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US 7,888,071 B2Granted
DNA encoding IL-2 fusion proteins with modulated selectivity
AssigneeMerck Patent GmbH
InventorsStephen D. Gillies, Pascal Andre Stein, Kin-Ming Lo
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Abstract
The invention provides cytokine fusion proteins with an increased therapeutic index, and methods to increase the therapeutic index of such fusion proteins. The fusion proteins of the invention are able to bind to more than one type of cytokine receptor expressed on cells and also bind to more than one cell type. In addition, the fusion proteins of the invention exhibit a longer circulating half-life in a patient's body than the corresponding naturally occurring cytokine.
Claims26
A DNA encoding a fusion protein comprising a non-IL-2 moiety fused to a mutant IL-2 moiety,
- wherein the mutant IL-2 moiety comprises an amino acid substitution changing an aspartic acid to a threonine at a position corresponding to position 20 of a mature human IL-2 protein,
- wherein the mature human IL-2 protein consists of the amino acid sequence set forth in SEQ ID NO:3,
- wherein said fusion protein exhibits greater selectivity than a reference protein towards cells expressing a high affinity receptor,
- wherein said reference protein comprises the non-IL-2 moiety fused to a non-mutant IL-2 moiety, and
- wherein said selectivity is measured as a ratio of activation of cells expressing IL-2Rαβγ receptor relative to activation of cells expressing IL-2Rβγ receptor.
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Dependencies are inferred from the claim text.