WO1997026930A1 - Adsorbant pour immunoglobulines et complexes de celles-ci, procede et dispositif d'adsorption - Google Patents
Adsorbant pour immunoglobulines et complexes de celles-ci, procede et dispositif d'adsorption Download PDFInfo
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- WO1997026930A1 WO1997026930A1 PCT/JP1997/000161 JP9700161W WO9726930A1 WO 1997026930 A1 WO1997026930 A1 WO 1997026930A1 JP 9700161 W JP9700161 W JP 9700161W WO 9726930 A1 WO9726930 A1 WO 9726930A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
- C07K17/02—Peptides being immobilised on, or in, an organic carrier
-
- 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
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
- B01J20/3204—Inorganic carriers, supports or substrates
-
- 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
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
- B01J20/3206—Organic carriers, supports or substrates
- B01J20/3208—Polymeric carriers, supports or substrates
- B01J20/321—Polymeric carriers, supports or substrates consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
-
- 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
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
- B01J20/3206—Organic carriers, supports or substrates
- B01J20/3208—Polymeric carriers, supports or substrates
- B01J20/3212—Polymeric carriers, supports or substrates consisting of a polymer obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
-
- 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
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3214—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the method for obtaining this coating or impregnating
- B01J20/3217—Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond
- B01J20/3219—Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond involving a particular spacer or linking group, e.g. for attaching an active group
-
- 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
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3268—Macromolecular compounds
- B01J20/3272—Polymers obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
- B01J20/3274—Proteins, nucleic acids, polysaccharides, antibodies or antigens
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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
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3268—Macromolecular compounds
- B01J20/328—Polymers on the carrier being further modified
- B01J20/3282—Crosslinked polymers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3679—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
- A61M2202/0415—Plasma
- A61M2202/0417—Immunoglobulin
Definitions
- the present invention relates to an adsorbent and an adsorption device for adsorbing immunoglobulin and Z or an immunoglobulin complex, and a method for adsorbing and removing immunoglobulin and / or an immunoglobulin complex.
- an immunoadsorbent in which protein A having binding properties to immunoglobulin is immobilized on a silylation matrix Japanese Patent Application Laid-Open No. 62-242628
- adsorbent for immunoglobulin and / or immunoglobulin complex in which a hydrophobic compound is immobilized on an insoluble carrier JP-A-57-122875
- the adsorbents that have been tried so far, for example, the protein A adsorbent described above, have a functional group Protein A derived from Staphylococcus aureus with a molecular weight of about 420,000 daltons
- adsorbents for adsorbing immunoglobulin and immunoglobulin complex or immunoglobulin complex include the above-mentioned pathogenic immunoglobulin from the viewpoints of safety, stability, adsorption specificity, adsorption capacity and the like.
- I * which is not suitable for use in treating diseases caused by the presence of purines and / or immunoglobulin complexes in body fluids.
- An object of the present invention is to provide high adsorption specificity for immunoglobulin and immunoglobulin or immunoglobulin complex, and extremely low decrease in adsorption characteristics during sterilization or storage, high stability and high safety.
- An object of the present invention is to provide an adsorbent, an adsorbent S using the adsorbent, and a method for adsorbing and removing immunoglobulin and immunoglobulin or immunoglobulin complex.
- the present inventors have proposed (1) various proteins known as immunoglobulin-binding proteins such as protein A, protein G, protein H, protein, and rheumatoid factor (Naoyuki Tsuchiya, Clinical Immunity, Vol. 23, & 96- 903 (1991); P. Akesson et al., Mol. Immunol., Vol. 27, 523-531 (1990); and Bjorck, J. Immunol., 1194-1197 (1988 ⁇ )) Has very low adsorption specificity for immunoglobulin and / or immunoglobulin complex.
- Peptides having amino acid residues of about several tens or less are heterologous. The antigenicity to the living body is extremely low as compared with the natural macromolecular protein of (3).
- Protein G is one of the immunoglobulin-binding proteins and is a protein with a molecular weight of about 50,000 daltons present in the bacterial cell wall of Streptococcus ⁇ .
- the cDNA has already been cloned, and from the amino acid sequence deduced from this cDNA, protein G is composed of 448 amino acid residues, and there are several similar repetitive amino acid sequences within the sequence. However, it has been speculated that this repetitive amino acid sequence E is a binding domain for albumin and immunoglobulin. See, for example, SE Fahnesyook et al., J. BacterioL, Vol. 167, pp. 870-880 (1986); U. Sjobring et al., J. Biol, Chem., Vol. 266, pp. 399-405 (1991). That.
- the present inventors also examined the sterilization stability of 7-line sterilization by binding one of these peptides, C3 peptide, to a carrier. Was not enough. Therefore, various studies were carried out by sequentially modifying any amino acid of this C3 peptide into another amino acid using genetic engineering techniques. As a result, it has high t, affinity for immunoglobulin and / or immunoglobulin complex, and its peptide ligand adsorption performance even after X-ray sterilization
- the adsorbent of the present invention for adsorbing the immunoglobulin and / or the immunoglobulin complex has a peptide in which a peptide capable of adsorbing the immunoglobulin and / or the immunoglobulin complex is immobilized on a water-insoluble carrier. It has one or two amino acid sequences selected from the amino acid sequences shown in column E of the sequence table in column E.
- the adsorbent for adsorbing the immunoglobulin and the immunoglobulin complex of the present invention is water.
- a peptide derivative is immobilized on an insoluble carrier, and the peptide derivative has at least one of amino acid deletion, substitution, insertion, or addition to the amino acid sequence shown in SEQ ID NO: 1 in the sequence listing. And can adsorb immunoglobulin and immunoglobulin or immunoglobulin complexes.
- At least one property among the heat stability, drug stability, r-ray sterilization stability and autoclave sterilization stability of the peptide derivative is the amino acid sequence described in SEQ ID NO: 1.
- the peptides it has are also excellent.
