A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 38/29 (2006.01) A61P 5/18 (2006.01) C07K 14/365 (2006.01) C07K 14/635 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2454275
The present invention relates to conformationally constrained parathyroid hormone (PTH) analogs, and methods of preparing and using the PTH analogs. The invention provides novel PTH polypeptide derivatives containing amino acid substitutions at selected positions in the polypeptides. The invention provides derivatives of PTH (1-34), 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) and PTH(1-1 0) polypeptides, wherein at least one residue in each polypeptide is a helix, preferably an a-helix, stabilizing residue. The invention also provides methods of making such peptides. Further, the invention encompasses compositions and methods for use in limiting undesired bone loss in a vertebrate at risk of such bone loss, in 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.
L'invention concerne des analogues d'hormone parathyroïde (PTH) à contrainte conformationnelle, et des procédés de préparation et d'utilisation desdits analogues PTH. L'invention concerne également de nouveaux dérivés de polypeptide PTH contenant des substitutions d'amino acide à des positions sélectionnées desdits polypeptides. L'invention concerne, en outre, des dérivés de polypeptides PTH (1-34), 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), et PTH(1-10) dans lesquels au moins un résidu de chaque polypeptide possède une hélice, de préférence une hélice stabilisant ledit résidu. L'invention concerne enfin des compositions et des méthodes d'utilisation permettant de limiter une perte osseuse indésirable chez un vertébré qui risque une telle perte osseuse, de traiter des états caractérisés par une perte osseuse indésirable ou par le besoin de croissance osseuse, par exemple, de traiter des fractures ou des anomalies des cartilages, et d'élever les niveaux d'AMP cyclique dans des cellules lorsque nécessaire.
Gardella Thomas J.
Kronenberg Henry M.
Potts John T.
Shimizu Naoto
Mbm Intellectual Property Law Llp
The General Hospital Corporation
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