Regulation of human epithin-like serine-protease
OwnerYonghong Xiaoinventor
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Abstract
Reagents which regulate human epithin-like serine protease activity and reagents which bind to human epithin-like serine protease gene products can be used to regulate extracellular matrix degradation. Such regulation is particularly useful for treating metastasis of malignant cells, tumor angiogenesis, inflammation, atherosclerosis, neurodegenerative diseases, COPD, and pathogenic infections.
Claims72
An isolated polynucleotide encoding a epithin-like serine protease polypeptide and being selected from the group consisting of:
- a) a polynucleotide encoding a epithin-like serine protease polypeptide comprising an amino acid sequence selected form the group consisting of:
- amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:
- 10;
- the amino acid sequence shown in SEQ ID NO:
- 10;
- amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:
- 24;
- the amino acid sequence shown in SEQ ID NO:
- 24;
- amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:
- 27;
- and
- the amino acid sequence shown in SEQ ID NO:
- 27.
- b) a polynucleotide comprising the sequence of SEQ ID NO:
- 25 or 26;
- c) a polynucleotide which hybridizes under stringent conditions to a polynucleotide specified in (a) and (b);
- d) a polynucleotide the sequence of which deviates from the polynucleotide sequences specified in (a) to (c) due to the degeneration of the genetic code;
- and
- e) a polynucleotide which represents a fragment, derivative or allelic variation of a polynucleotide sequence specified in (a) to (d).
A cDNA encoding a polypeptide comprising the amino acid sequence shown in SEQ ID NO:
- 10, 24 and 27.
An expression vector comprising a polynucleotide which encodes a polypeptide comprising the amino acid sequence shown in SEQ ID NO:
- 10, 24 and 27.
A host cell comprising an expression vector which encodes a polypeptide comprising the amino acid sequence shown in SEQ ID NO:
- 10, 24 and 27.
A purified polypeptide comprising the amino acid sequence shown in SEQ ID NO:
- 10, 24 and 27.
A fusion protein comprising a polypeptide having the amino acid sequence shown in SEQ ID NO:
- 10, 24 and 27.
A method of producing a polypeptide comprising the amino acid sequence shown in SEQ ID NO:
- 10, 24 and 27, comprising the steps of:
- culturing a host cell comprising an expression vector which encodes the polypeptide under conditions whereby the polypeptide is expressed;
- and isolating the polypeptide.
A method of detecting a coding sequence for a polypeptide comprising the amino acid sequence shown in SEQ ID NO:
- 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24 and 27, comprising the steps of:
- hybridizing a polynucleotide comprising 11 contiguous nucleotides of SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 25 or 26 to nucleic acid material of a biological sample, thereby forming a hybridization complex;
- and
- detecting the hybridization complex.
A method of detecting a polypeptide comprising the amino acid sequence shown in SEQ ID NO:
- 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 27, comprising the steps of:
- contacting a biological sample with a reagent that specifically binds to the polypeptide to form a reagent-polypeptide complex;
- and
- detecting the reagent-polypeptide complex.
A method of screening for agents which can modulate the activity of a human epithin-like serine protease, comprising the steps of:
- contacting a test compound with a polypeptide comprising an amino acid sequence selected from the group consisting of:
- (1) amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:
- 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 27 and (2) the amino acid sequence shown in SEQ ID NO:
- 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 27;
- and
- detecting binding of the test compound to the polypeptide, wherein a test compound which binds to the polypeptide is identified as a potential agent for regulating activity of the human epithin-like serine protease.
A method of screening for agents which modulate an activity of a human epithin-like serine protease, comprising the steps of:
- contacting a test compound with a polypeptide comprising an amino acid sequence selected from the group consisting of:
- (1) amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:
- 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 27 and (2) the amino acid sequence shown in SEQ ID NO:
- 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 27;
- and
- detecting an activity of the polypeptide, wherein a test compound which increases the activity of the polypeptide is identified as a potential agent for increasing the activity of the human epithin-like serine protease, and wherein
- a test compound which decreases the activity of the polypeptide is identified as a potential agent for decreasing the activity of the human epithin-like serine protease.
A method of screening for agents which modulate an activity of a human epithin-like serine protease, comprising the steps of:
- contacting a test compound with a product encoded by a polynucleotide which comprises the nucleotide sequence shown in SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 25 or 26;
- and
- detecting binding of the test compound to the product, wherein a test compound which binds to the product is identified as a potential agent for regulating the activity of the human epithin-like serine protease.
A method of reducing activity of a human epithin-like serine protease, comprising the step of:
- contacting a cell with a reagent which specifically binds to a product encoded by a polynucleotide comprising the nucleotide sequence shown in SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 25 or 26, whereby the activity of a human epithin-like serine protease is reduced.
A pharmaceutical composition, comprising:
- a reagent which specifically binds to a polypeptide comprising the amino acid sequence shown in SEQ ID NO:
- 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 27;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition, comprising:
- a reagent which specifically binds to a product of a polynucleotide comprising the nucleotide sequence shown in SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 25 or 26;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition, comprising:
- an expression vector encoding a polypeptide comprising the amino acid sequence shown in SEQ ID NO:
- 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 27;
- and
- a pharmaceutically acceptable carrier.
A method of treating an epithin-like serine protease dysfunction related disease, comprising the step of:
- administering to a patient in need thereof a therapeutically effective dose of a reagent that modulates a function of a human epithin-like serine protease,
- whereby symptoms of the epithin-like serine protease dysfunction related disease are ameliorated.
Dependencies are inferred from the claim text.