- the peptide derivative contains the amino acid sequence of SEQ ID NO: 3.
- (Lys) n or (Cys) m is added to the amino and / or carboxyl terminus of the peptide or the derivative thereof, wherein n and m are integers from 0 to 9. is there.
- the above-mentioned peptide or peptide derivative consists of 70 amino acids or less.
- autoclaving has been performed.
- aerial sterilization has been performed.
- the water-insoluble carrier is porous.
- said water-insoluble carrier is hydrophilic.
- the exclusion limit molecular weight of the water-insoluble carrier is 150,000 or more
- the adsorbent of the present invention is used for adsorbing and removing immunoglobulin and immunoglobulin or immunoglobulin complex present in blood, plasma, or other body fluid obtained from a living body.
- the method for adsorptive removal of immunoglobulin and / or immunoglobulin complex of the present invention comprises a step of contacting the adsorbent described in any of the above with a solution containing immunoglobulin and / or immunoglobulin complex.
- An apparatus for adsorbing and removing immunoglobulin and Z or an immunoglobulin complex according to the present invention includes the adsorbent described above in a container having an inlet and an outlet for a solution, and then moving the adsorbent out of the container. Outflow prevention means is provided.
- the solution containing the immunoglobulin and Z or the immunoglobulin complex is blood, plasma, or other body fluid obtained from a living body.
- FIG. 1 is a schematic diagram of a plasmid pUCNTMK3P47 for expressing a JIK3P47 peptide.
- DM encoding MK3P47 peptide inserted between Ndel and Hindlll of pUCNTMK3P47 is described in each example. It replaces other peptides with DM which encodes.
- FIG. 2 shows denaturation curves of MG56 and M3G56 MK3P47 peptides by guanidine hydrochloride.
- FIG. 3 shows a denaturation curve of the MK3P47, MP47K3, MP47, and MP47C peptides with guanidine hydrochloride.
- FIG. 4 shows an excess heat capacity curve in thermal denaturation of MK3G56 peptide by DASM-4.
- FIG. 5 shows the excess heat capacity curve in the thermal denaturation of IK3P47 peptide (by DASM-4).
- FIG. 6 shows the adsorption of the immunoglobulin and the immunoglobulin complex of the present invention.
- Figure 7 is a graph showing the results of examining the relationship between flow velocity and pressure loss using three types of gels. Best form gland for carrying out the invention
- amino acid residues are described by the following abbreviations: Ala; L-alanine residue, Asp; L-aspartic acid residue, Asri; L-asparagine residue, Cys; L cysteine residue Group, Gin; L-glutamine residue, Glu; L-glutamic acid residue, Gly; L-glycine residue, lie; L-isoleucine residue, Leu; L-mouth isine residue, Lys; L-lysine residue Phe; L-phenylalanine residue; Thr; L-threonine residue; Trp; L-tributophane residue; Tyr; L-tyrosine residue; Val;
- N-terminus amino terminus
- C-terminus carboxyl terminus
- a peptide derivative refers to a peptide containing at least one of amino acid deletion, substitution, insertion, or addition in the amino acid sequence described in SEQ ID NO: 1 in the sequence listing.
- thermostability is referred to in terms of the heat denaturation temperature of the peptide derivative.
- “Excellent in thermostability” means that the thermal denaturation temperature of the peptide derivative is higher than the thermal denaturation temperature of the peptide consisting of the amino acid of SEQ ID NO: 1.
- the method for measuring the heat denaturation temperature there is a method in which the measurement is performed in an aqueous solution such as physiological saline using an adiabatic differential scanning calorimeter.
- drug stability refers to the rate of denaturation of the peptide after drug treatment relative to the non-drug treated peptide.
- “Excellent drug stability” means that the modification ratio of the peptide derivative is the modification ratio of the peptide consisting of the amino acid of SEQ ID NO: 1.
- Examples of methods for determining the peptide denaturation ratio include: the fluorescence intensity of the peptide measured after treatment at 30 for 10 minutes in an aqueous solution containing an appropriate concentration of guanidine hydrochloride; There is a method of comparing the fluorescence intensity of the peptide with that of the peptide.
- a-ray sterilization means that 7 rays are irradiated from a source containing a radioisotope described in (i) Radiation method in the irradiation method of “sterilization method” of the Japanese Pharmacopoeia Law. By killing microorganisms.
- the y-ray sterilization method there is a method of irradiating each adsorbent in an aqueous solution with a radiation source containing cobalt 60 or the like.
- 7-beam sterilization stability refers to the ratio of the non- ⁇ -sterilized peptide derivative's adsorption capacity to immunoglobulin to the non- ⁇ -sterilized peptide's adsorption capacity to immunoglobulin.
- “Excellent in 7-line sterilization stability” means that the residual ratio of the adsorbing power of the peptide derivative is larger than that of the peptide consisting of the amino acid of SEQ ID NO: 1.
- high-pressure steam sterilization means heating in saturated steam at an appropriate temperature and pressure as described in (iii) High-pressure steam method in “Sterilization method” of the Japanese Pharmacopoeia Law. By killing microorganisms.
- high-pressure steam sterilization method there is a method in which an adsorbent in an aqueous solution is autoclaved at 121 ⁇ for 20 minutes.
- the autoclaving stability refers to the ratio of the adsorbing power of the peptide derivative to immunoglobulin before autoclaving to the adsorbing power of the treated peptide derivative to immunoglobulin.
- Excellent high-pressure steam sterilization stability means that the residual ratio of the adsorbing power of the peptide derivative is ⁇ t compared to the residual ratio of the adsorbing power of the peptide consisting of the amino acid of SEQ ID NO: 1.
- the adsorption functional group peptide used in the adsorbent of the present invention has one or two kinds of amino acid sequences selected from the amino acid sequences described in SEQ ID NO: 1 in the sequence listing, and manipulates this amino acid sequence. They may be contained in return or in combination.
