Bacterical/permability-increasing protein(BPI) deletion analogs

Abstract

Novel BPI deletion analogs are provided that consist of amino acid residues 10 through 193 of mature human BPI wherein the cysteine residue at BPI amino acid position 132 is replaced by another amino acid. Fusion proteins comprising these analogs are also provided, as are polynucleotides encoding these products, materials and methods for their recombinant production, compositions and medicaments of these products, and therapeutic uses for these products.

1 . A bactericidal/permeability-increasing protein (BPI) deletion analog consisting of amino acid residues 10 through 193 of mature human BPI, wherein a cysteine residue at position 132 is replaced by a different amino acid.  
     
     
         2 . The BPI deletion analog of  claim 1  wherein the amino acid replacing said cysteine residue is a non-polar amino acid selected from the group consisting of alanine and serine.  
     
     
         3 . The BPI deletion analog of  claim 1  wherein the cysteine residue at position 132 is replaced by alanine.  
     
     
         4 . A polynucleotide encoding the BPI deletion analog of  claim 1 .  
     
     
         5 . A polynucleotide encoding the BPI deletion analog of  claim 3 .  
     
     
         6 . The polynucleotide of  claim 4  further comprising the twenty-seven amino acid leader sequence of BPI.  
     
     
         7 . The polynucleotide of  claim 4  which is a DNA.  
     
     
         8 . An expression vector comprising the DNA according to  claim 7 .  
     
     
         9 . A host cell stably transformed or transfected with the DNA of  claim 7  in a manner allowing expression in said host cell of said polypeptide deletion analog.  
     
     
         10 . A eukaryotic host cell according to  claim 9 .  
     
     
         11 . The host cell of  claim 10  which is a CHO cell.  
     
     
         12 . A method for producing a BPI deletion analog polypeptide comprising growing a host cell according to  claim 9  in a suitable culture medium and isolating said polypeptide from said host cell or said culture medium.  
     
     
         13 . The polypeptide product of the method of  claim 12 .  
     
     
         14 . A composition comprising the BPI deletion analog of  claim 1  and a pharmaceutically-acceptable diluent, adjuvant, or carrier.  
     
     
         15 . A composition comprising the BPI deletion analog of  claim 3  and a pharmaceutically-acceptable diluent, adjuvant, or carrier.  
     
     
         16 . A composition comprising the BPI deletion analog of  claim 13  and a pharmaceutically-acceptable diluent, adjuvant, or carrier.  
     
     
         17 . An improved method of administering a BPI protein product to a subject comprising administering the composition of  claim 14  to said subject.  
     
     
         18 . An improved method of administering a BPI protein product to a subject comprising administering the composition of  claim 15  to said subject.  
     
     
         19 . An improved method of administering a BPI protein product to a subject comprising administering the composition of  claim 16  to said subject.