Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments
First Claim
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1. A method for determining an increased likelihood of pharmacological effectiveness of treatment by an EGFR tyrosine kinase inhibitor in an individual diagnosed with non-small cell lung cancer comprising:
- determining the presence or absence of at least one nucleotide variance in exon 18, 19, or 21 of the epidermal growth factor receptor (EGFR) gene in DNA from a non-small cell lung cancer tumor sample from the individual, wherein the presence of at least one nucleotide variance selected from;
1) an in-frame deletion in exon 19 of the EGFR gene consisting of a deletion within codons 746 to 753 that results in amino acid changes comprising a deletion of at least amino acids leucine, arginine, and glutamic acid at position 747, 748, and 749 of SEQ ID NO;
512;
2) a substitution in exon 21 that results in an amino acid change consisting of a substitution of arginine for leucine at position 858 (L858R) of SEQ ID NO;
512, or a substitution in exon 21 that results in an amino acid change consisting of a substitution of glutamine for leucine at position 861 (L861Q) of SEQ ID NO;
512;
or3) a substitution in exon 18 that results in an amino acid change consisting of a substitution of cysteine for glycine at position 719 (G719C) of SEQ ID NO;
512;
indicates an increased likelihood of pharmacological effectiveness of treatment by an EGFR tyrosine kinase inhibitor in the individual.
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Abstract
The present invention is directed to a method for determining the responsiveness of cancer to an epidermal growth factor receptor (EGFR) treatment. In a preferred embodiment, the presence of at least one variance in the kinase domain of the erbB1 gene confers sensitivity to the tyrosine kinase inhibitor gefitinib. Thus, a diagnostic assay for these mutations will allow for the administration of gefitinib, erlotinib and other tyrosine kinase inhibitors to those patients most likely to respond to the drug.
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21 Claims
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1. A method for determining an increased likelihood of pharmacological effectiveness of treatment by an EGFR tyrosine kinase inhibitor in an individual diagnosed with non-small cell lung cancer comprising:
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determining the presence or absence of at least one nucleotide variance in exon 18, 19, or 21 of the epidermal growth factor receptor (EGFR) gene in DNA from a non-small cell lung cancer tumor sample from the individual, wherein the presence of at least one nucleotide variance selected from; 1) an in-frame deletion in exon 19 of the EGFR gene consisting of a deletion within codons 746 to 753 that results in amino acid changes comprising a deletion of at least amino acids leucine, arginine, and glutamic acid at position 747, 748, and 749 of SEQ ID NO;
512;2) a substitution in exon 21 that results in an amino acid change consisting of a substitution of arginine for leucine at position 858 (L858R) of SEQ ID NO;
512, or a substitution in exon 21 that results in an amino acid change consisting of a substitution of glutamine for leucine at position 861 (L861Q) of SEQ ID NO;
512;
or3) a substitution in exon 18 that results in an amino acid change consisting of a substitution of cysteine for glycine at position 719 (G719C) of SEQ ID NO;
512;indicates an increased likelihood of pharmacological effectiveness of treatment by an EGFR tyrosine kinase inhibitor in the individual. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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12. A method for determining an increased likelihood of pharmacological effectiveness of treatment by an EGFR tyrosine kinase inhibitor in an individual diagnosed with non-small cell lung cancer comprising:
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determining the presence or absence of at least one nucleotide variance in exon 19, or 21 of the epidermal growth factor receptor (EGFR) gene in DNA from a non-small cell lung cancer tumor sample from the individual, wherein the presence of at least one nucleotide variance selected from; 1) an in-frame deletion in exon 19 of the EGFR gene consisting of a deletion within codons 746 to 753 that results in amino acid changes comprising a deletion of at least amino acids leucine, arginine, and glutamic acid at position 747, 748, and 749 of SEQ ID NO;
512;
or2) a substitution in exon 21 that results in an amino acid change consisting of a substitution of arginine for leucine at position 858 (L858R) of SEQ ID NO;
512, or a substitution in exon 21 that results in an amino acid change consisting of a substitution of glutamine for leucine at position 861 (L861Q) of SEQ ID NO;
512;indicates an increased likelihood of pharmacological effectiveness of treatment by an EGFR tyrosine kinase inhibitor in the individual. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20, 21)
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Specification