- a peptide selected from the amino acid sequence described in SEQ ID NO: 1 in the Sequence Listing is a protein G described in B. Guss et al., EBO J., Vol. 5, 1567-: 1575 (1986).
- a peptide containing two selected amino acid sequences repeated arbitrarily for example, two C 1 and one C 2, two C 1 and one C 3, one C 2 And two C3, and a peptide containing two C1 and two C3. It may consist essentially of only the amino acid sequence of SEQ ID NO: 1 in the sequence listing, or further contain any amino acid residue or amino acid sequence at the N-terminal and / or C-terminal of this amino acid sequence. It may be.
- the adsorptive functional group peptide derivative used in the adsorbent of the present invention is obtained by adding at least one of amino acid deletion, substitution, insertion, and no or addition to the amino acid sequence shown in SEQ ID NO: 1 in the sequence listing.
- peptide having at least one amino acid sequence may be composed of only one amino acid sequence or may be composed of a combination of two or more amino acid sequences.
- any amino acid residue or amino acid sequence may be present at the N-terminus and the amino or C-terminus of the amino acid sequence.
- Suitable peptide derivatives include, for example, (Lys) n or (Cys) m at the N-terminus and / or C-terminus with respect to at least one amino acid sequence selected from the amino acid sequences described in SEQ ID NO: 3 in the sequence listing. (Where n and m are integers from 0 to 9). In particular, those having (Cys) m at the C-terminus are more preferable.
- Such peptide derivatives may have the ability to adsorb immunoglobulin and / or immunoglobulin complexes in body fluids, and more preferably, after autoclaving, heat treatment, drug treatment, or 7-line sterilization. It has an excellent adsorption capacity as compared to the peptide of SEQ ID NO: 1.
- a combination of the above peptide and peptide derivative can be used for the adsorbent of the present invention.
- the peptide or peptide derivative used in the adsorbent of the present invention is prepared by a commonly used peptide synthesis method, for example, a liquid phase synthesis method such as a solid phase synthesis method, a stepwise extension method, and a fragment condensation method. Or a peptide or peptide derivative
- g Replacement form (Rule 2 May be ligated to a vector and introduced into a host to produce a recombinant peptide or a recombinant peptide derivative by a genetic engineering method.
- a peptide or peptide derivative can be synthesized as follows. (1) An amino acid corresponding to the C-terminal of the peptide to be synthesized is bound to a support insoluble in an organic solvent.
- the peptide chain is cleaved from the support and the protecting group is removed.
- Hydrogen fluoride is often used for this purpose, but trifluoroacetic acid (TFA) is appropriate from the viewpoints of safety and ease of handling.
- TFA trifluoroacetic acid
- the cleaved peptide is reacted in 95% TFA containing 1,2-ethanedithiol: anisole (1: 3) to remove the protecting group and cleave from the support to recover the crude peptide. .
- This is precipitated with ethyl ether to obtain a crude purified peptide.
- the crude peptide obtained above can be purified by various methods known to those skilled in the art.
- HPLC high performance liquid chromatography
- reversed phase column a reversed phase column
- the fraction corresponding to the obtained chromatographic peak is collected and freeze-dried.
- the synthesized peptide is confirmed by primary sequence analysis using an amino acid sequencer, amino acid composition analysis, and the like.
- the DNA encoding the amino acid sequence of the target peptide is used.
- Replacement form (Rule 26) Is synthesized and introduced into a phage or plasmid vector. This is inserted into an appropriate microorganism (for example, Escherichia coli) to select and obtain a transformant, and cultured by a known method. It is within the skill of a person skilled in the art to purify and isolate the desired peptide from the culture supernatant or cells. In addition, yeast and Bacillus subtilis can be easily used as a host if an appropriate vector is selected.
- an appropriate microorganism for example, Escherichia coli
- yeast and Bacillus subtilis can be easily used as a host if an appropriate vector is selected.
- the water-insoluble carrier used as the support of the adsorbent of the present invention is not particularly limited.
- the water-insoluble carrier used in the present invention include inorganic carriers such as glass beads and silica gel, synthetic polymers such as cross-linked polyvinyl alcohol, cross-linked polyacrylate, cross-linked polyacrylamide, cross-linked polystyrene, and crystalline cell openings.
- hydrophilic carrier refers to a carrier having a contact angle between a flat plate and water of 60 ° or less when a compound constituting the support is formed into a flat plate.
- examples of such carriers include polysaccharides such as cellulose, chitosan, sepharose, and dextran, polyvinyl alcohol, saponified ethylene-vinyl acetate copolymer, polyacrylamide, polyacrylic acid, polymethacrylic acid, and polymethyl methacrylate.
- porous cellulose gel is
- the gel is composed of cellulose, the gel is hydrophilic, has a large number of hydroxyl groups available for ligand binding, and has low non-specific adsorption;
- the present invention is not limited to only these carriers.
- the above carriers may be used alone, or two or more of them may be used in combination.
- the first required property of the water-insoluble carrier used in the present invention is to have a large number of pores of an appropriate size, that is, to be porous.
- the immunoglobulin and Z or the immunoglobulin complex to which the adsorbent of the present invention is adsorbed have molecular weights ranging from 160,000 to 1,000,000 and cannot be specified. Therefore, in order to adsorb this protein efficiently, it is preferable that immunoglobulin and Z or the immunoglobulin complex can enter the pores with a certain large probability, but it is preferable that entry of other proteins does not occur as much as possible.
- the average pore size of the porous carrier is preferably from 300 to 10,000 angstroms.
- the mercury intrusion method is most often used for measuring the pore diameter of the pores, but this method cannot be applied to the porous water-insoluble carrier used in the present invention in many cases. Therefore, it is appropriate to use the exclusion limit molecular weight as a standard of the pore diameter.
