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Abstract

The present invention relates to recombinant human interleukin-3 (hIL-3) variant or mutant proteins (muteins) in which segments of the polypeptide sequence of the human IL-3 polypeptide have been replaced by segments of the murine (mouse) interleukin-3 (mIL-3) polypeptide to form human/murine chimeric hybrid polypeptides. The human/mouse hybrid IL-3 may have amino acid deletions at the N-terminus or the C-terminus or at both the N- and C- termini and in some cases may also contain additional amino acid substitutions or deletions. The human/murine IL-3 muteins retain at least one biological activity of native hIL-3 and may also exhibit an improved side effects profile such as a reduction in the stimulation of leukotriene release or histamine release. The invention also relates to pharmaceutical compositions containing the h/m IL-3 hybrids and methods for using them. Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the IL-3 hybrid muteins, related microbial expression systems, and processes for making the IL-3 hybrids using the microbial expression systems.

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First Claim