Conformationally constrained parathyroid hormone (PTH) analogs with lactam bridges

US7521528B2 · kind B2 · utility

Assignee

• The General Hospital Corporation · US

Inventors

• Thomas J. Gardella · Needham, US
• Henry M. Kronenberg · Belmont, US
• John T. Potts, Jr. · Newton, US

Key dates

• Filing date: Jan 24, 2003
• Grant date: Apr 21, 2009
• Expiry date: Jan 24, 2023

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P19/10
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention relates to methods of treatment of mammalian conditions characterized by decreases in bone mass with conformationally constrained parathyroid hormone (PTH) analogs and derivatives of those analogs containing PTH polypeptide derivatives containing at least one Glu or Lys substitution at position 6 and/or 10, some with installed lactam bridges between the side chains of Lys and Glu. The invention provides derivatives of PTH (1-34), PTH(1-33), PTH(1-32), PTH(1-31), PTH(1-30), PTH(1-29), PTH(1-28), PTH(1-27), PTH(1-26), PTH(1-25), PTH(1-24), PTH(1-23), PTH(1-22), PTH (1-21), PTH(1-20), PTH(1-19), PTH(1-18), PTH(1-17), PTH(1-16), PTH(1-15), PTH(1-14), PTH(1-13), PTH(1-12), PTH(1-11), PTH(1-10) and PTH(1-9) polypeptide. The invention also provides methods of preparing the PTH analogs. Further, the invention encompasses treating conditions that are characterized by undesired bone loss or by the need for bone growth, e.g. in treating fractures or cartilage disorders and for raising cAMP levels in cells where deemed necessary.