Chimeric neuregulins and method of making and use thereof
AssigneeMorehouse School of Medicine
InventorByron D. FORD
Life of this patent
Estimating the term…
Abstract
Composition containing a chimeric neuregulin polypeptides and method of making such polypeptides are disclosed. The chimeric neuregulin comprises a first moiety of at least 10 amino acids, wherein the first moiety is derived from a first polypeptide; and a second moiety of at least 5 amino acids, wherein the second moiety is derived from a second polypeptide; wherein the first polypeptide is a neuregulin and the chimeric neuregulin exhibits an enhanced binding affinity to integrin, Erb 3, or Erb 4 comparing to that of the first neuregulin.
Claims15
1-22. (canceled)
A method for ameliorating neuronal damage in a subject, comprising:
- administering to said subject an effective amount of a pharmaceutical composition comprising:
- a chimeric neuregulin polypeptide having an integrin domain that binds to an integrin and an Erb3/4 binding domain that binds to Erb3 and/or Erb4, said chimeric neuregulin polypeptide comprising:
- a neuregulin backbone derived from a native neuregulin polypeptide;
- and a donor fragment of at least one amino acid;
- wherein said donor fragment (1) replaces a target fragment in said native neuregulin polypeptide, wherein said donor fragment differs from said target fragment by at least one amino acid, or (2) is inserted into an insertion site of said neuregulin polypeptide;
- and wherein said donor fragment forms at least a portion of said integrin binding domain and/or at least a portion of said Erb3/4 binding domain of said chimeric neuregulin polypeptide, and
- a pharmaceutically acceptable carrier.
A method for preventing or ameliorating secondary neuronal injury and inflammation following traumatic brain injury (TBI), comprising:
- administering into a subject in need of such treatment an effective amount of a pharmaceutical composition comprising:
- a chimeric neuregulin polypeptide having an integrin domain that binds to an integrin and an Erb3/4 binding domain that binds to Erb3 and/or Erb4, said chimeric neuregulin polypeptide comprising:
- a neuregulin backbone derived from a native neuregulin polypeptide;
- and a donor fragment of at least one amino acid;
- wherein said donor fragment (1) replaces a target fragment in said native neuregulin polypeptide, wherein said donor fragment differs from said target fragment by at least one amino acid, or (2) is inserted into an insertion site of said neuregulin polypeptide;
- and wherein said donor fragment forms at least a portion of said integrin binding domain and/or at least a portion of said Erb3/4 binding domain of said chimeric neuregulin polypeptide, and
- a pharmaceutically acceptable carrier.
A method for ameliorating blood vessel damage caused by acute mechanical or chemical assault in a subject, comprising:
- administering to said subject an effective amount of a pharmaceutical composition comprising:
- a chimeric neuregulin polypeptide having an integrin domain that binds to an integrin and an Erb3/4 binding domain that binds to Erb3 and/or Erb4, said chimeric neuregulin polypeptide comprising:
- a neuregulin backbone derived from a native neuregulin polypeptide;
- and a donor fragment of at least one amino acid;
- wherein said donor fragment (1) replaces a target fragment in said native neuregulin polypeptide, wherein said donor fragment differs from said target fragment by at least one amino acid, or (2) is inserted into an insertion site of said neuregulin polypeptide;
- and wherein said donor fragment forms at least a portion of said integrin binding domain and/or at least a portion of said Erb3/4 binding domain of said chimeric neuregulin polypeptide, and
- a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.