Therapeutic uses of bactericidal/permeability-increasing protein dimer products

DETAILED DESCRIPTION The present invention provides significant improvements in therapeutic uses of BPI protein products through the provision of product formulations which include BPI protein products in the form of physiologically stable covalently or non-covalently linked dimeric associations of BPI protein product monomers ("BPI dimers" or "dimeric BPI protein products") which have been discovered to possess enhanced in vivo biological activity in comparison to monomeric product forms.
In preferred therapeutic formulations of the invention, dimeric forms of BPI protein products constitute greater than 50 percent by weight of such products.
Because of the enhanced in vivo activity of dimeric associations of BPI protein product monomers, product formulations including greater than 75 percent by weight, greater than 90 percent by weight and 95 percent or more by weight dimeric product are successively more preferred.
Therapeutic BPI protein product formulations of the present invention preferably include homodimeric products, but heterodimeric products are also within the contemplation of the invention.
Formulations, also preferably include dimeric and, if any, monomeric forms of BPI protein products to the exclusion of higher molecular weight multimer forms such as trimers and the like.
Except for formulations or cotreatments developed specifically to include agents that are non-BPI protein products, including, for example, antibiotics and the like as additional active ingredients, formulations or cotreatments according to the invention are substantially free of contaminating materials such as DNA, endotoxin and potentially immunogenic proteins and peptides (including human or recombinant host cell proteins and peptides) which might disqualify the formulations or cotreatments from regulatory acceptance.
The invention also provides uses of a bactericidal/permeability-increasing protein product composition containing greater than 50 percent of a stable covalently or non-covalently linked dimeric product for the manufacture of a medicament for neutralizing endotoxin for the treatment of conditions associated with endotoxin, including exposure to gram-negative bacterial endotoxin in circulation, endotoxemia, gram-negative bacterial infection, mycobacterial infection, and depressed reticuloendothelial cell system function