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ANTIBODY-BINDING PEPTIDE コモンズ

外国特許コード F180009479
整理番号 2013002533
掲載日 2018年9月18日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2013JP007583
国際公開番号 WO 2014115229
国際出願日 平成25年12月25日(2013.12.25)
国際公開日 平成26年7月31日(2014.7.31)
優先権データ
  • 特願2013-013217 (2013.1.28) JP
発明の名称 (英語) ANTIBODY-BINDING PEPTIDE コモンズ
発明の概要(英語) The present invention relates to a polypeptide which: exhibits binding activity with respect to Fc regions of immunoglobulin G; can be suitably used for the detection, purification, immobilization, or elimination of antibodies, immunoglobulin G, or protein including Fc regions of immunoglobulin G; and comprises an amino acid sequence indicted in any of formulae (1)-(4) below: formula (1) (SEQ ID NO.: 1) Y-D-P-x-T-G-T-W-R-S-x-[IL]; formula (2) (SEQ ID NO.: 10) R-[QRS]-x-x-[GS]-Y-D-P-R-T-G-T-W-R-S-S-I-A-Y-G-G; formula (3) (SEQ ID NO.: 20) G-V-V-R-Q-W-S-G-x-x-x-x-x-x-x-x-R-S-S-I-A-Y-G-G; and formula (4) (SEQ ID NO.: 23) D-A-A-W-H-L-G-E-L-V-W-A-T-Y-Y-D-P-E-T-G-T-W-x-P-D-W-x-x-M (in the formulae, x represents any amino acid residue, and "[ ]" signifies any one of the amino acid residues presented within the "[ ]").
従来技術、競合技術の概要(英語) BACKGROUND ART
Monoclonal antibodies used for therapeutic use, the medicament is a so-called antibody, exceeds 300 billion dollars per year sales is, among the largest magnitude of bio-pharmaceuticals, pharmaceutical industries throughout one of the most rapid growth drives have segment.To date, one of the three full-size 23 and monoclonal antibodies which uses a monoclonal antibody fragment type, already in some of the blockbuster sales year billions of dollars are greater than 10. 1995 Year to 2007 years from the start of the trial pharmaceutical candidate monoclonal antibodies of the 3 - fold or more increases and, continues to extend further from the number of the (non-patent document 1).
Such an antibody in accordance with the increase the growth of the pharmaceutical market, antibody, immunoglobulin or immunoglobulin g of g Fc region containing protein (hereinafter, also referred to herein as an antibody) of molecules with a joining property to create, research and development related to the improvement in performed.This is because, such a molecule, an antibody useful in research and production, especially an antibody pharmaceutical production during affinity chromatography purification step used in the recovery of the huge demand is expected in accordance with the present.In addition, which are widely used for purification purpose the recovery of the antibody are derived from staphylococcal protein A is disadvantageous in terms of stability and manufacturing cost also recognized the reason.The current, and that various molecules that bind to the antibodies and the like have been researched and developed approach (non-patent document 2) but, one of these is the development of antibody-binding peptides.Exemplary of some of such.
Suzuki et al., 7 residues or 12 residues of the linear peptides were presented in M13 phage library using a filamentous bacteriophage, human IgG Fc region of a polypeptide with binding activity to a plurality of identified, the presence or absence of the binding region Fc enzyme linked immunosorbent assay (ELISA) (Patent Document 1) was measured by.They were identified from a plurality of the sequences were made and the consensus sequence was extracted, as well as binding to human IgG, horse, sheep, rabbit, guinea pig, goat, cat, dog, bovine, porcine, from mice IgG Fc ELISA of the binding activity was confirmed by region.
DeLano et al., circularized by disulfide bonds Xaai Cys Xaaj Cys Xaak (in the formula is i+j+k=18 i j k r.) M13 cyclic peptide represented by the phage library presented using a filamentous bacteriophage, for binding to human IgG Protein A Staphylococcus aureus 20 residues derived from a competing reaction for obtaining a plurality of the cyclic peptide. They further, these peptides extracted from the consensus sequence of 13 residues (Asp Cys Ala Trp His Leu Gly Glu Leu Val Trp Cys Thr) cyclic peptide Fc-III(SEQ ID NO:165) was prepared, in the competing reactions of the protein A Ki =100nm has been found that the competitive inhibition ability. IgG Fab fragment of the antigen binding site capable of fusion Fc-III, experiments using rabbit Fab in in vivo half-life can be improved in the disclosed (patent document 2, non-patent document 3). Also Dias et al., this cyclic peptide Fc-III D L Pro residues of the body and further using FcBP-2 MACROLACTAM was introduced to prepare a, in which the binding IgG (Fc-III of the dissociation constant for the binding K KD =185 nm) aD were successfully increased to=2 nm (non-patent document 4).
Fassina et al., residue Lys (Arg Thr Xaa) having a branch structure4 Lys2 Lys Gly (SEQ ID NO:166) represented by synthetic tetra polypeptide library screening, compete with peptide TG19318 protein A (non-patent document 5) was produced. TG19318 Rabbit IgG K is toD binding which has=300 nm, this product is further immobilized by affinity chromatography, human, bovine, horse, pig, mouse, rat, goat, sheep sera can be contained in the purified IgG (non-patent document 6) shown.
