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Title: US5869265: Ileal bile acid transporter compositions and methods
[ Derwent Title ]


Country: US United States of America

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50 pages

 
Inventor: Dawson, Paul A.; Chapel Hill, NC

Assignee: Wake Forest University, Winston-Salem, NC
other patents from WAKE FOREST UNIVERSITY (616825) (approx. 75)
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Published / Filed: 1999-02-09 / 1996-06-26

Application Number: US1996000669435

IPC Code: Advanced: A61K 38/00; A61K 39/395; A61K 48/00; A61P 1/04; A61P 1/16; A61P 3/06; A61P 3/08; A61P 9/00; C07H 21/04; C07K 7/08; C07K 14/47; C07K 14/705; C07K 16/18; C12N 15/09; C12N 15/12; C12P 21/02; C12P 21/08; C12Q 1/68; G01N 33/577; G01N 33/92; C12R 1/91;
Core: A61P 1/00; A61P 3/00; C07H 21/00; C07K 7/00; C07K 14/435; more...
IPC-7: C12N 5/10; C12N 15/12; G01N 33/53;

ECLA Code: C07K14/47; C12Q1/68P; G01N33/92;

U.S. Class: Current: 435/007.2; 435/069.1; 435/252.3; 435/254.11; 435/320.1; 435/325; 530/350; 536/023.5;
Original: 435/007.2; 435/069.1; 435/320.1; 435/325; 435/252.3; 435/254.11; 536/023.5; 530/350;

Field of Search: 435/7.2,7.21,69.1,320.1,325,252.3,254.11 530/350 536/23.5

Government Interest:

DESCRIPTION
    The government owns rights in the present invention pursuant to grant number DK08718 from the National Institutes of Health.

Priority Number:
1996-06-26  US1996000669435
1993-12-29  US1993000176126
1994-12-29  WO1994US0014431

Abstract:     The use of the cloned genes for the ileal/renal bile acid cotransporter to screen for compounds that inhibit or activate bile acid cotransporter activity is disclosed. When expressed in the cell membrane of a suitable host cell, the cotransporters coded for by these clones transport bile acids with the proper enzymatic and pharmacological profiles including ion dependence, bile acid substrate affinity and bile acid substrate specificity. Also disclosed are vectors comprising a cloned gene encoding an ileal/renal bile acid transporter and cells transformed with such vectors for screening compounds that modulate ileal/renal bile acid cotransporter activity. The cloned genes are useful for obtaining the ileal/renal bile acid cotransporter gene sequences to screen for candidate substances that modulate ileal/renal bile acid cotransporter gene expression.

Attorney, Agent or Firm: Arnold, White & Durkee ;

Primary / Asst. Examiners: Kemmerer, Elizabeth C.; Kaufman, Claire M.

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Related Applications:
Application Number Filed Patent Pub. Date  Title
US1993000176126 1993-12-29    1996-12-31  Ileal bile acid transporter compositions and methods


       
Parent Case:     This application is a continuation of application Ser. No. 08/176,126, filed Dec. 29, 1993 now U.S. Pat. No. 5,589,358.

Designated Country: AM AP BB BG BR BY CN CZ FI GE HU KE KG KP KR KZ LK LT LV MD MG MN  AT BE CH DE DK ES FR GB GR IE IT LI LU MC 

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First Claim:
Show all 3 claims
I claim:     1. A method of screening substances as modulators of mammalian ileal/renal bile acid cotransporter activity comprising the following steps:
  • obtaining a candidate substance;
  • introducing an isolated nucleic acid molecule into a suitable host cell wherein the nucleic acid molecule encodes a mammalian ileal/renal bile acid cotransporter selected from the group consisting of: a) a protein comprising the sequence of SEQ ID NO:2 or SEQ ID NO:4, and b) a protein which is encoded by a naturally occurring nucleic acid molecule that hybridizes to a nucleic acid having the sequence of SEQ ID NO:1 or SEQ ID NO:3 under conditions including 50% formamide buffer at 42° C. for 11 hours followed by washing in 0.2× SSC at 65° C. for 30 minutes;
  • expressing said nucleic acid molecule encoding a mammalian ileal/renal bile acid cotransporter from said host cell;
  • contacting said host cell with said candidate substance in the presence of cotransporter substrates; and
  • determining an effect of said candidate substance on said cotransport activity, wherein an increase or decrease in cotransport activity in the presence of said candidate substance is indicative of a modulator.


