Il-11 muteins
AssigneeINSERM Institut National de la Sante et de la Rech
InventorsFrancois Paris, Yannick Jacques, Jean Content, Xiao-Ming Wang, Dimitri Harmegnies, Joachim Grotzinger
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Abstract
The present invention relates to new IL-11 muteins of which site I hydrophobocity has been increased. These muteins act as IL-11 agonist or hyperagonist, and are notably useful as anti-thrombocytopenia agents, and as agents improving the resistance of an organism to the deleterious in vivo effects induced by radiation or chemotherapy during the treatment of cancer or for the preparation of patient to transplantation.
Claims49
A method to produce an IL-11 agonist, which comprises producing a protein having the sequence of an IL-11 mutein that is derivable from a wild-type IL-11 sequence by replacement of at least two non-hydrophobic amino acids within the epitope for IL-11Rα by hydrophobic ones.
An IL-11 mutein, the sequence of which comprises a sequence which is derivable from the complete sequence of a wild-type IL-11:
- by replacement of the hydrophilic amino acids at positions 182 and 186 (positions computed by reference to the complete wild-type sequence) by X1 and X2 respectively, X1 and X2 being chosen from the group comprising:
- Valine (symbol=V or Val),
- Alanine (symbol=A or Ala),
- Proline (symbol=P or Pro),
- Leucine (symbol=L or Leu),
- Isoleucine (symbol=I or Ile),
- Phenylalanine (symbol=F or Phe),
- Methionine (symbol=M or Met), and
- Tryptophan (symbol=W or Trp),
- and by deletion of a N-terminal portion that does not exceed the first 34 N-terminal amino acids.
Dependencies are inferred from the claim text.