Factor C for treating gram-negative bacterial infection

Details Factor C for treating gram-negative bacterial infection Factor C for treating gram-negative bacterial infection

2011-05-10

2011-05-10

Navarro, Mark (Department: 1645)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

C424S184100, C424S185100, C424S192100, C424S193100, C424S197110, C424S236100, C424S278100, C424S547000, C435S069700, C435S069800, C514S001100, C514S002100, C514S002200, C530S390100

Reexamination Certificate

active

07939492

ABSTRACT:
Recombinant fragments of Factor C are disclosed. These proteins and peptides show great potency in recognizing, binding to, neutralizing and removing endotoxin. These molecules can thus be used for anti-microbial, anti-endotoxin, and anti-sepsis therapy. SSCrFCES is a 38 kDa protein representing the LPS-binding domain of Factor C. The ability of SSCrFCES to bind lipid A was analyzed using an ELISA-based assay as well as surface plasmon resonance. Surface plasmon resonance similarly carried out for SSCrFC-sushi-1,2,3-GFP, SSCrFC-sushi-1GFP, and SSCrFC-sushi-3GFP confirmed their superior affinity for endotoxin. The 50% endotoxin-neutralizing concentration of SSCrFCES against 200 EU of endotoxin is 0.069 μM, suggesting that SSCrFCES is an effective inhibitor of LAL coagulation cascade. Although partially attenuated by human serum, as low as 1 μM of SSCrFCES inhibits the LPS-induced secretion of hTNF-α and hIL-8 by THP-1 and human pheripheral blood mononuclear cells with a potency more superior than polymyxin B. SSCrFCES is non-cytotoxic, with a clearance rate of 4.7 ml/minute. The LD90of SSCrFCES for LPS lethality in mice is achieved at 2 μM. These results demonstrate the endotoxin-neutralizing capability of SSCrFCES in vitro and in vivo, as well as its potential for use in the treatment of endotoxin-induced septic shock. Also embodied in this application is the use of the sushi peptides and their mutant derivatives as potent antimicrobials.

REFERENCES:
patent: 5439807 (1995-08-01), Grinna
patent: 5565362 (1996-10-01), Rosen
patent: 5648244 (1997-07-01), Kuliopulos et al.
patent: 5712144 (1998-01-01), Ding
patent: 5858706 (1999-01-01), Ding et al.
patent: 5985590 (1999-11-01), Ding et al.
patent: 6719973 (2004-04-01), Ding et al.
patent: WO 99/15676 (1999-04-01), None
patent: WO 00/26366 (2000-05-01), None
Pui et al., J. of Endotoxin Res. 1997. vol. 4:391-400).
Alberts et al.,Molecular Biology of the Cell, pp. 557-560, 1994.
Ding et al., “Expression of full length and deletion homologues ofCarcinoscorpius rotundicaudaFactor C inSaccharomyces cerevisiae: Immunoreactivity and endotoxin binding”J. Endotoxin Res. 4(1):33-43, 1997.
Ding et al., “Molecular cloning and sequence analysis of Factor C cDNA from the Singapore horseshoe crab,Carcinoscorpius rontundicauda”, Mol. Mar. Biol. and Biotechnol. 4(1):90-103, 1995.
Dwarakanath et al., “The Cys-rich and EGF-like domains ofCarcinoscorpius rotundicaudaFactor C yields soluble fusion protein with GFP”,Biotech, Lett. 19(10:1147-1150, 1997.
Muta et al., “Limulus Factor C. an endotoxin-sensitive serine protease zymogen with a mosaic structure of complement-like, epidermal growth factor-like, and lectin-like domains”,J. Biol. Chem. 226(10):6554-6561, 1991.
Pui et al., “Recombinant Factor C fromCarcinoscorpius rotundicaudabinds endotoxin”New Developments on Marine Biotechnology(ed. Le Gal and Halvorson), Plenum Press, New York, pp. 151-154, 1998.
Pul et al., “Yeast recombinant Factor C from horseshoe crab binds endotoxin and causes bacteriostasis”,J. Endotox. Res. 4(6):391-406, 1997.
Roopashree et al., “Expression ofCarcinoscorpius rotundicaudaFactor C inPichia pastoris”, Mol. Marine Biol. and Biotech. 5(4):334-343, 1996.
Tan et al., “Definition and endotoxin binding sites in horseshoe crab Factor C recombinant sushi proteins and neutralization of endotoxin by sushi peptides”,FASEB Journal14(2):1801-1813, 2000.
Tan et al., “High-affinity LPS binding domain(s) in recombinant Factor C of a horseshoe crab neutralizes LPS-induced lethality”,FASEB Journal14(7):859-870, 2000.

Affiliated with

Also associated with

Rating

Factor C for treating gram-negative bacterial infection does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Factor C for treating gram-negative bacterial infection, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Factor C for treating gram-negative bacterial infection will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2632944