- the exclusion limit molecular weight is the molecular weight of the molecule with the smallest molecular weight among the molecules that cannot enter (exclude) pores in gel permeation chromatography (Hatano Hatano, Toshihiko Hanai, Experimental High Performance Liquid) Chromatograph, Dojin, 1988). Exclusion limit molecular weights are generally for globular proteins,
- the pore size of pores suitable for adsorption of immunoglobulin and / or immunoglobulin complex has an exclusion limit molecular weight of 150,000 or more. That is, when a carrier having an exclusion limit molecular weight of less than 150,000 is used, the amount of adsorbed and removed immunoglobulin and immunoglobulin or immunoglobulin complex is small, and its practicality is reduced. Therefore, the preferred exclusion limit molecular weight of the carrier used in the present invention is 150,000 or more.
- the exclusion limit molecular weight exceeds 5 million, there is no particular problem as long as plasma or serum is used as a body fluid, but macromolecules that do not interact with the ligand physically block the binding site of the ligand, In effect, it tends to lower the amount of effective ligand.
- the exclusion limit molecular weight exceeds 5,000,000, the proportion of platelet adhesion tends to increase, and the adsorbent of the present invention is used as a DHP (direct blood port flow) type blood purification system. When used in, sufficient performance cannot always be exhibited.
- the exclusion limit molecular weight is 5,000,000 or less, there is no particular problem in any usage, and the exclusion limit molecular weight is desirably 5,000,000 or less in order to use the adsorbent of the present invention for various applications. Therefore, the more preferred exclusion limit molecular weight of the carrier used in the present invention is from 10,000 to 5,000,000.
- the porous structure of the carrier considering the adsorption capacity per unit volume of the adsorbent, total porosity is preferable to surface porosity, the pore volume is 20% or more, and the specific surface area is 3 mVg or more. It is preferred that The carrier may be in any shape such as a bead, a fiber, a membrane (including a hollow fiber), and the like.
- the surface of the carrier has a functional group that can be used for the reaction for immobilizing the ligand, which is advantageous for immobilizing the ligand.
- these functional groups include a hydroxyl group, an amino group, an aldehyde group, a carboxyl group, a thiol group, a silanol group, an amide group, an epoxy group, a halogen group, a succinylimide group, and an acid anhydride group.
- the carrier used in the present invention either a hard carrier or a soft carrier can be used.
- the carrier used in the present invention is more preferably a rigid carrier.
- the term “hard carrier” refers to, for example, in the case of a granular gel, when the gel is uniformly filled in a glass cylindrical column (inner diameter 9 min, column length 150 band) under the following conditions, and an aqueous fluid is allowed to flow. It means that the relationship between the pressure loss P and the flow rate has a linear relationship up to a pressure of 0.3 kg / cm 2 .
- a glass cylindrical column (with an inner diameter of 15 m
- ⁇ indicates Toyopearl HW65.room, Cell mouth fine GC700m, and ⁇ indicates Biogel-A5m.
- the adsorption efficiency is improved by reducing the steric hindrance of the peptide or the peptide derivative, and in order to suppress non-specific adsorption, It is more preferable to immobilize via a hydrophilic spacer.
- a hydrophilic spacer for example, it is preferable to use a polyalkylene oxide derivative in which both terminals are substituted with a carboxyl group, an amino group, an aldehyde group, an epoxy group, or the like.
- the peptide or peptide derivative introduced into the above-mentioned carrier and the organic compound used as a spacer are relatively stable and low molecular weight substances, for example, proteins such as enzymes and antibodies.
- the immobilization reaction conditions are less restrictive than in the case of immobilization. Therefore, the immobilization method is not particularly limited. However, considering that the adsorbent can be used for extracorporeal circulation treatment and blood purification, it is necessary to apply an immobilization method in which peptides are not easily removed from the carrier during sterilization or treatment of the adsorbent. More preferred.
- Typical methods include (1) taking out a body fluid, storing it in a bag or the like, mixing it with an adsorbent to adsorb and remove immunoglobulins and / or immunoglobulin complexes, and then filtering out the adsorbent for immunology.
- a method for obtaining a body fluid from which glopurine immunoglobulin and no or a complex have been removed (2) a container equipped with a filter having a body fluid inlet and an outlet, and a filter through which the body fluid passes but the adsorbent does not pass.
- the adsorbent of the present invention is suitable for this method because it can remove the epiglobulin glopurine complex.
- the container 7 shown in FIG. 6 includes a solution inlet or outlet 1, a solution outlet or inlet 2, the immunoglobulin and immunoglobulin or immunoglobulin complex adsorbent 3 of the present invention, and the components contained in the solution and the solution. It has adsorbent outflow prevention means 4 and 5 and a column 6 that can pass but cannot pass immunoglobulin and / or immunoglobulin complex adsorbent.
- the shape and material of this container are not particularly limited, but preferably, for example, a cylindrical container having a capacity of about 20 to 400 nil and a diameter of about 2 to 10 cm is used.
- Amino acids are Fmoc-L-Ala, Fmoc-L-Asn (Trt), Fioc-L-Asp (OtBu), Fmoc-L-Cys (Trt), Fmoc-L-Gln (Trt)> Fmoc-L-Glu (0tBu), Fraoc-L-Gly, Fmoc-L-Ile, Fraoc-le-Leu, Fmoc-L-Lys (Boc) Fmoc-i Phe, Fraoc-le Thr (tBu), Fsi oc-L-Trp, Fmoc -Tyr (tBu) and Fnoc-L-Val were used, and the amount used was about 5-fold molar (0.5 raraol) with respect to the substrate in the vial.
- Trt, 0tBu, Boc, and tBu represent a trityl group, a tertiary butyl ester, a tertiary butyloxycarbonyl group, and an o-tertiary butyl group, respectively.
- the obtained support was washed sequentially with tert-amyl alcohol, acetic acid, and getyl ether on a 3G-3 pore glass filter, and then dried under vacuum. Thus, a dried support was obtained.
- 20 ml of TFA, 1,2-ethanedithiol 2601, and anisol 7 ⁇ 0 ⁇ l were added to the obtained support 1, and the mixture was stirred at room temperature for 1.5 hours. Thereafter, the mixture was separated from the support with a 3G-3 pore glass filter, and the mixture was concentrated under reduced pressure at 35.
