WO2002022817A2 - Nuclear receptor l66 and methods of use - Google Patents

Nuclear receptor l66 and methods of use Download PDF

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Publication number
WO2002022817A2
WO2002022817A2 PCT/EP2001/010323 EP0110323W WO0222817A2 WO 2002022817 A2 WO2002022817 A2 WO 2002022817A2 EP 0110323 W EP0110323 W EP 0110323W WO 0222817 A2 WO0222817 A2 WO 0222817A2
Authority
WO
WIPO (PCT)
Prior art keywords
leu
ser
glu
lys
thr
Prior art date
Application number
PCT/EP2001/010323
Other languages
French (fr)
Other versions
WO2002022817A3 (en
Inventor
Georg Casari
Michael HÖFER
David Jackson
Harald Kranz
Kerstin Otte
Bettina Remmel
Jörg SUCKOW
Original Assignee
Lion Bioscience Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lion Bioscience Ag filed Critical Lion Bioscience Ag
Priority to EP01982261A priority Critical patent/EP1317542A2/en
Priority to AU2002213893A priority patent/AU2002213893A1/en
Priority to CA002420932A priority patent/CA2420932A1/en
Publication of WO2002022817A2 publication Critical patent/WO2002022817A2/en
Publication of WO2002022817A3 publication Critical patent/WO2002022817A3/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70567Nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Abstract

The present invention relates to a novel nuclear receptor called 'L66' or also FXR-β a homologue of the FXR-α, a prototypical type 2 nuclear receptor. The invention also relates to the isolated nucleic acid sequence of L66 and the isolated protein thereof. The invention further relates to processes for isolating and/or producing the nucleic acid or the protein as well as methods of use of the receptor L66.

