US 7,622,266 B2Granted

Identification of a synthetic ligand for retinoic acid receptor beta

AssigneeInstitut Pasteur

InventorsHugues Blaudin de The, Agnes Marchio, Pierre Tiollais, Anne Dejean

Life of this patent

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Abstract

A method for identifying a synthetic ligand for retinoic acid receptor β comprises providing a sample, including a synthetic compound, exposing the sample to cultured cells, wherein the cultured cells comprise RARβ, determining if transcriptional expression of a gene encoding RARβ is upregulated compared to transcriptional expression of a control gene, and choosing a sample that upregulates the expression of RARβ as being a synthetic ligand for RARβ.

Claims7

Dependent claims

A method for identifying a synthetic ligand for a retinoic acid receptor comprising the amino acid sequence

MetPheAspCysMetAspValIeuSerValSerProGlyGlnIleLeu
AspPheTyrThrAlaSerProSerSerCysMetLeuGlnGluLysAla
LeuLysAlaCysPheSerGlyLeuThrGlnThrGluTrpGlnHisArg
HisThrAlaGlnSerIleGluThrGlnSerThrSerSerGluGluLeu
ValProSerProProSerProLeuProProProArgValTyrLysPro
CysPheValCysGlnAspLysSerSerGlyTyrHisTyrGlyValSer
AlaCysGluGlyCysLysGlyPhePheArgArgSerIleGlnLysAsn
MetIleTyrThrCysHisArgAspLysAsnCysValIleAsnLysVal
ThrArgAsnArgCysGlnTyrCysArgLeuGlnLysCysPheGluVal
GlyMetSerLysGluSerValArgAsnAspArgAsnLysLysLysLys
GluThrSerLysGlnGluCysThrGluSerTyrGluMetThrAlaGlu
LeuAspAspLeuThrGluLysIleArgLysAlaHisGlnGluThrPhe
ProSerLeuCysGlnLeuGlyLysTyrThrThrAsnSerSerAlaAsp
HisArgValArgLeuAspLeuGlyLeuTrpAspLysPheSerGluLeu
AlaThrLysCysIleIleLysIleValGluPheAlaLysArgLeuPro
GlyPheThrGlyLeuThrIleAlaAspGlnIleThrLeuLeuLysAla
AlaCysLeuAspIleLeuIleLeuArgIleCysThrArgTyrThrPro
GluGlnAspThrMetThrPheSerAspGlyLeuThrLeuAsnArgThr
GlnMetHisAsnAlaGlyPheGlyProLeuThrAspLeuValPheThr
PheAlaAsnGlnLeuLeuProLeuGluyMetAspAspThrGluThrGly
LeuLeuSerAlaIleCysLeuIleCysGlyAspArgGlnAspLeuGlu
GluProThrLysVAlAspLysLeuGlnGluProLeuLeuGluAlaLeu
LysIleTyrIleArgLysArgArgProSerLysProHisMetPhePro
LysIleLeuMetLysIleThrAspLeuArgSerIleSerAlaLysGly
alaGluArgValIleThrLeulysMetGluIleProGlySerMetPro
ProLeuIleGlnGluMetMetGluAsnSerGluGlyHisGluProLeu
ThrProSerSerSerGlyAsnThrAlaGluHisSerProSerIleSer
ProSerSerValGluAsnSerGlyValSerGlnSerProLeuValGln
comprising:
(A) providing a sample comprising a synthetic compound;
(B) exposing the sample to cultured cells, wherein the cultured cells comprise the retinoic acid receptor;
(C) determining if transcriptional expression of a gene in the cell comprising
ATGTTTGACTGTATGGATGTTCTGTCAGTGAGTCCTGGGCAAATCCTGATT
CTACACTGCGAGTCCGTCTTCCTGCATGCTCCAGGAGAAAGCTCTCAAAGC
ATGCTTCAGTGGATTGACCCAAACCGAATGGCAGCATCGGCACACTGCTCA
ATCAATTGAAACACAGAGCACCAGCTCTGAGGAACTCGTCCCAAGCCCCCC
ATCTCCACTTCCTCCCCCTCGAGTGATCAAACCCTGCTTCGTCTGCCAGGA
CAAATCATCAGGGTACCACTATGGGGTCAGCGCCTGTGAGGGATGAAGGGC
TTTTTCCGCAGAAGTATTCAGAAGAATATGATTTACACTTGTCACCGAGAT
AAGAACTGTGTTATTAATAAAGTCACCAGGAATCGATGCCAATACTGTGCG
ACTCCAGAAGTGCTTTGAAGTGGGAATGTCCAAAGAATCTGTCAGGAATGA
CAGGAACAAGAAAAAGAAGGAGACTTCGAAGCAAGAATGCACAGAGAGCTA
TGAAATGACAGCTGAGTTGGACGATCTCACAGAGAAGATCCGAAAAGCTCA
CCAGGAAACTTTCCCTTCACTCTCGCAGCTGGGTAAATACACCACGAATTC
CAGTGCTGACCATCGAGTCCGACTGGACCTGGGCCTCTGGGACAAATTCAG
TGAACTGGCCACCAAGTGCATTATTAAGATCGTGGAGTTTGCTAAACGTCT
GCCTGGTTTCACTGGCTTGACCATCGCAGACCAAATTACCCTGCTGAAGGC
CGCCTGCCTGGACATCCTGATTCTTAGAATTTGCACCAGGTATACCCCAGA
ACAAGACACCATGACTTTCTCAGACGGCCTTACCCTAAATCGAACTCAGAT
GCACAATGCTGGATTTGGTCCTCTGACTGACCTTGTGTTCACTTTGCCAAC
CAGCTCCTGCCTTTGGAAATGGATGACACAGAAACAGGCCTTCTCAGTGCC
ATCTGCTTAATCTGTGGAGACCGCCAGGACCTTGAGGAACCGACAAAAGTA
GTAAAGCTACAAGAACCATTGCTGGAAGCACTAAAAATTTATATCAGAAAA
AGACGACCCAGCAAGCCTCACATGTTTCCAAAGATCTTAATGAAAATCACA
GATCTCCGTAGCATCAGTGCTAAAGGTGCAGAGCGTGTAATTACCTTGAAA
ATGGAAATTCCTGGATCAATGCCACCTCTCATTCAAGAAATGATGGAGAAT
TCTGAAGGACATGAACCCTTGACGCCAAGTTCAAGTGGGAACACAGCAGAG
CACAGTCCTAGCATCTCACCCAGCTCAGTGGAAAACAGTGGGGTCAGTCAG
TCACCACTCGTGCAATAA
is upregulated compared to transcriptional expression of a control gene in, the cell;
(D) choosing a sample that upregulates transcriptional expression in (C) as being a synthetic ligand for the retinoic acid receptor.

