Tissue plasminogen activator-like protease
AssigneeHuman Genome Sciences, Inc.
InventorsPaul A. Moore, Steven M. Ruben, Reinhard Ebner
Life of this patent
Estimating the term…
Abstract
The present invention relates to a novel t-PALP protein which is a member of the serine protease family. In particular, isolated nucleic acid molecules are provided encoding the human t-PALP protein. t-PALP polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of t-PALP activity. Also provided are diagnostic methods for detecting circulatory system-related disorders and therapeutic methods for treating circulatory system-related disorders.
Claims20
An isolated nucleic acid molecule nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) a nucleotide sequence encoding the t-PALP polypeptide having the amino acid sequence at positions −21 to 242 of SEQ ID NO:2) or the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209023;
- (b) a nucleotide sequence encoding the t-PALP polypeptide having the amino acid sequence at positions −20 to 242 of SEQ ID NO:2) or the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in ATCC Deposit No. 209023;
- (c) a nucleotide sequence encoding the mature t-PALP polypeptide having the amino acid sequence at positions 1 to 242 in SEQ ID NO:2, or as encoded by the cDNA clone contained in the ATCC Deposit No. 209023;
- (d) a nucleotide sequence encoding the kringle domain of the t-PALP polypeptide having the amino acid sequence at positions 4 to 63 in SEQ ID NO:2, or as encoded by the cDNA clone contained in the ATCC Deposit No. 209023;
- (e) a nucleotide sequence encoding the protease domain of the t-PALP polypeptide having the amino acid sequence at positions 64 to 242 in SEQ ID NO:2, or as encoded by the cDNA clone contained in the ATCC Deposit No. 209023;
- (f) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d) or (e) above.
An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues n-242 of SEQ ID NO:2, where n is an integer in the range of −20-64;
- (b) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues −20-m of SEQ ID NO:2, where m is an integer in the range of 230 to 241;
- (c) a nucleotide sequence encoding a polypeptide having the amino acid sequence consisting of residues n-m of SEQ ID NO:2, where n and m are integers as defined respectively in (a) and (b) above;
- and
- (d) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete t-PALP amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209023 wherein said portion excludes from 1 to about 63 amino acids from the amino terminus of said complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209023;
- (e) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete t-PALP amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209023 wherein said portion excludes from 1 to about 11 amino acids from the carboxy terminus of said complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209023;
- and
- (f) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete t-PALP amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209023 wherein said portion include a combination of any of the amino terminal and carboxy terminal deletions in (d) and (e), above.
An isolated t-PALP polypeptide comprising an amino acid sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) the amino acid sequence positions −20 to 242 of SEQ ID NO:2 or the complete t-PALP amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in ATCC Deposit No. 209023;
- (b) the amino acid sequence of the mature form of the t-PALP polypeptide having the amino acid sequence at positions 1 to 242 in SEQ ID NO:2, or as encoded by the cDNA clone contained in the ATCC Deposit No. 209023;
- (c) the amino acid sequence of the kringle domain of the t-PALP polypeptide having the amino acid sequence at positions 4 to 63 in SEQ ID NO:2, or as encoded by the cDNA clone contained in the ATCC Deposit No. 209023;
- and
- (d) the amino acid sequence of the mature form of the t-PALP polypeptide having the amino acid sequence at positions 64 to 242 in SEQ ID NO:2, or as encoded by the cDNA clone contained in the ATCC Deposit No. 209023.
An isolated polypeptide comprising an epitope-bearing portion of the t-PALP protein, wherein said portion is selected from the group consisting of:
- a polypeptide comprising amino acid residues from about Ser-1 to about His-10 in SEQ ID NO:2;
- about Glu-14 to about Leu-23 in SEQ ID NO:2;
- about Arg-50 to about Trp-60 in SEQ ID NO:2;
- about Pro-70 to about Gln-86 in SEQ ID NO:2;
- about Ala-98 to about Val-107 in SEQ ID NO:2;
- about Leu-117 to about Gln-126 in SEQ ID NO:2;
- about Arg-134 to about Gly-146 in SEQ ID NO:2;
- about Ser-172 to about Gln-182 in SEQ ID NO:2;
- about Gln-185 to about Arg-194 in SEQ ID NO:2;
- about Thr-206 to about Val-216 in SEQ ID NO:2;
- and about Thr-222 to about Thr-231 in SEQ ID NO:2.
An isolated nucleic acid molecule comprising a polynucleotide having a sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) the nucleotide sequence of clone HTAAM28R (SEQ ID NO:4);
- (b) the nucleotide sequence of clone HFKBA12R (SEQ ID NO:5);
- (c) the nucleotide sequence of clone HAPBL24R (SEQ ID NO:6);
- (d) the nucleotide sequence of clone HLMFG34R (SEQ ID NO:7);
- (e) the nucleotide sequence of clone HHPGT42R (SEQ ID NO:8);
- (f) the nucleotide sequence of clone HSSAX27R (SEQ ID NO:9);
- (g) the nucleotide sequence of clone HSSES93R (SEQ ID NO:10);
- (h) the nucleotide sequence of a portion of the sequence shown in FIGS. 1A, 1B, and 1C (SEQ ID NO:1) wherein said portion comprises at least 50 contiguous nucleotides from nucleotide about 1 to about 110 and from nucleotide about 630 to about 750;
- (i) the nucleotide sequence of a portion of the sequence shown in FIGS. 1A, 1B, and 1C (SEQ ID NO:1) wherein said portion consists of nucleotides 1 to 2000, 1 to 1500, 1 to 1000, 1 to 500, 1 to 250, 250 to 2000, 250 to 1500, 250 to 1000, 250 to 500, 500 to 2000, 500 to 1500, 500 to 1000, 1000 to 2000, and 1000 to 1500;
- and
- (j) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), (e), (f), (g), (h) or (i) above.
Dependencies are inferred from the claim text.