Nucleic acid encoding sodium channels in dorsal root ganglia

• US 6,573,067 B1
• Filed: 07/16/1999
• Issued: 06/03/2003
• Est. Priority Date: 01/29/1998
• Status: Expired due to Term

• Current Assignee: Yale University
• Original Assignee: Yale University
• Inventors: Waxman, Stephen G., Dib-Hajj, Sulayman
• Primary Examiner(s): PAK, MICHAEL D
• Application Number:
  US09/354,147
• Time in Patent Office: 1,418 Days
• Field of Search: 435/69.1, 435/325, 435/320.1, 536/23.4, 536/23.5
• US Class Current: 435/69.1
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 51/02 characterised by the carrier , i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
• CPC Class Codes: A61K 51/10 Antibodies or immunoglobulins; Fragments thereof , the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants

Abstract

A novel tetrodotoxin resistant sodium channel is described, along with isolated nucleotides that encode this receptor. Methods for identifying agents that modulate the Na⁺ current through the receptor are provided, as well as related therapeutic and diagnostic methods.

Claims

1. An isolated nucleic acid molecule encoding a protein capable of producing a sodium current and comprising at least about eighty (80) percent nucleotide sequence identity to SEQ ID NO:

41.

4. An isolated nucleic acid molecule of claim 2 or 1, wherein the nucleic acid molecule comprises SEQ ID NO:

41.

5. An isolated nucleic acid molecule of claim 4, wherein the nucleic acid molecule consists of SEQ ID NO:

41.

6. An isolated nucleic acid molecule of claim 2 or 1, wherein the nucleic acid molecule comprises nucleotides 31 to 5403 of SEQ ID NO:

41.

7. An isolated nucleic acid molecule of claim 6, wherein the nucleic acid molecule consists of nucleotides 31 to 5403 of SEQ ID NO:

41.

9. An isolated nucleic acid molecule of claim 2 or 1, wherein the nucleic acid molecule is human.

10. An isolated nucleic acid molecule of claim 9, wherein the molecule is a cDNA molecule.

11. An isolated nucleic acid molecule of claim 1, wherein the percent nucleotide sequence identity to SEQ ID NO:

41 is at least about eighty-five (85) percent.

12. An isolated nucleic acid molecule of claim 1, wherein the percent nucleotide sequence identity to SEQ ID NO:

41 is at least about ninety (90) percent.

13. An isolated nucleic acid molecule of claim 1, wherein the percent nucleotide sequence identity to SEQ ID NO:

41 is at least about ninety-five (95) percent.

14. An isolated nucleic acid molecule of claim 1, wherein the percent nucleotide sequence identity to SEQ ID NO:

41 is at least about ninety-nine (99) percent.

15. An isolated nucleic acid molecule of claim 2 or 1, wherein said nucleic acid molecule is operably linked to one or more expression control elements.

16. A vector comprising an isolated nucleic acid molecule of claim 2 or 1.

17. A host cell comprising the vector of claim 16.

18. A host cell of claim 17 wherein the host is selected from the group consisting of prokaryotic and eukaryotic hosts.

19. A host cell transformed to contain the nucleic acid molecule of claim 2 or 1.

20. A method for producing a polypeptide, comprising the step of culturing a host cell of claim 19 under conditions in which the protein encoded by the nucleic acid is expressed.

21. The method of claim 20, wherein the host cell is selected from the group consisting of prokaryotic and eukaryotic hosts.

22. The isolated nucleic acid molecule of claim 2 or 1, wherein said isolated nucleic acid encodes a protein capable of producing a sodium current and hybridizes to a nucleic acid molecule comprising the complement of SEQ ID NO:

41 under moderately stringent conditions.

2. An isolated nucleic acid molecule encoding SEQ ID NO:

42.

3. An isolated nucleic acid molecule comprising nucleotides 628 to 4328 of SEQ ID NO:

41.

8. An isolated nucleic acid molecule of 2 or 1, wherein the nucleic acid molecule encodes a tetrodotoxin-resistant, voltage-gated sodium channel α

subunit.