Baxter International Inc.

Mayo Foundation for Medical Education and Research

Palatin Technologies Incorporated

Nextran Inc.

Lisa E Diamond

John S Logan

Shubh D Sharma

Annette M Shadiack

Ajay K Sharma

Carl Spana

Cunqi Cui

Alexander Schwarz

Thomas A Davis

Guerard W Byrne

Dennis C Earle

Geurard W Byrne

Multiple agent therapy for treatment of sexual dysfunction, including male erectile dysfunction, with sequential administration a type V phosphodiesterase inhibitor (PDE-5), such as sildenafil, preferably wherein the PDE-5 inhibitor is administered by oral dose means, and a melanocortin 3 and/or 4 receptor agonist, such as Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH (PT-141) preferably wherein the PT-141 is formulated for and administered by intranasal means, and further preferably wherein the PDE-5 inhibitor is administered prior to PT-141.

Multiple agent therapy for sexual dysfunction

Porcine nucleic acid sequences flanking potentially infectious porcine endogenous retroviral (PERV) insertion sites have been identified and isolated. The unique flanking sequences include porcine nucleic acid sequences that flank the 3' end and porcine nucleic acid sequences that flank the 5&#x2032; end of PERV insertion sites. The present invention provides compositions and methods for detecting presence of PERV in a sample, particularly those with infectious potential. In addition, the invention relates to breeding of pigs or selection of porcine tissue that is free of infectious PERV for use as a xenotransplant tissue.

Elimination of endogenous porcine retrovirus

One aspect of the present invention relates to methods and compositions for attenuating xenograft rejection by administering, to an animal receiving the xenograft, an amount of a polymer-derivatized xenoantigen (hereinafter &ldquo;xenopolymer&rdquo;) effective for inhibiting or lessening the severity of hyperacute rejection response (HAR), or other immunological response to the graft, that is dependent on the presence of the xenoantigen on the grafted tissues or cells. In certain embodiments, the xenopolymer is administered in an amount sufficient to neutralize host antibodies (&ldquo;xenoreactive antibodies&rdquo; or &ldquo;XNA&rdquo;) immunoreactive with the xenoantigen. The xenopolymer may additionally, or alternatively, be used as a tolerogen (or anergen) for the xenoantigen, e.g., able to suppress, to some degree, the production/secretion of XNAs by the immune system of the host.

Inhibition of xenoreactive antibodies

A method of xenotransplanting organs, tissues, cells or non-viable components which reduces or prevents antibody-mediated rejections, including hyperacute rejection, is provided wherein transgenic animals are produced that express at least one enzyme which masks or reduces the level of the antigenic Gal.alpha.(1,3)Gal or gal epitope, and at least one complement inhibitor such as CD59, DAF and/or MCP. The transgenic animals which express both a gal epitope-reducing enzyme and a complement inhibitor will have masked or reduced levels of the gal epitope and will be much less likely to produce an antibody-mediated rejection following transplantation, and the expression of the complement inhibitor will also suppress complement activation and reduce even further a severe immune reaction following the transplantation of donor organs, tissue, cells or non-viable components from the transgenic animals so produced. In addition, transgenic animals are provided which express a plurality of complement inhibitors or other proteins from a locus of genes at a single integration site. The present invention is thus advantageous in that it can provide xenogeneic organs, tissues, cells and non-viable components which can be transplanted safely and effectively into humans with a reduction or elimination of antibody-mediated rejection to an extent not previously possible, and which will significantly reduce the need to obtain donor organs, tissues, cells or non-viable components from human or primate donors.

Method of producing transgenic animals for xenotransplantation

Growing community of inventors

Princeton, NJ, United States of America

Lisa E Diamond