Inhibin analogs
AssigneeHudson Institute of Medical Research
InventorsCraig Harrison, Kelly Walton
Life of this patent
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Abstract
The present invention relates to inhibin analogs, their method of production and their use in the treatment and prophylaxis of disease or conditions associated with reduced levels of inhibin and activin-mediated signaling.
Claims21
A mammalian inhibin analog precursor protein comprising a heterodimer of α-subunit and β-subunit precursors, wherein:
- i) the α-subunit has an amino acid sequence of SEQ ID NO:6 or an amino acid sequence having at least 90% sequence identity thereto after optimal alignment, and
- ii) the β-subunit is
- a βA-subunit having an amino acid sequence of SEQ ID NO:
- 2 or an amino acid sequence having at least 90% sequence identity thereto after optimal alignment, or
- a βB-subunit having an amino acid sequence of SEQ ID NO:
- 12 or an amino acid sequence having at least 90% sequence identity thereto after optimal alignment;
- wherein the α-subunit and the β-subunit precursors each have proprotein convertase cleavage sites, wherein at least one proprotein convertase cleavage sites is modified by an amino acid substitution mutation to render it more efficiently cleaved by the proprotein convertase to generate bioactive inhibin, and wherein the modified proprotein convertase cleavage site is ISSRKKRSVSS (SEQ ID NO:18).
A method for generating a bioactive inhibin analog said method comprising co-expressing in a cell or cell line a nucleic acid molecule encoding an α-subunit having the amino acid sequence as set forth in SEQ ID NO:8 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:8 after optimal alignment with the proviso that it comprises at least one modified proprotein convertase site to enable more efficient cleavage by the convertase and a β-subunit having the amino acid sequence as set forth in SEQ ID NO:4 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:4 after optimal alignment with the proviso that it comprises at least one modified proprotein convertase site to enable more efficient cleavage by the convertase for a time and under conditions sufficient for an inhibin precursor protein to be produced, cleaved by a proprotein convertase and secreted from the cell or cell line as a bioactive inhibin analog.
Dependencies are inferred from the claim text.