Multitrophic and multifunctional chimeric neurotrophic factors
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsEric M. Shooter, Ulrich Suter, Nancy P. Ip, Stephen P. Squinto, Mark E. Furth, Ronald M. Lindsay
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AssigneeRegeneron Pharmaceuticals, Inc.
InventorsEric M. Shooter, Ulrich Suter, Nancy P. Ip, Stephen P. Squinto, Mark E. Furth, Ronald M. Lindsay
Estimating the term…
The present invention relates to chimeric neurotrophic factors which comprise at least a portion of a naturally occurring cellular factor and a portion of at least one other molecule such that the resulting chimeric molecule has neurotrophic activity. It is based, in part, on the discovery that chimeric molecules comprising portions of both NGF and BDNF are likely to possess neurotrotrophic activity, and in some cases exhibit a spectrum of activity larger than that of either parent molecule. It is further based on the discovery that chimeric molecules comprising neurotrophic factor sequences as well as additional peptide sequences may retain neurotrophic activity, and in some cases may exhibit a more potent activity than the parent factor. The chimeric neurotrophic factor molecules of the invention provide a number of advantages relative to naturally occurring neurotrophic factors. Chimeric neurotrophic factors may be used to provide, for example, the activity of two neurotrophic factors in a single molecule, or may serve as superagonists of an endogenous neurotrophic factor, thereby enabling an increased biological response at lower doses.
A chimeric protein which has neurotrophic activity and which consists essentially of a first neurotrophic factor, wherein about 3 to about 13 consecutive amino acids of said first neurotrophic factor are replaced by a similarly sized amino acid sequence of a second neurotrophic factor such that the resulting chimeric protein differs in sequence by at least 3 amino acids from the first neurotrophic factor.
A chimeric protein which has neurotrophic activity and which consists essentially of a portion of a member of the neurotrophin family and, the myc peptide having the sequence GLU-GLN-LYS-LEU-ILE-SER-GLU-GLU-ASP-LEU, wherein said myc peptide confers on said chimeric protein a neurotrophic activity not displayed by the neurotrophin.
A chimeric protein having an amino acid sequence substantially as set forth for chimera S6 in FIG. 10.
Dependencies are inferred from the claim text.