AU2001273907A1 - A method of producing IgG - Google Patents
A method of producing IgGInfo
- Publication number
- AU2001273907A1 AU2001273907A1 AU2001273907A AU2001273907A AU2001273907A1 AU 2001273907 A1 AU2001273907 A1 AU 2001273907A1 AU 2001273907 A AU2001273907 A AU 2001273907A AU 2001273907 A AU2001273907 A AU 2001273907A AU 2001273907 A1 AU2001273907 A1 AU 2001273907A1
- Authority
- AU
- Australia
- Prior art keywords
- igg
- fraction
- plasma
- removal
- collecting
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Description
A method of producing IgG.
Field of the invention
The present invention relates to a method of producing IgG for medical applications. The method of the invention provides an IgG product having low anticomplementary activity (AC A).
Background of the invention
IgG prepared from human plasma is widely used in the treatment of agammaglobulinaemia, idiopathic thrombocytopenic purpura and in the prophylaxis of certain diseases. IgG preparations are administered intramuscularly as well as intravenously.
Within the field of the art it is well known that isolated IgG preparations have marked anticomplementary activities (ACA). It has been shown that the components responsible for these activities are aggregates of IgG that form either spontaneously or as a result of the isolation procedure. These anticomplementary aggregates have been shown to be harmful in several clinical applications of the IgG products. For example, intravenous administration of IgG preparations can give rise to adverse side reactions, including anaphylactic shock.
Several solutions have been proposed to overcome the problem with ACA in IgG preparations. For example, in US 3 966 906 a process is described for treating a crude gamma globulin fraction of serum with pepsin to disaggregate IgG and reduce anticomplement activity. However, the therapeutic effect provided by such a preparation is unacceptably short since it is rapidly excreted. Another drawback with the pepsin treated immunoglobulins is that their Fc binding capacity is lower than for native immunoglobulins.
Attempts have been made to stabilise pepsin treated IgG preparations, such as by polyethylene glycol (PEG) see for example WO 86/06993.
To solve the problem with high ACA activity it has been proposed to chemically modify the IgG preparations. For example, in US 3 902 262 a portion of the disulphide linkages of the IgG molecule is reduced to -SH groups and then the -SH groups are alkylated.
For obvious reasons, it would be desirable to have an IgG product which is free from enzymatic and other chemical modification and to be as close to native as possible. A method fulfilling
these criteria has been described in "An improved chromatographic method for production of IgG from human plasma" by I. Andersson, L-O Lindquist, J. Berglδf, presented at the "XXIII Congress of the ISBT", Amsterdam, The Netherlands, July 2-8, 1994). However, this procedure also shows unsatisfactory high ACA-levels and does not fulfil the FDA and EU requirements for intravenous drugs.
Known methods for the manufacture of IgG compositions typically comprise several steps selected amongst: a) buffering plasma, for instance either by subjecting the plasma to an appropriate gel filtration chromatography or by diafiltration; b) removing euglobulins, such as by precipitation; c) removing the albumin fraction (albumin), for instance by binding albumin and the like to an anion exchanger leaving the IgG in the unbound fraction (IgG fraction); d) purifying, after removal of euglobulins and albumin, the IgG fraction obtained in step (c) on an anion exchanger and collecting the unbound fraction; e) purifying the plasma fraction obtained in step (d) on a cation exchanger and collecting the bound fraction (adsorption and release of IgG); f) concentrating the IgG enriched plasma fraction obtained in step (e) (IgG released from the cation exchanger), preferably by ultrafiltration; g) inactivating viruses by adding virus inactivation chemicals, preferably a solvent/detergent (S/D) solution, to an IgG enriched plasma fraction, for instance the fraction obtained in step
CD; h) removing the virus antiviral chemicals added in step (g), preferably by adsorbing IgG to a cation exchanger and releasing and collecting the bound fraction; i) concentrating the bound fraction collected in step (h), for instance by ultrafiltration; j) formulating of the fraction concentrated in step (i); k) sterile filtration of the formulated IgG obtained in step (k).
Summary of the invention
The present invention provides a solution for producing IgG products having reduced ACA, by modifying earlier known methods.