58 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/384,481Filed 21 Mar 2006 · continuation
Priority: 16 Dec 1987
Published: US 2006/0189798 A124 Aug 2006
Granted: 24 Nov 2009
Term ends: Not estimatedThe source records don’t support an estimate.

Classification5 codes

C07K 14/70567
Receptors; Cell surface antigens; Cell surface determinants: nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors
C12Q 1/6876
Involving nucleic acids: nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C12Q 2600/158
Oligonucleotides characterized by their use: expression markers
C07K
Peptides

Family

Application07/133,687Parent of this continuation-in-part · filed 16 Dec 1987
Application07/134,130Parent of this continuation-in-part · filed 17 Dec 1987
Application07/209,009Parent of this continuation-in-part · filed 20 Jun 1988
Application07/278,136Parent of this continuation · filed 30 Nov 1988
Application07/649,342Parent of this continuation · filed 1 Feb 1991
Application10/307,339Parent of this continuation · filed 2 Dec 2002
US 2006/0189798 A1Pre-grant publication · published 24 Aug 2006
US 6,531,585 B1Parent of this continuation
US 5,149,781 AParent of this continuation-in-part
Application07/278,136Parent of this continuation-in-part
US 5,223,606 AParent of this continuation-in-part
US 2003/0153740 A1Published application
US 7,622,266 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A method for identifying a synthetic ligand for a retinoic acid receptor comprising the amino acid sequence

