Therapeutic uses of fibrinogen gamma prime variants

Abstract

The present invention relates to compositions comprising fibrinogen gamma prime variants for use in the treatment or prevention of an infection. The fibrinogen gamma prime variants in the composition comprise at least one fibrinogen gamma prime polypeptide chain. The compositions for use according to the invention may also comprise other fibrinogen variants. Compositions comprising fibrinogen gamma prime variants according to the invention improve survival time after infection up to more than 200 percent compared to WT fibrinogen. They may be used both therapeutically and prophylactically.

1 - 14 . (canceled) 
     
     
         15 . A composition for use in the treatment or prevention of an infection, the composition comprising a variant fibrinogen having two alpha polypeptide chains, two beta polypeptide chains and two gamma polypeptide chains, wherein at least one of the gamma polypeptide chains comprises a sequence according to SEQ ID NO. 3. 
     
     
         16 . The composition of  claim 15 , wherein one of the gamma polypeptide chains comprises a sequence according to SEQ ID NO. 1 and the other gamma polypeptide chain comprises a sequence according to SEQ ID NO. 3. 
     
     
         17 . The composition of  claim 15 , further comprising not more than about 75% of a fibrinogen comprising two alpha, two beta, and two gamma polypeptide chains with carboxyl-termini according to SEQ ID NO. 1, and wherein the 75% is by weight of a total fibrinogen in the composition. 
     
     
         18 . The composition of  claim 15 , wherein the variant fibrinogen in the composition is recombinant or plasma-derived or mixtures thereof. 
     
     
         19 . The composition of  claim 15 , wherein the infection in a human or animal subject is caused by or associated with a pathogen binding to the carboxyl-terminus of a fibrinogen gamma chain. 
     
     
         20 . The composition of  claim 15 , wherein the infection is caused by one or more pathogens selected from the group consisting of Gram negative bacteria, Gram positive bacteria, and fungi. 
     
     
         21 . The composition of  claim 20 , wherein the pathogen is selected from the group consisting of the genera  Escherichia, Bacteroides, Salmonella, Yersinia, Neisseria, Pseudomonas, Staphylococcus, Enterococcus, Streptococcus, Clostridium, Listeria, Bacillus; Aspergillus  and  Candida.    
     
     
         22 . The composition of  claim 21 , wherein the pathogen is  Staphylococcus aureus.    
     
     
         23 . The composition of  claim 22 , wherein the pathogen is selected from the group consisting of vancomycin resistant  S. aureus , methicillin-resistant  S. aureus , and multi-resistant  S. aureus  strains. 
     
     
         24 . The composition of  claim 15 , wherein the infection is selected from the group consisting of pneumonia, sepsis, bacteremia, peritonitis, endocarditis, skin or soft tissue infection, osteoarticular infections, prosthetic joint infection, bone infection, pleuropulmonary infection, wound infection, epidural abscesses, meningitis, toxic shock syndrome, urinary tract infection, and septic thrombophlebitis. 
     
     
         25 . The composition of  claim 15 , further comprising one or more antimicrobials. 
     
     
         26 . The composition of  claim 15 , wherein the composition is for administration by injection or infusion. 
     
     
         27 . The composition of  claim 15 , wherein the composition is for administration by intravenous, intra-arterial, intraperitoneal, intraglandular, or intravesicular injection or infusion. 
     
     
         28 . The composition of  claim 15 , further comprising a pharmaceutically-acceptable carrier. 
     
     
         29 . The composition of  claim 15 , wherein the composition is administered to humans, pets, poultry, livestock, sports animals or rodents.