NGF variants
AssigneeGenentech, Inc.
InventorsLeonard G. Presta, Roman Urfer, John W. Winslow
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Abstract
NGF variants which have trkC-binding activity and trkC-signal inducing activity are provided. The variants optionally have trkA or trkB binding and signal induction activity. The NGF variants of the present invention are useful in the treatment of neuronal disorders. Nucleic acids and expression vectors encoding the NGF variant neurotrophins are also provided.
Claims17
A human NGF variant having substitutions at amino acid positions G23, H84, and at either V18 or V20, but not at both V18 and V20, that impart trkC binding, and optionally having a substitution at D16 other than substitution D16A, said human NGF variant having at least 95% amino acid sequence identity with SEQ ID NO:
- 1, wherein said human NGF variant promotes neuronal survival or neurite outgrowth of a neuron selected from the group consisting of sympathetic ganglion neurons (SN), dorsal root ganglion neurons (DRG), nodose ganglion neurons (ND), and motoneurons as measured in a neuronal survival or a neurite outgrowth assay.
A human NGF variant having substitutions at amino acid positions G23, H84, and at either V18 or V20, but not at both V18 and V20, that impart trkC binding, and either F86 or T81 or both, and optionally having a substitution at D16 other than D16A, said human NGF variant having at least 95% amino acid sequence identity with SEQ ID NO:
- 1, wherein said human NGF variant promotes neuronal survival or neurite outgrowth of a neuron selected from the group consisting of sympathetic ganglion neurons (SN), dorsal root ganglion neurons (DRG), nodose ganglion neurons (ND), and motoneurons as measured in a neuronal survival or a neurite outgrowth assay.
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