Thus in a first aspect the invention relates to a method of producing IgG from plasma for medical applications, comprising at least: (i') removal of albumin resulting in an IgG fraction, (ii')
purifying IgG from an IgG fraction, which is derived from the IgG fraction obtained in step (i'), by adsorbing IgG to a cation exchanger and collecting the adsorbed IgG fraction, and (iii') virus inactivation in an IgG fraction derived from the IgG fraction collected in step (ii'). The method is characterized in
(I) concentrating the IgG fraction obtained in step (i'),
(II) adjusting pH to 4±0.1 of the IgG fraction released from the cation exchanger used in step (ii'), and preferably maintaining the pH below 6.0 during the remaining steps of the method; and
(HI) carrying out the virus inactivation (step iii') by using virus inactivation chemicals, preferably a solvent/detergent (S D) solution, at a temperature of 30°C ± 2°C for at least 4 hours.
Adjustment of pH to around 4 in (II) permits virus inactivation to be carried out at around 30°C.
In the corresponding earlier process, in which pH was 5,5, the level of the proteolytic activity at
30°C was unacceptable.
A preferred variant of the process according to the invention comprises steps (a)-(k) above in which the albumin removal step (c) corresponds to (i')? the cation exchange step (e) corresponds to (ii'), and the virus inactivation (g) corresponds to (iii').
The purification and/or removal steps above are preferably run as chromatography. Appropriate separation media used in these steps are hydrophilic in the sense that they are able to expose surfaces carrying hydrophilic groups, such as hydroxy, amido etc., to the liquid sample containing IgG. Appropriate separation media may be found amongst those that are based on synthetic polymers and/or biopolymers (for instance polysaccharides) carrying hydrophilic groups, as referred to above. Depending on where in the process the media is to be applied they may be uncharged, or may carry positively charged (e.g. ammonium groups) and/or negatively charged groups (e.g. carboxy groups and sulphonic acid groups). The following chromatographic media are preferred: step a) : Sephadex G25; step c): DEAE Sepharose FF; step d): Q Sepharose FF; step e): CM Sepharose FF; step h): CM Sepharose FF.
Sephadex and Sepharose (Amersham Pharmacia Biotech AB, Uppsala, Sweden) are based on cross-linked dextrand and agarose, respectively. DEAE means that the base matrix (cross-linked dextran is substituted with diethylaminoethyl groups. Analogously Q stands for quaternary ammonium groups, and CM for carboxy methyl groups.
The concentrating according to (I) is preferably performed immediately after albumin removal (for instance after step c as defined above) by ultrafiltration, to less than or equal to the volume of the starting plasma.
To be able to use an acetate buffer in the step for removal of virus inactivation chemicals (step h), the ionic strength is adjusted to about 1.40 mS before this step.
In a preferred embodiment, the method also comprises, in step (i) lowering of ionic strength to 0.5 mS ± 0.1, preferably by diafiltration against distilled water.
Detailed description of the invention
Below the invention will be described in more detail in association with the accompanying drawing, Figure 1, which schematically shows a preferred embodiment of the method according to the invention, wherein the characterising features of the method as defined in the claims are in bold letters.
Starting material
Both Recovered Plasma, Fresh Frozen Plasma and Source plasma can be used as starting material.
The following subclasses of plasma can be identified and used as starting material.
1. Cryosupernatant plasma that has passed a chromatographic step for adsorption of vitamin K dependent factors ( FIX, prothrombin, FVII, FX ).
2. Cryosupernant plasma from which the prothrombin complex has not been removed.
3. Plasma that has passed a gel filtration medium (preferably having exclusion limits in the same range as Sepharose 4FF (Amersham Pharmacia Biotech AB, Uppsala, Sweden) for
removal of FVIII and that has passed a chromatographic step for adsorption of vitamin K dependent factors (FIX, prothrombin, FVII, FX ).
4. Plasma that has passed a gel filtration medium for removal of FVIII and from which the prothrombin complex has not been removed.
The gel filtration medium preferably exclusion limits in the same range as Sepharose FF (Amersham Pharmacia Biotech AB).
In addition the starting material could also be free from ATIII and/ or Fibrinogen.
Below two non-limiting Examples of methods according to the invention to purify IgG are described. The methods are performed at room temperature, if nothing else is stated.
