Neublastin variants
AssigneeBiogen Idec MA Inc.
InventorsAnthony Rossomando, Laura Silvian, R. Blake Pepinsky
Life of this patent
Estimating the term…
Abstract
Variant Neublastin polypeptides having substitutions at selected amino acid residues are disclosed. Substitution at one or more selected amino acid residues decreases heparin binding and increases serum exposure of variant Neublastin polypeptides. Also disclosed are methods of using variant Neublastin polypeptides to treat disorders and activate the RET receptor in a mammal.
Claims30
A polypeptide comprising an amino acid sequence at least 80% identical to amino acids 15-113 of SEQ ID NO:1, wherein the amino acid sequence comprises at least one amino acid substitution, relative to SEQ ID NO:1, selected from the group consisting of:
- an amino acid other than arginine at the position corresponding to position 48 of SEQ ID NO:1;
- an amino acid other than arginine at the position corresponding to position 49 of SEQ ID NO:1;
- and
- an amino acid other than arginine at the position corresponding to position 51 of SEQ ID NO:1,
- wherein the polypeptide, when dimerized, binds to a complex containing GFRalpha3 and RET.
2-16. (canceled)
A polypeptide comprising amino acids 15-113 of SEQ ID NO:2, amino acids 15-113 of SEQ ID NO:3, amino acids 15-113 of SEQ ID NO:4, amino acids 15-113 of SEQ ID NO:5, amino acids 15-113 of SEQ ID NO:8, or amino acids 15-113 of SEQ ID NO:9.
18-19. (canceled)
A polypeptide comprising an amino acid sequence at least 80% identical to amino acids 15-113 of SEQ ID NO:1, wherein the amino acid sequence comprises at least one amino acid substitution, relative to SEQ ID NO:1, selected from the group consisting of:
- an amino acid other than serine at the position corresponding to position 20 of SEQ ID NO:1;
- an amino acid other than glutamine at the position corresponding to position 21 of SEQ ID NO:1;
- an amino acid other than histidine at the position corresponding to position 32 of SEQ ID NO:1;
- an amino acid other than arginine at the position corresponding to position 33 of SEQ ID NO:1;
- an amino acid other than arginine at the position corresponding to position 39 of SEQ ID NO:1;
- an amino acid other than serine at the position corresponding to position 46 of SEQ ID NO:1;
- an amino acid other than arginine at the position corresponding to position 68 of SEQ ID NO:1;
- an amino acid other than glycine at the position corresponding to position 72 of SEQ ID NO:1;
- an amino acid other than serine at the position corresponding to position 73 of SEQ ID NO:1;
- and
- an amino acid other than valine at the position corresponding to position 94 of SEQ ID NO:1,
- wherein the polypeptide, when dimerized, binds to a complex containing GFRalpha3 and RET.
32-34. (canceled)
A polypeptide comprising an amino acid sequence at least 80% identical to SEQ ID NO:1, wherein the amino acid sequence comprises at least one amino acid substitution, relative to SEQ ID NO:1, selected from the group consisting of:
- an amino acid other than arginine at the position corresponding to position 7 of SEQ ID NO:1;
- an amino acid other than arginine at the position corresponding to position 9 of SEQ ID NO:1;
- and
- an amino acid other than arginine at the position corresponding to position 14 of SEQ ID NO:1,
- wherein the polypeptide, when dimerized, binds to a complex containing GFRalpha3 and RET.
36-47. (canceled)
Dependencies are inferred from the claim text.