Abstract: A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or pharmaceutically acceptable salt thereofs, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or pharmaceutically acceptable salts thereof.

Abstract: The present invention provides Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula (I), or pharmaceutically acceptable salts thereof, wherein X1, X2, R1, R7, R8 and R9 are as herein described. The present invention also provides pharmaceutical compositions comprising these compounds and methods for their use in therapy. In particular, the present invention relates to the use of Btk inhibitor compounds of Formula (I) in the treatment of Btk mediated disorders.

Abstract: Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.

Abstract: Disclosed are compounds of Formula A-1, or a salt thereof: Formula A-1, where J, K, Q and R1 are as defined herein, which compounds have properties for inhibiting sodium ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A-1 or their salts, and methods of treating pain (e.g. chronic pain), or cough or itch disorders using the same.

Abstract: The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to human or cynomolgous monkey LAG3 as well as immunoglobulin chains thereof and polynucleotides encoding the same along with injection devices comprising such antibodies or fragments. Vaccines including such antibodies and fragments as well as compositions comprising the antibodies and fragments (e.g., including anti-PD1 antibodies) are included in the invention. Methods for treating or preventing cancer or infection using such compositions are also provided. In addition, methods for recombinant expression of the antibodies and fragments are part of the present invention.

Abstract: The present disclosure describes an IHC assay for detecting and quantifying spatially proximal pairs of PD-1-expressing cells (PD-1+ cells) and PD-Ligand-expressing cells (PD-L+ cells) in tumor tissue, and the use of the assay to generate proximity biomarkers that are predictive of which cancer patients are most likely to benefit from treatment with a PD-1 antagonist. The disclosure also provides methods for testing tumor samples for the proximity biomarkers, as well as methods for treating subjects with a PD-1 antagonist based on the test results.

Abstract: The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.

Abstract: The present invention is directed to heteroaryl compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

Abstract: Disclosed herein is a peptide containing conjugate comprising (P)c-(L)d-(G)e, wherein P is a peptide and each occurance of P is independently selected from Table 2; L is an optional linker and each occurance of L, if present, is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. The conjugate can be administered to a subject either alone or in combination with a composition comprising R-(L)a-(G)b, wherein R is an oligonucleotide as defined herein, to inhibit expression of a gene of the subject.

Abstract: A security system determines authorizations for entities to access data objects. The security system may train an adaptive model to predict the intent of a user who provides authorization for various entities or other users. In an embodiment, the adaptive model may be configured to determine latent properties of training data by identifying common parameters between entities that are, or are not, permitted to access given data object(s). The training data may include previous authorizations provided to the entities. Based on the identified common parameters, the model may generate usage expressions for determining a likelihood that the user intends to provide authorization for a given entity to access the given data object. If the likelihood is greater than a threshold value, the security system may provide a recommendation to the user to provide the authorization for the given entity.

Abstract: The present invention relates to 6-5 membered fused pyridine ring compounds according to Formula (I) or a pharmaceutically acceptable salt thereof or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of 6-5 membered fused pyridine ring compounds according to Formula (I) in the treatment of Bruton's Tyrosine Kinase (Btk) mediated disorders.

Abstract: The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to human or cynomolgous monkey LAG3 as well as immunoglobulin chains thereof and polynucleotides encoding the same along with injection devices comprising such antibodies or fragments. Vaccines including such antibodies and fragments as well as compositions comprising the antibodies and fragments (e.g., including anti-PD1 antibodies) are included in the invention. Methods for treating or preventing cancer or infection using such compositions are also provided. In addition, methods for recombinant expression of the antibodies and fragments are part of the present invention.

Abstract: The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to human or cynomolgous monkey LAG3 as well as immunoglobulin chains thereof and polynucleotides encoding the same along with injection devices comprising such antibodies or fragments. Vaccines including such antibodies and fragments as well as compositions comprising the antibodies and fragments (e.g., including anti-PD1 antibodies) are included in the invention. Methods for treating or preventing cancer or infection using such compositions are also provided. In addition, methods for recombinant expression of the antibodies and fragments are part of the present invention.

Abstract: The present invention relates to Fused Tricyclic Heterocycle Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, Y, m, R1, R2, R3, R3, R3, R4, R5 and R9 are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocycle Derivative, and methods of using the Fused Tricyclic Heterocycle Derivatives for treating or preventing HIV infection in a subject.

Abstract: The present invention relates to the use of certain SGLT-2 inhibitors, such as ertugliflozin or a pharmaceutically acceptable salt or a co-crystal thereof, for treating, reducing the risk of and/or preventing heart failure, myocardial infarction, cardiovascular disease or cardiovascular death in animals without type 2 or type 1 diabetes mellitus, or in animals with pre-diabetes, or in animals with type 2 or type 1 diabetes mellitus or pre-diabetes.

Abstract: The present invention relates to metallo-?-lactamase inhibitor compounds of Formula I: (I) and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2 and RB are as defined herein. The present invention also relates to compositions which comprise a metallo-?-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more ?-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.

Abstract: The present invention is directed to pyrazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the pyrazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

Abstract: Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

Abstract: The instant invention relates to liquid pharmaceutical compositions containing CGRP receptor antagonists. The CGRP receptor antagonist liquid pharmaceutical compositions of the instant invention are alcohol-free, low volume liquid pharmaceutical compositions that can be taken without water for the treatment of migraine headache.

Abstract: The present invention relates to bicyclic aryl monobactam compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein A1, L, M, W, X, Y, Z, RX and Rz are as defined herein. The present invention also relates to compositions which comprise a bicyclic aryl monobactam compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of one or more beta-lactamase inhibitor compounds.