Polymer conjugates of mutated neublastin
AssigneeBiogen Idec MA Inc.
InventorsDinah Wen-Yee Sah, R. Blake Pepinsky, Paula Ann Boriack-Sjodin, Stephan S. Miller, Anthony Rossomando, Laura Silvian
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Abstract
A dimer comprising a mutated neublastin polypeptide coupled to a polymer is disclosed. Such dimers exhibit prolonged bioavailability and, in preferred embodiments, prolonged biological activity relative to wild-type forms of neublastin.
Claims68
An isolated polypeptide comprising an amino acid sequence at least 90% identical to amino acids 8-113 of SEQ ID NO:1, wherein the polypeptide includes at least one amino acid substitution selected from the group consisting of:
- (a) an amino acid other than arginine at the position corresponding to position 14 in SEQ ID NO:1;
- (b) an amino acid other than arginine at the position corresponding to position 39 in SEQ ID NO:1;
- (c) an amino acid other than arginine at the position corresponding to position 68 in SEQ ID NO:1;
- and
- (d) an amino acid other than asparagine at the position corresponding to position 95 in SEQ ID NO:1,
- wherein the polypeptide, when dimerized, binds to GFRα3.
A polypeptide comprising an amino acid sequence at least 95% identical to amino acids 15-113 of SEQ ID NO:2 (NBN99), wherein the polypeptide includes at least one amino acid substitution selected from the group consisting of:
- (a) an amino acid other than arginine at the position corresponding to position 39 in SEQ ID NO:2;
- (b) an amino acid other than arginine at the position corresponding to position 68 in SEQ ID NO:2;
- and
- (c) an amino acid other than asparagine at the position corresponding to position 95 in SEQ ID NO:2,
- wherein the polypeptide, when dimerized, binds to GFRα3.
Dependencies are inferred from the claim text.