ANTI FGF23 ANTIBODY AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

• US 20090148461A1
• Filed: 02/13/2008
• Published: 06/11/2009
• Est. Priority Date: 02/14/2007
• Status: Active Grant

• Current Assignee: Kyowa Kirin Co., Ltd. (Kirin Holdings Company Limited)
• Original Assignee: Kirin Pharma KK
• Inventors: Yoshida, Hitoshi, Yamazaki, Yuji, Yamashita, Takeyoshi, Hasegawa, Hisashi, Aono, Yukiko, Shimada, Takashi, Urakawa, Itaru
• Granted Patent: US 7,883,705 B2
• Time in Patent Office: Days
• US Class Current: 424/152.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/12 for electrolyte homeostasis
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

To provide an antibody against FGF23 and a pharmaceutical composition such as a preventive or therapeutic agent which can prevent or treat by suppressing an action of FGF23 by using the antibody. An antibody or its functional fragment against human FGF23 produced by hybridoma C10 (Accession No. FERM BP-10772).

Claims

1. An isolated antibody against human FGF23, or a functional fragment thereof, comprising a heavy chain variable region or a light chain variable region having the same amino acid sequence as an antibody produced by hybridoma C10 (Accession No. FERM BP-10772).

6. The functional fragment of claim 1, wherein said functional fragment is a peptide fragment selected from the group consisting of Fab, Fab′

, F (ab′

)₂, disulfide stabilized Fv (dsFv), dimerized V region (diabody), single chain Fv (scFv) and CDR.

7. The isolated antibody against human FGF23 of claim 1, or a functional fragment thereof, comprising a heavy chain or light chain having an amino acid sequence in which one or several amino acids are deleted, substituted or added.

8. The isolated antibody against human FGF23 of claim 1, wherein the class of the antibody is selected from the group consisting of IgG, IgA, IgE, and IgM.

9. The isolated antibody against human FGF23 of claim 8, wherein the subclass of the IgG antibody is selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.

10. A pharmaceutical composition, comprising as an active ingredient, the isolated antibody against human FGF23 of claim 1, or a functional fragment thereof.

11. A pharmaceutical composition which can control phosphorus metabolism and/or vitamin D metabolism by FGF23 and comprises, as an active ingredient, the isolated antibody against human FGF23 of claim 1, or a functional fragment thereof.

12. A pharmaceutical composition for prevention or treatment of diseases that are associated with mineral metabolism disorders comprising as an active ingredient, the isolated antibody against human FGF23 of claim 1, or a functional fragment thereof.

13. The pharmaceutical composition according to claim 12, wherein the disease which is associated with mineral metabolism disorders is selected from the group consisting of neoplastic osteomalachia, ADHR, XLH, fibrous dysplasia, McCune-Albright syndrome, and autosomal recessive hypophosphatemia.

14. A pharmaceutical composition for prevention or treatment of a disease selected from the group consisting of osteoporosis, rickets, hypercalcemia, hypocalcaemia, heterotrophic calcification, osteosclerosis, Paget'"'"'s disease, hyperparathyroidism, hypoparathyroidism, and pruritis, comprising as an active ingredient, the isolated antibody against human FGF23 of claim 1, or a functional fragment thereof.

2. An isolated antibody against human FGF23, or a functional fragment thereof, comprising a heavy chain variable region comprising an amino acid sequence from the amino acid at position 20 of SEQ ID NO:

12 to the amino acid at position 136 of SEQ ID NO;

12 or a light chain variable region comprising an amino acid sequence from the amino acid at position 23 of SEQ ID NO;

14 to the amino acid at position 128 of SEQ ID NO;

14.

3. The antibody of claim 2 wherein the antibody against human FGF23 or the functional fragment thereof comprises a heavy chain variable region and a light chain variable region and wherein the heavy chain variable region comprises an amino acid sequence from the amino acid at position 20 of SEQ ID NO:

12 to the amino acid at position 136 of SEQ ID NO;

12; and

the light chain variable region comprises an amino acid sequence from the amino acid at position 23 of SEQ ID NO;

14 to the amino acid at position 128 of SEQ ID NO;

14.

4. An isolated antibody against human FGF23 produced by hybridoma C10 (Accession No. FERM BP-10772) or a functional fragment thereof.

5. An isolated antibody or a functional fragment thereof which binds to all or part of an epitope on human FGF23, to which an antibody produced by hybridoma C10 (Accession No. FERM BP-10772) binds.

15. A hybridoma C10 (Accession No. FERM BP-10772).

16. An isolated nucleic acid encoding a heavy chain variable region comprising the sequence from the nucleotide at position 58 of SEQ ID NO:

11 to the nucleotide at position 408 of SEQ ID NO;

11.

18. A vector comprising the nucleic acid of claim 16.

19. A host cell comprising the vector of claim 18.

20. A method for producing an antibody against human FGF23 or a functional fragment thereof, comprising the step of culturing the host cell according to claim 19 to express an antibody against human FGF23 or a functional fragment thereof.

17. An isolated nucleic acid encoding a light chain variable region comprising the sequence from the nucleotide at position 67 of SEQ ID NO:

13 to the nucleotide at position 384 of SEQ ID NO;

13.

21. A vector comprising the nucleic acid of claim 17.

24. A host cell comprising the vector of claim 21.

22. An isolated nucleic acid encoding a heavy chain variable region and a light chain variable region comprising the sequence from the nucleotide at position 58 of SEQ ID NO:

11 to the nucleotide at position 408 of SEQ ID NO;

11 and the sequence from the nucleotide at position 67 of SEQ ID NO;

13 to the nucleotide at position 384 of SEQ ID NO;

13.

23. A vector comprising the nucleic acid of claim 22.

25. A host cell comprising the vector of claim 23.

26. A method for producing an antibody against human FGF23 or a functional fragment thereof, comprising the step of culturing the host cell according to claim 25 to express an antibody against human FGF23 or a functional fragment thereof.