GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

The invention relates to substituted pyridine derivatives that are inhibitors of the activity of DNA methyltransferase 1 (DNMT1). The invention also relates to pharmaceutical compositions comprising such compounds and methods of using such compounds in the treatment of cancer, pre-cancerous syndromes, beta haemoglobinopathy disorders, and other diseases associated with inappropriate DNMT1 activity.

Disclosed herein are new O-biphenyl- and O-phenylheteroarylmannoside compounds and compositions and their application as pharmaceuticals for use in the treatment of human disease. Methods of inhibition of FimH activity in human subjects are also provided for the treatment of diseases such as urinary tract infection.

The present disclosure is related to methods for treating chronic hepatitis B. The methods comprise administering to a subject in need thereof a therapeutically effective amount of bepirovirsen, wherein the subject has a HBsAg baseline level of not greater than a threshold level.

The present invention provides a series of 2,4-dioxotetrahydropyrimidinyl derivatives that bind cereblon, and their application as degrons in PROTACs. Androgen receptor PROTACs containing the 2,4-dioxotetrahydropyrimidinyl containing degrons and medical uses of these PROTACS are also disclosed.

A method for determining a state of a cell, the cell being placed in a sample in contact with a culture medium, includes illuminating the sample with a light source and acquiring an image of the sample with an image sensor, the image sensor lying in a detection plane. From the acquired image, a position of the cell in a plane parallel to the detection plane is located and a refractive index or a relative refractive index of the cell is estimated, the relative refractive index corresponding to a refractive index of the cell relative to the refractive index of the culture medium. From the estimation, an index of interest of the cell is determined. From the index, a state of the cell among predetermined states is classified, the predetermined states including at least one apoptosis state and one living state.

The present invention relates to pharmaceutical products comprising fluticasone furoate for use in the treatment of COPD patients, particularly a subgroup of COPD patients that through analysis have been identified as possessing an eosinophil blood count of ≥150 cells/μl. The present invention is further directed to methods for treating a patient with COPD which methods include identifying a patient that will respond to treatment and administering a pharmaceutical product of the present invention comprising fluticasone furoate to said patient.

The present disclosure provides engineered carboxyesterase enzymes that have the ability to catalyze amide bond formation. Also provided are polynucleotides encoding the carboxyesterase enzymes, host cells capable of expressing the engineered carboxyesterase enzymes, and methods of using the engineered carboxyesterase enzymes to make commercially valuable amides. Also provided are amides that are made using the engineered carboxyesterase enzymes.

Disclosed herein is a method of treating cancer, such as multiple myeloma, involving the combination of an anti-BCMA antigen binding protein (e.g., an anti-BCMA antibody) and a proteasome inhibitor (e.g. bortezomib). The combinations can also include an anti-inflammatory compound (e.g. dexamethasone).

Aspects of the disclosure are directed to mitigating ocular toxicity in patients undergoing treatment for B-cell disorders, including cancers. Such treatment may include administering a therapeutically effective dose of a component of a B-cell disorder therapy, monitoring for signs of ocular toxicity, and, if such signs are present, adjusting the dose of that component for a subsequent administration. Monitoring for signs of ocular toxicity may include performing an ophthalmic examination of the patient, including performing a visual assessment and corneal assessment of the patient. The ophthalmic examination may include selecting visual assessment options from predefined and selectable visual assessment options and include selection corneal assessment options from predefined and selectable corneal assessment options. An overall keratopathy visual acuity (KVA) grade may be determined based on the selected visual acuity assessment options and the selected corneal assessment options.

The present disclosure relates to heterobifunctional molecules, referred to as cytotoxicity targeting chimeras (CyTaCs) or antibody recruiting molecules (ARMs) that are able to simultaneously bind a target cell-surface protein as well as an exogenous antibody protein. The present disclosure also relates to agents capable of binding to a receptor on a surface of a pathogenic cell and inducing the depletion of the pathogenic cell in a subject for use in the treatment of cancer, inflammatory diseases, autoimmune diseases, viral infection, or bacterial infection.