Process for producing immunolobulins for intravenous administration and other immunolobulin products

A technology of immunoglobulin and products, which is applied in the field of immunoglobulin products and medical applications, can solve problems such as transfer and hepatitis C virus infection, and achieve the effect of improving product purity

Inactive Publication Date: 2001-09-05
CSL BEHRING AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, after several years of clinical use, IVIG from some manufactu

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0110] Purification method steps of immunoglobulin (except Example 5, others are all operated under the condition of 5±3°C)

[0111] Step 1: Preparation of Cohn Fraction II+III Paste:

[0112]From human plasma by standard Cohn fractionation (Cohn E, et al., 1946, J. American Chemical Society, 459-475) modified by Kristler-Nitschmann (Kristler P and Nitschmann HS, 1952, Vox Sang, 7, 414-424). A paste of Cohn fractions II+III was prepared separately. After removal of the cryoprecipitate, and if desired, adsorption of certain plasma proteins (such as Factor IX and antithrombin) on, for example, an ion exchange material and / or a matrix called Heparin Sepharose® (heparin agarose) Thereafter, precipitation was performed with ethanol.

[0113] For suitable conditions (pH, ethanol concentration, temperature, protein concentration) for preparing fraction II-III pastes, see "Blood Separation and Plasma Components", edited by Hams, Wiley-Liss, New York, 1991. A filter aid is added bef...

Embodiment 2

[0128] Example 2 The product obtained by this method is compared with other IVIG products. Analysis results 2 A small amount of 3mg / ml 2 Undetectable monomer and dimer content 98.3% 3 96.8% 97.6% 3 99.4% polymers and aggregates 0.8% 3 1.6% 3 1:2 negative negative negative Negative Anti-B > 1:2 Negative Negative Negative Negative Fc Function 169% 121% 132% 178% Subclass Distribution IgG1 60.0% 61.9% 67.7% 56.6% IgG2 35.8% 33.1% 27.2% 39.4% IgG3 3.5% 3.6% 4.4% 2.6% IgG4 0.7% 1.4% 0.6% 1.5% IgA 2.96mg / l 54.7mg / l 0.85mg / l 1.36mg / l IgM 0.28mg / l 39.1mg / l 0.99mg / l 0.16mg / l Tween80 4 0.02mg / mlPH 6.7 5.7 6.7 5.6Total protein concentration 97g / l 45g / l 50g / l 51g / l maltose or glucose 20mg / ml 92mg / ml 15mg / ml 88mg / ml

[0129] 1: Not corrected for HSA; 2: Manufacturer's declaration; 3: Corrected for HSA peak; 4: Used as a stabilizer Purity (protein composition):

[0130] Pharmacopoeial purity requires IVIG preparations to be at least 95% IgG...

Embodiment 3

[0166] clinical trial results

[0167] According to the guidelines of ICH and CPMP / 388 / 95, clinical research is carried out on the product of the present invention, and the product of the present invention is also called IVIG, SSI.

[0168] Pharmacokinetic, efficacy and safety tests have been conducted. Clinical trials have included 4 groups of patients: primary immunodeficiency syndrome (15 patients), secondary immunodeficiency syndrome (6 patients), idiopathic thrombocytopenic purpura (15 patients) and chronic inflammatory demyelination Polyneuropathy (5 cases).

[0169] The dose used in patients with primary immunodeficiency syndrome or secondary immunodeficiency syndrome is 0.2-0.4g / kg at intervals of 2-5 weeks. The dose used in patients with idiopathic thrombocytopenic purpura is 400 mg / kg body weight per day for 5 consecutive days, or 1000 mg / kg body weight per day for 2 consecutive days.

[0170] Safety was tested for serum transaminases, serum inosine and viral mark...

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Abstract

The presenten invention also relates to a liquid immunoglobulin G (IgG) product which has a purity of more than 95%, a content of IgG monomers and dimers of at least 95% and, a content of IgA of less than 6 mg of IgA/I. The liquid product is stable and ready for instant intravenous administration.

Description

Field of the invention [0001] The present invention relates to a method for purifying immunoglobulin, ie immunoglobulin G (IgG), from crude plasma or crude plasma protein components. The invention also relates to an immunoglobulin product and the medical use of such an immunoglobulin product. Background of the invention [0002] Human normal immunoglobulin (HNI) was introduced in the late 1940s for the prevention and treatment of some infectious diseases. By Cohn & Oncley's refrigerated ethanol fractionation (Cohn E et al., (1946), J. ACS., 68, 459-475), (Oncley et al., (1949), J. ACS., 71, 541-550), and later Kistler And Nitschmann also carried out the improved method and prepared HNI, which proved to be safe and effective when administered subcutaneously or intramuscularly, avoiding the spread of viral infection. [0003] Congenital or acquired complete or partial absence of immunoglobulins (primary and secondary immunodeficiency syndromes, respectively) manifests in fre...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P31/12A61P43/00C07KC07K1/18C07K1/30C07K16/06
CPCC07K16/065A61K39/39591A61P31/12A61P43/00C07K16/06
Inventor 因加·劳森伯厄·泰斯纳
Owner CSL BEHRING AG
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