This disclosure provides a multimeric human immunodeficiency virus (HIV) protein binding molecule, e.g., an dimeric IgA or a pentameric or hexameric IgM binding molecule, comprising at least two bivalent binding units, or variants or fragments thereof, each comprising at least two antibody heavy chain constant regions or fragments thereof, wherein each heavy chain constant region or fragment thereof is associated with an HIV antigen binding domain. Also provided are compositions comprising the multimeric binding molecules, polynucleotides encoding the multimeric binding molecules, and methods to make and use the multimeric binding molecules.

The present invention relates to Tetracyclic Heterocycle Compounds of Formula ##STR00001##
and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, R.sup.1, R.sup.2, R.sup.3 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.

The present invention relates to antibody derivatives against HIV based on a mutated CD4-IgG scaffold with enhanced antiviral and immunomodulatory activities. These antibody derivatives are characterized for having an increased ability to (i) block the entry of human immunodeficiency virus (HIV) into host cells and (ii) elicit effector functions through the activation of natural killer (NK) cells. The present invention further relates to nucleic acids, vectors and host cells expressing said antibody derivatives, as well their therapeutic and diagnostic applications in human health.

The present invention relates to Tetracyclic Heterocycle Compounds of Formula

##STR00001##

and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, R.sup.1, R.sup.2, R.sup.3 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.

A rotorcraft includes a rotor hub coupled to a mast and a plurality of rotor extensions. Each rotor extension is configured to secure a rotor blade to the rotor hub and includes a first connector configured to attach the rotor extension to a rotor blade, a second connector configured to attach the rotor extension to the rotor hub; a shaft disposed between the first and second connectors, and a damper mount attached to the second connector. The rotorcraft also includes a fairing enclosing the damper and at least a portion of the rotor hub.

The invention relates to nucleic acids, including lentiviral vectors and lentiviral vector particles, encoding at least one Hepatitis B virus (HBV) envelop surface of genotypes A and/or C antigen, at least one polymerase of genotypes A and/or C antigen, at least one HBX protein of genotypes A and/or C antigen, at least one HBV consensus core of genotypes A and/or C antigen, and at least one HBV consensus core MHCI and MHCII epitopes of genotypes A and/or C antigen. The invention encompasses these lentiviral vectors and lentiviral vector particles, methods of making the vectors, and their use, including medicinal uses. The lentiviral vectors and lentiviral vector particles are for use in administering to humans to induce immune responses against the HBV antigens.

This disclosure provides a multimeric human immunodeficiency virus (HIV) protein binding molecule, e.g., an dimeric IgA or a pentameric or hexameric IgM binding molecule, comprising at least two bivalent binding units, or variants or fragments thereof, each comprising at least two antibody heavy chain constant regions or fragments thereof, wherein each heavy chain constant region or fragment thereof is associated with an HIV antigen binding domain. Also provided are compositions comprising the multimeric binding molecules, polynucleotides encoding the multimeric binding molecules, and methods to make and use the multimeric binding molecules.

Provided are improved compositions and methods for achieving gene therapy in hematopoietic cells and hematopoietic precursor cells, including erythrocytes, erythroid progenitors, and embryonic stem cells. Also provided are improved gene therapy methods for treating hematopoietic-related disorders. Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.

Therapeutic formulations containing CD34+ stem cells derived from negative selection are described. The cells within the formulations can be genetically-modified for a number of therapeutic purposes. The disclosure is particularly useful for the treatment of patients with fragile stem cells or stem cells with low CD34+ expression levels.