-cell engaging molecule by a bolus intravenous infusion at dosing intervals of at least a week.

Abstract: The present invention is directed to methods of identifying and treating a human subject harboring a tumor or other disease comprising assessing HRG gene expression at an mRNA level in the human subject and administering a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at an mRNA level is assessed as high. The present invention is also directed to methods of identifying a human subject harboring a tumor or other disease comprising assessing HRG gene expression at an mRNA level in the human subject and withholding a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at an mRNA level is assessed as low.

Abstract: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: Provided herein is a process comprising heating a composition comprising (P)-compound A or a salt thereof and a solvent to a temperature of 250° C. to 350° C. to form racemized compound A. Also provided is a process for isolating (P)-compound A from a composition comprising (P)-compound A and a tartrate, as described herein. Further provided herein, is a process for isolating a free acid of a tartrate or a hydrate thereof from a composition comprising a tartrate, (P)-compound A, and an organic solvent.

Abstract: Provided herein are IL-21 muteins and fusion proteins comprising the same for use in methods of treating a disease. Related conjugates, nucleic acids, vectors, host cells, pharmaceutical compositions and kits are also provided herein. Methods of making the IL-21 muteins and fusion proteins comprising the same, as well as methods of treating a subject in need thereof, are provided by the present disclosure. Further provided are PD-1 antigen-binding proteins.