CN107413320A - A kind of application of protein A affinity chromatography medium - Google Patents
A kind of application of protein A affinity chromatography medium Download PDFInfo
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- CN107413320A CN107413320A CN201710237976.4A CN201710237976A CN107413320A CN 107413320 A CN107413320 A CN 107413320A CN 201710237976 A CN201710237976 A CN 201710237976A CN 107413320 A CN107413320 A CN 107413320A
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
- B01J20/265—Synthetic macromolecular compounds modified or post-treated polymers
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- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
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- B01J20/28019—Spherical, ellipsoidal or cylindrical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/22—Affinity chromatography or related techniques based upon selective absorption processes
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Abstract
The invention provides a kind of application of Protein A Chromatography medium, the Protein A Chromatography medium obtains using the polymer microballoon of vinyl-containing monomers as raw material after the modification of surface hydrophilicity dendritic macromole, activation and albumin A coupling.The protein A affinity chromatography medium of the present invention is used as antibody and Fc fusion proteins isolate and purify medium, can increase substantially flow velocity, disengaging time is short, and good separating effect, cost is cheap, is suitable for the fast separating and purifying of antibody class and Fc fusion proteins.
Description
Technical field
The present invention relates to the fields such as chemical material synthesis and biological medicine downstream technique, and in particular to a kind of albumin A is affine
The application of chromatography media.
Background technology
In recent years, antibody drug is quickly grown.2016, it was antibody medicine to have 6 in the medicine of 10 before global marketing volume
Thing, and first 5 are.Three classical steps of the purifying generally use of antibody drug or two-step chromatography, and albumin A affinity media with
Multiple regions single-minded adsorption capacity unique to antibody Fc section, can be used as antibody capture step, a step process is on albumin A aglucon
Most impurity in cell fermentation liquid is can remove, up to more than 99% purity.With the development of antibody drug, as antibody
The affinity chromatography medium of capture also achieves fast development.
But protein A affinity chromatography medium is costly, chromatography media cost in antibody drug downstream purification technique can be accounted for
85%.Therefore, the selection of affinity chromatography medium, not only it is related to the quality of product, is also relate to the competitiveness of product in market.Egg
White A affinity chromatography mediums occur that albumin A aglucon comes off in antibody purification procedures, if these technique related impuritieses can not be rear
Removed well in continuous technique, then the risk for causing immune response be present.The protein A affinity chromatography aglucon of early stage comes off seriously,
Filler manufacturer is directed to increasing the chemical resistance of medium, thus can reduce the use cost of filler and improve the matter of product
Amount.Therefore, main flow protein A affinity chromatography medium such as GE MabSelect SuRe at present, are alkali-proof medium, are resistant to 0.1-
0.5N NaOH are cleaned.The cleaning and sterilization of the protein A affinity chromatography medium of these stability enhancing, can use goldstandard hydrogen-oxygen
Change sodium solution to carry out, albumen precipitation thing on filler, hydrophobic proteins, nucleic acid, interior is attached to so as to remove efficiently at low cost
Toxin and virus etc..
At present, domestic antibody producing mostly uses import protein A affinity chromatography medium.Such as GE MabSelect SuRe,
Its matrix is the agarose microbeads of high crosslinking, and advantage is that hydrophily is splendid, good biocompatibility, and it is big to be especially suitable for antibody class biology
Molecule isolates and purifies；But shortcoming is that its structure is partially soft, and particle diameter distribution is wider, dress post repeatability in actual use be present
Difference, the problems such as mechanical strength is low.The Prosep Ultra Plus of Millipore companies are also a kind of using relatively broad egg
White A affinity chromatography mediums, matrix are the controllable glass bead architectures in duct, good hydrophilic property, and carrying capacity is very high.But glass bead architectures
Have a critical defect for its can not resisting high-concentration NaOH clean this goldstandard, thus limit its in Large Scale Biology sample should
With.
The protein A affinity chromatography medium of the present invention is used as antibody and Fc fusion proteins isolate and purify medium, and carrying capacity is high, can be big
Amplitude improves flow velocity, and disengaging time is short, good separating effect, and dress post is reproducible, and high mechanical strength, cost is cheap, is suitable for
The fast separating and purifying of antibody class and Fc fusion proteins, spy release the present invention.
