Parathyroid hormone analogues for the treatment of osteoporosis
US6541450B1 · kind B1 · utility
Assignee
Inventors
Key dates
| Filing date | Mar 28, 2000 |
| Grant date | Apr 1, 2003 |
| Priority date | — |
| Expiry date | Mar 28, 2020 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07K14/635
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
This invention describes analogues of human parathyroid hormone which have increased activities in bone restoration, and increased bioavailability. The peptides described are derivatives of hPTH-(1-31) which are cyclized for example, by formation of lactams between either Glu22 and Lys26 or Lys26 and Asp30. In addition, the natural Lys27 may be substituted by either a Leu or other hydrophobic residues, such as Ile, norleucine, Met, Val, Ala, Trp, or Phe. Typically, these analogues have enhanced abilities to stimulate adenylyl cyclase in rat osteosarcoma cells, and show increased activities in bone restoration, using the ovariectomized rat model. The analogues also show enhanced activities and bioavailabilities, as demonstrated by their hypotensive effects in the rat. An assay which correlates hypotensive activity with osteogenic activity is also described.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.