G.d. Searle & Company

Pharmacia Corporation

Joseph Polazzi

John Patrick McKearn

John Warren Thomas

Alan Michael Easton

Barbara Kure Klein

Sarah Ruth Braford-Goldberg

S Christopher Bauer

Maire Helena Caparon

Mark Allen Abrams

Kumnan Paik

Peter O Olins

Peter Q Olins

The present invention relates to recombinant human interleukin-3 (hIL-3) variant or mutant proteins (muteins). These hIL-3 muteins contain amino acid substitutions and may also have amino acid deletions at both the N- and C-termini. The invention also relates to pharmaceutical compositions containing the hIL-3 muteins and methods for using them. Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the hIL-3 muteins, related microbial expression systems, and processes for making the hIL-3 muteins using the microbial expression systems. Included in the present invention are deletion mutants of hIL-3 in which from 1 to 14 amino acids have been deleted from the N-terminus, and from 1 to 15 amino acids (a.a.119 to 133) have been deleted from the C-terminus, and which also contain amino acid substitutions in the polypeptide. These hIL-3 multiple mutation polypeptides may have biological activities similar to or better than hIL-3 and, in some cases, may also have an improved side effect profile.

Methods of using interleukin-3 (IL-3) mutant polypeptides for ex-vivo expansion of hematopoietic stem cells

Interleukin-3 (IL-3) mutant polypeptides and their recombinant production

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Chesterfield, MO, United States of America

Joseph Polazzi