The content of the invention
It is an object of the invention to overcome the shortcomings of the prior art, there is provided a kind of protein A affinity chromatography medium is answered
With separative efficiency is high, effect is good, cost is low, is adapted to industrialization to isolate and purify antibody and Fc fusion proteins on a large scale.
To reach above-mentioned purpose, the technical scheme is that：A kind of application of protein A affinity chromatography medium, the egg
White A affinity chromatography mediums are as chromatography media applied in the isolating and purifying of antibody and Fc fusion proteins；The affine layer of albumin A
Medium is analysed using the polymer microballoon of vinyl-containing monomers as matrix, through the modification of hydrophilic resin dendritic macromolecules, activation, coupling protein
Obtained after A aglucons and sealing.
Wherein, the protein A affinity chromatography medium is porous polymer microsphere medium.
Wherein, the hydrophilic resin dendritic macromolecules be modified to be grafted on the polymer microballoon surface functional groups it is hydrophilic
Property dendritic macromole, the hydrophilic resin dendritic macromolecules include but is not limited to hyperbranched polyethylene alcohol or polyglycereol class is divided greatly
Son.
Wherein, the activation is to connect functional group on the polymer microballoon surface, and the functional group includes but is not limited to
Epoxy, amino, carboxyl class functional group.
Activation, which can refer to, utilizes the coupling agents such as epoxychloropropane, BDDE and Hydrophilic modification
The functional groups such as the hydroxyl of microsphere surface react, and unreacted one end includes epoxy construction.
Wherein, the coupling protein A aglucons, for by albumin A ligand cou to the polymer microballoon activate after surface
On functional group.
Coupling protein A (or albumin A coupling) can refer to the ring using microsphere surface after the sulfydryl in Protein A molecules and activation
Epoxide is reacted, and forms the rock-steady structure of thioether bond.
Wherein, the sealing can refer to using after the small molecule containing hydroxyl, sulfydryl or amino and coupling protein A aglucons
The active function group on polymer microballoon surface reacted, eliminate unreacted active function group.
Wherein, the polymer microballoon of the vinyl-containing monomers as matrix is that uniform particle diameter, porose single dispersing are more
Hole microballoon.
Wherein, the vinyl-containing monomers include at least one mono-vinyl monomer, or include at least one more vinyl
Monomer.
Wherein, the diameter range of the polymer microballoon of the vinyl-containing monomers is 5~100 μm；The list containing vinyl
The pore diameter range of the polymer microballoon of body is 80~120nm.
Wherein, the protein A affinity chromatography medium is pure applied to the separation of antibody and Fc fusion proteins as chromatography media
, can be with 20mM PBS+150mM NaCl, pH7.0-pH8.0 or 50mM sodium dihydrogen phosphates+100mMNaAc+150mM during change
The buffer solutions such as NaCl, pH7.0-pH8.0 are as balance phase, with buffer solutions such as 50mM Gly, pH3.0-pH4.0 as elution phase.
Suitable vinyl-containing monomers include but is not limited to the vinyl monomer for becoming known for polymerization process, such as in U.S.
Vinyl monomer disclosed in state's patent (US Pat.4572819), typical vinyl monomer include：Styrene, methylbenzene
Ethene, all isomers of vinyltoluene and to vinyltoluene, all isomers of ethyl styrene, propylbenzene second
Alkene, vinyl naphthalene, vinyl anthracene and its mixture.Vinyl monomer can also combine with other copolymerizable monomers.Such list
The example of body includes but is not limited to alkene nitrile and acrylic ester monomer, such as acrylonitrile, methacrylonitrile, acrylate, methyl
Acrylate and its mixture.
Also at least one multi-vinyl monomer, described multi-vinyl monomer bag can be included in the monomer of above polymerisation
Include by divinylbenzene, one and the mixture to a divinylbenzene, trivinylbenzene, divinyl toluene, divinyl
Dimethylbenzene, divinyl naphthalene, and its derivative.These compounds can use individually or with two kinds or more of mixture.
Particularly preferred multi-vinyl monomer mixture forms by one and to a divinylbenzene.
