Method for down-regulating gdf-8 activity

A - Human Necessities – 61 – K

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Details

A61K 39/00 (2006.01) A61K 38/18 (2006.01) A61K 48/00 (2006.01) C07K 14/475 (2006.01) C12N 15/12 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2379852

Disclosed are novel methods for increasing muscle mass by means of immunization against Growth Differentiation Factor 8 (GDF-8, myostatin). Immunization is preferably effected by administration of analogues of GDF-8 which are capable of inducing antibody production against homologous GDF-8. Especially preferred as an immunogen is homologous GDF-8 which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the tertiary structure of the homologous GDF-8. Also disclosed are nucleic acid vaccination against GDF-8 and vaccination using live vaccines as well as methods and means useful for the vaccination. Such methods and means include methods for identification of useful immunogenic GDF-8 analogues, methods for the preparation of analogues and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

Cette invention concerne de nouveaux procédés permettant d'accroître la masse musculaire par immunisation contre le facteur de différentiation de croissance 8 (GDF-8, myostatine). L'immunisation se fait de préférence par administration d'analogues de GDF-8 qui sont capables d'induire la production d'anticorps contre des GDF-8 homologues. L'immunogène préféré consiste en un GDF-8 homologue qui a été modifié par l'introduction d'une seule ou de plusieurs épitopes de cellules T de promiscuité, immuno-dominantes et étrangères, ceci tout en préservant sensiblement la structure tertiaire du GDF-8 homologue. Cette invention concerne également une vaccination par acide nucléique contre le GDF-8 et une vaccination à l'aide de vaccins vivants, ainsi que des procédés et moyens utiles à la vaccination. Ces procédés et ces moyens comprennent des procédés permettant d'identifier des analogues de GDF-8 immunogènes utiles, des procédés de préparation des analogues et de formulations pharmaceutiques, ainsi que des fragments d'acide nucléique, des vecteurs, des cellules transformées, des polypeptides et des formulations pharmaceutiques.

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