- the adsorbent was produced as follows by immobilizing the above peptide on porous sepharose.
- Thiopropyl Sepharose 6B (Pharmacia LKB) was used as Sepharose.
- 50 ml of distilled water was added to 50 mg of thiopropyl sepharose 6B, and the mixture was left at room temperature for 5 minutes to swell the resin. Then, distilled water was removed and replaced with a 0.1 M Tris-HCl ( ⁇ 7.5) coupling buffer containing 0.5 M NaCl.
- This peptide-immobilized adsorbent was sufficiently washed with lOmM phosphate buffer (pH 7.2) containing 150 mM NaCl, and subjected to suction filtration to obtain a target peptide-sepharose adsorbent.
- the adsorption performance of a heat-aggregated complex (a model of an immunocomplex) in blood was evaluated using serum of a healthy person.
- the adsorbent 501 (1 volume) was collected in a vial, and 20 g of a heat-aggregated complex (see Makino Masahiko et al., Clinical Immunity, Volume 18, pages 111 to 119, (1986)) was obtained.
- the serum of 150 1 (3 volumes) containing / mi was added and incubated with shaking at 37 ⁇ for 2 hours.
- untreated support 501 (1 volume) was added with healthy human serum 1501 (3 volumes) containing 20 // g / ml of the heat-aggregated complex, and 37 ⁇ Incubate with shaking for 2 hours. Thereafter, the suspension was centrifuged at 5, ⁇ for 1 minute, and the amount of complex in the supernatant was measured using an in vitro diagnostic kit “Frelyzer Clq-CIC” manufactured by Fujirebio Co., Ltd. .
- Table 1 shows the results.
- the adsorption rate of the heat-aggregated complex was shown as an adsorption rate (%) calculated from the value of the control serum using the following formula.
- Adsorbability of immunoglobulins (IgG, IgA, Ig) was quantified using an in vitro diagnostic drug “N-Atsusei TIA” kit sold by Nitto Bo.
- Table 2 shows the results.
- IgG subclass IgG ,, I gG 2, IgG 3, IgG, and quantitated by measuring kit according immunodiffusion (SRID) method, which is available from the binding site Corporation. The results are shown in Table 3.
- Adsorption removal rate (%) ⁇ 1 x 100 complex concentration in control solution
- the adsorbent was evaluated for its ability to adsorb circulating immune complexes in blood, using the sera of rheumatic patients. Collect the above adsorbent in a 50 1 (1 volume) vial,
- Serum 1501 (3 volumes) of gusset patients was added and incubated at 37 with shaking for 2 hours.
- rheumatoid patient serum 150/1 (3 volumes) was added to the untreated support 50/1 (1 volume) and incubated at 37 with shaking for 2 hours. Thereafter, the suspension was centrifuged at 5,000 rpm for 1 minute, and the amount of the complex in the supernatant was measured by the method described in Test 1. The results are as shown in Table 4, and are shown as the adsorption rate (%) calculated from the value of the control serum.
- the immunoglobulin (IgG, IgA, IgM) adsorption capacity was also determined using the above method. Table 5 shows the results. Table 4
- the adsorbent 501 produced in Example 1 was suspended in 1 ml of 10 mM phosphate buffer (pH 7.2) containing 150 fflM NaCl and stabilized by high-pressure steam sterilization, and was suspended in an autoclave sterilizer under pressure under a pressure of 12 1 ⁇ . Heat treated for minutes. Evaluation of adsorptivity of autoclaved adsorbent
- Example 2 Using the adsorbent obtained in Example 1 and the above adsorbent subjected to autoclave sterilization, serum was subjected to suspension treatment in the same manner as in Example 2, and the complex and immunity in the resulting supernatant were obtained. The degree of globulin was measured, and the adsorption removal rate was calculated. The results are shown in Tables 6 and 7.
- DNA encoding the MK3P47 peptide described in SEQ ID NO: 4 was synthesized.
- This DM is designed so that it can be ligated using restriction enzyme sites (Ndel on the 5 ′ side and Hindlll on the 3 ′ side) of the pUCNT vector (Japanese Patent Laid-Open Publication No. Hei 4-212692).
- the DNA having the sequence was ligated and pUCNT vector thus cleaved restriction enzyme digestion Ndel and Hindl ll (Takara Shuzo Co., Ltd.), according to instructions by using Takara Shuzo DNA Ligation Kit Ver. 2, P UCNTMK3P47 vector ( Figure 1) was fabricated.
- pUCNTMK3P47 vector DNA was introduced into E. coli HB101 strain (Funakoshi), and transformants were selected using the resistance to the antibiotic ampicillin as an index. Plasmid DNA was extracted from this transformant by a conventional method, and the sequence was determined to confirm that the pUCNTMK3P47 vector had the designed DM sequence.
- shake this transformant in 6 L of L-broth 5 g / L NaC 10 g / L bactotrypsin, 5 g / L yeast extract
- the cells were cultured, and the cells were collected by centrifugation (6000 rpm, 4 minutes using a Hitachi RPR9-2 rotor for 4 minutes).
- the pellet obtained here was suspended in 300 ml of TE buffer (20 mM Tris-HCK ImM EDTA: pH 7.5) and subjected to ultrasonic crushing (3 times on ice using BRANSON250 for 6 minutes). Subsequently, centrifugation (15000 rpm, 20 minutes with 4 using a Hitachi RPR16 rotor) was performed, and the supernatant was recovered. The supernatant obtained here was subjected to a heat treatment at 70 ° C for 10 minutes, and further centrifuged (15000 rpm, 4 using a Hitachi RPR16 rotor for 20 minutes) to collect 300 nl of the supernatant. The MK3P47 peptide was purified from the resulting supernatant by HPLC.