MetPheAspCysMetAspValIeuSerValSerProGlyGlnIleLeu
AspPheTyrThrAlaSerProSerSerCysMetLeuGlnGluLysAla
LeuLysAlaCysPheSerGlyLeuThrGlnThrGluTrpGlnHisArg
HisThrAlaGlnSerIleGluThrGlnSerThrSerSerGluGluLeu
ValProSerProProSerProLeuProProProArgValTyrLysPro
CysPheValCysGlnAspLysSerSerGlyTyrHisTyrGlyValSer
AlaCysGluGlyCysLysGlyPhePheArgArgSerIleGlnLysAsn
MetIleTyrThrCysHisArgAspLysAsnCysValIleAsnLysVal
ThrArgAsnArgCysGlnTyrCysArgLeuGlnLysCysPheGluVal
GlyMetSerLysGluSerValArgAsnAspArgAsnLysLysLysLys
GluThrSerLysGlnGluCysThrGluSerTyrGluMetThrAlaGlu
LeuAspAspLeuThrGluLysIleArgLysAlaHisGlnGluThrPhe
ProSerLeuCysGlnLeuGlyLysTyrThrThrAsnSerSerAlaAsp
HisArgValArgLeuAspLeuGlyLeuTrpAspLysPheSerGluLeu
AlaThrLysCysIleIleLysIleValGluPheAlaLysArgLeuPro
GlyPheThrGlyLeuThrIleAlaAspGlnIleThrLeuLeuLysAla
AlaCysLeuAspIleLeuIleLeuArgIleCysThrArgTyrThrPro
GluGlnAspThrMetThrPheSerAspGlyLeuThrLeuAsnArgThr
GlnMetHisAsnAlaGlyPheGlyProLeuThrAspLeuValPheThr
PheAlaAsnGlnLeuLeuProLeuGluyMetAspAspThrGluThrGly
LeuLeuSerAlaIleCysLeuIleCysGlyAspArgGlnAspLeuGlu
GluProThrLysVAlAspLysLeuGlnGluProLeuLeuGluAlaLeu
LysIleTyrIleArgLysArgArgProSerLysProHisMetPhePro
LysIleLeuMetLysIleThrAspLeuArgSerIleSerAlaLysGly
alaGluArgValIleThrLeulysMetGluIleProGlySerMetPro
ProLeuIleGlnGluMetMetGluAsnSerGluGlyHisGluProLeu
ThrProSerSerSerGlyAsnThrAlaGluHisSerProSerIleSer
ProSerSerValGluAsnSerGlyValSerGlnSerProLeuValGln
comprising:
(A) providing a sample comprising a synthetic compound;
(B) exposing the sample to cultured cells, wherein the cultured cells comprise the retinoic acid receptor;
(C) determining if transcriptional expression of a gene in the cell comprising
ATGTTTGACTGTATGGATGTTCTGTCAGTGAGTCCTGGGCAAATCCTGATT
CTACACTGCGAGTCCGTCTTCCTGCATGCTCCAGGAGAAAGCTCTCAAAGC
ATGCTTCAGTGGATTGACCCAAACCGAATGGCAGCATCGGCACACTGCTCA
ATCAATTGAAACACAGAGCACCAGCTCTGAGGAACTCGTCCCAAGCCCCCC
ATCTCCACTTCCTCCCCCTCGAGTGATCAAACCCTGCTTCGTCTGCCAGGA
CAAATCATCAGGGTACCACTATGGGGTCAGCGCCTGTGAGGGATGAAGGGC
TTTTTCCGCAGAAGTATTCAGAAGAATATGATTTACACTTGTCACCGAGAT
AAGAACTGTGTTATTAATAAAGTCACCAGGAATCGATGCCAATACTGTGCG
ACTCCAGAAGTGCTTTGAAGTGGGAATGTCCAAAGAATCTGTCAGGAATGA
CAGGAACAAGAAAAAGAAGGAGACTTCGAAGCAAGAATGCACAGAGAGCTA
TGAAATGACAGCTGAGTTGGACGATCTCACAGAGAAGATCCGAAAAGCTCA
CCAGGAAACTTTCCCTTCACTCTCGCAGCTGGGTAAATACACCACGAATTC
CAGTGCTGACCATCGAGTCCGACTGGACCTGGGCCTCTGGGACAAATTCAG
TGAACTGGCCACCAAGTGCATTATTAAGATCGTGGAGTTTGCTAAACGTCT
GCCTGGTTTCACTGGCTTGACCATCGCAGACCAAATTACCCTGCTGAAGGC
CGCCTGCCTGGACATCCTGATTCTTAGAATTTGCACCAGGTATACCCCAGA
ACAAGACACCATGACTTTCTCAGACGGCCTTACCCTAAATCGAACTCAGAT
GCACAATGCTGGATTTGGTCCTCTGACTGACCTTGTGTTCACTTTGCCAAC
CAGCTCCTGCCTTTGGAAATGGATGACACAGAAACAGGCCTTCTCAGTGCC
ATCTGCTTAATCTGTGGAGACCGCCAGGACCTTGAGGAACCGACAAAAGTA
GTAAAGCTACAAGAACCATTGCTGGAAGCACTAAAAATTTATATCAGAAAA
AGACGACCCAGCAAGCCTCACATGTTTCCAAAGATCTTAATGAAAATCACA
GATCTCCGTAGCATCAGTGCTAAAGGTGCAGAGCGTGTAATTACCTTGAAA
ATGGAAATTCCTGGATCAATGCCACCTCTCATTCAAGAAATGATGGAGAAT
TCTGAAGGACATGAACCCTTGACGCCAAGTTCAAGTGGGAACACAGCAGAG
CACAGTCCTAGCATCTCACCCAGCTCAGTGGAAAACAGTGGGGTCAGTCAG
TCACCACTCGTGCAATAA
is upregulated compared to transcriptional expression of a control gene in, the cell;
(D) choosing a sample that upregulates transcriptional expression in (C) as being a synthetic ligand for the retinoic acid receptor.

