Fibroblast growth factor (FGF23) nucleic acids

• US 7,223,563 B2
• Filed: 07/10/2001
• Issued: 05/29/2007
• Est. Priority Date: 07/19/2000
• Status: Expired due to Term

• Current Assignee: ADVANCED RESEARCH & TECHNOLOGY INSTITUTE, Ludwig-Maximilians-Universitat Munchen Abeteilung Mediziniche Genetik
• Original Assignee: ADVANCED RESEARCH & TECHNOLOGY INSTITUTE, Ludwig-Maximilians-Universitat Munchen
• Inventors: Meitinger, Thomas, White, Ken, Econs, Michael, Strom, Tim Matthias
• Primary Examiner(s): Saoud; Christine J.
• Application Number:
  US09/901,938
• Publication Number:
  US 20020156001A1
• Time in Patent Office: 2,149 Days
• Field of Search: 435/69.1, 435/69.4, 435/320.1, 435/243, 435/69.7, 435/325, 536/23.1, 536/23.4, 536/23.5, 514/44
• US Class Current: 435/69.4
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 3/12 for electrolyte homeostasis
• CPC Class Codes: C07K 14/50 Fibroblast growth factor [FGF]
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

The invention relates to novel nucleic acids encoding a fibroblast growth factor-23(FGF23) and proteins encoded thereby, mutations in which are associated with autosomal dominant rickets (ADHR). The invention further relates to methods of diagnosing and treating hypophosphatemic and hyperphosphatemic disorders comprising inhibiting or stimulating, respectively, the biological activity of FGF23 in a patient. The invention also relates to methods of treating osteoporosis, dermatomyositis, and coronary artery disease comprising stimulating the biological activity of FGF23 in a patient.

Claims

1. An isolated nucleic acid comprising SEQ ID NO:

1.

2. The isolated nucleic acid of claim 1, said isolated nucleic acid further comprising a nucleic acid encoding a tag polypeptide.

3. The isolated nucleic acid of claim 2, wherein said tag polypeptide is selected from the group consisting of a myc tag polypeptide, a glutathione-S-transferase tag polypeptide, a green fluorescent protein tag polypeptide, a myc-pyruvate kinase tag polypeptide, a His6 tag polypeptide, an influenza virus hemagglutinin tag polypeptide, a flag tag polypeptide, and a maltose binding protein tag polypeptide.

4. The isolated nucleic acid of claim 1, said nucleic acid further comprising a promoter/regulatory sequence operably linked thereto.

5. A vector comprising the isolated nucleic acid of claim 1.

6. The vector of claim 5, said vector further comprising a nucleic acid comprising a promoter/regulatory sequence operably linked thereto.

7. A recombinant cell comprising the vector of claim 5.

8. A method of making an isolated protein, said method comprising (a) culturing the recombinant cell of claim 7 under conditions such that said protein is expressed;

and (b) recovering said protein.

9. A recombinant cell comprising the isolated nucleic acid of claim 1.

10. A composition comprising the isolated nucleic acid of claim 1 and a pharmaceutically-acceptable carrier.

11. An isolated nucleic acid comprising a sequence having at least 99% sequence identity with SEQ ID NO:

1, wherein the polypeptide encoded by said nucleic acid has the ability to increase phosphate transport.

12. An isolated nucleic acid encoding a polypeptide having at least 98% sequence identity with amino acid sequence of SEQ ID NO:

2, wherein said polypeptide has the ability to increase phosphate transport.

13. An isolated nucleic acid included in DSMZ Deposit No. DSM 13530, wherein said nucleic acid comprises SEQ ID NO:

1.

14. An isolated nucleic acid that is the complement of SEQ ID NO:

1.

15. A vector comprising the isolated nucleic acid of claim 14.

16. The vector of claim 15, said vector further comprising a promoter/regulatory sequence operably linked thereto.

17. A recombinant cell comprising the isolated nucleic acid of claim 14.

18. A composition comprising the isolated nucleic acid of claim 14 and a pharmaceutically-acceptable carrier.

19. An isolated nucleic acid which is 99% identical to the complement of SEQ ID NO:

1.