Use of the receptor GPR86

• US 7,879,564 B2
• Filed: 12/21/2006
• Issued: 02/01/2011
• Est. Priority Date: 07/01/2004
• Status: Expired due to Fees

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Messager, Sophie, Dixon, John, Malinge, Isabelle, Carlton, Mark, Hendrick, Alan, Brice, Nicola, Zahn, Dirk
• Primary Examiner(s): Saoud; Christine J
• Assistant Examiner(s): LOCKARD, JON MCCLELLAND
• Application Number:
  US11/644,011
• Publication Number:
  US 20070248545A1
• Time in Patent Office: 1,503 Days
• Field of Search: None
• US Class Current: 435/7.2
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/0356 Animal model for processes and diseases of the central nervous system, e.g. stress, learning, schizophrenia, pain, epilepsy
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• CPC Class Codes: A61K 49/0008 Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/70571 for neuromediators, e.g. serotonin receptor, dopamine receptor
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: G01N 2333/726 G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 2800/24 Immunology or allergic disorders SLE G01N2800/104
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/566 using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

We describe a method of identifying a molecule suitable for the treatment, prophylaxis or alleviation of a GPR86 associated disease, in particular inflammatory disease or pain, the method comprising determining whether a candidate molecule is an agonist or antagonist of GPR86 polypeptide, in which the GPR86 polypeptide comprises the amino acid sequence shown in SEQ ID NO: 3 or SEQ ID NO: 5 or SEQ ID NO: 7, a fragment thereof or a sequence which is at least 90% identical thereto.

Claims

1. An in vitro method of identifying a candidate molecule for the treatment, prophylaxis or alleviation of pain, the method comprising:

exposing a candidate molecule to a GPR86 polypeptide comprising the amino acid sequence shown in SEQ ID NO;

7 or a sequence identical to at least 98% of SEQ ID NO;

7, wherein the candidate molecule is not a protein and is not an antibody;

measuring binding of the candidate molecule to the GPR86 polypeptide, wherein a candidate molecule which binds to GPR86 is a candidate for treatment, prophylaxis, or alleviation of pain.

2. The method of claim 1 wherein the GPR86 polypeptide comprises the amino acid sequence shown in SEQ ID NO:

7.

3. The method of claim 1 further comprising:

testing in vitro to determine that the candidate is an antagonist of GPR86.

4. The method of claim 3 wherein the testing comprises:

contacting (a) a cell comprising a GPR86 receptor polypeptide comprising the amino acid sequence shown in SEQ ID NO;

7 or a sequence identical to at least 98% of SEQ ID NO;

7 coupled with G-protein G_i with (b) the candidate compound; and

determining cyclic AMP (cAMP) level in said cell, wherein when said level is raised as a result of said contacting, the candidate compound is identified as a molecule suitable for the treatment, prophylaxis, or alleviation of pain.

5. The method of claim 3 wherein the testing comprises:

contacting (a) a cell comprising a GPR86 receptor polypeptide comprising the amino acid sequence shown in SEQ ID NO;

7 or a sequence identical to at least 98% of SEQ ID NO;

7 coupled with G<sub>α

16</sub> with (b) the candidate compound; and

determining intracellular calcium level in said cell, wherein when said level is lowered as a result of said contacting, the candidate compound is identified as a molecule suitable for the treatment, prophylaxis, or alleviation of pain.

6. An in vitro method of identifying a molecule suitable for the treatment, prophylaxis or alleviation of pain, the method comprising:

contacting (a) a cell comprising a GPR86 receptor polypeptide comprising the amino acid sequence shown in SEQ ID NO;

7 or a sequence identical to at least 98% of SEQ ID NO;

7 coupled with G-protein G_i with (b) a candidate compound, wherein the candidate molecule is not a protein and is not an antibody; and

determining cyclic AMP (cAMP) level in said cell, wherein when said level is raised as a result of said contacting, the candidate compound is identified as a molecule suitable for the treatment, prophylaxis, or alleviation of pain.

7. The method of claim 6 wherein the GPR86 polypeptide comprises the amino acid sequence shown in SEQ ID NO:

7.

8. An in vitro method of identifying a molecule suitable for the treatment, prophylaxis or alleviation of pain, the method comprising:

contacting (a) a cell comprising a GPR86 receptor polypeptide comprising the amino acid sequence shown in SEQ ID NO;

7 or a sequence identical to at least 98% of SEQ ID NO;

7 coupled with G<sub>α

16</sub> with (b) a candidate compound, wherein the candidate molecule is not a protein and is not an antibody; and

determining intracellular calcium level in said cell, wherein when said level is lowered as a result of said contacting, the candidate compound is identified as a molecule suitable for the treatment, prophylaxis, or alleviation of pain.

9. The method of claim 8 wherein the GPR86 polypeptide comprises the amino acid sequence shown in SEQ ID NO:

7.