US 2002/0166131 A1Published application

Transgenic gpcr expressing animals

AssigneeMillennium Pharmaceuticals, Inc.

InventorsANDREW D. J. GOODEARL, M. ALEXANDRA GLUCKSMANN

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Abstract

The invention provides isolated nucleic acids molecules, designated muscarinic acetylcholine receptor 6 (“mACHR-6”) nucleic acid molecules, which encode polypeptides involved in the modulation of acetylcholine responses in acetylcholine responsive cells. The invention also provides antisense nucleic acid molecules, expression vectors containing mACHR-6 nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which an mACHR-6 gene has been introduced or disrupted. The invention still further provides isolated mACHR-6 polypeptides, fusion polypeptides, antigenic peptides, and anti-mACHR-6 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Claims23

Dependent claims

An isolated nucleic acid molecule selected from the group consisting of:

a) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2;
b) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:5;
c) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:32;
d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2;
e) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:5, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:5;
f) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:32, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:32;
g) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO:1 under stringent conditions;
and
h) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:5, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO:4 under stringent conditions;
and
i) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:32, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO:31 under stringent conditions.

8 more elements

A method for detecting the presence of a polypeptide selected from the group consisting of:

a) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;
b) a polypeptide comprising the amino acid sequence of SEQ ID NO:5;
c) a polypeptide comprising the amino acid sequence of SEQ ID NO:32;
d) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2;
e) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:5, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:5;
f) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:32, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:32;
g) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1 under stringent conditions;
h) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:5, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:4 under stringent conditions;
and
i) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:32, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:31 under stringent conditions;
in a sample, the method comprising the steps of:
i) contacting the sample with a compound which selectively binds to the polypeptide;
and
ii) determining whether the compound binds to the polypeptide in the sample.

11 more elements

A method for detecting the presence of a nucleic acid molecule selected from the group consisting of:

a) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;
b) a polypeptide comprising the amino acid sequence of SEQ ID NO:5;
c) a polypeptide comprising the amino acid sequence of SEQ ID NO:32;
d) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2;
e) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:5, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:5;
f) a fragment of a polypeptide comprising the amino-acid sequence of SEQ ID NO:32, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:32;
g) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1 under stringent conditions;
h) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:5, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:4 under stringent conditions;
and
i) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:32, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:31 under stringent conditions;
in a sample, the method comprising the steps of:
i) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule;
and
ii) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample.

11 more elements

A method for identifying a compound which binds to a polypeptide selected from the group consisting of:

a) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;
b) a polypeptide comprising the amino acid sequence of SEQ ID NO:5;
c) a polypeptide comprising the amino acid sequence of SEQ ID NO:32;
d) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2;
e) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:5, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:5;
f) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:32, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:32;
g) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1 under stringent conditions;
h) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:5, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:4 under stringent conditions;
and
i) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:32, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:31 under stringent conditions,
the method comprising the steps of:
i) contacting the polypeptide, or a cell expressing the polypeptide with a test compound;
and
ii) determining whether the polypeptide binds to the test compound.

11 more elements

A method for modulating the activity of a polypeptide selected from the group consisting of:

a) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;
b) a polypeptide comprising the amino acid sequence of SEQ ID NO:5;
c) a polypeptide comprising the amino acid sequence of SEQ ID NO:32;
d) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2;
e) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:5, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:5;
f) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:32, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:32;
g) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1 under stringent conditions;
h) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:5, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:4 under stringent conditions;
and
i) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:32, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:31 under stringent conditions,
the method comprising the steps of:
i) contacting a cell expressing the polypeptide with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.

9 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/349,755Filed 8 Jul 1999
Priority: 4 Dec 1997
Published: 7 Nov 2002
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07K 14/70571
Receptors; Cell surface antigens; Cell surface determinants: for neuromediators, e.g. serotonin receptor, dopamine receptor
A01K 2217/05
Genetically modified animals: animals comprising random inserted nucleic acids
A61K 38/00
Medicinal preparations containing peptides
C07K 2319/00
Fusion polypeptide

Family

Application08/985,090Continuation · filed 4 Dec 1997
Application09/042,780Division · filed 17 Mar 1998
Application09/349,755Division · filed 8 Jul 1999
Application09/349,755Continuation · filed 8 Jul 1999
US 5,882,893 ARelated patent
US 2002/0166131 A1This patent

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

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