- Example 6 Using the same method as in Example 4, a DM of SEQ ID NO: 7 encoding the MP47K3 peptide described in SEQ ID NO: 6 was synthesized, and this DM and pUCNT vector were used to prepare a pUCNTMP47K3 vector. did. Next, Escherichia coli was transformed, the obtained transformant was cultured (6 L), and the desired MP47K3 peptide was purified to obtain 600 mg of a high-purity standard.
- SEQ ID NO: 7 encoding the MP47K3 peptide described in SEQ ID NO: 6 was synthesized, and this DM and pUCNT vector were used to prepare a pUCNTMP47K3 vector. did.
- Escherichia coli was transformed, the obtained transformant was cultured (6 L), and the desired MP47K3 peptide was purified to obtain 600 mg of a high-purity standard.
- Example 6 Example 6
- DNA of SEQ ID NO: 13 encoding the MK3G56 peptide described in SEQ ID NO: 12 was synthesized, and a pUCNTMK3G56 vector was prepared using this DNA and one pUCNT vector.
- Escherichia coli was transformed, the resulting transformant was cultured (6 L), and the desired MK3G56 peptide was purified to obtain 1.0 g of a high-purity standard.
- Example 10 Using the same method as in Example 4, the DNA of SEQ ID NO: 15 encoding the MK3-7M peptide described in SEQ ID NO: 14 was synthesized, and the PUCNTMK3-7M vector was synthesized using this DNA and the pUCNT vector. Was prepared. Then, Escherichia coli was transformed, and the obtained transformant was cultured (6), and the desired MK3-7M peptide was purified to obtain 800 mg of a high-purity standard.
- SEQ ID NO: 15 encoding the MK3-7M peptide described in SEQ ID NO: 14 was synthesized, and the PUCNTMK3-7M vector was synthesized using this DNA and the pUCNT vector.
- Escherichia coli was transformed, and the obtained transformant was cultured (6), and the desired MK3-7M peptide was purified to obtain 800 mg of a high-purity standard.
- Example 10 Example 10
- DNA of SEQ ID NO: 17 encoding the MG56 peptide described in SEQ ID NO: 16 was synthesized, and a pUCNTMG56 vector was prepared using this DNA and the pUCNT vector. did.
- Escherichia coli was transformed, the resulting transformant was cultured (6 L), and the desired MG56 peptide was purified to obtain 400 mg of a high-purity standard.
- a 1 mg / ml aqueous solution of each of the peptides obtained in Examples 4 to 8 and Example 10 was diluted to lO g / ml with a 0 to 8 M guanidine hydrochloride solution (30 te) to obtain a F-2000 manufactured by Hitachi, Ltd.
- the fluorescence intensity at ⁇ 340 ⁇ ( ⁇ 278 ⁇ excitation) was measured with a shape spectrofluorometer. The results are shown in Figs.
- the vertical axis plots fluorescence intensity (%), and the horizontal axis plots guanidine concentration 00.
- ⁇ indicates MG56 peptide
- ⁇ indicates MK3G56 peptide
- ⁇ indicates HK3P47 peptide.
- ⁇ indicates the ⁇ 3 ⁇ 47 peptide
- ⁇ indicates the ⁇ 47 ⁇ 3 peptide
- ⁇ indicates the ⁇ 47 ⁇ peptide
- X indicates the MP47C peptide.
- the epoxy-activated gel was suck-dried (aspirated on a glass filter G3 for 15 minutes with an aspirator), and the epoxy-activated gel 18 was dissolved in! 110.0 borate buffer 2.71111 (0.1M Sodium acid, 0.1M sodium chloride aqueous solution (10 ml), 0.1N sodium hydroxide aqueous solution (8.74 ml), water was added to make 20 ral), and lOrag's MK3P47 peptide (SEQ ID NO: 4) was added. The reaction was carried out with shaking at 40 for 60 hours.
- a calibration curve was prepared, and the peptide concentration before and after the reaction and the amount immobilized were calculated. As a result, the reaction yield of the peptides of the gel is 34%, the immobilized amount was found to be 2. lmg / ml gel 0
- the concentration of IgG is measured using the in vitro diagnostic drug “N-Atsusei TIA” assay kit sold by Nitto Ubo, Inc.
- the IC port is measured by the enzyme immunoassay Flereiza Clq-CIC, Fujirebio Co., Ltd. ) The manufacturer's manual was followed. The results are shown in Table 8,
- An adsorbent GCL2000aiMK3G56 and an adsorbent 7 GCL2000raMK3G56 were obtained in the same manner as in Example 13, except that the MK3G56 peptide obtained in Example 8 was used.
- the reaction yield of the peptide to the gel was 40%, and the immobilization amount was 2.5 ing / ml gel.
- the IgG adsorption rate and IC adsorption rate of the obtained GCL2000mliK3G56 or 7 GCL2000mMK3G56 are as shown in Table 8.
- GCL2000mMK3G56 which uses recombinant MK3G56 peptide as a carrier in which Lys-Lys-Lys- is added to the C-terminal peptide as a functional group immobilized on the carrier, showed relatively high adsorption rates for IgG and IC. However, most of the adsorption capacity was lost by the a-line sterilization treatment.
- the IgG adsorption rate and 1C adsorption rate of the obtained GCL2000mMP47K3 or yGCL2000mMP47K3 are as shown in Table 8.
- the GCL2000roMP47K3 which uses the recombinant peptide MP 47K3 as a ligand, in which the 47th Asp of the C3 peptide is converted to Pro, and -Lys-Lys-Lys is added to the C-terminal side as a functional group immobilized on the carrier 7-line sterilization stability in IC and IgG adsorption capacity is greater than in the case of using MK3G56 peptide as an example carrier.
- GC700D1 a cellulosic porous hard gel (manufactured by Chisso Corporation, molecular weight cutoff of globular proteins of 400,000)
- 21 ml of epichlorohydrin was added, and the mixture was reacted for 1 hour while stirring at 40. After the completion of the reaction, the resultant was sufficiently washed with water to obtain an epoxy-activated gel.