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PCT Number: PCT/US94/14431    WO9517905

PCT Pub./Filed Dates: 1995-07-06 / 1994-12-29

§ 371 / 102(e) Dates: 1996-06-26 / 1996-06-26

Forward References: Show 1 U.S. patent(s) that reference this one

       
U.S. References: Go to Result Set: All U.S. references   |  Forward references (1)   |   Backward references (2)   |   Citation Link

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Patent  Pub.Date  Inventor Assignee   Title
Buy PDF- 26pp US5389543  1995-02 Bunzow et al.  Duke University Cloned genes encoding the D1 dopamine receptor
Buy PDF- 35pp US5589358  1996-12 Dawson   Ileal bile acid transporter compositions and methods
       
Foreign References:
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Publication Date IPC Code Assignee   Title
Buy PDF- 148pp WO9517905 1995-07  A61K 38/17 DAWSON, Paul, A. ILEAL BILE ACID TRANSPORTER COMPOSITIONS AND METHODS 


Other Abstract Info: CHEMABS 123(17)224430M DERABS C1995-246189

Other References:
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  • Xu et al., Isolation, characterization, and expression of mouse ICAM-2 complementary and genomic DNA, J. Immunol., 149(8): 2650-2655, Oct. 1992.
  • Bai et al., Cloning and analysis of the 5' flanking sequence of the rat N-methyl-D-aspartate receptor 1 (NMDAR1) gene, Biochim. Acta, 1152: 197-200, 1993. (4 pages) [ISI abstract]
  • Abe et al., Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction, J. Biol. Chem., 267(19): 13361-13368, Jul. 1992. (8 pages) Cited by 67 patents [ISI abstract]
  • Alves et al., "Bile Acid Transport into Hepatocyte Smooth Endoplasmic Reticulum Vesicles Is Mediated by Microsomal Epoxide Hydrolase, a Membrane Protein Exhibiting Two Distinct Topological Orientations," J. Biol. Chem., 268(27):20148-20155, 1993. (8 pages) Cited by 2 patents [ISI abstract]
  • Barnard and Ghishan, "Taurocholate Transport by Human Ileal Brush Border Membrane Vesicles," Gastroenterology, 93:925-933, 1987. (9 pages) Cited by 2 patents
  • Barnes et al., "The Role of Tublar Reabsorption in the Renal Excretion of Bile Acids," Biochem. J., 166:65-73, 1977. (9 pages) Cited by 2 patents
  • Becker et al., "Characterisation of the ATP-dependent Taurocholate-carrier Protein (gp110) of the Hepatocyte Canalicular Membrane," Eur. J. Biochem., 214:539-548, 1993. (10 pages) Cited by 2 patents [ISI abstract]
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  • Galeazzi and Javitt, "Bile Acid Excretion: the Alernnate Pathway in the Hamster," J. Clin. Invest., 60:693-701, 1977. (9 pages) Cited by 2 patents
  • Gong et al., "Effect of Antiserum to a 99 kDa Polypeptide on the Uptake of Taurocholic Acid by Rat Ileal Brush Border Membrane Vesicles," Biochem. Biophys. Res. Commun., 179(1):204-209, 1991. (6 pages) Cited by 2 patents [ISI abstract]
  • Hagenbuch et al., "Functional Expression Cloning and Characterization of the Hepatocyte Na+ /Bile Acid Cotransport System," Proc. Natl. Acad. Sci. USA, 88:10629-10633, 1991. (5 pages) Cited by 4 patents [ISI abstract]
  • Hofmann et al., "Biological and Medical Aspects of Active Ileal Transport of Bile Acids," Anneals of Medicine, 23:169-175, 1991. (7 pages) [ISI abstract]
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  • Lack and Weiner, "Bile Salt Transport Systems," The Bile Acids, 2:33-54, 1973.
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  • Lin et al., "Identification of Cytosolic and Microsomal Bile Acid-binding Proteins in Rat Ileal Enterocytes," J. Biol. Chem., 265(25):14986-14995, 1990. (10 pages) Cited by 2 patents
  • Lin et al., "Timed Photoaffinity Labeling and Characterization of Bile Acid Binding and Transport Proteins in Rat Ileum," Am. J. Physiol., 265(Gastrointest. Liver Physiol. 28):G56-G62, 1993. (7 pages) Cited by 2 patents [ISI abstract]
  • Mullins et al., "Characterization of the Ileal Na+ /Bile Salt Co-transporter in Brush Border Membrane Vesicles and Functional Expression in Xenopus laevis Oocytes,"Biochem. J., 285:785-790, 1992. (6 pages) Cited by 2 patents [ISI abstract]
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  • Sippel et al., "The Rat Liver Ecto-ATPase Is Also a Canalicular Bile Acid Transport Protein," J. Biol. Chem., 268(3):2083-2091, 1993. (9 pages) Cited by 2 patents [ISI abstract]
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  • Von Dippe et al., "Na+ -dependent Bile Acid Transport by Hepatocytes is Mediated by a Protein Similar to Microsomal Epoxide Hydrolase," Am. J. Physiol., 264(Gastrointest. Liver Physiol. 27):G528-G534, 1993. (7 pages) Cited by 2 patents [ISI abstract]
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  • Wong et al., "Cloning and Characterization of the Ileal Bile Acid Transporter," American Association for the Study of Liver Diseases, Nov. 4-7, 1993, Chicago, Illinois, abstract only.
  • Wong et al., "Cloning and Characterization of the Ileal Bile Acid Transporter," AASLD Abstacts, 18(4):143 A, Pt. 2, 1993.
  • Zimmerli et al., "Multispecificity of Na+ -dependent Taurocholate Uptake in Basolateral (Sinusoidal) Rat Liver Plasma Membrane Vesicles," J. Pharmacol. Exp. Ther., 250(1):301-308, 1989. (8 pages) Cited by 2 patents


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