CN105017418A - Monoclonal antibody purification process - Google Patents
Monoclonal antibody purification process Download PDFInfo
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Abstract
The present invention discloses a monoclonal antibody purification process, which comprises: 1) carrying out affinity chromatography; 2) adjusting the pH value of the affinity chromatography eluent to 3.3-3.8, and carrying out virus inactivation; 3) adjusting the pH value to a neutral pH value, and carrying out deep filtration; 4) carrying out anion exchange chromatography; and 5) carrying out cation exchange chromatography. According to the present invention, the low-pH value and high-salt washing step is added to the affinity chromatography to remove the host protein and DNA while the deep filtration is used after the low-pH value virus inactivation to carry out the clarifying treatment, such that the separation effect of the affinity chromatography on the antibody monomer and the polymer is improved so as to increase the purity of the monoclonal antibody product.
Description
Technical field
The present invention relates to biological field, particularly relate to the purification technique of monoclonal antibody.
Background technology
1997, Genentech company of the U.S. successfully developed the monoclonal antibody drug in first man source, has stepped the first step of monoclonal antibody medicine industrialization.Short more than 10 years history, antibody drug presents irresistible developing state, there is several numeral that status and the development prospect of antibody drug can be described: the gross sales (GS) of global treatment monoclonal antibody medicine in 2010 reaches 44,000,000,000 dollars, if add monoclonal antibody diagnosis and the research reagent of 10,000,000,000 dollars, the total market size of monoclonal antibody medicine has reached 55,000,000,000 dollars, and the total market size of monoclonal antibody medicine in 2011 has reached 62,800,000,000 dollars.And in 2009 before this year with 2008, this numeral is respectively 40,000,000,000 dollars and 37,000,000,000 dollars (data from State Statistics Bureau).Current, there is monoclonal antibody development project in nearly all big drug firm.
Although the growth of increasing on monoclonal antibody drug of world economy downslide risk trend affects to some extent, but the rise of monoclonal antibody drug is irresistible, along with deepening continuously of monoclonal antibody drug research, the continuous release of new drug, in future, global monoclonal antibody medicine still can keep higher rate of increase.Analyses and prediction, by 2015, global monoclonal antibody medicine sales volume was expected to reach about 98,000,000,000 dollars.But current antibody drug list criticizes that output is the highest just reaches kilogram levels, and the single dose consumption of antibody drug is microgram, milligram level.The value of visible antibody drug far exceedes gold.The product of costliness like this, manufacturing process just seems especially important, and any imperfection of technique all may cause great loss.
The manufacture of antibody drug is the most complicated loaded down with trivial details with downstream process again.Downstream process comprises multiple step, and at present conventional is the method for separating liquid phase chromatography of affinity chromatography, cation-exchange chromatography and anion-exchange chromatography.Although be all adopt this several chromatography method, concrete parameter is different, Fillers selection is different all can produce diverse result.
Affinity chromatography is as the first step of chromatographic separation, and general action is the product of catching in fermentation supernatant.Based on the principle of the disposable absorption of specificity, the product after affinity chromatography generally can reach the monomer purity being greater than 80%, can also ensure the higher rate of recovery simultaneously.But antibody drug not only needs to ensure monomer purity, also need to reduce as much as possible the residual of host protein and DNA.The purifying process of most of antibody product all rides in subsequent step the removal of host protein (HCP) and DNA, but absolute removal amount, affinity chromatography is only removes host protein and the maximum step of DNA, so remove in this step of affinity chromatography the pressure that host protein as much as possible and DNA can alleviate subsequent step greatly.
Affinity chromatography wash-out collects liquid after too low pH inactivation of virus, with in ealkaline buffer and time generally can be more muddy, this situation is generally a small amount of residual HCP and DNA and produces co-precipitation when pH4 – 6 and cause.If this part Impurity removal may be reduced some rate of recovery a little but more HCP and DNA can be removed, be also more conducive to the carrying capacity improving follow-up virus-eliminating filtering film simultaneously, thus reduce costs.
Cation-exchange chromatography is mainly used in removing superpolymer, can remove host protein and DNA further simultaneously.Conventional method is after less salt loading, uses high eluting salt, selects the salt concn be applicable to by target protein wash-out, thus reaches separating effect.But conventional elution mode resolving power is lower, target protein purity can only be improved slightly, poor for the acid-basicity analogue separating effect less with target protein charge differences.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of monoclonal antibody-purified processing method, and it can improve the purity of monoclonal antibody product.
