The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Aug. 05, 1997
Filed:
Nov. 30, 1994
Mien-Chie Hung, Houston, TX (US);
Toshihiko Utsumi, Yamaguchi, JP;
Jim Klostergaard, Kingwood, TX (US);
Board of Regents,The University of Texas System, Austin, TX (US);
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.