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Last Updated: March 29, 2024

Claims for Patent: 5,955,425


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Summary for Patent: 5,955,425
Title: Parathyroid hormone analogues for the treatment of osteoporosis
Abstract:This invention describes analogs of human parathyroid hormone which have increased activities in bone restoration, and increased bioavailabilities. The peptides described are derivatives of hPTH-(1-31) which have lactams formed for example, between either Glu.sup.22 and Lys.sup.26 or Lys.sup.26 and Asp.sup.30. In addition, the natural Lys.sup.27 may be substituted by either a Leu or other hydrophobic residues, such as Ile, norleucine, Met, Val, Ala, Trp, or Phe. Typically, these analogs have enhanced abilities to stimulate adenylyl cyclase in rat osteosarcoma cells, and show increased activities in bone restoration, using the ovariectomized rat model. The analogs also show enhanced activities and bioavailabilities, as demonstrated by their hypotensive effects in the rat.
Inventor(s): Morley; Paul (Ottawa, CA), Neugebauer; Witold (Ottawa, CA), Ross; Virginia J. S. (Gloucester, CA), Whitfield; James F. (Ottawa, CA), Willick; Gordon E. (Orleans, CA), Barbier; Jean-Rene (Gatineau, CA)
Assignee: National Research Council of Canada (CA)
Application Number:08/691,647
Patent Claims:1. A human parathyroid hormone hPTH-( 1-31) analogue in which position 27 is Leu, Ile, Nle or Met and which has been cyclized between Glu.sup.22 and Lys.sup.26 to form a lactam.

2. An analogue according to claim 1, having either a free amide C-terminal ending or a free carboxyl C-terminal ending.

3. An analogue according to claim 1, having the SEQ ID NO:3.

4. A composition for administration to a warm-blooded animal comprising a human parathyroid hormone hPTH-(1-31) analogue according to claim 1 in association with a pharmaceutically acceptable carrier or excipient.

5. A method of treating osteoporosis in a warm-blooded animal comprising administering to an animal in need of same a therapeutically effective amount of the human parathyroid hormone hPTH-(1-31) analogue according to claim 1.

6. A human parathyroid hormone hPTH-(1-31) analogue in which position 27 is Leu and which has been cyclized between Glu.sup.22 and Lys.sup.26 to form a lactam.

7. A composition for administration to a warm-blooded animal comprising a human parathyroid hormone hPTH-(1-31) analogue according to claim 6 in association with a pharmaceutically acceptable carrier or excipient.

8. A method of treating osteoporosis in a warm-blooded animal comprising administering to an animal in need of same a therapeutically effective amount of the human parathyroid hormone hPTH-(1-31) analogue according to claim 6.

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