For solving the problems of the technologies described above, monoclonal antibody-purified processing method of the present invention, step comprises:
1) affinity chromatography;
2) regulate pH value to 3.3 ~ 3.8 of affinity chromatography elutriant, carry out inactivation of virus;
3) adjust ph is to neutral, carries out Depth Filtration;
4) anion-exchange chromatography;
5) cation-exchange chromatography.
Preferably, the affinity chromatography of step 1) after introduction of the sample, before wash-out, washs chromatography column with the high concentration salt solutions of pH value 5.0 ~ 5.5, concentration 1 ~ 3M.Such as, first can wash chromatography column with the mixing solutions of 20mM citric acid-sodium citrate (or Acetic acid-sodium acetate) and 1M sodium-chlor, then use 20mM citric acid-sodium citrate (or Acetic acid-sodium acetate) to wash chromatography column.Wherein, sodium-chlor also can replace with Repone K or potassium sulfocyanate.
Depth Filtration described in step 3) can adopt the secondary deep bed filter in 0.1 ~ 0.5 μm of aperture.
Preferably, the cation-exchange chromatography of step 5), before wash-out, first with damping fluid (pH value 6.0 ~ 9.0) the washing cation-exchange chromatography post of high ph-values, then out can before change the balance liquid of low ph value at target protein peak.
Compared with existing purification process, monoclonal antibody-purified processing method of the present invention has the following advantages and beneficial effect:
1., by adding washing step in affinity chromatography, effectively removes the impurity such as superpolymer, fragment, HCP and DNA, improve antibody purity, avoid simultaneously and repeatedly dilute and regulate pH.
2. by the low pH deactivation of affinity chromatography elutriant and in and after, add depth filtration step, eliminate host protein, DNA and superpolymer further, improve the purity of antibody.When the product later stage nanofiltration of clarifying treatment is removed viral after filtration, carrying capacity is higher, is not easy blocking.And not through the product later stage nanofiltration easily stifled film of Depth Filtration, be also difficult to pass through when carrying out virus removal confirmatory experiment.
3. by cation-exchange chromatography, increase high pH salt wash step, remove acid and alkaline impurities, the CEX main peak purity of product is improve more than at least 5%.
Embodiment
Understanding more specifically for having technology contents of the present invention, feature and effect, now in conjunction with specific embodiments, technical scheme of the present invention being described in detail.The indices related in embodiment adopts following detection method: SEC(monomer purity) adopt Size Exclusion High Performance liquid phase chromatography to detect, CEX(electric charge purity) adopt cationic exchange high performance liquid chromatography to detect, residual HCP adopts enzyme-linked immunosorbent assay to detect, residual DNA adopts quantitative polyase chain reaction to detect, residual ProA(a-protein) adopt enzyme-linked immunosorbent assay to detect.
Embodiment 1 Trastuzumab is monoclonal antibody-purified
1. a-protein affinity chromatography
Step 1, with the water for injection drip washing chromatography column of 3 times of column volumes, then uses the NaOH(50mM of 3 times of column volumes) and mixing solutions sterilization chromatography column NaCl(1M), then use the water for injection drip washing chromatography column of 3 times of column volumes.
Step 2, balances chromatography column with the damping fluid (20mM Sodium phosphate dibasic-SODIUM PHOSPHATE, MONOBASIC+150mM NaCl, pH7.4) of 5 times of column volumes.
Step 3, loading, allows sample retain 4 minutes on post.
Step 4, with 20mM Sodium phosphate dibasic-SODIUM PHOSPHATE, MONOBASIC+150mM NaCl, pH7.4 drip washing is to A280 baseline, then damping fluid (20mM citric acid-sodium citrate+1M the NaCl of 5 times of column volumes is used, pH5.5) chromatography column is washed, the damping fluid of 3 times of column volumes (20mM citric acid-sodium citrate, pH5.5) is used to wash chromatography column again.
By increasing by twice buffer solution step in step 4, greatly reduce the residual of HCP in affinity chromatography elutriant.Before not increasing washing step, in affinity chromatography elutriant, the residual quantity of HCP is generally 10
3ppm rank, after increasing washing step, HCP residual quantity reduces 60%-80%, and concrete data are in table 1:
Table 1 affinity chromatography adds the HCP residual quantity after washing step
From table 1, after affinity chromatography adds suitable washing step, HCP residual quantity significantly reduces, and is reduced to 2520ppm from 8374ppm.
Step 5, with damping fluid (20mM citric acid-sodium citrate, pH3.6) by whole for target protein wash-out out.