Anticomplementary activity (ACA) refers to measurements in the final product, is measured according to Eur. Pharmacopoeia Monograph (1997) page 963 (2.6.17) and should not be higher than 1 CH o/mg immunoglobulin.
Example 1
625 L of thawed plasma is buffer exchanged into a 0.005 M NaAc (sodium acetate) pH 7 on a column of diameter Di = 800 mm and bed height of H = 600 mm, packed with Sephadex G-25 C. The flow is more than 100 cm/h, preferably 300 cm/h corresponding to a flow rate of 1500
L/h.
The eluted plasma is collected in a tank and IM acetic acid is added during stirring until the pH 5.2 is reached. The plasma is left standing without stirring for 4-12 hours at a temperature of 4- 10°C. After standing the formed euglobulin precipitation is removed by centrifugation.
The plasma is adjusted with IM NaAc , pH 5.2 to a final ionic strength of I = 1.4 mS (Range I = 1.30 - 1.50 ). The pH shall be between 5.15 - 5.25.
The plasma is applied in 6 cycles, 25 - 30 g of albumin per litre gel, on a column of Di = 1000 mm and H = 150 mm, packed with DEAE Sepharose FF and equilibrated with 0.020 M NaAc, pH 5.2. The linear flow rate is more than 60 cm/h, preferably 120 cm h corresponding to a flow
rate of 942 IJh. In the equilibration buffer the IgG will pass the column whilst the albumin is adsorbed. After 3 cycles the column is washed with 1.7 Vc (Vc = bed volume ) of 0.15 M NaAc pH 4.0 + 0.5 M NaCl, 0.5 Vc of 0.5 M NaOH and 1.7 Vc of 0.15 M NaAc pH 4.0.
The IgG fraction of about 2350 L is concentrated by ultrafiltration to a final volume less or equal to 625 L, preferably 400 - 500 L. The procedure shall be started at the latest, when the whole fraction is collected from the DEAE Sepharose column.
The IgG solution is pH adjusted to pH 6.5 (6.45-6.55) with IM NaOH and the ionic strength is adjusted to 1.40 mS (1.30-1.50 mS) by adding of WFI water (WFI = water for injection).
The IgG solution is applied in 6 cycles on a column of Di = 1000 mm and H = 150 mm, packed with Q Sepharose FF and equilibrated with 0.020 M NaAc, pH 6.5. Linear flow rate is more than 30 cm/h preferably 100 cm/h corresponding to 785 L/h. After 3 cycles the column is washed with 0.5 Vc of 0.5 M NaOH and 1.7 Vc of 0.15 M NaAc pH 4.0 The break through fraction containing IgG is directly adsorbed on the next column of Di = 800 mm and H = 80 mm and packed with CM Sepharose FF. When the IgG fraction from all 6 cycles has been pumped through, the column is washed with 10 Vc of 0.01 M Glycine buffer, pH 7.0. The IgG is then eluted with 7 Vc of 0.1 M Glycine + 0.15 M NaCl pH 9.0.
The pH of the solution is adjusted to 4.0+ 0.1 with IM HAc (Acetic acid) and concentrated by ultrafiltration to about 5% IgG.
Virus inactivation chemicals, Triton X-100 and TNBP, are added to the IgG solution during stirring. This mixture is transferred to the incubation tank for heat treatment at 30°C± 2°C for 4- 16 hours. The ionic strength of the solution is adjusted to 1.40 mS by dilution with WFI and applied in 1 cycle on another column of Di = 800 mm and H = 80 mm, packed with CM Sepharose FF and equilibrated with 0.020 M NaAc buffer pH 4.0. The linear flow rate is more than 40 cm/h, preferably 80 cm h, corresponding to 400 L/h. After application the column is washed with 10 Vc of 0.01 M Glycine buffer pH 7.0 in order to remove the inactivation chemicals. The IgG is eluted with 7 Vc of 0.1 M Glycine + 0.15 M NaCl pH 9.0 at the same flow rate and adjusted to pH 4.0 with IM HC1. The solution is then concentrated by ultrafiltration to 5% to 7% IgG and the ionic strength is adjusted by diafiltration to 0.5 mS+0.2 mS. Finally the solution is adjusted to 5.0%.