Claims

L-0020-O1- O-01.ST25 ttcagttttt gacgccttct gtaatgcagc ctgatcctca gtggttaaat tttcaaatcc 600 tgggagtccc ttggtaaact tcattagccc ttgtatgtgc aggactgata cctctgagag 660 tctcagaaaa cttagttcgg ggttggaacc ctcctgcaga agtttgcttg tttctcccaa 720 gggaatcatg gatttttggt gagcagtcac tatggtattc agaagccgat gttcctcttg 780 agttagagtc atgttgtcct gaaccccttt cccagatctg gtgctggatg acacgtgttt 840 ggtgtctgct ccttcatctt ccacttggat ggcagggtac agggcaggcc cgtgcttgaa 900 gttcttgcga agtctctttg acttacactg gatctctgtg agcaaacatt ctgccaacat 960 ccccaccgcc ttoeacttct -tcagtctgca- ctcttggcat tttctgcgca tgtacatgtc 1020 catttcacag tgaccaccgt tcttgcaaga atacactgca ttcttggtaa tgctacgccg 1080 gaaaaagcct ttgcacccct cacaagtaag tgcattgtag tgatatcctg atgccttatc 1140 accgcagacc atgcagagca tgtcatcttg acccttccag cgtaaagaac aagttgctct 1200 gcacctttgt gccccaggga attcatcttc atcatcgtga acaaccacat aagtggactg 1260 accagattct cgagcgtcga gtccacacca actgcctcca ctgtactgtg gatccaagcc 1320 atgtgtgttg aaatgacttt gtaaagatgg ggactgtaac gctggaggaa actgagcggt 1380 agaatattga caatagggtg gttcttggaa atctgtatca cacagctgat aatggaattg 1440 ttctggcaaa atatctggtt ttattaacat 1470
<210> 19
<211> 489
<212> PRT
<213> Mus musculus
<400> 19
Met Leu He Lys Pro Asp H e Leu Pro Glu Gin Phe His Tyr Gin Leu 1 5 10 15
Cys Asp Thr Asp Phe Gi n Gl u Pro Pro Tyr Cys Gi n Tyr Ser Thr Ala 20 25 30
Seite 13 L-0020-O1-WO-01.ST25 Gin Phe Pro Pro Ala Leu Gin Ser Pro Ser Leu Gin Ser His Phe Asn 35 40 45
Thr His Gly Leu Asp Pro Gin Tyr Ser Gly Gly Ser Trp Cys Gly Leu 50 55 60
Asp Ala Arg Glu Ser Gly Gin Ser Thr Tyr Val Val Val His Asp Asp 65 70 75 80
Glu Asp Glu Phe Pro Gly Ala Gin Arg Cys Arg Ala Thr Cys Ser Leu 85 90 95
Arg Trp Lys Gly Gin Asp Asp Met Leu Cys Met Val Cys Gly Asp Lys 100 105 110
Ala -Ser Gly' tyr.- His -. yr- Asn« Ala Leu'Thr Cys Glu Gly Cys Lys Gly;-, 115 120 125
Phe Phe Arg Arg Ser He Thr Lys Asn Ala Val Tyr Ser Cys Lys Asn 130 135 140
Gly Gly His Cys Glu Met Asp Met Tyr Met Arg Arg Lys Cys Gin Glu 145 150 155 160
Cys Arg Leu Lys. Lys Cys Lys Ala Val Gly Met Leu Ala Glu Cys Leu 165 170 175
Leu Thr Glu He Gin Cys Lys Ser Lys Arg Leu Arg Lys Asn Phe Lys 180 185 190
His Gly Pro Ala Leu Tyr Pro Ala He Gin Val Glu Asp Glu Gly Ala 195 200 205
Asp Thr Lys His Val Ser Ser Ser Thr Arg Ser Gly Lys Gly Val Gin 210 215 220
Asp Asn Met Thr Leu Thr Gin Glu Glu His Arg Leu Leu Asn Thr He 225 230 235 240
Val Thr Ala His Gin Lys Ser Met He Pro Leu Gly Glu Thr Ser Lys 245 250 255
Leu Leu Gin Glu Gly Ser Asn Pro Glu Leu Ser Phe Leu Arg Leu Ser 260 265 270
Glu Val Ser Val Leu His He Gin Gly Leu Met Lys Phe Thr Lys Gly 275 280 285
Seite 14 L-0020-01-WO-01. ST25
Leu Pro Gly Phe Glu Asn Leu Thr Thr Glu Asp Gin Ala Ala Leu Gin 290 295 300
Lys Ala Ser Lys Thr Glu Val Met Phe Leu His Val Ala Gin Leu Tyr 305 310 315 320
Gly Gly Lys Asp Ser Thr Ser Gly Ser Thr Met Arg Pro Ala Lys Pro 325 330 335
Ser Ala Gly Thr Leu Glu Val His Asn Pro Ser Ala Asp Glu Ser Val 340 345 350
His Ser Pro Glu Asn Phe Leu Lys Glu Gly Tyr Pro Ser Ala Pro Leu 355 360 365
Thr Asp He Thr Lys Glu Phe He Ala Ser Leu Ser Tyr Phe Tyr Arg 370 375 380
Arg Met Ser Glu Leu His Val Ser Asp Thr Glu Tyr Ala Leu Leu Thr 385 390 395 400
Ala Thr Thr Val Leu Phe Ser Asp Arg Pro Cys Leu Lys Asn Lys Gin 405 410 415
His He Glu Asn Leu Gin Glu Pro Val Leu Gin Leu Leu Phe Lys Phe 420 425 430
Ser Lys Met Tyr His Pro Glu Asp Pro Gin His Phe Ala His Leu He 435 440 445
Gly Arg Leu Thr Glu Leu Arg Thr Leu Ser His Ser His Ser Glu He 450 455 460
Leu Arg Met Trp Lys Thr Lys Asp Pro Arg Leu Val Met Leu Phe Ser 465 470 475 480
Glu Lys Trp Asp Leu His Ser Phe Ser 485
<210> 20
<211> 16200
<212> DNA
<213> Mus musculus
<400> 20 ctttggggtc atagcattta ttaggtattg ttagttccat ttactgtgtt cctattgtgc 60
Seite 15
PCT/EP2001/010323 2000-09-16 2001-09-07 Nuclear receptor l66 and methods of use WO2002022817A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP01982261A EP1317542A2 (en) 2000-09-16 2001-09-07 Nuclear receptor l66 and methods of use
AU2002213893A AU2002213893A1 (en) 2000-09-16 2001-09-07 Nuclear receptor l66 and methods of use
CA002420932A CA2420932A1 (en) 2000-09-16 2001-09-07 Novel mammalian nuclear receptor l66 and methods of use