- An adsorbent GC700mMP47 and an adsorbent yGC700mMP47 were obtained in the same manner as in Example 13, except that the obtained epoxy-activated gel and the MP47 peptide obtained in Example 6 were used.
- the reaction yield of the peptide was 42%, and the amount immobilized was 2.6 mg / ml gel.
- the IgG adsorption rate and IC adsorption rate of the obtained GC700mMP47 or 7GC700mMP47 are as shown in Table 8.
- GC700mMP47 which uses as a ligand the recombinant peptide MP47 obtained by converting the 47th Asp of the C3 peptide to Pro, uses the recombinant C3 peptide (MG56) described in Example 18 as a ligand. Compared with, the 7-line sterilization stability in IC and IgG adsorption capacity was greatly improved.
- Example 17
- An adsorbent GC700mMG56 and an adsorbent yGC700nMG56 were obtained in the same manner as in Example 13, except that the epoxy activated gel obtained in Example 16 and the MG56 peptide obtained in Example 10 were used.
- the reaction yield of the peptide on the gel was 6496, and the amount of immobilization was 4. Omg / ml gel.
- GC700mMG56 which uses the recombinant C3 peptide MG56 as a ligand, showed a relatively high adsorption rate for IC and IgG, but lost most of its adsorption ability by 7-line sterilization.
- Example 19
- GC700nMP47 whose ligand is a recombinant peptide MP47C in which the 47th Asp of the C3 peptide is replaced by Pro and a functional group immobilized on the carrier -Cys is attached to the C-terminus, is a recombinant C-peptide.
- the adsorbent GC700m obtained in Example 18 using the peptide (MG56) as a ligand The GC700m MG56 completely lost the IgG adsorption ability after autoclaving, whereas the autoclaving still showed a very small amount of 50%, even after autoclaving, of IgG and IgG. The adsorption rate was shown. Table 9
- the adsorbent on which the peptide of the present invention is immobilized By using the adsorbent on which the peptide of the present invention is immobilized, immunoglobulin and immunoglobulin complex can be selectively adsorbed and removed, and IgG 3 not adsorbed by protein A can also be adsorbed and removed. Furthermore, the adsorbent of the present invention is inexpensive, has excellent storage stability represented by thermal stability, can be subjected to autoclave sterilization, and is contained in body fluid even after drug treatment and sterilization. The resulting immunoglobulin and / or immunoglobulin complex can be efficiently adsorbed and removed.
- Xbb is Val or Ile
- Xcc is lie or Leu
- Xdd is Lys or Glu
- Xee is Glu or Ala
- Xif is Ala or Val
- Xgg is Val or Glu.
- Xbb stands for Val or Ile
- Xcc stands for lie or Leu
- Xdd stands for Lys or Glu
- Xee stands for Glu or Ala
- Xfi stands for Ala or Val
- Xgg stands for Val or Glu
- Xhh stands for Lys or Gly.
- Sequence type other nucleic acid synthetic DNA
- Sequence type nucleic acid
- Sequence type nucleic acid
- Sequence type other nucleic acid synthetic DNA
- Sequence type nucleic acid
- Sequence type other nucleic acid synthetic DNA
- Sequence type nucleic acid
- Sequence type nucleic acid
- Sequence type other nucleic acid synthetic DNA
- Type B5 Other nucleic acids Synthetic DNA
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Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97900774A EP0882463B1 (en) | 1996-01-25 | 1997-01-24 | Adsorbent for immunoglobulins and complexes thereof and adsorption device |
US09/117,233 US6133431A (en) | 1996-01-25 | 1997-01-24 | Adsorbent for immunoglobulins and complexes thereof, adsorption method, and adsorption device |
DE69733467T DE69733467T2 (de) | 1996-01-25 | 1997-01-24 | Adsorbtionsvorrichtung und absorbens für immunuglobine und deren komplexe |
KR10-1998-0705760A KR100445644B1 (ko) | 1996-01-25 | 1997-01-24 | 면역글로블린과그의복합체를위한흡착제,흡착방법그리고흡착장치 |
JP52673897A JP3908278B2 (ja) | 1996-01-25 | 1997-01-24 | 免疫グロブリンおよびその複合体の吸着材、吸着方法、および吸着装置 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP8/11281 | 1996-01-25 | ||
JP1128196 | 1996-01-25 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1997026930A1 true WO1997026930A1 (fr) | 1997-07-31 |
Family
ID=11773620
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1997/000161 WO1997026930A1 (fr) | 1996-01-25 | 1997-01-24 | Adsorbant pour immunoglobulines et complexes de celles-ci, procede et dispositif d'adsorption |
Country Status (7)
Country | Link |
---|---|
US (1) | US6133431A (ja) |
EP (1) | EP0882463B1 (ja) |
JP (1) | JP3908278B2 (ja) |
KR (1) | KR100445644B1 (ja) |
CA (1) | CA2244734A1 (ja) |
DE (1) | DE69733467T2 (ja) |
WO (1) | WO1997026930A1 (ja) |
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JP2003088381A (ja) * | 2001-09-18 | 2003-03-25 | Kanegafuchi Chem Ind Co Ltd | 新規ペプチド、生産方法、新規吸着体、吸着器および吸着方法 |