Ehrlich et al., similar to the technique of Suzuki et al., 7 residues or 12 residues of the linear peptides were presented in M13 phage library using a filamentous bacteriophage, pepsin digested humanized IgG obtained pFc ' fragment binding peptides were isolated (non-patent document 7).
Krook et al., 10 residues in length linear peptides were presented in M13 phage library using a filamentous bacteriophage, showing human IgG Fc binding to the region of the peptide was made.They ELISA IgG by the human and the peptide of porcine origin to stronger binding was confirmed to be (non-patent document 8).
Verdoliva et al., and branch structure residue Lys Cys residue introduced MACROLACTAM (Cys Xaa3)2 Lys Gly (SEQ ID NO:167) synthetic peptide represented by the screened against mouse monoclonal IgG, cohesive FcRM near the hinge region peptides was produced. They further constructed FcRM affinity chromatography with immobilized, purified IgG from mice and humans (non-patent document 9) reported.
Μg et al., Cys Xaa7-10 Cys cyclic peptide represented by the phage library presented using bacteriophage T7, binding to the region of the human IgG Fc produced a peptide that exhibits (non-patent document 10). They produced by the peptide, but not Fc region of a naturally-occurring, non-naturally occurring caused by acid treatment at a point to recognize structures, made up to this point is different from the above-described IgG-binding peptides. Itoh et al., the peptide is a human with an antibody pharmaceuticals, immunoglobulin preparation, produced by the acid treatment IgG contained in the reagent content of the non-naturally occurring structure can be checked also disclosed (patent document 3).
As described above, a plurality of antibody-binding peptides have been developed is, their molecular diversity is not sufficient.This is because, in addition to the above-described therapeutic applications, antibodies are useful in various regions of industry, since the various usages, molecular properties required for the antibody binding molecule is not uniform in some cases.Such as detection of antibodies, purified, immobilized or removal or the like in the practice, each antibody having properties suitable for the usage state of the binding molecule is required.More specifically, to bind any portion of the antibody or the like, how much the specificity of molecular recognition, how much the intensity of the affinity, the change of the binding/dissociation solution conditions can be controlled, a plurality of animal species or antibody that binds to, or binds only to specific antibodies of a certain species or, if the solubility or stability, or can be mass-produced, having suitable properties in the viewpoint of the antibody binding molecule is required.Furthermore in the case of peptide, or non-naturally occurring amino acid residues of the naturally-occurring or be composed of only the amino acid residues, the chemical structure or a branched or linear type or an annular-shaped type, stable in solution forms the three-dimensional structure, or can be used in the reductive environment, and the item of suitability judgment and the like.
Typically, such as short-chain polypeptide is stabilized by intramolecular disulfide bridge to achieve high functionalization is annular, the circularization a complicated chemical reaction is necessary and, for example, under reducing conditions such as under the condition it is difficult to achieve the disulfide bridges of the binding function may not be exhibited.As the disulfide bridges of the reducing conditions it is difficult to achieve a state that is assumed as an example, (1) the environment in the cytoplasm of the target IgG Fc region, (2) or a thiol group of a cysteine residue, for the purpose of chemically modifying the reducing agent is added in order to free radical environment CountMax.
Further, along with the expansion of the market pharmaceutical antibody, separation and purification of the antibody molecule with a target of highly advanced techniques and of analytic techniques as further in recent years has been strongly desired.
With respect to the analytical techniques, in (1) particular glycosylation post-translational modification of a variety of analytical techniques for molecules with a non-uniformity due to variations in the conformation of the antibody molecule, (2) the non-uniformity analysis techniques, (3) aggregates, a molecule with the non-uniformity for aggregate formation analysis techniques, the development of one of the expected 3. (Non-patent document 11).The antibody molecule may be by a variety of physical or chemical stress, alternatively folded state is different from the structure of a naturally-occurring normal (AFS) referred to as to form a non-naturally occurring structure have been reported.Such non-natural type structure is, the effect of the drug as well as a decrease in the cause of the adverse effects cause immunogenicity suggested is the risk of, non-naturally occurring structure of the antibody with an analytical technique (non-patent document 12) are.
Protein molecular shape or a three-dimensionally to demonstrate the structure of the analytical techniques include, X-ray crystal structure analysis, nuclear magnetic resonance, electron microscope, an ultra-centrifugal analysis, isoelectric focusing, dynamic light scattering, circular dichroism spectrum, liquid chromatography and the like, to satisfy the atomic level there is no way for both precision and throughput.For example, atomic level accuracy is capable of giving a three-dimensional structure information X-ray crystal structure analysis or nuclear magnetic resonance analysis time of the order of a few months in need.In addition, dynamic light scattering measurement can be completed within a few minutes or liquid chromatography of a small amount of an abrupt change of the molecules is mixed into the fine cannot be detected.For this reason, both atomic level precision and throughput convenient technique is demanded.
On the other hand, separation and purification techniques include, a molecule having a specific affinity for the antibody used as a ligand affinity chromatography technique (non-patent document 13) essential today.Current, this application is as a ligand, or a protein derived from a bacterium such as protein A g used naturally occurring proteins.These proteins has a good antibody affinity, and stability is low, the drawback of high manufacturing cost.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY
  • 発明者(英語)
  • WATANABE HIDEKI
  • HONDA SHINYA
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN TD TG
参考情報 (研究プロジェクト等) Biomedical Research Institue,Molecular and Cellular Breeding Research Group

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