The solution is formulated to the following composition: Sucrose lg/g IgG
- IgG 5%
- pH 4.0. ionic strength 0.5 mS ± 0.2 mS
After sterile filtration, filling and capping the solution is ready for delivery or storage.
ACA for different batches measured as defined above was found to be 0.5-0.7 CH5o/mg immunoglobulin.
Example 2
625 L of thawed plasma is buffer exchanged into a 0.005 M NaAc (sodium acetate) pH 7 on a column of diameter Di = 800 mm and bed height of H = 600 mm, packed with Sephadex G-25 C. The flow is more than 100 cm/h, preferably 300 cm/h corresponding to a flow rate of 1500 L/h.
The eluted plasma is collected in a tank and IM acetic acid is added during stirring until the pH 5.2 is reached. The plasma is left standing without stirring for 4-12 hours at a temperature of 4- 10°C. After standing the formed euglobulin precipitation is removed by centrifugation.
The plasma is adjusted with IM NaAc, pH 5.2 to a final ionic strength of I = 1.4 mS (Range I = 1.30 - 1.50 ). The pH shall be between 5.15 - 5.25.
The plasma is applied in 6 cycles, 25 - 30 g of albumin per litre gel, on a column of Di = 1000 mm and H = 150 mm, packed with DEAE Sepharose FF and equilibrated with 0.020 M NaAc, pH 5.2. The linear flow rate is more than 60 cm/h, preferably 120 cm/h corresponding to a flow rate of 942 L/h. In the equilibration buffer the IgG will pass the column whilst the albumin is adsorbed. After 3 cycles the column is washed with 1.7 Vc (Vc = bed volume) of 0.15 M NaAc pH 4.0 + 0.5 M NaCl, 0.5 Vc of 0.5 M NaOH and 1.7 Vc of 0.15 M NaAc pH 4.0.
The IgG fraction of about 2350 L is concentrated by ultrafiltration to a final volume less than or equal to 625 L, preferably 400fl500 L. The procedure shall be started at the latest, when the whole fraction is collected from the DEAE Sepharose column.
The IgG solution is pH adjusted to pH 6.5 (6.45-6.55) with IM NaOH and the ionic strength is adjusted to 1.40 mS (1.30-1.50 mS) by adding of WFI water (WFI = water for injection).
The IgG solution is applied in 4 cycles on column of Di = 1000 mm and H = 150 mm, packed with a mixed bed of DEAE Sepharose FF and Arginine Sepharose FF in a proportion 60%/40% and equilibrated with 0.020 M NaAc, pH 6.5. Linear flow rate is more than 30 cm/h, preferably 100 cm/h corresponding to 785 L/h. After 2 cycles the column is washed with 0.5 Vc of 0.5 M NaOH and 1.7 Vc of 0.15 M NaAc pH 4.0. The break through fraction containing IgG is directly adsorbed on the next column of Di = 800 mm and H = 80 mm, packed with CM Sepharose FF. When the IgG fraction from all 6 cycles has been pumped through, the column is washed with 10 Vc of 0.01 M Glycine buffer, pH 7.0. The IgG is then eluted with 7 Vc of 0.1 M Glycine + 0.15 M NaCl pH 9.0.
The pH of the solution is adjusted to 4.0+ 0.1 with IM HAc (Acetic acid) and concentrated by ultrafiltration to about 5% IgG.
Virus inactivation chemicals, Triton X-100 and TNBP, are added to the IgG solution during stirring. This mixture is transferred to the incubation tank for heat treatment at 30°C+ 2°C for 4- 16 hours. The ionic strength of the solution is adjusted to 1.40 mS by dilution with WFI and applied in 1 cycle on another column of Di = 800 mm and H = 80 mm, packed with CM Sepharose FF and equilibrated with 0.020 M NaAc buffer pH 4.0. The linear flow rate is more than 40 cm h, preferably 80 cm/h corresponding to 400 L/h. After application the column is washed with 10 Vc of 0.01 M Glycine buffer pH 7.0 in order to remove the inactivation chemicals. The IgG is eluted with 7 Vc of 0.1 M Glycine + 0.15 M NaCl pH 9.0 at the same flow rate and adjusted to pH 4.0 with IM HC1. The solution is then concentrated by ultrafiltration to 5% to 7% IgG and the ionic strength is adjusted by diafiltration to 0.5 mS+0.2 mS. Finally the solution is adjusted to 5.0%.