WO2008016221A1 (en) | 2006-06-27 | 2008-02-07 | Korea Research Institute Of Bioscience And Biotechnology | Cysteine-tagged staphylococcal protein g variant |
WO2009044650A1 (ja) * | 2007-10-05 | 2009-04-09 | Kaneka Corporation | 免疫グロブリンおよび/または免疫グロブリン複合体に結合活性を有する、標識されたペプチド、および上記ペプチドを用いた免疫グロブリンの検出方法または測定方法 |
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JP2009118749A (ja) * | 2007-11-12 | 2009-06-04 | National Institute Of Advanced Industrial & Technology | 安定な抗体結合性タンパク質 |
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WO2018180204A1 (ja) | 2017-03-31 | 2018-10-04 | 株式会社カネカ | 安定性改良型免疫グロブリン結合性ペプチド |
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01104273A (ja) * | 1987-07-14 | 1989-04-21 | Terumo Corp | 体液浄化材および体液浄化装置 |
JPH01158970A (ja) * | 1987-09-14 | 1989-06-22 | Terumo Corp | 直接血液潅流用免疫グロブリン吸着材および吸着装置 |
JPH01502076A (ja) * | 1986-02-14 | 1989-07-27 | ファルマシア エルケイビー バイオテクノロジー エイビー | プロテインgをコ−ドするクロ−ン化されたストレプトコッカス遺伝子及びプロテインgを生産するために組み替え微生物を構築するための用途 |
JPH02501985A (ja) * | 1987-11-20 | 1990-07-05 | クリエイティブ・バイオマリキュールズ・インコーポレーテッド | 免疫複合体の選択的除去 |
US5306812A (en) * | 1989-09-08 | 1994-04-26 | The Regents Of The University Of California | Immunoglobulin-binding polypeptides |
JPH06263795A (ja) * | 1992-09-30 | 1994-09-20 | Kuraray Co Ltd | ペプチドおよびこれを担体上に固定化してなる吸着剤 |
JPH0792167A (ja) * | 1993-09-24 | 1995-04-07 | Kinki Univ | IgE吸着材 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4614513A (en) * | 1984-08-13 | 1986-09-30 | Fred Hutchinson Cancer Research Center | Method and apparatus for treatment to remove immunoreactive substances from blood |
DE3664729D1 (en) * | 1985-04-09 | 1989-09-07 | Terumo Corp | Immunoglobulin adsorbent and adsorption apparatus |
SE459503B (sv) * | 1985-05-03 | 1989-07-10 | Excorim Kommanditbolag | Hybrid-dna-molekyl innefattande dna-sekvens som kodar foer protein g samt foerfarande foer framstaellning av protein g |
US5312901A (en) * | 1986-02-14 | 1994-05-17 | Pharmacia Lkb Biotechnology Ab | Cloned streptococcal genes encoding protein G and their use to construct recombinant microorganisms to produce protein G |
US4956296A (en) * | 1987-06-19 | 1990-09-11 | Genex Corporation | Cloned streptococcal genes encoding protein G and their use to construct recombinant microorganisms to produce protein G |
US5084398A (en) * | 1987-11-20 | 1992-01-28 | Creative Biomolecules | Selective removal of immune complexes |
-
1997
- 1997-01-24 CA CA002244734A patent/CA2244734A1/en not_active Abandoned
- 1997-01-24 US US09/117,233 patent/US6133431A/en not_active Expired - Lifetime
- 1997-01-24 DE DE69733467T patent/DE69733467T2/de not_active Expired - Lifetime
- 1997-01-24 WO PCT/JP1997/000161 patent/WO1997026930A1/ja active IP Right Grant
- 1997-01-24 EP EP97900774A patent/EP0882463B1/en not_active Expired - Lifetime
- 1997-01-24 JP JP52673897A patent/JP3908278B2/ja not_active Expired - Fee Related
- 1997-01-24 KR KR10-1998-0705760A patent/KR100445644B1/ko not_active IP Right Cessation
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01502076A (ja) * | 1986-02-14 | 1989-07-27 | ファルマシア エルケイビー バイオテクノロジー エイビー | プロテインgをコ−ドするクロ−ン化されたストレプトコッカス遺伝子及びプロテインgを生産するために組み替え微生物を構築するための用途 |
JPH01104273A (ja) * | 1987-07-14 | 1989-04-21 | Terumo Corp | 体液浄化材および体液浄化装置 |
JPH01158970A (ja) * | 1987-09-14 | 1989-06-22 | Terumo Corp | 直接血液潅流用免疫グロブリン吸着材および吸着装置 |
JPH02501985A (ja) * | 1987-11-20 | 1990-07-05 | クリエイティブ・バイオマリキュールズ・インコーポレーテッド | 免疫複合体の選択的除去 |
US5306812A (en) * | 1989-09-08 | 1994-04-26 | The Regents Of The University Of California | Immunoglobulin-binding polypeptides |
JPH06263795A (ja) * | 1992-09-30 | 1994-09-20 | Kuraray Co Ltd | ペプチドおよびこれを担体上に固定化してなる吸着剤 |
JPH0792167A (ja) * | 1993-09-24 | 1995-04-07 | Kinki Univ | IgE吸着材 |
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WO2008016221A1 (en) | 2006-06-27 | 2008-02-07 | Korea Research Institute Of Bioscience And Biotechnology | Cysteine-tagged staphylococcal protein g variant |
US8541005B2 (en) | 2006-06-27 | 2013-09-24 | Korea Research Institute Of Bioscience And Biotechnology | Cysteine-tagged streptococcal protein G variant |
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WO2016031902A1 (ja) * | 2014-08-28 | 2016-03-03 | 株式会社カネカ | Fab領域含有ペプチド用アフィニティー分離マトリックス |
JPWO2016031902A1 (ja) * | 2014-08-28 | 2017-06-15 | 株式会社カネカ | Fab領域含有ペプチド用アフィニティー分離マトリックス |
WO2018180204A1 (ja) | 2017-03-31 | 2018-10-04 | 株式会社カネカ | 安定性改良型免疫グロブリン結合性ペプチド |
Also Published As
Publication number | Publication date |
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DE69733467D1 (de) | 2005-07-14 |
DE69733467T2 (de) | 2006-03-23 |
KR100445644B1 (ko) | 2005-01-13 |
EP0882463A4 (en) | 2002-01-09 |
KR19990082040A (ko) | 1999-11-15 |
JP3908278B2 (ja) | 2007-04-25 |
US6133431A (en) | 2000-10-17 |
CA2244734A1 (en) | 1997-07-31 |
EP0882463A1 (en) | 1998-12-09 |
EP0882463B1 (en) | 2005-06-08 |
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