Monodisperse polymer micro-sphere can be prepared via different methods, and polymer microballoon of the present invention is anti-by polymerizeing
It should prepare；Polymerisation includes emulsion polymerization, emulsifier-free emulsion polymerization, micro-emulsion polymerization, mini-emulsion polymerization, dispersin polymerization, suspension
Polymerization and seeding polymerization, it is adapted to polymerisation such as dispersin polymerization, suspension polymerisation and the seeding polymerization of the present invention, is particularly suitable for this hair
Bright polymerisation such as suspension polymerisation and seeding polymerization, seeding polymerization has a variety of different methods to implement, such as Chinese invention is special
Sharp (CN101186661B), it is entitled《A kind of preparation method of polymer beads》Patent of invention in, disclose a kind of use
The seed manufacture method that is polymerize and be swelled simultaneously, Chinese invention Publication No. CN1362973A are entitled《For preparing list
The method of dispersed polymeres particle》Patent of invention in, proposition make monomer with gathering including the swellable seed polymer Zhi of single dispersing
The water-borne dispersions contact of thing, triggers polymerization to form microballoon in the presence of stabilizer.
The polymer microballoon of the present invention is has a pass, and general pore type microballoon is generally only containing polymer intermolecular in itself
Hole, its pore diameter is less than about 1nm, and has pass then to contain the additional hole unrelated with intermolecular hole, and its hole is straight
Footpath at least about 2nm, its pore diameter can reach hundreds of nanometers or close to micrometer range, gather in small in big polymer beads
The diameter is relatively smaller in polymer beads, when there is no perforating agent in the monomer or monomer mixture being added in seed grain,
For caused polymer beads by simply pore type, but when containing perforating agent, particle will be just to have pass.It polymerize formed with pass
The polymerisation of thing is published in United States Patent (USP) (USPat.4382124), and perforating agent is the solvent of the monomer mixture of polymerization,
But insoluble polymer, so that polymer is just separated once generating from single phase, when the polymerization generated in microballoon
The increase of thing concentration, perforating agent repel extrusion by polymer and leave the hole of interconnection in polymer microballoon.It is adapted to the present invention's
Perforating agent has C4~C10Alkanol include butanol, the amylalcohol of straight or branched, hexanol enanthol, octanol, nonyl alcohol, decyl alcohol, such as 4
The alcohol of monomethyl amyl group 1 (methyl isobutyl carbinol)；The Arrcostab of seven or more carbon atoms such as hexyl acetate, acetic acid one
2 one ethylhexyls, methyl oleate, dibutyl sebacate, dibutyl adipate and dibutyl carbonate；Aliphatic ketone such as methyl is different
Butyl ketone, isobutyrone；And aromatic hydrocarbon such as toluene, the appropriate mixing that contraposition, ortho position dimethylbenzene, or more are carried
Thing.
The preparation method of heretofore described protein A affinity chromatography medium is as follows：Contain ethene using as raw material or matrix
The monodisperse polymer micro-sphere of base monomer is put into reactor, modifies hydrophilic resin dendritic macromolecules, cleaning；Then, band is added
The monomer of active functional group activates 1~3h, cleaning；Albumin A aglucon to be coupled is added, reacts 16-24h, cleaning；Finally,
Sealing reagent reacting 2-6h is added, protein A affinity chromatography medium is can obtain after cleaning.
Wherein, hydrophilic resin dendritic macromolecules include but is not limited to hyperbranched polyethylene alcohol or polyglycereol class macromolecular.
Wherein, active function group includes but is not limited to epoxy, amino, carboxyl class functional group.
Wherein, the albumin A of the coupling can be the Protein A molecules containing sulfydryl.
Wherein, described sealing reagent can be with the small organic agents containing hydroxyl, sulfydryl or amino.
Wherein, the protein A affinity chromatography medium obtained with phosphate-buffered salt, acetate buffer salt, water washing, produces system successively
The protein A affinity chromatography medium got ready, and preserved with 20% ethanol.
Chromatographic technique, with continuously improving and developing, turn into apply extremely wide chemistry and bio-separation at present
The important means of analysis.Chromatography is when being distributed based on mixture to be separated between the two-phase of relative motion thing, chemistry or
The difference of physical property and make a kind of separation or analysis method that mixture is separated from each other.
