The present invention relates to the seminal discovery that P-selectin glycoprotein ligand-1 (PSGL-1) modulates the immune system and immune responses. Specifically, the present invention provides PSGL-1 agonists and antagonists which increase the survival of multifunctional T cells and viral clearance. The present invention further provides methods of treating infectious diseases, cancer and immune and inflammatory diseases and disorders using a PSGL-1 modulator.

The invention relates to PGT121-germline-targeting designs, trimer stabilization designs, combinations of those two, trimers designed with modified surfaces helpful for immunization regimens, other trimer modifications and on development of trimer nanoparticles and methods of making and using the same.

Fc-fusion protein derivatives against HIV have enhanced yield in mammalian cells, and extended antiviral and immunomodulatory activities. The Fc-fusion protein derivatives can block the entry of human immunodeficiency virus (HIV) into host cells, elicit effector functions through the activation of natural killer (NK) and other immune system cells, can be produced with high yield in mammalian cells, and have extended activity in vivo. Nucleic acids, vectors and host cells can express the Fc-fusion protein derivatives, which have therapeutic and diagnostic applications in human health.

The present disclosure relates generally to certain 6-azabenzimidazole compounds, pharmaceutical compositions comprising said compounds, and methods of making and using said compounds and pharmaceutical compositions. The compounds and compositions disclosed herein may be used for the treatment or prevention of diseases, disorders, or infections modifiable by hematopoietic progenitor kinase 1 (HPK1) inhibitors, such as HBV, HIV, cancer, and/or a hyper-proliferative disease.

The present invention relates to a novel compound that has antiviral activity, in particular, inhibitory activity against the integrase of the human immunodeficiency virus (HIV).

The subject of this invention is a novel annelated 9-hydroxy-1,8-dioxo-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrazine-7-carboxamide of general formula 1 or 2, or any stereoisomer, any pharmaceutically acceptable salt, any solvate, or any crystalline or polycrystalline form thereof

##STR00001## wherein ring A.sup.1 is an optionally methyl-substituted 5-7 membered saturated heterocycle or heterobicycle; ring A.sup.2 is a 5-6 membered optionally methyl-substituted saturated or partially saturated monocyclic heterocycle; ring A.sup.3 is a 5-6 membered monocyclic saturated cycloalkane or tetrahydro-2H-pyran; R is a 5-7 membered optionally substituted with one, two, or three optionally identical substituents monocyclic or bicyclic heterocyclic radical comprising 1-4 heteroatoms selected from the series O, S, and N except (2S,5R,13aS)-8-hydroxy-7,9-dioxo-N-{[3-(trifluoromethyl)-pyridin-2-yl]methyl}-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopurido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide (formula A4) and (1R,4S,12aR)-N-[(3,5-difluoropyridin-2-yl)methyl]-7-hydroxy-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide (formula A5).

The present disclosure provides pharmaceutical formulations of the compound of Formula I, Formula Ia, or Formula Ib, or a pharmaceutically acceptable salt thereof, and an aqueous vehicle. The pharmaceutical formulations of the disclosure are useful in treatment and prevention of viral infections in subjects in need thereof and are for administration by inhalation.

Compounds of Formula I, including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth:

##STR00001##

The disclosure provides anti-CD30 antibody-drug conjugates and methods of using the same to increase CD4.sup.+ T-cell lymphocyte count or treat 1-IIV infection. The disclosure also provides articles of manufacture or kits comprising said antibody drug-conjugates that bind to CD30 for increasing CD4.sup.+ T-cell lymphocyte count or treating HIV infection.

The disclosure provides anti-CD30 antibody-drug conjugates and methods of using the same to increase CD4.sup.+ T-cell lymphocyte count or treat 1-IIV infection. The disclosure also provides articles of manufacture or kits comprising said antibody drug-conjugates that bind to CD30 for increasing CD4.sup.+ T-cell lymphocyte count or treating HIV infection.

This disclosure relates to the use of an implantable device to deliver biologically active compounds at a controlled rate for an extended period of time and methods of manufactures thereof. The device is biocompatible and biostable, and is useful as an implant in patients (humans and animals) for the delivery of appropriate bioactive substances to tissues or organs.