Step 6, carries out manipulation of regeneration with the 1M acetic acid of 3 times of column volumes to chromatography column.
2. Depth Filtration after low pH deactivation
Affinity chromatography elutriant 1M acetic acid is adjusted to after pH3.3 ~ 3.8 carry out inactivation of virus, is adjusted to neutrality, then uses Mi Libo depth filter A1HC(Millipore Millistak+pod Filter A1HC with 1M Tris) carry out Depth Filtration, remove a large amount of HCP.HCP and DNA residual quantity and SEC purity are see table 2:
HCP and the DNA residual quantity of table 2 affinity chromatography elutriant after Depth Filtration and SEC purity
From table 2, affinity chromatography elutriant is after a step Depth Filtration, and HCP residual quantity obviously reduces, and is down to below 303ppm from 737ppm, and DNA is residual also meets FDA requirement completely.
3. anion-exchange chromatography
A1HC filtrate after Depth Filtration is directly flowed through the anion-exchange chromatography post with primary amino functionalities, collect stream and wear liquid.
4. cation-exchange chromatography
Step 1, with the water for injection drip washing of the 3 times of column volumes chromatography column with sulfonate functional groups, then to sterilize chromatography column with the 1M NaOH of 3 times of column volumes, then uses the water for injection drip washing chromatography column of 3 times of column volumes.
Step 2, balances chromatography column with the damping fluid (20mM citric acid-sodium citrate, pH5.5) of 5 times of column volumes.
Step 3, after the pH value of the anionic current containing target protein being worn liquid is adjusted to 5.5, loading, and allow sample retain 6 minutes on chromatography column.
Step 4, with the 20mM citric acid-sodium citrate solution drip washing of pH5.5 to A280 baseline, then damping fluid (20mM SODIUM PHOSPHATE, MONOBASIC-the Sodium phosphate dibasic of 1 times of column volume is used, pH7.3) wash chromatography column, then use the 20mM citric acid-sodium citrate solution washing chromatography column of the pH5.5 of 3 times of column volumes immediately.
By adding buffer solution step, with of short duration high ph-values damping fluid, heterogeneous acidic body lower for pI is first washed, target protein peak out before change the balance liquid of low ph value immediately into, thus ensureing that the prerequisite of the rate of recovery has been issued to the object being separated acidic impurities, concrete outcome is see table 3:
After increasing high pH washing before table 3 cation-exchange chromatography wash-out, the purity of monomer
From table 3, increase by a step height pH before cation-exchange chromatography wash-out and wash, most of acidic impurities can be removed, improve CEX, can also monomer purity be improved simultaneously.
Step 5, with the mixing solutions of 20mM citric acid-sodium citrate and 130mM sodium-chlor as elutriant (pH5.5), wash-out target protein, till protein peak comes out completely;
Step 6, carries out manipulation of regeneration with 1M sodium-chlor to chromatography column.
Xiu Meile is monoclonal antibody-purified for embodiment 2
The processing method of purifying is with embodiment 1, HCP and the DNA residual quantity of affinity chromatography elutriant after a step Depth Filtration and SEC purity are see table 4:
HCP and DNA residual quantity after table 4 affinity chromatography elutriant Depth Filtration and SEC purity
From table 4, affinity chromatography elutriant is after a step Depth Filtration, and HCP residual quantity obviously reduces, and is down to 86ppm from 226ppm, and DNA is residual also meets FDA requirement completely.
The purity of the finished product and residual index are see table 5:
Table 5 adopts the purity of the product of present invention process purification and residual index
From table 5, every purity of the Xiu Meile monoclonal antibody product of present invention process purification and residual index is adopted all to meet sFDA requirement.
Embodiment 3 Rituximab is monoclonal antibody-purified
The processing method of purifying is with embodiment 1, HCP and the DNA residual quantity of affinity chromatography elutriant after a step Depth Filtration and SEC purity are see table 6:
HCP and DNA residual quantity after table 6 affinity chromatography elutriant Depth Filtration and SEC purity
From table 6, affinity chromatography elutriant is after a step Depth Filtration, and HCP residual quantity obviously reduces, and is down to 127ppm from 794ppm, and DNA is residual also meets FDA requirement completely.
The purity of the finished product and residual index are see table 7:
Table 7 adopts the purity of the product of present invention process purification and residual index
From table 7, every purity of the Rituximab monoclonal antibody product of present invention process purification and residual index is adopted all to meet sFDA requirement.
