P-glycoproteins and uses thereof

• US 6,617,450 B1
• Filed: 09/28/2000
• Issued: 09/09/2003
• Est. Priority Date: 09/28/1999
• Status: Expired due to Fees

• Current Assignee: Corning Incorporated
• Original Assignee: Becton, Dickinson & Co
• Inventors: Crespi, Charles L., Stocker, Penny J., Steimel-Crespi, Dorothy T.
• Primary Examiner(s): Prouty, Rebecca E.
• Assistant Examiner(s): Rao, Manjunath N.
• Application Number:
  US09/672,810
• Time in Patent Office: 1,076 Days
• Field of Search: 530/350, 530/388.9, 536/23.5, 435/252.3, 435/320.1
• US Class Current: 536/23.5
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748

Abstract

The invention pertains to cynomologous monkey P-glycoproteins and related P-glycoproteins which include cynomologous-specific amino acids, as well as nucleic acids which encode those polypeptides. The present invention also includes fragments and biologically functional variants of the cynomologous monkey P-glycoprotein. The invention further relates to methods of using such cynomologous monkey P-glycoprotein nucleic acids and polypeptides, especially in methods for determining bioavailability of drugs and for screening for inhibitors of cynomologous PGP. Also included are cynomologous PGP inhibitors which inhibit cynomologous PGP activity by inhibiting the expression or function of cynomologous PGP.

Claims

1. An isolated nucleic acid molecule selected from the group consisting of

(a) nucleic acid molecules that code for the amino acid sequence of SEQ ID NO:

2 or SEQ ID NO;

4,

(b) variants of the nucleic acid molecules of (a) that encodes a P-glycoprotein having multidrug transport activity and an amino acid sequence that varies from SEQ ID NO;

2 or SEQ ID NO;

4 by 1, 2, 3, 4 or 5 amino acid, and

(c) complements of (a) or (b).

2. The isolated nucleic acid molecule of claim 1, wherein the isolated nucleic acid molecule codes for SEQ ID NO:

2.

3. The isolated nucleic acid molecule of claim 1, wherein the isolated nucleic acid molecule codes for SEQ ID NO:

4.

4. The isolated nucleic molecule of claim 1, wherein he isolated nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO:

1 or SEQ ID NO;

3.

5. An expression vector comprising the isolated nucleic acid molecule of claim 1 operably linked to a promoter.

6. A host cell transformed or transfected with the expression vector of claim 5.

7. The isolated nucleic acid molecule of claim 2, wherein the isolated nucleic acid molecule comprises nucleotides 100-3940 of SEQ ID NO:

1.

8. The isolated nucleic acid molecule of claim 3, wherein the isolated nucleic acid molecule comprises nucleotides 100-3949 of SEQ ID NO:

3.

9. An expression vector comprising the isolated nucleic acid molecule of claim 2 operably linked to a promoter.

10. A host cell transformed or transfected with the expression vector of claim 9.

11. An expression vector comprising the isolated nucleic acid molecule of claim 3 operably linked to a promoter.

12. A host cell transformed or transfected with the expression vector of claim 11.

13. An expression vector comprising the isolated nucleic acid molecule of claim 4 operably linked to a promoter.

14. A host cell transformed or transfected with the expression vector of claim 13.

15. An expression vector comprising the isolated nucleic acid molecule of claim 7 operably linked to a promoter.

16. A host cell transformed or transfected with the expression vector of claim 15.

17. An expression vector comprising the isolated nucleic acid molecule of claim 8 operably linked to a promoter.

18. A host cell transformed or transfected with the expression vector of claim 17.