Biotest Ag

Biotest Pharma Gmbh

Dieter Rudnick

Oliver Maneg

Michael Rodemer

Matthias Germer

Norbert Kothe

Veit Braun

Detlef Piechaczek

Wolfgang Möller

Wolfgang Moller

Wolfgang Moeller

Michael Kloft

Wolfgang Stephan

Ronald Kotitschke

Hans Schleussner

Herbert Dichtelmuller

Ulf Bethke

Detlef Rohm

Herbert Dichtelmueller

Eckhard Flechsig

Herwald Klein

Achim Hannappel

Hebert Dichtelmuller

Alexander Moehlenkamp-Roettger

An antibody preparation suitable for intravenous administration in humans includes IgG, IgA and at least 5% IgM antibodies by weight of the total amount of antibodies. The preparation is prepared from human plasma, has specific complement activating activity, and, in an in vitro assay with human serum suitable to determine the ability of the antibody preparation to activate complement unspecifically, the antibody preparation generates substantially no C5a and/or substantially no C3a. The antibody preparation can have medical uses.

Methods of treating viral infections by administering an antibody preparation comprising IGG, IGA and IGM

A process for the preparation of pharmaceutically acceptable immunoglobulin compositions from plasma-derived immunoglobulin fractions which allows the parallel preparation of immunoglobulin compositions enriched in IgG, IgM and IgA. In this process, immunoglobulin contained in Cohn fraction I/II/III or Kistler Nitschmann fraction A+I is resolubilized at conductivities of at least 1 mS/cm, and following removal of contaminating protein the resolubilized immunoglobulin is subjected to anion exchange chromatography to obtain IgG- and IgM/IgA-enriched immunoglobulin compositions. The IgG-enriched immunoglobulin composition is further subjected to treatment with a cation exchange material to obtain an immunoglobulin composition having a reduced properdin content.

Process for preparing immunoglobulin compositions

IgG, IgA and IgM antibody preparations, method of making and method of use in treatment

An antibody preparation suitable for intravenous administration in humans includes IgG, IgA and at least 5 % IgM antibodies by weight of the total amount of antibodies. The preparation is prepared from human plasma, has specific complement activating activity, and, in an in vitro assay with human serum suitable to determine the ability of the antibody preparation to activate complement unspecifically, the antibody preparation generates substantially no C5a and/or substantially no C3a. The antibody preparation can have medical uses.

Antibody preparations

A process is provided for the preparation of an immunoglobulin composition from a plasma fraction having immunoglobulins, and antibody preparations prepared utilizing the process.

Process for preparing an immunoglobulin composition

The invention relates to the fractionation of plasma or serum into at least one albumin fraction and one immunoglobulin fraction by hydrophobic interaction chromatography. The fractionation is carried out using an incremental salt gradient, especially an ammonium sulfate buffer. The invention also relates to preparations obtained by using said method and to their use.

Method for the chromatographic fractionation of plasma or serum, preparations, so obtained, and their use

An intravenously administrable polyclonal immunoglobulin preparation for the treatment and prophylaxis of bacterial infections containing at least 50% by weight of IgM in terms of the total content of immunoglobulin, exhibiting a low anticomplementary activity, being stable in aqueous solution, and being free of viruses. It can also consist of or also contain a mixture of several monoclonal IgM antibodies. The source material for its manufacture is an immunoglobulin-containing fraction of human, animal, or bacterial provenance. The fraction is treated with an anion exchanger that is eluted with a saline or pH gradient and the eluate is optionally subjected to gel filtration, treated before or after the chromatography with .beta.-propiolactone and PEG 4000, and optionally heated. Treatment with .beta.-propiolactone and ultraviolet light, treatment with solvents and detergents, or pasteurization can also be conducted. Proteins, sugars, or mixtures of amino acids are optionally added to the preparation.

Intravenously administerable polyclonal immunoglobulin preparation

Method of manufacturing an intravenously tolerable immunoglobulin-G preparation that is free of aggregates, vasoactive substances and proteolytic enzymes and accordingly appropriate for all types of patients, especially immunosuppressed patients, from a starting material that contains immunoglobulin G but from which the coagulation factors have been removed. The starting material is treated with 0.4 to 1.5% by volume of octanoic acid and then chromatographed, especially on an ion or cation exchanger or hydrophobic matrix.

Manufacturing intravenous tolerable immunoglobulin-G preparation

Process for the preparation of an immunoglobulin solution suitable for intravenous administration from a human blood protein fraction containing immunoglobulins IgG, IgA and IgM in partially concentrated from, with the process steps: addition of acetate buffer to the protein fraction, where appropriate removal of insoluble constituents by filtration, treatment with calcium phosphate and octanoic acid, centrifugation, removal of the supernatant and treatment thereof with an adsorbent, removal of the adsorbent and sterilization by filtration.

Process for the preparation of a pharmaceutical which contains IgG, IgA

To provide a simple method of preparing biologically active transferrin that can be employed on an industrial scale and that will result in extremely pure and natural transferrin containing no viruses and appropriate for both in-vitro and in-vivo applications, the .gamma.-globulins are precipitated from the fraction containing the transferrin, the precipitant is removed from the residual liquid by ultrafiltration or gel filtration, the liquid is adjusted to a prescribed ionic concentration and protein concentration and (a) treated with .beta.-propiolactone and the solution is subjected to ultraviolet radiation or (b) treated with specific detergents and subjected to ion-exchange chromatography, and the transferrin is concentrated and filtered sterile.

Method of preparing a high-purity, virus safe, biologically active

A method of producing a virus-safe, storage-stable, and intravenously tolerable immunoglobulin-G preparation. The object is to make the method appropriate for industrial-scale production and economical by means of the enrichment and multistage purification of a plasma that has had the coagulation factors removed from it or of a plasma fraction or serum fraction that contains immunoglobulin G accompanied by treatment with ion exchangers and by ultrafiltration. The precipitant is eliminated, by means of diafiltration or gelfiltration, either from the plasma that has had the coagulation factors removed from it or from the plasma fraction that contains the immunoglobulin G, and the desired ion composition is established. The resulting protein solution is subjected to fractionation over an ion exchanger to separate the immunoglobulin G. The proteolytic enzymes in the resulting immunoglobulin-G solution are removed by means of affinity chromatography over a dye linked sorbent and/or are ihibited by the addition of antithrombin III. The accordingly stabilized immunoglobulin-G solution is treated, at a protein concentration of 20 to 60 g/l and a pH 6.0 to 8.0, with 0.03 to 0.07% of .beta.-propiolactone, diluted to a protein concentration of 5 to 20 g/l and subjected to ultraviolet radiation. The accordingly sterilized dilute immunoglobulin-G solution is again diafiltered or gelfiltered to remove lower molecular-weight substances. The accordingly stabilized and sterilized solution is adjusted to the desired protein content of 2 to 16% and filtered sterile.

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Dreieich, Germany

Dieter Rudnick