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14094, a novel human trypsin family member and uses thereofRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Radionuclide Or Intended Radionuclide Containing; Adjuvant Or Carrier Compositions; Intermediate Or Preparatory Compositions, Attached To Antibody Or Antibody Fragment Or Immunoglobulin; Derivative14094, a novel human trypsin family member and uses thereof description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070009433, 14094, a novel human trypsin family member and uses thereof. Brief Patent Description - Full Patent Description - Patent Application Claims
RELATED APPLICATIONS [0001] This application is a divisional application of U.S. patent application Ser. No. 09/846,512, filed May 1, 2001 (pending), which is a continuation-in-part of U.S. patent application Ser. No. 09/633,300, filed Aug. 8, 2000 (abandoned), which claims the benefit of U.S. Provisional Application Ser. No. 60/200,621, filed Apr. 28, 2000, (abandoned), all of which are hereby incorporated in their entirety by reference. BACKGROUND OF THE INVENTION [0002] Four major classes of proteases are known and are designated by the principal functional group in their active site: serine, thiol, carboxyl, and metallo. Serine proteases are characterized by the presence of a unique serine residue that functions as a nucleophile to cleave peptide bonds. In some cases, the serine forms covalent adducts with substrates and inhibitors. The serine functions with two other principal residues of the active site, a histidine, and an acid, frequently aspartic acid. Together these three residues compose the catalytic triad which is a signature of the family. Serine proteases are divided into two major evolutionary families. One family is represented by the bacterial protease subtilisin. The other family is the trypsin-chymotrypsin family and includes chymotrypsin, trypsin, and elastase. Other members of the trypsin-chymotrypsin family include thrombin, plasmin, kallikrein, and acrosin. Members of the trypsin-chymotrypsin serine protease family are involved in a range of diverse cellular functions including, cell motility, cell growth and differentiation, hormone production, organogenesis, extracellular matrix regulation, blood clotting, and complementation activation. [0003] These proteases catalyze the hydrolysis of peptide bonds in proteins and peptides. While the various serine proteases catalyze this reaction in very similar ways, they differ in their preference for the amino acid side chains immediately C-terminal to the cleave site. Trypsin cleaves bonds only after lysine and arginine residues, whereas chymotrypsin cleaves bonds after large hydrophobic residues. Other proteases of this family have less distinct preferences for this position, but also depend to varying extents on the residues at neighboring positions. [0004] Some members of the trypsin serine protease family play critical roles in a variety of important biological events including regulating cell proliferation, tumor growth, tumor invasion, metastasis, development, and tissue remodeling. Accordingly, there is a need for identifying and characterizing novel trypsin serine proteases. SUMMARY OF THE INVENTION [0005] The present invention is based, in part, on the discovery of a novel trypsin family member, referred to herein as "14094". The nucleotide sequence of a cDNA encoding 14094 is shown in SEQ ID NO:1 and SEQ ID NO:11, and the amino acid sequence of a 14094 polypeptide is shown in SEQ ID NO:2 and SEQ ID NO:12. In addition, the nucleotide sequences of the coding region are depicted in SEQ ID NO:3 and SEQ ID NO:13. [0006] Accordingly, in one aspect, the invention features a nucleic acid molecule that encodes a 14094 protein or polypeptide, e.g., a biologically active portion of the 14094 protein. In a preferred embodiment the isolated nucleic acid molecule encodes a polypeptide having the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:12. In other embodiments, the invention provides isolated 14094 nucleic acid molecules having the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:11, SEQ ID NO:3, SEQ ID NO:13 or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______. In still other embodiments, the invention provides nucleic acid molecules that are substantially identical (e.g., naturally occurring allelic variants) to the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:11, SEQ ID NO:13 or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______. In other embodiments, the invention provides a nucleic acid molecule which hybridizes under a stringency condition described herein to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:11, SEQ ID NO:13 or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______, wherein the nucleic acid encodes a full length 14094 protein or an active fragment thereof. [0007] In a related aspect, the invention further provides nucleic acid constructs that include a 14094 nucleic acid molecule described herein. In certain embodiments, the nucleic acid molecules of the invention are operatively linked to native or heterologous regulatory sequences. Also included, are vectors and host cells containing the 14094 