Abstract: Glucose-responsive insulin conjugates that contain one or more linear oligomer sugar cluster are provided. Such insulin conjugates that may display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose, even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule.

Abstract: The present invention relates to an enzymatic synthesis of 4?-ethynyl-2?-deoxy nucleosides and analogs thereof, for example EFdA, that eliminates the use of protecting groups on the intermediates, improves the stereoselectivity of glycosylation and reduces the number of process steps needed to make said compounds. It also relates to the novel intermediates employed in the process.

Abstract: The present invention provides methods for treating patients by administering an immunogenic multivalent pneumococcal polysaccharide-protein conjugate vaccine which comprises a S. pneumoniae serotype 35B polysaccharide-protein conjugate, does not comprise a S. pneumoniae serotype 29 polysaccharide-protein conjugate, and provides protection against S. pneumoniae serotype 29.

Abstract: The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein ring A is a moiety selected from: and ring B, n, R1, R2, R2A, R3, and R3A are as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild congnitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof.

Abstract: In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I): and pharmaceutically acceptable salts thereof, wherein, ring A, R1 and R2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.

Abstract: The invention is related to the preparation of protected piperidine carboxylates suitable for use as intermediates that lead, via a series of additional process steps, including a sulfation of a hydroxy urea compound, to the preparation of the beta lactamase inhibitor (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide.

Abstract: The present invention relates to Tetracyclic Heterocycle Compounds of Formula and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, R1, R2, R3 and Ware as defined herein. The present invention also relates to compositions comprising at least one Tetracyclic Heterocycle Compound, and methods of using the Tetracyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.

Abstract: The invention relates to stable formulations of cyclic dinucleotide STING agonist compounds or pharmaceutically acceptable salts thereof. The invention further provides methods for treating various cancers with stable formulations of the invention. In some embodiments of the methods of the invention, the formulations are administered to a subject by intratumoral or subcutaneous administration.

Abstract: The present invention relates to Compounds of Formula I: and pharmaceutically acceptable salts or prodrug thereof, wherein R1, R2, R3, A and B are as defined herein. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treating or preventing cancer, inflammation, neurodegeneration disease and/or diabetes in a subject.

Abstract: The present invention relates to methods for producing a stable amorphous dispersion of a pharmaceutically active substance having poor water solubility by applying low frequency acoustic energy to a mixture comprising the active substance and at least one polymer and heating the mixture until a stable amorphous dispersion is formed. The methods of the invention are an effective means of converting a crystalline API to a substantially amorphous and stable form, i.e., wherein the crystallinity is less than about 5%. The methods of the invention result in more complete amorphization, increased solubility, drug loading and stability as compared typical amorphization or literature methods.

Abstract: Therapeutic combinations of immunoconjugates that bind to FOLR1 (e.g., IMGN853) with anti-PD-1 antibodies or antigen-binding fragments thereof (e.g., pembrolizumab) are provided. Methods of administering the combinations to treat cancers. e.g., ovarian, peritoneal, or fallopian tube cancers, with greater clinical efficacy and/or decreased toxicity are also provided.

Abstract: The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. 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 M4 muscarinic acetylcholine 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 M4 muscarinic acetylcholine receptors are involved.

Abstract: The present invention is directed to methods for inhibition of HIV reverse transcriptase, treatment of infection by HIV, prophylaxis of infection by HIV, and the treatment, prophylaxis and/or delay in the onset or progression of AIDS or ARC by administering a compound of structural Formula I or a pharmaceutically acceptable salt or co-crystal thereof, wherein X is —F or —Cl, less frequently than once daily.

Abstract: Genetically engineered antibodies containing non-native N-glycosylated sites, preparation of the antibodies in yeast and fungi, site-specific conjugation of drugs to these antibodies, and methods of treatment utilizing these antibodies are described herein.

Abstract: The present disclosure relates to compounds of formula I that are useful as modulators of 7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation (I).

Abstract: The present invention relates to Compounds of Formula I and Ia and pharmaceutically acceptable salts or prodrug thereof, wherein R1, R2, X, A and B are as defined herein. The present invention also relates to compositions comprising at least one compound of Formula I or Ia, and methods of using the compounds of Formula I or Ia for treating or preventing HIV infection in a subject.

Abstract: The present invention is directed to pyrrolidine compounds which are agonists 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: The present disclosure describes baseline and on treatment blood-based gene signature biomarkers that are predictive of tumor sensitivity to therapy with a PD-1 antagonist. The on-treatment biomarkers comprise a PD-L1 gene signature or an interferon gamma gene signature and the baseline gene signature biomarker comprises genes associated with the oxidative phosphorylation pathway. The disclosure also provides methods and kits for testing tumor samples for these biomarkers, as well as methods for treating subjects with a PD-1 antagonist based on the test results.

Abstract: The present invention provides methods for making polysaccharide-protein conjugates in which polysaccharides, typically from bacteria, are conjugated to a carrier protein by reductive amination under conditions which improve conjugation reaction consistency, increase consumption of protein during conjugation reaction, generate conjugates of higher molecular weight, and/or reduce the levels of free cyanide in the conjugate reaction product. The polysaccharide-protein conjugates obtained using these methods are useful for inclusion in multivalent vaccines.

Abstract: The present invention is directed to heteroarylpiperidine ether compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. 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 M4 muscarinic acetylcholine 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 M4 muscarinic acetylcholine receptors are involved.