The solution is formulated as in Example 1. After sterile filtration, filling and capping, the solution is ready for delivery or storage. ACA for different batches measured as defined above was found to be 0.5-0.7 CH5o/mg immunoglobulin.
Claims (7)
1. A method for producing IgG from plasma for medical applications, comprising at least: (i') removal of albumin resulting in an IgG fraction, (ii') purifying IgG from an IgG fraction, which is derived from the IgG fraction obtained in step (i'), by adsorbing IgG to a cation exchanger and collecting the adsorbed IgG fraction, and (iii') virus inactivation in an IgG fraction derived from the IgG fraction collected in step (ii'), characterized in
(I) concentrating the IgG fraction obtained in step (i'),
(II) adjusting pH to 4±0.1 in the IgG fraction released from the cation exchanger in step (ii'), and preferably maintaining the pH below 6.0 during the remaining steps of the method; and
(IE) carrying out the virus inactivation (step iii') by using chemicals at a temperature of 30°C ± 2°C for at least 4 hours.
2. The method of claim 1 comprising the steps: a) buffering of fresh plasma; b) removal of euglobulins; c) removal of albumin followed by (I) of claim 1; d) purification of plasma fraction obtained after removal of euglobulins and albumin on an anion exchanger and collecting the unbound plasma fraction (IgG fraction); e) purification of the IgG fraction obtained in step (d) on a cation exchanger and collecting the bound IgG plasma fraction including adjusting pH as defined in (II) of claim 1; f) concentration of the IgG plasma fraction collected in step (e); g) inactivation of virus as defined in (III) of claim 1 in the IgG plasma fraction collected in step (f); h) removal of the virus inactivation chemicals added in step (g) by adsorbing IgG to a cation exchanger and releasing and collecting the bound IgG plasma fraction; i) concentration of the IgG plasma fraction collected in step (h); j) formulation of the IgG plasma fraction concentrated in step (i); k) sterile filtration of the formulated IgG plasma fraction obtained in step (j);
3. The method according to anyone of claims 1-2, wherein the concentration according to is performed by ultrafiltration to less than the volume of the starting plasma.
4. The method according to anyone of claims 2-3, comprising an adjustment of ionic strength to about 1.40 mS before step h).
5. The method according to anyone of claims 2-4, wherein an acetate buffer is used in step h).
6. The method according to one or more of the above claims, also comprising lowering after step iii', preferably in step (i) of claim 2, of ionic strength to 0.5 mS + 0.1.
7. The method according to claim 6, wherein the lowering of the ionic strength is by diafilfration against distilled water.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0001128A SE0001128D0 (en) | 2000-03-30 | 2000-03-30 | A method of producing IgG |
| SE0001128-8 | 2000-03-30 | ||
| PCT/EP2001/003624 WO2001072844A2 (en) | 2000-03-30 | 2001-03-29 | A METHOD OF PRODUCING IgG |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2001273907A1 true AU2001273907A1 (en) | 2001-12-20 |
| AU2001273907B2 AU2001273907B2 (en) | 2006-02-02 |
Family
ID=20279068
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2001273907A Ceased AU2001273907B2 (en) | 2000-03-30 | 2001-03-29 | A method of producing IgG |
| AU7390701A Pending AU7390701A (en) | 2000-03-30 | 2001-04-02 | A method of producing igg |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU7390701A Pending AU7390701A (en) | 2000-03-30 | 2001-04-02 | A method of producing igg |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US6835379B2 (en) |
