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AssigneeThe Regents of the University of California
InventorsCorey S. Goodman, Thomas Kidd, Katja Brose, Marc Tessier-Lavigne
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Disclosed are methods and compositions for identifying agents which modulate the interaction of Robo and a Robo ligand and for modulating the interaction of Robo and a Robo ligand. The methods for identifying Robo:ligand modulators find particular application in commercial drug screens. These methods generally comprise (1) combining a Robo polypeptide, a Slit polypeptide and a candidate agent under conditions whereby, but for the presence of the agent, the Robo and Slit polypeptides engage in a first interaction, and (2) determining a second interaction of the Robo and Slit polypeptides in the presence of the agent, wherein a difference between the first and second interactions indicates that the aget modulates the interaction of the Robo and Slit polypeptides. The subject methods of modulating the interaction of Robo and a Robo ligand involve combining a Robo polypeptide, a Slit polypeptide and a modulator under conditions whereby, but for the presence of the modulator, the Robo and Slit polypeptides engage in a first interaction, whereby the Robo and Slit polypeptides engage in a second interaction different from the first interaction. In a particular embodiment, the modulator is dominant negative form of the Robo or Slit polypeptide.
An isolated antibody that specifically binds a slit protein comprising the sequence of SEQ. ID NO:2.
A composition comprising an antibody that specifically binds a slit protein comprising the sequence of SEQ ID NO:2.
An isolated antibody that specifically binds a Slit polypeptide comprising SEQ ID NO:2, or a subsequence thereof having at least 16 consecutive amino acids residues thereof and comprising one or more unboxed amino acid residues of SEQ ID NO:2 in at least one table selected from the group consisting of Table 1 and Table 2.
An isolated antibody that specifically binds a Slit polypeptide consisting of SEQ ID NO:2.
An isolated antibody that specifically binds a fragment of Slit polypeptide SEQ ID NO:2 having one or more Slit domain selected from the group of a leucine rich repeat, an EGF repeat and cysteine knot motif.
A composition comprising an antibody that specifically binds a Slit polypeptide comprising the sequence of SEQ ID NO:2, or a subsequence thereof having at least 16 consecutive amino acid residues thereof and comprising one or more unboxed amino acid residues of SEQ ID NO:2 in at least one table selected from the group consisting of Table 1 and Table 2, further comprising a pharmaceutically acceptable excipient.
A method of screening for an antibody that modulates Robo/Slit interaction comprising:
Dependencies are inferred from the claim text.