Patents Assigned to University of Michigan, The Board of Regents . . . et al.
  • Patent number: 5721212
    Abstract: Less toxic agents for reversal of heparin or low molecular weight heparin anticoagulation which are synthetic protamine-like polycationic peptides having a total cationic charge which is less than that of n-protamine. In preferred embodiments, arginine resides of n-protamine are replaced with lysine residues for ease of manufacture. Selective positively charged arginine residues have been replaced with an uncharged amino acid residue or its analog, such as glycine or glutamine, in order to reduce the total cationic charge on the polycationic peptide to the range of about ?+14! to ?+18!, preferably ?+16!. In specific embodiments, there are sequences of 29 amino acid residues wherein 4 to 5 clusters of 2 to 4 positively charged amino acids are separated by 2 to 6 neutral amino acids. The C-terminus and the N-terminus can be modified to mitigate against in vivo degradation by carboxypeptidases and aminopeptidases.
    Type: Grant
    Filed: July 9, 1996
    Date of Patent: February 24, 1998
    Assignee: University of Michigan, The Board of Regents . . . et al.
    Inventors: Thomas W. Wakefield, James C. Stanley, Philip C. Andrews