Splice variants of the EGF receptor
View Patent ↗The present invention relates to a novel form of human EGFR found in certain tumors and conditions. The protein is termed here mLEEK, and the cDNA that encodes it has also been isolated. The mLEEK protein is capable of efficiently inducing the transcription of multiple genes resulting in various physiologic processes. Antibodies directed against the protein can be used for improving the diagnosis of diseases or for the treatment of diseases. The protein itself can be directly used or blocked for therapeutic purposes. Nucleic acid based probes or PCR primers specific for the mLEEK sequence can be used for diagnostic purposes. Inhibitory nucleic acid based molecules, such as antisense, siRNA, or shRNA, may be used for therapeutic purposes. The mLEEK sequence is essentially formed by the skipping of exons 2 through 22 in the EGF receptor gene leading to a fusion of exon 1 to exon 23. Other mutants are disclosed, which include the fusion of exon 1 to exon 24 and the fusion of exons 1 to exon 28.
1. An isolated antibody specifically binding to a mutant EGFR polypeptide having an extracellular domain less than about 30 amino acids, having a cytoplasmic autophosphorylation domain, and being substantially identical to the amino acid sequence of one of an exon 1:23 fusion polypeptide according to SEQ ID NO: 5, an exon 1:24 fusion polypeptide according to SEQ ID NO: 7, and an exon 1:28 fusion polypeptide according to SEQ ID NO: 9.
2. The antibody of claim 1 which is a monoclonal antibody.
3. The antibody of claim 1 which is an antibody fragment.
4. The antibody of claim 1 which is a polyclonal antibody.
5. The antibody of claim 1 wherein the amino acid sequence of the exon 1:24 fusion polypeptide comprises a sequence LEEKKXWMIDADSR (SEQ ID NO: 10), wherein X is any or no amino acid.
6. The antibody of claim 1 wherein the amino acid sequence of the exon 1:28 fusion polypeptide comprises a sequence LEEKKEYINQSVP (SEQ ID NO: 11).