The application of Protein A Chromatography medium disclosed by the invention, coordinated using above-mentioned Protein A Chromatography medium as chromatography media
Appropriate chromatography buffer is applied to isolating and purifying for antibody and Fc fusion proteins, and achieve following has compared with prior art
Beneficial effect：
1st, Protein A Chromatography medium of the invention is used as chromatography media as a kind of brand-new material, relative to prior art
The chromatography media of middle separation antibody and Fc fusion protein, flow velocity increase substantially, either separative efficiency, or during sample separation
Between, all show more satisfactory separating effect, and use and the maintenance cost of instrument needed for reducing, be suitable for antibody and
Fc fusion proteins it is quick, efficient, isolate and purify on a large scale.
2nd, Protein A Chromatography medium of the invention is equal as base ball, particle diameter using the monodisperse polymer micro-sphere of vinyl-containing monomers
One, pore-size distribution is concentrated, and makes the particle diameter of Protein A Chromatography medium for preparing more uniform, pore-size distribution is concentrated, along with albumen
A chromatographic medium surface albumin A aglucons, particularly suitable for separation antibody and this kind of large biological molecule of Fc fusion proteins.
3rd, in the present invention Protein A Chromatography dielectric structure is stable, neither too hard, nor too soft, particle diameter distribution within the specific limits, therefore
Reproducible using fashionable dress post, high mechanical strength, flow velocity increases substantially, and cost is cheap, and suitable heavy industrialization makes extensively
With.
Brief description of the drawings
Fig. 1 is Protein A Chromatography medium SEM figures prepared by the raw material ball used in embodiment 1.
Fig. 2 is the antibody actual sample purification effect figure of Protein A Chromatography medium prepared by embodiment 1.
Fig. 3 is that Protein A Chromatography medium prepared by embodiment 2 is repeatedly used for chromatography antibody as chromatography media dress post
Actual curve Overlay figure.Wherein, abscissa unit is minute, and ordinate unit is AU, and every is analyzed plot against time starting point
It is zero, appearance time is also identical, and how much directly related the size at peak is with sample size, for details, reference can be made to embodiment 2.
Embodiment
Technical scheme is further described with reference to specific embodiment, but the present invention is not limited to this
A little embodiments.
Embodiment 1,
The polyacrylic acid ester microsphere voluntarily prepared using Suzhou Nano-micro Technology Co., Ltd..When microballoon prepares polymerization, Dan Yi
Contain part methyl glycidyl acrylate in alkenyl monomer.The hyperbranched polyethylene alcohol of commodity in use simultaneously
(Hyperbranched G5-PEG6k-OH, ALDRICH).20g polymer microballoons are first weighed in dry pallet, and (particle diameter is
50 μm, aperture is about 100nm), it is put into 100ml there-necked flasks.Then, 100mL beakers are taken and to prepare 20mL 0.6M NaOH molten
Liquid, wherein containing 2mg/mL sodium borohydrides, while add 20g hyperbranched polyethylenes alcohol (Hyperbranched G5-PEG6k-
OH, ALDRICH) and it is allowed to dispersing and dissolving.Then, the poly-vinyl alcohol solution after dissolving is added in above-mentioned flask.Mechanical agitation
Under the conditions of, 37 DEG C of reaction 3.5h.After reaction terminates, core is drained, and is first cleaned 2 times with 50mL deionized waters, then anhydrous with 50mL
Ethanol cleans 1 time, then is cleaned 3 times with 50mL deionized waters.Microballoon is put into heating mantle afterwards and activated.Added to above-mentioned flask
It is new to match somebody with somebody 30mL 2M NaOH, react 0.5h, 40 DEG C of reaction temperature, mixing speed 100rpm.Then, DMF 12.5mL, DCM are added
7.5mL, soak time 2.5h, 40 DEG C of activation temperature, mixing speed 100rpm.After activation terminates, core is drained, and is first gone with 50mL
Ionized water cleans 2 times, then is cleaned 3 times with 50mL washes of absolute alcohol 1 time, then with 50mL deionized waters.Obtained microballoon is drained
After 5min, 1.5g is respectively taken, 15mL EP pipes is added, 3.75mL 10mg/mL Protein A, 1.3M is added into the pipe
Na2SO4, 50mM PB, 1mM EDTA solution.After being sealed with sealed membrane, lead to nitrogen 5min, sealing, shaking table reaction 24h, reaction temperature
37 DEG C of degree, 200rpm.Reacted protein solution is filtered off into protein solution, and OD after measurement reaction respectively with needle tubing filter
Value, and record.Add 0.5mL mercapto glycerols, 4.5mL pH10.0Na2CO3Mixed liquor, after being sealed with sealed membrane, lead to nitrogen
5min, sealing, shaking table reaction 4h, 37 DEG C of reaction temperature.After having reacted, first settle, take 1.2mL natural subsidences volume to load 1mL
PP posts.Before test, cleaned successively with 10CV 0.1M Gly, PH3.0 and 10CV 0.02M PBS, 0.15M NaCl, PH7.0.