58 more elements

Facts

Application

11/384,481Filed 21 Mar 2006 · continuation

Priority

16 Dec 1987

Published

US 2006/0189798 A124 Aug 2006

Granted

24 Nov 2009

Term ends

Not estimatedThe source records don’t support an estimate.

Classification5 codes

C07K 14/70567
Receptors; Cell surface antigens; Cell surface determinants: nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors
C12Q 1/6876
Involving nucleic acids: nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C12Q 2600/158
Oligonucleotides characterized by their use: expression markers
C07K
Peptides

Family

Application07/133,687Parent of this continuation-in-part · filed 16 Dec 1987

Application07/134,130Parent of this continuation-in-part · filed 17 Dec 1987

Application07/209,009Parent of this continuation-in-part · filed 20 Jun 1988

Application07/278,136Parent of this continuation · filed 30 Nov 1988

Application07/649,342Parent of this continuation · filed 1 Feb 1991

Application10/307,339Parent of this continuation · filed 2 Dec 2002

US 2006/0189798 A1Pre-grant publication · published 24 Aug 2006

US 6,531,585 B1Parent of this continuation

US 5,149,781 AParent of this continuation-in-part

Application07/278,136Parent of this continuation-in-part

US 5,223,606 AParent of this continuation-in-part

US 2003/0153740 A1Published application

US 7,622,266 B2This patent

From the US filing history. Foreign family members aren’t listed.