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP00120370 2000-09-16
EP00120370.2 2000-09-16
EP01111658.9 2001-05-14
EP01111658 2001-05-14

Publications (2)

Publication Number Publication Date
WO2002022817A2 true WO2002022817A2 (en) 2002-03-21
WO2002022817A3 WO2002022817A3 (en) 2003-03-27

Family

ID=26071406

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2001/010323 WO2002022817A2 (en) 2000-09-16 2001-09-07 Nuclear receptor l66 and methods of use

Country Status (4)

Country Link
EP (1) EP1317542A2 (en)
AU (1) AU2002213893A1 (en)
CA (1) CA2420932A1 (en)
WO (1) WO2002022817A2 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003044167A2 (en) * 2001-11-15 2003-05-30 Isis Pharmaceuticals, Inc. Antisense modulation of human fxr expression
WO2003087140A1 (en) * 2002-04-13 2003-10-23 Lion Bioscience Ag NON-PRIMATE FXRb AS A LANOSTEROL SENSING NUCLEAR HORMONE RECEPTOR AND RELATED USES

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996021677A1 (en) * 1995-01-13 1996-07-18 The General Hospital Corporation Retinoid x receptor-interacting polypeptides and related molecules and methods
US5728548A (en) * 1995-06-29 1998-03-17 Genetics Institute, Inc. Retinoid receptor-1 (RR1) and DNA encoding RR1
US6005086A (en) * 1995-01-13 1999-12-21 The Salk Institute For Biological Studies Farnesoid activated receptor polypeptides, and nucleic acid encoding the same
WO2000057915A1 (en) * 1999-03-26 2000-10-05 City Of Hope Method of affecting cholesterol catabolism using nuclear bile acid receptor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996021677A1 (en) * 1995-01-13 1996-07-18 The General Hospital Corporation Retinoid x receptor-interacting polypeptides and related molecules and methods
US6005086A (en) * 1995-01-13 1999-12-21 The Salk Institute For Biological Studies Farnesoid activated receptor polypeptides, and nucleic acid encoding the same
US5728548A (en) * 1995-06-29 1998-03-17 Genetics Institute, Inc. Retinoid receptor-1 (RR1) and DNA encoding RR1
WO2000057915A1 (en) * 1999-03-26 2000-10-05 City Of Hope Method of affecting cholesterol catabolism using nuclear bile acid receptor

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
DATABASE EMBL [Online] Database accession no. AA974561 XP002202975 *
DATABASE EMBL [Online] Database accession no. AL358372 XP002202974 *
HUBER REID M ET AL: "Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters." GENE. NETHERLANDS 15 MAY 2002, vol. 290, no. 1-2, 15 May 2002 (2002-05-15), pages 35-43, XP002202973 ISSN: 0378-1119 *
WANG H ET AL: "ENDOGENOUS BILE ACIDS ARE LIGANDS FOR THE NUCLEAR RECEPTOR FXR/BAR" MOLECULAR CELL, CAMBRIDGE, MA, US, vol. 3, May 1999 (1999-05), pages 543-553, XP000905175 ISSN: 1097-2765 *
WONGI SEOL ET AL: "ISOLATION OF PROTEINS THAT INTERACT SPECIFICALLY WITH THE RETIONOIDX RECEPTOR: TWO NOVEL ORPHAN RECEPTORS" MOLECULAR ENDOCRINOLOGY, BALTIMORE, MD, US, vol. 9, no. 1, 1995, pages 72-85, XP000561076 ISSN: 0888-8809 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003044167A2 (en) * 2001-11-15 2003-05-30 Isis Pharmaceuticals, Inc. Antisense modulation of human fxr expression
WO2003044167A3 (en) * 2001-11-15 2004-02-12 Isis Pharmaceuticals Inc Antisense modulation of human fxr expression
WO2003087140A1 (en) * 2002-04-13 2003-10-23 Lion Bioscience Ag NON-PRIMATE FXRb AS A LANOSTEROL SENSING NUCLEAR HORMONE RECEPTOR AND RELATED USES

Also Published As

Publication number Publication date
EP1317542A2 (en) 2003-06-11
WO2002022817A3 (en) 2003-03-27
AU2002213893A1 (en) 2002-03-26
CA2420932A1 (en) 2002-03-21

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