Title:
32670, NOVEL HUMAN PHOSPHATIDYLSERINE SYNTHASE-LIKE MOLECULES AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO/2001/064851
Kind Code:
A2
Abstract:
Novel human phosphatidylserine synthase-like polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length human phosphatidylserine synthase-like proteins, the invention further provides isolated human phosphatidylserine synthase-like fusion proteins, antigenic peptides, and anti-human phosphatidylserine synthase-like antibodies. The invention also provides human phosphatidylserine synthase-like nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a human phosphatidylserine synthase-like gene has been introduced or disrupted. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.
Inventors:
MEYERS RACHEL A (US)
Application Number:
PCT/US2001/006005
Publication Date:
September 07, 2001
Filing Date:
February 23, 2001
Export Citation:
Assignee:
MILLENNIUM PHARM INC (US)
MEYERS RACHEL A (US)
MEYERS RACHEL A (US)
International Classes:
C12N9/12; C12N15/54; (IPC1-7): C12N9/12; C12N15/11; C12N15/54; C12N15/62; C12N15/85; C12N5/10; C07K16/40; C12Q1/68; G01N33/573; G01N33/577; G01N33/68
Domestic Patent References:
| WO2001032888A2 | 2001-05-10 |
Other References:
KUGE OSAMU ET AL: "Cloning of a Chinese hamster ovary (CHO) cDNA encoding phosphatidylserine synthase (PSS) II, overexpression of which suppresses the phosphatidylserine biosynthetic defect of a PSS I-lacking mutant of CHO-K1 cells." JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 31, 1997, pages 19133-19139, XP002179772 ISSN: 0021-9258 cited in the application
STONE SCOT J ET AL: "Cloning and expression of murine liver phosphatidylserine synthase (PSS)-2: Differential regulation of phospholipid metabolism by PSS1 and PSS2." BIOCHEMICAL JOURNAL, vol. 342, no. 1, 15 August 1999 (1999-08-15), pages 57-64, XP002179773 ISSN: 0264-6021
DATABASE EMBL [Online] 29 June 1999 (1999-06-29) MARRA M., ET AL.: "The WashU-NCI mouse EST project 1999" Database accession no. AI747377 XP002179774
DATABASE EMBL [Online] 21 December 1996 (1996-12-21) EVANS G.A., ET AL.: "Template" Database accession no. U73630 XP002179775
STONE SCOT J ET AL: "Cloning and expression of murine liver phosphatidylserine synthase (PSS)-2: Differential regulation of phospholipid metabolism by PSS1 and PSS2." BIOCHEMICAL JOURNAL, vol. 342, no. 1, 15 August 1999 (1999-08-15), pages 57-64, XP002179773 ISSN: 0264-6021
DATABASE EMBL [Online] 29 June 1999 (1999-06-29) MARRA M., ET AL.: "The WashU-NCI mouse EST project 1999" Database accession no. AI747377 XP002179774
DATABASE EMBL [Online] 21 December 1996 (1996-12-21) EVANS G.A., ET AL.: "Template" Database accession no. U73630 XP002179775
Attorney, Agent or Firm:
Coulter, Kathryn L. (NC, US)
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Claims:
THAT WHICH IS CLAIMED :
| 1. | An isolated nucleic acid molecule selected from the group consisting of : a) a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to the nucleotide sequence of SEQ ID NO : 1 or SEQ ID NO : 3, wherein said nucleotide sequence encodes a polypeptide having biological activity ; b) a nucleic acid molecule comprising a fragment of at least 20 nucleotides of the nucleotide sequence of SEQ ID NO : 1 or SEQ ID NO : 3 ; c) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO : 2 ; 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 naturally occurring allelic variant of a biologically active polypeptide comprising the amino acid sequence of SEQ ID NO : 2, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising the complement of SEQ ID NO : 1 or SEQ ID NO : 3 under stringent conditions ; and f) a nucleic acid molecule comprising the complement of a), b), c), d), or e). |
| 2. | The isolated nucleic acid molecule of claim 1, which is selected from the group consisting of : a) a nucleic acid comprising the nucleotide sequence of SEQ ID NO : 1, SEQ ID NO : 3, or a complement thereof ; and b) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO : 2, or a complement thereof. |
| 3. | The nucleic acid molecule of claim 1 further comprising vector nucleic acid sequences. |
| 4. | The nucleic acid molecule of claim 1 further comprising nucleic acid sequences encoding a heterologous polypeptide. |
