Abstract: The present invention relates to a method for manipulating the high mannose glycoform content of recombinant glycoproteins by regulating ornithine metabolism during cell culture.

Abstract: The present invention relates to methods for purifying nucleic acids. In particular, the present invention relates to a method for separating guanine-rich oligonucleotides from quadruplex secondary structures formed from the oligonucleotides using monolithic anion exchange chromatography. Mobile phase parameters that control quadruplex formation and enable separation of the intact quadruplex from the single-strand oligonucleotide are also described.

Abstract: The present invention relates to RNAi constructs for reducing expression of the MARC1 gene. Methods of using such RNAi constructs to treat or prevent liver fibrosis and fatty liver diseases, such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, are also described.

Abstract: The present invention relates to chemically-modified RNAi constructs for reducing expression of a target gene. In particular, the invention relates to specific patterns of modified nucleotides to be incorporated into RNAi constructs to improve in vivo stability and efficacy. Also described are pharmaceutical compositions comprising the chemically-modified RNAi constructs and methods of inhibiting target gene expression in vivo by administering the chemically-modified RNAi constructs, for example, to treat or ameliorate various disease conditions.

Abstract: The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.

Abstract: The present invention provides compositions and methods relating to or derived from antigen binding proteins capable of inducing ?-Klotho, and or FGF21-like mediated signaling. In embodiments, the antigen binding proteins specifically bind to a complex comprising ?-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c.

Abstract: An injection device, method, and system for drug delivery includes a container for storing a drug, the container having a stopper movably disposed in the container for expelling the drug; an injection drive mechanism having a plunger for acting on the stopper and an energy source having a first selected potential energy for exerting a force on the plunger to cause the plunger to act on the stopper to expel the drug; and a plunger loading mechanism for substantially preventing the plunger from accelerating to a predetermined velocity before it acts on the stopper. The plunger loading mechanism may be a spring having a second selected potential energy for reducing or eliminating a distance between the plunger and the stopper, prior to the plunger accelerating to the velocity. The second selected potential energy of the spring may be less than the first selected potential energy of the energy source.

Abstract: The present invention provides stable pharmaceutical compositions of pegylated carfilzomib compounds, methods for preparing the compositions, and uses of the compositions for treating cancer, including hematologic malignancies such as multiple myeloma. The compositions can be stored in frozen form or lyophilized to dry solid form.

Abstract: The present disclosure provides crystalline and amorphous forms of 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one, including several anhydrous, hydrate and solvate forms, and solid state forms thereof, pharmaceutical compositions, and methods of treating a disease mediated by KRAS G12C inhibition.

Abstract: A medical device with limited computational capability includes medical hardware, a first register to store a static, substantially unique identifier of the medical device, a second register to store a static encryption key, an interface to receive and transmit data over a short-range communication link, and processing hardware. The processing hardware is configured to apply the static encryption key to the identifier of the medical device to generate an encrypted identifier, transmit the encrypted identifier of to another device via the interface, receive an encrypted identifier of the other device, decrypt the encrypted identifier of the other device using the static encryption key to determine an identifier of the other device, generate a dynamic encryption key using the identifier of the medical device and the identifier of the other device, and apply the dynamic encryption key to medical data transmitted between the medical device and the other device.

Abstract: Compounds of formula (I): as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.

Abstract: Methods of treating metabolic diseases and disorders using an antigen binding protein specific for the GIPR polypeptide are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the antigen binding protein is administered in combination with a GLP-1 receptor agonist.

Abstract: The invention provides a method for controlling contaminants in biopharmaceutical purification processes by using light scattering and UV absorbance to establish a determinant. The invention makes use of multi-angle light scattering (MALS) and UV as a continuous monitoring system to provide information about the elution peak fractions in real-time instead of conventional pooling methods that rely on a predetermined percent UV peak max value to initiate the pooling process; regardless of product quality.

Abstract: The invention encompasses methods of treatment of interferon gamma (IFN-?)-mediated diseases using IFN-? inhibitors, such as anti-huIFN-? antibodies, wherein levels of expression of one or more biomarkers are determined either before administration of the IFN-? inhibitor and/or after administration. Also contemplated are methods of treatment using particular, pharmacodynamically effective doses of an anti-huIFN-? antibody.

Abstract: GDF15 molecules are provided herein. In some embodiments, the GDF15 molecule is a GDF15-Fc fusion, in which a GDF15 region is fused to an Fc region. In some embodiments, the GDF15 region is fused to the Fc region via a linker. Also, provided herein are methods for making and using GDF15 molecules.

Abstract: The present invention relates to RNAi constructs for reducing expression of the PNPLA3 gene. Methods of using such RNAi constructs to treat or prevent liver disease, nonalcoholic fatty liver disease (NAFLD) are also described.

Abstract: The present invention relates to antibody constructs comprising a domain which binds to a MAGEB2 peptide complexed with an HLA and optionally, another domain which binds to CD3. Moreover, the invention provides polynucleotides encoding the antibody constructs, vectors comprising said polynucleotides and host cells transformed or transfected with said polynucleotides or vectors. Furthermore, the invention provides processes for producing the antibody constructs of the invention, medical uses of said antibody constructs, and kits comprising said antibody constructs.

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, or a stereoisomer thereof; 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 invention relates to the use of the Chemokine (C—C motif) ligand 20 (CCL20) as a biomarker to stratify or identify populations of patients suffering from interleukin-23 (IL23)-mediated diseases (e.g., Crohn's disease) responsive to treatment with an, anti-IL23 antagonist (including, e.g., anti-IL23 antibodies). Levels of CCL20 above or below a predetermined threshold can be used, for example, (i) to determine whether a patient with an IL23-mediated disease or disorder such a Crohn's disease is eligible or non-eligible for treatment with a therapeutic agent, (ii) to determine whether treatment with a certain agent should be commenced, suspended, or modified, (iii) to diagnose whether the IL23-mediated disease is treatable or not treatable with a specific therapeutic agent, or (iv) to predict the outcome of treating the IL23-mediated disease with a specific therapeutic agent. CCL20 can be used in combination with other IL23 pathway biomarkers such as IL22 and/or lipocalin-2 (LCN2).

Abstract: The present invention relates to chemical compounds having a general formula (I), as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.