Transgene S.a.

Transgene 6.a.

Rainer Bischoff

Abdesslame Nazih

Denis Heissler

Yves Cordier

Hanno V Kolbe

Klaus Schughart

Danis Heissler

Glycerolipid compounds useful for the transfer of an active substance into a target cell

The present invention relates to a composition which is intended for transferring at least one therapeutically active substance into the interior of a target cell, characterized in that it comprises a mixture of at least one therapeutically active substance and at least one polar compound which is selected from a specific group of aprotic polar compounds. The therapeutically active substance is preferably a polynucleotide, and the polar compound is DPSO, which improves the ability of the polynucleotide to be transfected into the interior of the cells. The compositions according to the invention can be used as a diagnostic therapeutic, prophylactic or vaccinal medicament for treating the human or animal body by means of gene therapy.

Compositions for the delivery of polynucleotides to cells

The present invention relates to lipid compounds of formula I, wherein said compounds are optionally in a cationic form and are optionally combined with one or more biologically acceptable anions. The present invention also relates to complexes comprising at least one cationic lipid compound of the formula I and an active substance comprising negative charges. The present invention further relates to methods of gene therapy using the complexes of the present invention.

Lipid compounds and compositions containing same used for the transfer of at least an active substance, in particular a polynucleotide, in a target cell and therapeutic use

The invention concerns a complex comprising at least a lipid and at least a therapeutically active substance useful for transferring said substance into a target cell, characterised in that said lipid is of formula (I): in which: n,, n,, identical or different are whole numbers between 0 and 1; R,, identical or different are: a) selected among the group consisting of a hydrogen atom and alkyl radicals with 1 to 6 carbon atoms optionally substituted, independently of one another, by a hydroxyl radical; or b) in one particular case for which n,&equals;n,&equals;1, R,and R,can form together a divalent alkylene chain of 2 to 3 carbon atoms (C,-C,); R,, R,, identical or different are alkyl radicals of 1 to 6 carbon atoms or can together form a divalent alkylene chain of 2 to 3 carbon atoms (C,-C,); m, p, identical or different are whole numbers between 1 and 10; R,, R,, identical or different are selected in the group consisting of radicals of formula: 1) R,C(&boxH;O)&mdash;X&mdash; in which: X&equals;NH, O, S; R,is an alkyl or alkenyl radical of 6 to 23 carbon atoms (C,-C,), linear or branched; 2) R,R,NC(&boxH;O)&mdash; in which: R,, R,, identical or different are selected among the group consisting of the hydrogen atom or alkyl or alkenyl radicals of 6 to 23 carbon atoms, linear or branched, provided that R,, R,, cannot simultaneously correspond to the hydrogen atom; 3) and one of the radicals R,, R,can moreover correspond to the hydrogen atom. The invention also concerns the use of said complex in gene therapy.

Lipid complexes for transferring at least a therapeutically active substance, in particular a polynucleotide into a target cell and use in gene therapy

The invention is related to a method for preparing an homogenous suspension of stable lipid-nucleic acid complexes or particles, comprising: a) combining one or more cationic lipids, one or more colipids, and one or more stabilizing additives to form a lipid suspension, b) combining the lipid suspension with a nucleic acid to form a complex or a particle, and optionally c) subjecting the complex or particle to a sizing procedure. It also concerns an homogenous suspension produced notably by the above method.

Process of making cationic lipid-nucleic acid complexes

The invention concerns novel of compounds of formula (I) in which: R,and R,, identical or different are C,-C,alkyl or alkenyl radicals, linear or branched or &mdash;C(&boxH;O)-(C,-C,) alkyl or &mdash;C(&boxH;O)-(C,-C,) alkenyl, linear or branched, X is the oxygen atom or an amino &mdash;NR,radical, R,being a hydrogen atom or an inferior alkyl radical of 1 to 4 carbon atoms; n is a positive whole number from 1 to 6; m is a positive whole number from 1 to 6, and when n>1, m can be identical or different. The invention also concerns novel compositions of said compounds and of active substances in particular therapeutically, comprising at least a negative charge for inserting said active substances in cells. It concerns in particular novel complexes, of which the active substance consists of one or several nucleic acids, useful for cell transfection.

Growing community of inventors

Barseback, Sweden

Rainer Bischoff