Embodiment 4 Mabthera is monoclonal antibody-purified
The processing method of purifying is with embodiment 1, and the purity of the finished product and residual index are see table 8:
Table 8 adopts the purity of the product of present invention process purification and residual index
From table 8, every purity of the Mabthera monoclonal antibody product of present invention process purification and residual index is adopted also all to meet sFDA requirement.
Claims (7)
1. monoclonal antibody-purified processing method, is characterized in that, step comprises:
1) affinity chromatography;
2) regulate pH value to 3.3 ~ 3.8 of affinity chromatography elutriant, carry out inactivation of virus;
3) adjust ph is to neutral, carries out Depth Filtration;
4) anion-exchange chromatography;
5) cation-exchange chromatography.
2. method according to claim 1, is characterized in that, step 1), affinity chromatography after introduction of the sample, before wash-out, with the brine chromatography column of pH value 5.0 ~ 5.5, concentration 1-3M.
3. method according to claim 2, is characterized in that, includes sodium-chlor, Repone K or potassium sulfocyanate in described salts solution.
4. method according to claim 3, it is characterized in that, step 1), affinity chromatography after introduction of the sample, before wash-out, first wash chromatography column with the mixing solutions of 20mM citric acid-sodium citrate or Acetic acid-sodium acetate and 1M sodium-chlor, then wash chromatography column with 20mM citric acid-sodium citrate or Acetic acid-sodium acetate.
5. method according to claim 1, is characterized in that, step 3), and described Depth Filtration adopts the secondary deep bed filter in 0.1 ~ 0.5 μm of aperture.
6. method according to claim 1, is characterized in that, step 5), and cation-exchange chromatography, before wash-out, first uses the buffer solution cation-exchange chromatography post of pH value 6.0 ~ 9.0, target protein peak out before change balance liquid into again.
7. method according to claim 6, is characterized in that, described damping fluid is the 20mM SODIUM PHOSPHATE, MONOBASIC-disodium phosphate soln of pH7.3.
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|---|---|---|---|---|
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101889025A (en) * | 2007-10-30 | 2010-11-17 | 健泰科生物技术公司 | Antibody purification by cation exchange chromatography |
| CN102219848A (en) * | 2011-05-25 | 2011-10-19 | 浙江海正药业股份有限公司 | Purification method for recombinant human interferon beta-1a |
| CN102492040A (en) * | 2011-12-29 | 2012-06-13 | 嘉和生物药业有限公司 | Method for purifying anti-HER2 or/and anti-HER3 antibody proteins |
| CN102711828A (en) * | 2009-10-20 | 2012-10-03 | 雅培制药有限公司 | Isolation and purification of anti-IL-13 antibodies using protein a affinity chromatography |
| CN103059125A (en) * | 2012-12-27 | 2013-04-24 | 浙江海正药业股份有限公司 | Purification method for recombinant human follicle-stimulating hormone |
| CN103379949A (en) * | 2010-10-11 | 2013-10-30 | Abbvie公司 | Processes for purification of proteins |
| CN106749660A (en) * | 2016-12-27 | 2017-05-31 | 嘉和生物药业有限公司 | The method that host protein is effectively removed in monoclonal antibody downstream purification process |
-
2014
- 2014-03-27 CN CN201410120032.5A patent/CN105017418B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101889025A (en) * | 2007-10-30 | 2010-11-17 | 健泰科生物技术公司 | Antibody purification by cation exchange chromatography |
| CN102711828A (en) * | 2009-10-20 | 2012-10-03 | 雅培制药有限公司 | Isolation and purification of anti-IL-13 antibodies using protein a affinity chromatography |
| CN103379949A (en) * | 2010-10-11 | 2013-10-30 | Abbvie公司 | Processes for purification of proteins |
| CN102219848A (en) * | 2011-05-25 | 2011-10-19 | 浙江海正药业股份有限公司 | Purification method for recombinant human interferon beta-1a |
| CN102492040A (en) * | 2011-12-29 | 2012-06-13 | 嘉和生物药业有限公司 | Method for purifying anti-HER2 or/and anti-HER3 antibody proteins |
| CN103059125A (en) * | 2012-12-27 | 2013-04-24 | 浙江海正药业股份有限公司 | Purification method for recombinant human follicle-stimulating hormone |
| CN106749660A (en) * | 2016-12-27 | 2017-05-31 | 嘉和生物药业有限公司 | The method that host protein is effectively removed in monoclonal antibody downstream purification process |
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