| EP (1) | EP1268551B1 (en) |
| JP (1) | JP2003530326A (en) |
| CN (1) | CN1419566A (en) |
| AT (1) | ATE260297T1 (en) |
| AU (2) | AU2001273907B2 (en) |
| BR (1) | BRPI0109740B8 (en) |
| CA (1) | CA2402784A1 (en) |
| DE (1) | DE60102144T2 (en) |
| IL (1) | IL151667A0 (en) |
| PT (1) | PT1268551E (en) |
| RU (1) | RU2266914C2 (en) |
| SE (1) | SE0001128D0 (en) |
| TR (1) | TR200400701T4 (en) |
| WO (1) | WO2001072844A2 (en) |
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|---|---|---|---|---|
| CN100451031C (en) * | 2003-09-05 | 2009-01-14 | 东丽株式会社 | Method of preparing solution having composition of biological components |
| ES2380538T3 (en) * | 2003-09-05 | 2012-05-16 | Toray Industries, Inc. | Method of preparing a solution for proteomic analysis |
| EP1532983A1 (en) | 2003-11-18 | 2005-05-25 | ZLB Bioplasma AG | Immunoglobulin preparations having increased stability |
| TWI391399B (en) | 2005-05-25 | 2013-04-01 | Hoffmann La Roche | Method for determining the concentration of a salt for eluting a polypeptide |
| US20070049732A1 (en) * | 2005-09-01 | 2007-03-01 | Zurlo Eugene J | Ultra-high yield intravenous immune globulin preparation |
| US8293242B2 (en) * | 2005-09-01 | 2012-10-23 | Plasma Technologies, Llc | Ultra-high yield of alpha-1-anti-trypsin |
| US7879332B2 (en) * | 2005-09-01 | 2011-02-01 | Plasma Technologies, Llc | Ultra-high yield intravenous immune globulin preparation |
| CN100362022C (en) * | 2005-11-07 | 2008-01-16 | 中国人民解放军第二军医大学 | Cuttlebone polysaccharide CPS-1 and its preparation and use |
| US20070128693A1 (en) * | 2005-12-06 | 2007-06-07 | Advantek Serum Laboratories Limited3/F | Method for the inactivation and removal of dengue virus from biological samples |
| WO2007136327A1 (en) * | 2006-05-22 | 2007-11-29 | Ge Healthcare Bio-Sciences Ab | A method of producing igg |
| US20100158893A1 (en) * | 2008-12-19 | 2010-06-24 | Baxter International Inc. | Systems and methods for obtaining immunoglobulin from blood |
| MY157239A (en) | 2009-05-27 | 2016-05-13 | Baxalta Inc | A method to produce a highly concentrated immunoglobulin preparation for subcutaneous use |
| ES2968448T3 (en) | 2009-12-18 | 2024-05-09 | Csl Ltd | Polypeptide purification procedure |
| US20130116413A1 (en) * | 2009-12-29 | 2013-05-09 | Dr. Reddy's Laboratories, Inc. | Purification of proteins |
| AU2011212440B2 (en) | 2010-02-04 | 2015-01-22 | Csl Behring Ag | Immunoglobulin preparation |
| EP2361636A1 (en) | 2010-02-26 | 2011-08-31 | CSL Behring AG | Immunoglobulin preparation and storage system for an immunoglobulin preparation |
| US8772462B2 (en) | 2010-05-26 | 2014-07-08 | Baxter International Inc. | Removal of serine proteases by treatment with finely divided silicon dioxide |
| AU2010202125B1 (en) | 2010-05-26 | 2010-09-02 | Takeda Pharmaceutical Company Limited | A method to produce an immunoglobulin preparation with improved yield |
| US8796430B2 (en) | 2010-05-26 | 2014-08-05 | Baxter International Inc. | Method to produce an immunoglobulin preparation with improved yield |
| MX349005B (en) * | 2011-08-26 | 2017-07-06 | Baxalta Inc | Method for reducing the thromboembolic potential of a plasma-derived immunoglobulin composition. |
| TWI629283B (en) | 2012-02-23 | 2018-07-11 | 巴克斯歐塔公司 | Fraction i-iv-1 precipitation of immunoglobins from plasma |
| MX369444B (en) | 2012-02-29 | 2019-11-08 | Baxalta Inc | Igg stimulated remyelination of peripheral nerves. |
| AU2013203043B2 (en) | 2013-03-15 | 2016-10-06 | Takeda Pharmaceutical Company Limited | Methods to produce a human plasma-derived igg preparation enriched in brain disease-related natural iggs |
