Tyrosine kinase receptors and ligands

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues

Reexamination Certificate

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Reexamination Certificate

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06852838

ABSTRACT:
The present invention provides for a gene, designated as musk, that encodes a novel tyrosine kinase receptor expressed in high levels in denervated muscle. The invention also provides for an isolated polypeptide which activates MuSK receptor. The invention further provides for a polypeptide which is functionally equivalent to the MuSK activating polypeptide. The invention also provides assay systems that may be used to detect and/or measure ligands that bind the musk gene product. The present invention also provides for diagnostic and therapeutic methods based on molecules that activate MuSK.

REFERENCES:
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The Journal of Neuroscience, vol. 12, No. 9, Sep. 1992, pp. 3535-3544, Rupp, F., et al.: Structure and Chromosomal Localization of the Mammalian Agrin Gene.
EMBL Database, Apr. 22, 1995, Heidelberg, Hillier, L., et al.: “The WashU-Merck EST project, AC R12830.”
EMBL Database, Oct. 7, 1995, Heidelberg, Jay, P.: “Human cDNAs from HE6W library, AC H58758.”
NEURON, vol. 8, No. 6, Jun. 1992, pp. 1079-1086, Ferns, M., et al.: “RNA Splicing Regulates Agrin-Mediated Acetylcholine Receptor Clustering Activity on Cultured Myotubes.”
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NEURON, vol. 16, Apr. 1996, pp. 755-767, Gesemann, et al.: “Alternative Splicing of Agrin Alters in Binding to Heparin, Dystroglycan, and the Putative Agrin Receptor.”
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The EMBO Journal, vol. 15., No. 11, pp. 2625-2631, Meier, T., et al.: “AChR phosphorylation and aggregation induced by an agrin fragment that lacks the binding domain for α-dystroglycan.”, 1996.
The Journal of Cell Biology, vol. 128, No. 4, Feb. 1995, pp. 625-636, Gesemann, M., “Acetylcholine Receptor-aggregating Activity Of Agrin Isoforms and Mapping of the Active Site.”
The Journal of Cell Biology, vol. 128, No. 6, Mar. 1995, pp. 1121-1129, Wallace, B.: “Regulation of the interaction of nicotinic acetylcholine receptors with the cytoskeleton by agrin-activated protein tyrosine kinase.”
Annual Reviews in Neuroscience, vol. 18, 1995, pp. 443-462, Bowe, M. and Fallon, J.: “The Role Of Agrin in Synapse Formation.”
CELL, vol. 85, No. 4, May 17, 1996, pp. 513-523, Glass, D., et al.: “Agrin Acts via a MuSK Receptor Complex.”

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