Patent FR-2978457-A1 (FR)
Title: New compound comprising a nucleic acid having a specified sequence and encoding a polypeptide having a specified sequence or a polypeptide having a specified sequence, useful for treating atherosclerosis and cardiac hypertrophy
Inventor: DELABAR JEAN-MAURICE
IPC: A61K38/45
Filed: 2011-07-27
Abstract: Compound comprising (a) a nucleic acid having a sequence of SEQ ID NO: 2 (a 2292 base pair sequence fully defined in the specification) and encoding (b) a polypeptide having a sequence of SEQ ID NO: 1 (a 763 amino acid sequence fully defined in the specification), or (c) a nucleic acid having a sequence that has at least 83%, preferably 95% identity with the sequence of SEQ ID NO: 2 or (d) a polypeptide having a sequence of SEQ ID NO:1 or (e) a polypeptide having a sequence that has at least 83%, preferably 95% identity with the sequence of SEQ ID NO:1, is new. Independent claims are included for: (1) an adenoviral vector comprising (a), (b), (c), a promoter such as a primate hepatocyte-specific promoter including human promoter of al-antitrypsin having a sequence of SEQ ID NO: 3 (a 903 base pair sequence fully defined in the specification), a promoter of the human cholesterol 7-alpha-hydroxylase having a sequence of SEQ ID NO: 6 (a 1000 base pair sequence fully defined in the specification) or a promoter of the human factor IX having a sequence of SEQ ID NO: 7 (a 1000 base pair sequence fully defined in the specification), a nucleic acid having at least 90%, preferably 98% identity with the sequence of SEQ ID NO: 3, SEQ ID NO: 6 and SEQ ID NO: 7, optionally an enhancer comprising genes having liver-specific expression of greater than 99%, a nucleic acid having at least 90%, preferably 98% identity with sequences of SEQ ID NO: 4, SEQ ID NO: 8 and SEQ ID NO: 9, an intron with a specificity of hepatic expression of greater than 90% or a nucleic acid having at least 90%, preferably 98% identity with one of the four sequences of SEQ ID NO: 5, SEQ ID NO: 10 and SEQ ID NO: 11, where the enhancer includes a alpha 1-microglobulin enhancer having a sequence of SEQ ID NO: 4 (a 168 base pair sequence fully defined in the specification), an apolipoprotein E enhancer having a sequence of SEQ ID NO: 8 (a 176 base pair sequence fully defined in the specification) or a phenylalanine hydroxylase enhancer having a sequence of SEQ ID NO: 9 (a 40 base pair sequence fully defined in the specification), the intron includes apo A-I intron having a sequence of SEQ ID NO: 5 (a 235 base pair sequence fully defined in the specification), intron I of lipoprotein II having a sequence of SEQ ID NO: 10 (a 211 base pair sequence fully defined in the specification) or aldolase B intron having a sequence of SEQ ID NO: 11 (a 275 base pair sequence fully defined in the specification) and the intron is located between the nucleic acid and the promoter; (2) a non embryonic mammalian cell such as a human cell transfected with a vector; (3) a transfected mammalian cell such as a human liver cell; a pharmaceutical composition comprising the compound; and (4) in vitro determination of the evolution of the inflammatory condition of a patient during the treatment using the pharmaceutical composition comprising measuring a concentration of paraoxonase-1 protein having a sequence of SEQ ID NO: 14 in a blood sample of the patient and determining the evolution of the inflammatory condition of the patient. ACTIVITY : Antiarteriosclerotic; Cardiant; Hepatotropic; Antiinflammatory; Neuroprotective; Nootropic. MECHANISM OF ACTION : None given.