| FR3018450B1 (en) * | 2014-03-11 | 2016-04-15 | Lab Francais Du Fractionnement | PROCESS FOR THE PREPARATION OF HUMAN PLASMA PROTEINS |
| CN104231065A (en) * | 2014-09-09 | 2014-12-24 | 青岛康大食品有限公司 | Purification preparation method of globulin in rabbit blood |
| CN108473530B (en) | 2015-10-15 | 2022-12-23 | 普莱泽玛科技有限公司 | Method for extracting protein from blood plasma |
| MX2018009331A (en) * | 2016-02-03 | 2018-11-09 | Plasma Tech Llc | Methods for extracting proteins from a blood-based material. |
| US10815270B1 (en) | 2019-09-20 | 2020-10-27 | Plasma Technologies, Llc | Compositions and methods for high efficiency protein precipitation |
| US10836790B1 (en) * | 2019-09-20 | 2020-11-17 | Plasma Technologies, Llc | Therapeutic protein compositions and methods |
| US20230142480A1 (en) | 2020-03-31 | 2023-05-11 | Takeda Pharmaceutical Company Limited | A method to produce an immunoglobulin preparation from c-1 inhibitor depleted plasma |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3927111C3 (en) * | 1989-08-17 | 1994-09-01 | Biotest Pharma Gmbh | Process for the preparation of unmodified intravenous IgM and / or IgA-containing immunoglobulin preparations |
| ES2074490T5 (en) * | 1990-03-22 | 2004-02-16 | Biotest Pharma Gmbh | PROCEDURE FOR THE PREPARATION OF A PREPARATION OF IMMUNOGLOBULIN G TOLERABLE INTRAVENOUSLY. |
| DE4118912C1 (en) * | 1991-06-08 | 1992-07-02 | Biotest Pharma Gmbh, 6072 Dreieich, De | |
| EP0659767B2 (en) * | 1993-12-27 | 2002-11-06 | ZLB Bioplasma AG | Process to prepare an anti-D immunoglobulin G concentrate and pharmaceutical compositions comprising it |
| US5429746A (en) * | 1994-02-22 | 1995-07-04 | Smith Kline Beecham Corporation | Antibody purification |
| US5886154A (en) * | 1997-06-20 | 1999-03-23 | Lebing; Wytold R. | Chromatographic method for high yield purification and viral inactivation of antibodies |
| IL121900A (en) * | 1997-10-07 | 2001-12-23 | Omrix Biopharmaceuticals Ltd | Method for the purification of immunoglobulins |
| AU753468B2 (en) * | 1998-06-09 | 2002-10-17 | Csl Behring Ag | Process for producing immunoglobulins for intravenous administration and other immunoglobulin products |
| ES2527915T3 (en) * | 1998-06-09 | 2015-02-02 | Csl Behring Ag | Liquid immunoglobulin G (IgG) product |
| DE19923027C2 (en) * | 1999-05-19 | 2002-09-19 | Aventis Behring Gmbh | Virus inactivation method |
-
2000
- 2000-03-30 SE SE0001128A patent/SE0001128D0/en unknown
-
2001
- 2001-03-29 AT AT01940271T patent/ATE260297T1/en not_active IP Right Cessation
- 2001-03-29 AU AU2001273907A patent/AU2001273907B2/en not_active Ceased
- 2001-03-29 RU RU2002124857/04A patent/RU2266914C2/en not_active IP Right Cessation
- 2001-03-29 EP EP20010940271 patent/EP1268551B1/en not_active Expired - Lifetime
- 2001-03-29 PT PT01940271T patent/PT1268551E/en unknown
- 2001-03-29 BR BRPI0109740A patent/BRPI0109740B8/en not_active IP Right Cessation
- 2001-03-29 IL IL15166701A patent/IL151667A0/en not_active IP Right Cessation
- 2001-03-29 WO PCT/EP2001/003624 patent/WO2001072844A2/en active IP Right Grant
- 2001-03-29 DE DE60102144T patent/DE60102144T2/en not_active Expired - Fee Related
- 2001-03-29 CN CN01807338A patent/CN1419566A/en active Pending
- 2001-03-29 US US10/220,929 patent/US6835379B2/en not_active Expired - Lifetime
- 2001-03-29 TR TR2004/00701T patent/TR200400701T4/en unknown
- 2001-03-29 JP JP2001571775A patent/JP2003530326A/en active Pending
- 2001-03-29 CA CA002402784A patent/CA2402784A1/en not_active Abandoned
- 2001-04-02 AU AU7390701A patent/AU7390701A/en active Pending
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