EGF motif protein, EGFL6 materials and methods
OwnerJohn Ford, Vinod Asundi +8inventors
InventorsJohn Ford, Vinod Asundi, Chenghua Liu, Y. Tom Tang, Victoria Yamasaki, George Yeung, Jie Zhang, Ping Zhou, Hua Zhou, Radoje T. Drmanac
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Abstract
The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins. In particular, the polypeptides of the invention is useful for detecting cancers.
Claims67
An isolated polynucleotide encoding a polypeptide comprising:
- (a) the amino acid sequence set forth in SEQ ID NO:
- 4, or the mature protein portion thereof,
- (b) the amino acid sequence set forth in SEQ ID NO:
- 6, or the mature protein portion thereof,
- (c) the amino acid sequence set forth in SEQ ID NO:
- 24, or the mature protein portion thereof,
- (d) the amino acid sequence set forth in SEQ ID NO:
- 28, or the mature protein portion thereof;
- (e) the amino acid sequence set forth in SEQ ID NO:
- 30, or the mature protein portion thereof;
- or
- (f) the amino acid sequence set forth in SEQ ID NO:
- 32, or the mature protein portion thereof.
An isolated polypeptide comprising:
- (a) the amino acid sequence of SEQ ID NO:
- 4,
- (b) the amino acid sequence of SEQ ID NO:
- 6,
- (c) the amino acid sequence of SEQ ID NO:
- 24,
- (d) the amino acid sequence of SEQ ID NO:
- 28 or
- (e) the mature protein portion of any one of (a)-(d),
A method for diagnosing cancer comprising the step of detecting a polynucleotide having the nucleotide sequence set forth in SEQ ID NO:23, a fragment thereof, or a nucleotide sequence having at least about 90% sequence identity to SEQ ID NO:
- 23 in a human sample.
The method of claim 18 wherein the cancer diagnosed is selected from the group consisting of lung cancer, brain cancer, prostate cancer, breast cancel, skin cancer, lymphoma, sarcoma, leukemia and colon cancer.
A method for diagnosing cancer comprising the step of detecting an EGFL6 polypeptide comprising the mature protein portion of the amino acid sequence set forth in SEQ ID NO:
- 24 or an amino acid sequence having at least about 90% sequence identity to SEQ ID NO:
- 24 in a human sample.
A method of inhibiting proliferation of cells expressing an EGFL6 polypeptide or variant thereof having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:
- 24, comprising the step of contacting said cells with an antibody or fragment thereof that specifically binds said EGFL6 or variant thereof.
A method of inhibiting proliferation of cells expressing an EGFL6 polypeptide or variant thereof having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:
- 24, comprising the step of contacting said cells with an antisense polynucleotide that specifically binds a polynucleotide encoding said EGFL6 or variant thereof.
A pharmaceutical composition comprising an antibody or fragment thereof that specifically binds an EGFL6 polypeptide or variant thereof having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:
- 24, and a pharmaceutically acceptable carrier.
A gene delivery vector comprising an antisense polynucleotide that specifically binds to a polynucleotide encoding an EGFL6 polypeptide or variant thereof having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:
- 24.
A method of treating cancer comprising administering a compound that inhibits the proliferation promoting activity of an EGFL6 polypeptide or a variant thereof having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:
- 24.
A method for identifying a candidate inhibitor of EGFL6-induced cell proliferation comprising the step of measuring EGFL6-induced cell proliferation in the presence of and absence of a test compound, and identifying the test compound as a candidate inhibitor of EGFL6 induced cell proliferation when proliferation is decreased in the presence of the test compound.
A method of detecting a cancerous cell expressing the polynucleotide of SEQ ID NO:
- 23 in a biological sample, comprising
- a) contacting the sample with a labeled polynucleotide complementary to said polynucleotide of SEQ ID NO:
- 23 or a fragment thereof for a period sufficient to form a complex;
- and
- b) detecting the complex, so that if a complex is detected, the cell is detected.
34 The method of claim 31 wherein the labeled polynucleotide comprises a radioisotope, affinity label, enzymatic label or flourescent label.
35 The method of claim 31, wherein the cancerous cell is a selected from the group consisting of lung cancer cells, brain cancer cells, prostate cancer cells, breast cancer cell, skin cancer cells, lymphoma cells, sarcoma cells, leukemia cells and colon cancer cells.
A method of detecting a cancerous cell expressing the polypeptide of SEQ ID NO:
- 24 in a biological sample, comprising
- a) contacting the sample with an antibody or fragment thereof that specifically binds to the polypeptide of SEQ ID NO:
- 24 or a fragment thereof for a period sufficient to form a complex;
- and
- b) detecting the complex, so that if a complex is detected, the cell is detected.
