Designed ankyrin repeat domains with altered surface residues
AssigneeMolecular Partners AG
InventorsKaspar BINZ, Johannes SCHILLING, Patrik FORRER, Victor LEVITSKY, Natalia VENETZ, Marcel WALSER
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Abstract
The present invention relates to designed ankyrin repeat domains with altered surface residues, as well as to proteins comprising such a designed ankyrin repeat domain, nucleic acids encoding such domains or proteins, methods of preparing such proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such proteins, nucleic acids or pharmaceutical compositions in the treatment of diseases.
Claims23
1-15. (canceled)
A ankyrin repeat domain comprising an N-terminal capping module having a glutamine (Q) at a position corresponding to position 8 of SEQ ID NO:
- 69 and/or having a leucine (L), valine (V), isoleucine (I), methionine (M), or alanine (A) at a position corresponding to position 15 of SEQ ID NO:
- 69.
An ankyrin repeat domain comprising an N-terminal capping module having an amino acid sequence DLGKKLLQAARAGQLDEVRELLKAGADVNA (SEQ ID NO:
- 75), wherein up to 10 amino acids of SEQ ID NO:
- 75 in positions other than position 8 and/or position 15 are optionally exchanged by other amino acids.
A protein comprising a ankyrin repeat domain, wherein said ankyrin repeat domain comprises an N-terminal capping module having a glutamine (Q) at a position corresponding to position 8 of SEQ ID NO:
- 69 and/or having a leucine (L), valine (V), isoleucine (I), methionine (M), or alanine (A) at a position corresponding to position 15 of SEQ ID NO:
- 69, wherein said protein has a prolonged terminal half-life compared to a protein comprising a ankyrin repeat domain comprising an N-terminal capping module having a glutamic acid (E) at a position corresponding to position 8 of SEQ ID NO:
- 69 and/or having an aspartic acid (D) at a position corresponding to position 15 of SEQ ID NO:
- 69.
A method of prolonging the terminal half-life of a protein comprising a ankyrin repeat domain, the method comprising the step of introducing in an N-terminal capping module of said ankyrin repeat domain a glutamine (Q) at a position corresponding to position 8 of SEQ ID NO:
- 69 and/or a leucine (L), valine (V), isoleucine (I), methionine (M), or alanine (A) at a position corresponding to position 15 of SEQ ID NO:
- 69.
Dependencies are inferred from the claim text.