Pharmacia & Upjohn Ab

Esperion Therapeutics, Inc.

Pharmacia Ab

Hans Ageland

Josefine Persson

Folke Tjerneld

Lena Romander

Lena Nystr&ouml;m

Lena Nyström

The present invention relates to a process for purifying a hydrophobic or amphiphilic compound, by first mixing a starting material containing the hydrophobic or amphiphilic compound with a first polymeric material, water and at least one of a second polymeric material and a surfactant, wherein the first polymeric material and the second polymeric material and/or surfactant are immiscible in the resulting primary aqueous solution. The process further comprises maintaining the primary aqueous solution for a period of time sufficient for essentially separating the phases formed, and then removing the phase containing the main portion of the hydrophobic or amphiphilic compound and the second polymeric material and/or surfactant. The second polymeric material and/or surfactant are separated from the hydrophobic or amphiphilic compound, and subsequently recycled to the initial mixing step. The present invention further relates to a composition for use in purification of apolipoprotein A (ApoA) or apolipoprotein E (ApoE), said composition comprising a first polymeric material and a surfactant, said first polymeric material and surfactant being immiscible in the primary aqueous solution obtained after mixing with water. ApoA or ApoE produced by the inventive process can be used for the manufacture of a medicament in the treatment of atherosclerosis and cardiovascular diseases, sepsis or peripheral atherosclerosis as well as in a method for treatment of atherosclerosis and cardiovascular diseases, sepsis or peripheral atherosclerosis when administered in a therapeutically effective amount.

Process for purifying a compound

The present invention relates to a composition for use in purification of apolipoprotein A (ApoA) or apolipoprotein E (ApoE), said composition comprising a first and a second polymeric material, wherein the first and second polymeric material are immiscible in the primary aqueous solution, and wherein the second polymeric material is amphiphilic and water soluble. The invention further relates to a process for purifying ApoA or ApoE, or variants or mixtures thereof, by first mixing ApoA or ApoE, the composition containing a first and second polymeric material and water. The resulting primary aqueous solution is maintained for a period of time sufficient for essentially separating the phases formed, and removing the phase containing the second polymeric material and the main portion of ApoA or ApoE. Subsequently, the second polymeric material is separated from ApoA or ApoE. The thus produced ApoA or ApoE can be used for the manufacture of a medicament in the treatment of atherosclerosis and cardiovascular diseases, sepsis or peripheral atherosclerosis as well as in a method for treatment of atherosclerosis and cardiovascular diseases, sepsis or peripheral atherosclerosis when administered in a therapeutically effective amount.

Process for purifying a protein

A substantially endotoxin-free ApoA or ApoE is produced by recombinant DNA technique, suitably in . Medicaments and methods for treatment of atherosclerosis or cardiovascular diseases employ ApoA or ApoE purified by a process comprising contacting a first aqueous solution comprising ApoA or ApoE and endotoxins with a matrix comprising an immobilized compound with an end group comprising two or three nitrogen atoms bonded to a carbon atom for attaching the endotoxins to the matrix, and subsequently treating the matrix comprising the immobilized compound with a second aqueous solution comprising a surfactant for releasing the ApoA or ApoE while the endotoxins remain attached to the matrix. Alternatively, the ApoA or ApoE is purified by a process comprising contacting the first aqueous solution comprising ApoA or ApoE and endotoxins with an anion-exchange matrix for attaching the ApoA and ApoE to the matrix, treating the anion-exchange matrix with a second aqueous solution comprising a compound comprising two or three nitrogen atoms bonded to a carbon atom for releasing the endotoxins while the ApoA or ApoE remains attached to th matrix, and then releasing the ApoA or ApoE from the matrix.

Purified Apo A and Apo E compounds and methods for using them

A substantially endotoxin-free ApoA or ApoE is produced by recombinant DNA technique, suitably in E. coli. Medicaments and methods for treatment of atherosclerosis or cardiovascular diseases employ ApoA or ApoE purified by a process comprising contacting a first aqueous solution comprising ApoA or ApoE and endotoxins with a matrix comprising an immobilized compound with an end group comprising two or three nitrogen atoms bonded to a carbon atom for attaching the endotoxins to the matrix, and subsequently treating the matrix comprising the immobilized compound with a second aqueous solution comprising a surfactant for releasing the ApoA or ApoE while the endotoxins remain attached to the matrix. Alternatively, the ApoA or ApoE is purified by a process comprising contacting the first aqueous solution comprising ApoA or ApoE and endotoxins with an anion-exchange matrix for attaching the ApoA and ApoE to the matrix, treating the anion-exchange matrix with a second aqueous solution comprising a compound comprising two or three nitrogen atoms bonded to a carbon atom for releasing the endotoxins while the ApoA or ApoE remains attached to the matrix, and then releasing the ApoA or ApoE from the matrix.

Growing community of inventors

Bromma, Sweden

Hans Ageland