A method of inhibiting proliferation of a cancer cell, comprising the step of contacting said cell with an antibody or fragment thereof that specifically binds the polypeptide of SEQ ID NO:
- 24.
A method of inhibiting proliferation of a cancer cell, comprising the step of contacting said cell with an antisense polynucleotide that specifically binds a polynucleotide encoding the mature protein coding portion of SEQ ID NO:
- 24.
A method of reducing tumor size in a patient suffering from cancer, comprising the step of administering to the patient an inhibitor of the activity of the polypeptide of SEQ ID NO:
- 24, wherein the inhibitor specifically binds to said polypeptide.
A method of reducing tumor size in a patient suffering from cancer, comprising the step of administering to the patient an inhibitor of the activity of the polypeptide of SEQ ID NO:
- 24, wherein the inhibitor specifically binds to an EGFL6 receptor polypeptide.
A method of reducing tumor size in a patient suffering from cancer comprising the step of administering to the patient an antibody or fragment thereof that specifically binds to the polypeptide of SEQ ID NO:
- 24.
A method of reducing tumor size in a patient suffering from cancer comprising the step of administering to the patient an antisense polynucleotide that specifically binds a polynucleotide encoding the mature protein coding portion of SEQ ID NO:
- 24.
A method of inhibiting tumorgenicity in a cancer cell, comprising the step of contacting said cell with an antibody or fragment thereof that specifically binds the polypeptide of SEQ ID NO:
- 24.
A method of inhibiting tumorgenicity in a cancer cell, comprising the step of contacting said cell with an antisense polynucleotide that specifically binds a polynucleotide encoding the mature protein coding portion of SEQ ID NO:
- 24.
A pharmaceutical composition comprising an amount of an antibody or fragment thereof that specifically binds to the polypeptide sequence of SEQ ID NO:
- 24 in a pharmaceutically acceptable carrier, wherein the amount of antibody of fragment thereof effectively inhibits EGFL6 polypeptide activity.
A pharmaceutical composition comprising an amount of an antibody or fragment thereof that specifically binds to the polypeptide sequence of SEQ ID NO:
- 24 in a pharmaceutically acceptable carrier, wherein the amount of antibody of fragment thereof effectively inhibits tumorgenicity.
A pharmaceutical composition comprising an amount of an antibody or fragment thereof that specifically binds to the polypeptide sequence of SEQ ID NO:
- 24 in pharmaceutically acceptable carrier, wherein the amount of antibody or fragment thereof effectively reduces tumor size.
A pharmaceutical composition comprising an amount of an antibody or fragment thereof that specifically binds to the polypeptide sequence of SEQ ID NO:
- 24 in pharmaceutically acceptable carrier, wherein the amount of antibody or fragment thereof effectively inhibits proliferation of a cancerous cell.
A pharmaceutical composition comprising an amount of an antisense polynucleotide that specifically binds to a polynucleotide encoding the mature protein coding portion of SEQ ID NO:
- 24 in a pharmaceutically acceptable carrier, wherein the amount of antisense polynucleotide effectively inhibits EGFL6 polypeptide activity.
A pharmaceutical composition comprising an amount of an antisense polynucleotide that specifically binds to a polynucleotide encoding the mature protein coding portion of SEQ ID NO:
- 24 in a pharmaceutically acceptable carrier, wherein the amount of antisense polynucleotide effectively inhibits tumorgenicity.
A pharmaceutical composition comprising an amount of an antisense polynucleotide that specifically binds to a polynucleotide encoding the mature protein coding portion of SEQ ID NO:
- 24 in a pharmaceutically acceptable carrier, wherein the amount of anitisense polynucleotide effectively reduces tumor size.
A pharmaceutical composition comprising an amount of an antisense polynucleotide that specifically binds to a polynucleotide encoding the mature protein coding portion of SEQ ID NO:
- 24 in a pharmaceutically acceptable carrier, wherein the amount of anitisense polynucleotide effectively inhibits proliferation of a cancerous cell.
An antibody or fragment thereof that specifically binds a polypeptide consisting of
- (a) the amino acid sequence of SEQ ID NO:
- 4,
- (b) amino acids 1-502 of SEQ ID NO:
- 4, or
- (c) amino acid 42-250 of SEQ ID NO:
- 4.
An antibody or fragment thereof that specifically binds a fragment of SEQ ID NO:
- 4 comprising one or more epidermal growth factor (EGF) motif regions selected from the group consisting of amino acids 42-56 of SEQ ID NO:
- 4, amino acids 57-107 of SEQ ID NO:
- 4, amino acids 108-165 of SEQ ID NO:
- 4, amino acids 166-211 of SEQ ID NO:
- 4 and amino acids 212-250 of SEQ ID NO:
- 4.
Dependencies are inferred from the claim text.