C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 14/525 (2006.01) A61K 9/127 (2006.01) A61K 38/19 (2006.01) C07K 1/107 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2091771
2091771 9206995 PCTABS00012 A novel TNF-preparation with high cytolytic activity is disclosed. The TNF preparation includes modified forms of tumor necrosis factor associated with the surface of liposomes of small diameter (between 0.02-0.05 µm) known as SUV's. The tumor necrosis factor molecule is modified at up to 3 amino residues per trimer with nearly complete retention ($m(k)80-95 %) of biological activity. The modified TNF amino residues are modified to include long chain fatty acids via TNF lysyl side chains and/or N-terminal amino groups. The disclosed modified TNF molecules provide a highly efficient method for preparing liposome-associated TNF complexes in either standard MLVs or SUVs having enhanced in vivo stability. The binding of said modified TNF molecules to the surface of small unilamellar vesicles is with up to 100 % efficiency. Pharmacologically acceptable preparations of modified TNF for the particular treatment of TNF-responsive tumors are also provided. Methods of preparing liposome associated-lipophilic TNF molecules are provided. The liposomes of the present invention are decribed as small unilamellar vesicles (SUV). The liposomes of the present invention feature particularly small diameters in the range of 0.02 - 0.05 µm in diameter. Highly efficient methods of preparing stable, surface-associated protein liposome complexes having enhanced stability in vivo are also provided.
Hung Mien-Chie
Klostergaard Jim
Utsumi Toshihiko
Bereskin & Parr
The Board Of Regents Of The University Of Texas System
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