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AssigneesProgenics Pharmaceuticals, Inc., Aaron Diamond AIDS Research Centre (ADARC)
InventorsJames M. Binley, Norbert Schuelke, William C. Olson, Paul J. Maddon, John P. Moore
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This invention provides a DNA which upon transcription produces an RNA encoding a modified HIV-1 gp140 polypeptide, which polypeptide upon cleavage produces a modified gp120 and a modified ectodomain of gp41 which together form a complex exhibiting enhanced binding to HIV-1 neutralizing antibodies and reduced binding to HIV-1 non-neutralizing antibodies, wherein the modifications comprise an A492C mutation in gp120 and a T596C mutation in gp41, said mutations being numbered by reference to the HIV-1 isolate JR-FL, and resulting in a disulfide bond between gp120 and ectodomain gp41 which stabilizes the otherwise non-covalent gp120-gp41 interaction.
A DNA which upon transcription produces an RNA encoding a modified gp140 polypeptide of an HIV-1 isolate, which polypeptide upon cleavage produces a modified gp120 and a modified gp41 ectodomain which together form a complex, said complex (i) exhibiting enhanced binding to HIV-1 neutralizing antibodies and reduced binding to HIV-1 non-neutralizing antibodies, wherein the modified gp120 comprises an A492C mutation and the modified gp41 ectodomain comprises a T596C mutation, said mutations being numbered by reference to HIV-1 JR-FL, and (ii) permitting the formation of a disulfide bond between the modified gp120 and the modified gp41 ectodomain which stabilizes the complex.
A DNA which upon transcription produces an RNA encoding a modified gp140 polypeptide of an HIV-1 isolate, which polypeptide upon cleavage produces a modified gp120 and a modified gp41 ectodomain which together form a complex, said complex (i) exhibiting enhanced binding to HIV-1 neutralizing antibodies and reduced binding to HIV-1 non-neutralizing antibodies, wherein the modified gp120 comprises a V35C mutation, a Y39C mutation, a W44C mutation, a P484C mutation, a G486C mutation, a A488C mutation, a P489C mutation, a T490C mutation, or a A492C mutation and the modified gp41 ectodomain comprises a D580C mutation, a W587C mutation, a T596C mutation, a V599C mutation, a P600C mutation, or a W601C mutation, said mutations being numbered by reference to HIV-1 JR-FL, and (ii) permitting formation of a disulfide bond between the modified gp120 and the modified gp41 ectodomain which stabilizes the complex.
Dependencies are inferred from the claim text.