| 5. | A host cell which contains the nucleic acid molecule of claim 1. |
| 6. | The host cell of claim 5 which is a mammalian host cell. |
| 7. | A nonhuman mammalian host cell containing the nucleic acid molecule of claim 1. |
| 8. | An isolated polypeptide selected from the group consisting of : a) a biologically active polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO : 1 or SEQ ID NO : 3 ; b) 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 the complement of SEQ ID NO : 1 or SEQ ID NO : 3 under stringent conditions ; c) 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 ; and d) a polypeptide having at least 60% sequence identity to the amino acid sequence SEQ ID NO : 2, wherein the polypeptide has biological activity. |
| 9. | The isolated polypeptide of claim 8 comprising the amino acid sequence of SEQ ID NO : 2. |
| 10. | The polypeptide of claim 8 further comprising heterologous amino acid sequences. |
| 11. | An antibody which selectively binds to a polypeptide of claim 8. |
| 12. | A method for producing 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 a fragment of the amino acid sequence of SEQ ID NO : 2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO : 2 ; c) a biologically active 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 the complement of SEQ ID NO : 1 or SEQ ID NO : 3 ; and d) a polypeptide having at least 60% sequence identity to the amino acid sequence of SEQ ID NO : 2, wherein said polypeptide has biological activity comprising culturing the host cell of claim 5 under conditions in which the nucleic acid molecule is expressed. |
| 13. | A method for detecting the presence of a polypeptide of claim 8 in a sample, comprising : a) contacting the sample with a compound which selectively binds to a polypeptide of claim 8 ; and b) determining whether the compound binds to the polypeptide in the sample. |
| 14. | The method of claim 13, wherein the compound which binds to the polypeptide is an antibody. |
| 15. | A kit comprising a compound which selectively binds to a polypeptide of claim 8 and instructions for use. |
| 16. | A method for detecting the presence of a nucleic acid molecule of claim 1 in a sample, comprising the steps of : a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule ; and b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample. |
| 17. | The method of claim 16, wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe. |
| 18. | A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of claim 1 and instructions for use. |
| 19. | A method for identifying a compound which binds to a polypeptide of claim 8 comprising the steps of : a) contacting a polypeptide, or a cell expressing a polypeptide of claim 8 with a test compound ; and b) determining whether the polypeptide binds to the test compound. |
| 20. | The method of claim 19, wherein the binding of the test compound to the polypeptide is detected by a method selected from the group consisting of : a) detection of binding by direct detecting of test compound/polypeptide binding ; b) detection of binding using a competition binding assay ; c) detection of binding using an assay for 32670mediated synthesis of phosphatidylserine. |
| 21. | A method for modulating the activity of a polypeptide of claim 8 comprising contacting a polypeptide or a cell expressing a polypeptide of claim 8 with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide. |
| 22. | A method for identifying a compound which modulates the activity of a polypeptide of claim 8, comprising : a) contacting a polypeptide of claim 8 with a test compound ; and b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound that modulates the activity of the polypeptide. |
Description:
patent (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European patent (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE, TR), OAPI patent (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG).
Published: -with international search report (88) Date of publication of the international search report: 21 March 2002 For two-letter codes and other abbreviations, refer to the"Guid- ance Notes on Codes and Abbreviations"appearing at the begin- ning of each regular issue of the PCT Gazette.