Natriuretic compounds, conjugates, and uses thereof

Details Natriuretic compounds, conjugates, and uses thereof Natriuretic compounds, conjugates, and uses thereof

A - Human Necessities

61

K

A61K 38/00 (2006.01)

Patent

CA 2568363

Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, enteral, subcutaneous, pulmonary, and intravenous forms of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the natriuretic compound are also disclosed, having an amino acid sequence that is other than the native sequence.

L'invention concerne des composés natriurétiques modifiés et leurs conjugués. En particulier, l'invention concerne des formes conjuguées de hBNP comprenant au moins une fraction de modification liée à celles-ci. Les conjugués des composés natriurétiques modifiés conservent leur activité de stimulation de production de cGMP, de liaison avec le récepteur NPR-A et, dans certaines formes d'exécution, une demi-vie en circulation améliorée, comparativement aux composés natriurétiques non modifiés correspondants. Des formes orales, parentérales, entérales, sous-cutanées, pulmonaires et intraveineuses des composés et des conjugués peuvent être préparées comme traitements et/ou thérapies pour des états cardiaques, en particulier des insuffisances cardiaques congestives. L'invention concerne en outre des fractions de modification comprenant des structures oligomères ayant des longueurs et des configurations variées. L'invention concerne également des analogues du composé natriurétique présentant une séquence aminoacide qui est différente de la séquence native.

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