Protein A affinity chromatography medium SEM figures are shown in accompanying drawing 1, it is seen that its particle diameter is very homogeneous.
Protein A affinity chromatography medium 1mL PP posts manufactured in the present embodiment are taken, are rinsed with equilibrium liquid.AKTA purifier
Instrument is before use, first with pure water rinsing and balance, and baseline is zeroed after balance.20mM PBS, 150mM NaCl, pH7.0 and
50mM Gly, pH3.0 are respectively as balance phase and elution phase, system Pump Wash.Pillar is connected to system AKTA
Purifier, pay attention to preventing bubble from entering in connection procedure, pump is run with certain flow rate during connection, and junction portion is filled with mobile phase
Share in the benefit wet, pillar upper end is also full of with mobile phase, is then connected.Pillar uses 50mM Gly, pH3.0 and 20mM PBS successively,
Each 10CV of 150mM NaCl, pH7.0 are rinsed to baseline and balanced.Start to enter antibody cell culture supernatant sample with 0.25mL/min, with
5mL quantitative loop sample introduction mL, and with elution antibody, it is molten with 0.1mL 1M NaAc are put into advance to treat that starting occurs in eluting peak
The 50mL EP pipes of liquid collect 4.9mL, adjust pH value to 5.5.If conductance is higher than 5mS/cm, below 5mS/cm is adjusted to pure water.Separation
Enrichment result figure is shown in accompanying drawing 2.It can be seen that the protein A affinity chromatography medium of preparation can be by the fast and effective separation and concentration of antibody.
The present embodiment is 50 μm from particle diameter, and the single dispersing polyvinyl microballoon that aperture is about 100nm is base ball, is made
The diameter for the protein A affinity chromatography medium that must be prepared and aperture also in an approximate range, are used as the fixation of liquid chromatogram
Phase, relative to protein A affinity chromatography medium in the prior art, flow velocity can increase substantially, either separative efficiency, or sample
Disengaging time, preferable separating effect is all shown, be suitable for antibody rapidly and efficiently separation and concentration.
Embodiment 2
Reaction unit is same as Example 1, using Suzhou Nano-micro Technology Co., Ltd.Polyvinyl
(monodisperse particles particle diameter is 15 μm to microballoon, and aperture is about).It is same in mono-vinyl monomer when microballoon prepares polymerization
Sample contains part methyl glycidyl acrylate.Reaction controlling and ball step is washed with embodiment 1.
With reference to embodiment 1, product microballoon 1g manufactured in the present embodiment is taken, loads 50 with slurry method under 1450psi pressure
In × 2.1mm stainless steel chromatographic column.Then by the post on Waters high performance liquid chromatographs (e2695), with
0.05mol/L sodium dihydrogen phosphate+0.1mol/L sodium acetate+0.1mol/L sodium chloride is equilibrium liquid, 0.05mol/L glycine, PH
=3.0 be eluent.Chromatographiccondition and process see the table below.
As shown in Figure 3, the fast of antibody class material can be realized to test result by showing the protein A affinity chromatography medium of the present invention
Fast separation detection.
The protein A affinity chromatography medium of the present invention is used as antibody and Fc fusion proteins isolate and purify medium, and carrying capacity is high, can be big
Amplitude improves flow velocity, and disengaging time is short, good separating effect, and dress post is reproducible, and high mechanical strength, cost is cheap, is suitable for
The quick analysis of antibody class and Fc fusion proteins.
Above-described is only the preferred embodiment of the present invention, it is noted that for one of ordinary skill in the art
For, without departing from the concept of the premise of the invention, various modifications and improvements can be made, these belong to the present invention
Protection domain.
