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Novel polypeptide and its dnaRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, 25 Or More Peptide Repeating Units In Known Peptide Chain StructureNovel polypeptide and its dna description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20050261192, Novel polypeptide and its dna. Brief Patent Description - Full Patent Description - Patent Application Claims
TECHNICAL FIELD [0001] The present invention relates to partial peptides of cubilin and their functions. BACKGROUND ART [0002] The level of HDL-cholesterol [cholesterol contained in HDL (high density lipoprotein); hereinafter, sometimes abbreviated to "HDL-C"] is known as a negative risk factor in coronary artery diseases. Various drugs has been developed for the purpose of raising that level, but thus developed drugs, such as fibrate type drugs, are not sufficient though they raise HDL-C levels significantly. Besides, such rise in HDL-C levels represents a consequential factor. Recent studies using transgenic mice, etc. have revealed that, as long as the true purpose is to extract cholesterol from foci of arteriosclerosis, what is needed is technology to raise the level of apolipoprotein A-I (hereinafter, sometimes abbreviated to "apo A-I") that plays a major role in the cholesterol extraction. [0003] Apo A-I in plasma exists for the most part as HDL in the form of complexes with phospholipid, cholesterol, cholesterol ester and so on. These complexes are catabolized mainly in the liver. However, it is known that in some diseases such as hypertriglyceridemia, HDL particles with increased triglyceride (hereinafter, sometimes abbreviated to "TG") contents are converted into smaller apo A-I particles by various lipases and then catabolized mainly in the kidney. The catabolism in the kidney is achieved as follows: small particles of apo A-I that have been filtered through the uriniferous tubule are re-absorbed in the proximal tubule and then degraded. Kozyraki et al. have been reported that cubilin (GenBank Accession No. AF034611) molecules expressed on the uriniferous tubule epithelium and known to bind to vitamin B.sub.12-intrinsic factor complex and LDL receptor-related protein (LRP)-associated protein (hereinafter, sometimes abbreviated to "RAP") also bind to apo A-I (see, for example, Nature Medicine Vol. 5, No. 6, 656-661 (1999); Proc. Natl. Acad. Sci. USA, Vol. 96, 10158-10163 (1999)). However, relations between the binding of cubilin to apo A-I and plasma apo A-I or HDL concentration, or relations between this binding and arteriosclerosis have not yet been elucidated. [0004] The binding of cubilin to apo A-I may be an important finding for the development of therapeutics for hypo-high density lipoproteinemia, which is a problem in diseases such as high hypertriglyceridemia, and for the development of drugs for treating arteriosclerosis at the root. To specify the apo A-I-binding domain in cubilin molecules is extremely useful, for example, for developing anti-cubilin-apo A-I-binding domain antibody and screening for certain low molecular weight compounds. [0005] Thus, the finding that the apo A-I-binding site is located in a specific region in cubilin molecules is extremely important in view of clinical application, and the identification of this binding site has been eagerly awaited. Furthermore, the raising of serum apo A-I concentration and HDL concentration by administering a substance that inhibits the binding of apo A-I to cubilin partial fragments, and therapeutics for arteriosclerosis comprising such a substance have been eagerly awaited in order to treat hypertriglyceridemia, hypercholesterolemia and arteriosclerotic diseases. DISCLOSURE OF THE INVENTION [0006] The present invention provides the identification of the apo A-I-binding site on cubulin; the construction of a screening method for a compound that inhibits the binding of a cubilin fragment comprising the identified binding site to apo A-I; and a medicine comprising a compound obtained by the constructed screening method. [0007] To specify the apo A-I-binding site in cubilin molecules leads to clinical application of apo A-I-binding fragments of cubilin per se, antibodies thereto, and low molecular weight compounds that inhibit the binding of cubilin figments to apo A-I. [0008] As a result of intensive and extensive researches, the present inventors have found apo A-I-binding activity in the CUB7-CUB14 fragment peptide (Blood 91, 3593-3600 (1998)) and the CUB9-CUB14 fragment peptide of cubilin. Then, the inventors have developed an experimental system for measuring apo A-I-binding using these fragments. Based on these findings, the inventors have made further investigations. Thus, the present invention has been achieved. [0009] The present invention relates to: [0010] (1) A polypeptide having the ability to bind to apolipoprotein A-I which is a partial fragment of cubilin, an amide or ester of said polypeptide, or a salt of said polypeptide, [0011] (2) The polypeptide, amide or ester thereof, or salt thereof of (1) above, wherein the polypeptide is characterized by having an amino acid sequence identical or substantially identical with the amino acid sequence as shown in SEQ ID NO: 10, [0012] (3) The polypeptide, amide or ester thereof, or salt thereof of (1) above, wherein the polypeptide has the amino acid sequence as shown in SEQ ID NO: 10, [0013] (4) The polypeptide, amide or ester thereof, or salt thereof of (1) above, wherein the polypeptide is characterized by having an amino acid sequence identical or substantially identical with the amino acid sequence as shown in SEQ ID NO: 19, [0014] (5) The polypeptide, amide or ester thereof, or salt thereof of (1) above, wherein the polypeptide has the amino acid sequence as shown in SEQ ID NO: 19, [0015] (6) A DNA comprising a DNA encoding the polypeptide of (1) above, [0016] (7) The DNA of (6) above, wherein the DNA comprises the base sequence as shown in SEQ ID NO: 9, [0017] (8) The DNA of (6) above, wherein the DNA comprises the base sequence as shown in SEQ ID NO: 22, [0018] (9) A recombinant vector comprising the DNA of (6) above, [0019] (10) A transformant transformed with the recombinant vector of (9) above, [0020] (11) A method of producing the polypeptide, amide or ester thereof, or salt thereof of (1) above, which is characterized by culturing the transformant of (10) above and allowing the transformant to produce the polypeptide, [0021] (12) An antibody to the polypeptide, amide or ester thereof, or salt thereof of (1) above, Continue reading about Novel polypeptide and its dna... 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