Black bear parathyroid hormone and methods of using black bear parathyroid hormone

• US 8,987,201 B2
• Filed: 12/07/2009
• Issued: 03/24/2015
• Est. Priority Date: 12/07/2009
• Status: Active Grant

• Current Assignee: Michigan Technological University
• Original Assignee: Michigan Technological University
• Inventors: Donahue, Seth W.
• Primary Examiner(s): KEMMERER, ELIZABETH
• Application Number:
  US13/514,362
• Publication Number:
  US 20120244232A1
• Time in Patent Office: 1,933 Days
• Field of Search: None
• US Class Current: 514/11.8
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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: C07K 14/635 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides

Abstract

Black bear parathyroid hormone (PTH) and functional fragments thereof are provided. Also provided are methods of using black bear PTH and functional fragments for increasing cAMP in a bone-forming cell; reducing apoptosis in a bone-forming cell; decreasing the ratio of expression levels of Bax protein to Bcl-2 protein in a bone-forming cell; increasing the expression level of one or more of a bone matrix protein, a transcriptional activator, or a transcriptional regulator in a bone-forming cell; enhancing bone mineral density, increasing bone mass, decreasing bone loss, or reducing the incidence of bone fractures, or any combination thereof, in a subject; also provided are antibodies directed against black bear parathyroid hormone (PTH) and functional fragments thereof.

Claims

1. A method of increasing cAMP levels in a bone-forming cell comprising administering 0.10 μ

g/kg per day to 40 μ

g/kg per day of a polypeptide comprising SEQ ID NO;

2 to a human subject in need thereof.

2. A method of reducing apoptosis in a bone-forming cell comprising administering 0.10 μ

g/kg per day to 40 μ

g/kg per day of a polypeptide comprising SEQ ID NO;

2 to a human subject in need thereof.

3. A method of decreasing the ratio of expression levels of Bax protein to Bcl-2 protein in a bone-forming cell comprising administering 0.10 μ

g/kg per day to 40 μ

g/kg per day of a polypeptide comprising SEQ ID NO;

2 to a human subject in need thereof.

4. A method of increasing the expression level of one or more of a bone matrix protein, a transcriptional activator, or a transcriptional regulator in a bone-forming cell comprising administering 0.10 μ

g/kg per day to 40 μ

g/kg per day of a polypeptide comprising SEQ ID NO;

2 to a human subject in need thereof.

5. A method of enhancing bone mineral density, increasing bone mass, decreasing bone loss, or reducing the incidence of bone fractures, or any combination thereof, in a human subject in need thereof, comprising contacting a bone-forming cell in the subject with 0.10 μ

g/kg per day to 40 μ

g/kg per day of a polypeptide comprising SEQ ID NO;

2.

6. The method of claim 5, wherein the subject is a post-menopausal female human afflicted with osteoporosis.

7. The method of claim 5 further comprising administering vitamin D and calcium to the subject.

8. A method of increasing bone volume, increasing bone mineral apparent density, increasing number of trabecular struts, increasing thickness of trabecular struts, increasing trabecular bone mineralization, increasing cortical bone volume, decreasing cortical porosity, or decreasing serum calcium, or any combination thereof, in a human subject in need thereof, comprising contacting a bone-forming cell in the subject with 0.10 μ

g/kg per day to 40 μ

g/kg per day of a polypeptide comprising SEQ ID NO;

2.

9. The method of claim 8, wherein the subject is a post-menopausal female human afflicted with osteoporosis.

10. The method of claim 8, further comprising administering vitamin D and calcium to the subject.