Drug – bio-affecting and body treating compositions – Lymphokine
Patent
1994-11-30
1997-08-05
Russel, Jeffrey E.
Drug, bio-affecting and body treating compositions
Lymphokine
424450, 530351, 530410, A61K 9127, A61K 3819, C07K 1113
Patent
active
056539746
ABSTRACT:
A tumor necrosis factor (TNF) preparation with high cytolytic activity is described. The TNF preparation includes modified forms of TNF associated with or encapsulated within liposomes. The TNF molecule is modified at up to 3 amino acid residues per trimer with nearly complete retention (80-95%) of biological activity. Amino acid residues of the TNF are modified to include long chain fatty acids via TNF lysyl side chains and/or N-terminal amino acid groups. The disclosed modified TNF molecules provide a highly efficient method for preparing liposome-associated or encapsulated TNF complexes in either standard multilamellar vesicles (MLVs) or small unilamellar vesicles (SUVs) having enhanced in vivo stability. The liposomes of the present invention feature particularly small diameters in the range of 0.02-0.05 um in diameter. The binding of the modified TNF molecules to the surface of SUVs is up to 100% efficiency. Pharmacologically acceptable preparations of modified TNF for the particular treatment of TNF-responsive tumors are also provided. Methods of preparing liposomal-lipophilic TNF molecules are provided. Highly efficient methods of preparing stable, surface-associated protein liposome complexes having enhanced stability in vivo are also provided.
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Hung Mien-Chie
Klostergaard Jim
Utsumi Toshihiko
Board of Regents,The University of Texas System
Carroll Kathleen
Russel Jeffrey E.
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