nucleic acid molecules of the invention e.g., vectors and host cells suitable for producing 14094 nucleic acid molecules and polypeptides. [0008] In another related aspect, the invention provides nucleic acid fragments suitable as primers or hybridization probes for the detection of 14094-encoding nucleic acids. [0009] In still another related aspect, isolated nucleic acid molecules that are antisense to a 14094 encoding nucleic acid molecule are provided. [0010] In another aspect, the invention features, 14094 polypeptides, and biologically active or antigenic fragments thereof that are useful, e.g., as reagents or targets in assays applicable to treatment and diagnosis of 14094-mediated or -related disorders. In another embodiment, the invention provides 14094 polypeptides having a 14094 activity. Preferred polypeptides are 14094 proteins including at least one trypsin domain, and, preferably, having a 14094 activity, e.g., a 14094 activity as described herein. [0011] In other embodiments, the invention provides 14094 polypeptides, e.g., a 14094 polypeptide having the amino acid sequence shown in SEQ ID NO:2, SEQ ID NO:12, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC Accession Number ______; an amino acid sequence that is substantially identical to the amino acid sequence shown in SEQ ID NO:2, SEQ ID NO:12 or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC Accession Number ______; or an amino acid sequence encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under a stringency condition described herein to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:11, SEQ ID NO:13 or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______, wherein the nucleic acid encodes a full length 14094 protein or an active fragment thereof. [0012] In a related aspect, the invention further provides nucleic acid constructs which include a 14094 nucleic acid molecule described herein. [0013] In a related aspect, the invention provides 14094 polypeptides or fragments operatively linked to non-14094 polypeptides to form fusion proteins. [0014] In another aspect, the invention features antibodies and antigen-binding fragments thereof, that react with, or more preferably specifically bind 14094 polypeptides. [0015] In another aspect, the invention provides methods of screening for compounds that modulate the expression or activity of the 14094 polypeptides or nucleic acids. [0016] In still another aspect, the invention provides a process for modulating 14094 polypeptide or nucleic acid expression or activity, e.g. using the screened compounds. In certain embodiments, the methods involve treatment of conditions related to aberrant activity or expression of the 14094 polypeptides or nucleic acids, such as conditions involving aberrant or deficient cellular proliferation or differentiation. [0017] The invention also provides assays for determining the activity of or the presence or absence of 14094 polypeptides or nucleic acid molecules in a biological sample, including for disease diagnosis. [0018] In still another aspect, the invention provides a process for modulating 14094 polypeptide or nucleic acid expression or activity, e.g. using the screened compounds. In certain embodiments, the methods involve treatment of conditions related to aberrant activity or expression of the 14094 polypeptides or nucleic acids, such as conditions involving aberrant or deficient cellular proliferation or differentiation, or tumor invasion or metastasis. [0019] In yet another aspect, the invention provides methods for inhibiting the proliferation or inducing the killing or differentiation, of a 14094-expressing cell (e.g., a 14094-expressing hyperproliferative cell), comprising contacting the cell with a an agentm e.g., a compound identified using the methods described herein) that modulates the activity, or expression, of the 14094 polypeptide or nucleic acid, thereby inhibiting the proliferation or inducing the killing or differentiation of the 14094-expressing cell. [0020] In a preferred embodiment, the contacting step is effective in vitro or ex vivo. In other embodiments, the contacting step is effected in vivo, e.g., in a subject (e.g., a mammal, e.g., a human), as part of a therapeutic or prophylactic protocol. [0021] In a preferred embodiment, the hyperproliferative cell is found in a solid tumor, a soft tissue tumor, or a metastatic lesion. Preferably, the tumor is a sarcoma, a carcinoma, or an adenocarcinoma. Preferably, the hyperproliferative cell is found in a cancerous or pre-cancerous tissue, e.g., a cancerous or pre-cancerous tissue where a 14094 polypeptide or nucleic acid is expressed, e.g., breast, ovarian, colon, liver, lung, kidney, or brain cancer. Most preferably, the hyperproliferative cell is found in a tumor from the breast, ovary, colon, liver or lung. Continue reading about 14094, a novel human trypsin family member and uses thereof... Full patent description for 14094, a novel human trypsin family member and uses thereof Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this 14094, a novel human trypsin family member and uses thereof patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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