Abstract: The present invention relates to Tricyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein X, Y, Z, R1 and n are as defined herein. The present invention also relates to compositions comprising at least one Tricyclic Heterocycle Compound, and methods of using the Tricyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.

Abstract: The present disclosure provides conjugates which comprise an insulin molecule conjugated via a conjugate framework to one or more separate ligands that include a first saccharide, and wherein the conjugate framework also comprises a fatty chain (e.g., a C8-30 fatty chain). In certain embodiments, a conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic (PK) and/or pharmacodynamic (PD) property of the conjugate is sensitive to serum concentration of a second saccharide. In certain embodiments, a conjugate is also characterized by having a protracted PK profile. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: Provided herein are treatments of conditions ameliorated by counteracting tumor mediated immune suppression. More specifically, provided herein are anti-PD-1/LAG-3/TIGIT trispecific antibodies, anti-PD-1/LAG3 bispecific antibodies, anti-LAG3 antibodies and antigen-binding fragments. Also provided here are methods and uses of these antibodies and antigen-binding fragments in the treatment of cancer or infectious disease.

Abstract: A solids charging containment apparatus and method for mixing a solvent with a dry powder, comprising a dual compartment isolator for safely removing the dry powder from a dry powder container, a mixing vessel, and a negative cascading pressure controller. The dual compartment isolator comprises a staging compartment, a charging compartment and a raw material entry port, which is connected to the staging compartment and configured to isolate the dry powder container from the surrounding atmosphere. The mixing vessel includes a mixing chamber and a solids charging port fluidly connecting the mixing chamber to a containment valve in the charging compartment of the dual compartment isolator. The negative cascading pressure controller generates negative pressure in both the staging compartment and the charging compartment. The containment apparatus and method may be used to produce a slurry or solution mixture of solvent and dry powder during drug processing.

Abstract: The invention provides compositions of anti-PD-1 antibodies or antigen-binding fragments thereof with less than or equal to about 3.0% oxidation of Met105 in the CDRH3 heavy chain region, and methods of obtaining the purified compositions. The invention also provides compositions comprising anti-PD-1 antibody main species and acidic species thereof, wherein the amount of acidic species is about 1.0-12.0%.

Abstract: The instant invention provides for novel lipid nanoparticle (LNP) formulations, containing cationic lipids, for use as vaccine adjuvants and/or as antigen delivery systems. It is an object of the instant invention to provide LNP formulations that demonstrate enhancements in humoral and/or cellular immunogenicity of vaccine antigens, particularly subunit vaccine antigens, when utilized alone or in combination with immunostimulatory agents (e.g. small molecule or oligonucleotide TLR agonists). The instant invention further identifies physical and chemical properties of the LNP formulations that can be manipulated to enhance antigen efficiency and adjuvant tolerability in vivo.

Abstract: The present invention relates to methods for the recombinant expression of chlamydia major outer membrane protein (MOMP) comprising transforming a population of E. coli host cells with an expression vector comprising a nucleic acid molecule that encodes chlamydia MOMP and encodes a leader sequence for targeting the MOMP to the outer membrane of the cell, wherein the nucleic acid molecule is operatively linked to a promoter. The method of the invention allows expression of MOMP in the outer membrane of the cell, which leads to protein folding that is more like native MOMP relative to a MOMP protein that is expressed intracellularly. Also provided by the invention are uses of the recombinant MOMP in pharmaceutical compositions and methods for the treatment and/or prophylaxis of chlamydia infection and/or the effects thereof.

Abstract: The present disclosure is directed to pyridinone derivatives of Formula I and their use for selectively killing HIV infected GAG-POL expressing cells without concomitant cytotoxicity to HIV nave cells, and for the treatment of infection by HIV, or for the treatment, prophylaxis or delay in the onset or progression of AIDS or AIDS Related Complex (ARC).

Abstract: The present invention provides processes for the preparation of 2-fluoroadenine, as well as certain intermediates useful in the preparation of 2?-deoxy-4?-C-ethynyl-2-fluoroadenosine (EFdA): EFdA.

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: This invention relates to novel implant drug delivery systems for long-acting delivery of antiviral drugs. These compositions are useful for the treatment or prevention of human immunodeficiency virus (HIV) infection.

Abstract: The present invention provides a number of process improvements related to the conjugation of capsular polysaccharides from Streptococcus pneumoniae to a carrier protein. These process are serotype specific and include acid hydrolysis, addition of sodium chloride to the reductive amination reaction, and addition of sucrose to dissolve polysaccharides. Polysaccharide-protein conjugates prepared using the processes of the invention can be included in multivalent pneumococcal conjugate vaccines.

Abstract: The present invention is directed to processes for preparing a diazepane compound which is an antagonist of orexin receptors, and which is useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is further directed to crystalline forms of this diazepane compound and pharmaceutical compositions thereof.

Abstract: Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof: Also disclosed herein are uses of the compounds disclosed herein in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.

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: Disclosed are dihydroisoxazole compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, E, and R1 are as defined herein. Also disclosed are compositions which comprise at least one of these dihydroisoxazole compounds, methods for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by Mycobacterium tuberculosis comprising administering a therapeutically effective amount of these dihydroisoxazole compounds and/or a pharmaceutically acceptable salt thereof, or a composition comprising such compound and/or salt.

Abstract: Disclosed are a process and an automated facility for manufacturing a purified protein of interest. The protein of interest can be a recombinant or naturally occurring protein and/or a therapeutic or other medically useful protein. For example, the disclosed process and automated facility are useful for manufacturing a purified protein drug substance.

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 XI activation inhibitors.

Abstract: Disclosed are a process and an automated facility for manufacturing a purified protein of interest. The protein of interest can be a recombinant or naturally occurring protein and/or a therapeutic or other medically useful protein. For example, the disclosed process and automated facility are useful for manufacturing a purified protein drug substance.

Abstract: The present invention provides a process improvement related to the conjugation of capsular polysaccharides from Streptococcus pneumoniae (S. pneumoniae) serotype 35B to a carrier protein. The serotype 35B polysaccharide-protein conjugate, prepared by the disclosed process, is, among other things, more immunogenic than similar conjugates made by prior art methods. S. pneumoniae serotype 35B polysaccharide-protein conjugates prepared using the processes of the invention can be included in multivalent pneumococcal conjugate vaccine compositions.