Claims (10)
1. a kind of application of protein A affinity chromatography medium, it is characterised in that the protein A affinity chromatography medium is situated between as chromatography
Matter is applied in the isolating and purifying of antibody and Fc fusion proteins；The protein A affinity chromatography medium is with the poly- of vinyl-containing monomers
Compound microballoon is matrix, is obtained after the modification of hydrophilic resin dendritic macromolecules, activation, coupling protein A aglucons and sealing.
2. the application of protein A affinity chromatography medium as claimed in claim 1, it is characterised in that the protein A affinity chromatography is situated between
Matter is porous microsphere medium.
3. the application of protein A affinity chromatography medium as claimed in claim 1, it is characterised in that the hydrophilic resin is dendritic big
Molecular modification is that hydrophilic resin dendritic macromolecules are grafted on the polymer microballoon surface functional groups, and the hydrophilic resin is dendritic
Macromolecular includes but is not limited to hyperbranched polyethylene alcohol or polyglycereol class macromolecular.
4. the application of protein A affinity chromatography medium as claimed in claim 1, it is characterised in that the activation is described poly-
Compound microsphere surface connects functional group, and the functional group includes but is not limited to epoxy, amino, carboxyl class functional group.
5. the application of protein A affinity chromatography medium as claimed in claim 1, it is characterised in that the coupling protein A aglucons,
For by the surface functional groups after albumin A ligand cou to polymer microballoon activation.
6. the application of protein A affinity chromatography medium as claimed in claim 1, it is characterised in that the sealing, which refers to utilize, to be contained
The active function group on the small molecule of hydroxyl, sulfydryl or amino and the polymer microballoon surface after coupling protein A aglucons carries out anti-
Should, eliminate unreacted active function group.
7. the application of protein A affinity chromatography medium as claimed in claim 1, it is characterised in that described as matrix to contain second
The polymer microballoon of alkenyl monomer is uniform particle diameter, porose porous mono-dispersion microsphere.
8. the application of protein A affinity chromatography medium as claimed in claim 7, it is characterised in that the vinyl-containing monomers bag
Containing at least one mono-vinyl monomer, or include at least one multi-vinyl monomer.
9. the application of protein A affinity chromatography medium as claimed in claim 7, it is characterised in that the vinyl-containing monomers
The diameter range of polymer microballoon is 5~100 μm；The pore diameter range of the polymer microballoon of the vinyl-containing monomers be 80~
120nm。
10. the application of protein A affinity chromatography medium as claimed in claim 1, it is characterised in that the protein A affinity chromatography
Medium is applied to antibody and when isolating and purifying of Fc fusion proteins as chromatography media, with 20mM PBS+150mM NaCl,
The buffer solutions such as pH7.0-pH8.0 or 50mM sodium dihydrogen phosphate+100mMNaAc+150mM NaCl, pH7.0-pH8.0 are as balance
Phase, with buffer solutions such as 50mM Gly, pH3.0-pH4.0 as elution phase.
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Cited By (5)
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| CN108905990A (en) * | 2018-05-25 | 2018-11-30 | 江苏珐玛赛谱生物科技有限公司 | A kind of mutain A（Protein A）Affinity chromatography medium |
| CN109174022A (en) * | 2018-08-22 | 2019-01-11 | 武汉瑞法医疗器械有限公司 | A kind of process for fixation of blood purification adsorbent material |
| CN112341663A (en) * | 2020-10-28 | 2021-02-09 | 苏州纳微科技股份有限公司 | ProteinA affinity chromatography medium of PMMA matrix and preparation method and application thereof |
| CN114437204A (en) * | 2020-10-30 | 2022-05-06 | 苏州盛迪亚生物医药有限公司 | Method for purifying antibody or Fc fusion protein |
| CN116836245A (en) * | 2023-06-01 | 2023-10-03 | 苏州华诺生物科技有限公司 | Recombinant protein synthesized based on characteristic algorithm control and application thereof |
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| CN114437204A (en) * | 2020-10-30 | 2022-05-06 | 苏州盛迪亚生物医药有限公司 | Method for purifying antibody or Fc fusion protein |
| CN116836245A (en) * | 2023-06-01 | 2023-10-03 | 苏州华诺生物科技有限公司 | Recombinant protein synthesized based on characteristic algorithm control and application thereof |
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