JP5992831B2 - 非機能性オリゴマーp2x7受容体に対する抗体 - Google Patents
非機能性オリゴマーp2x7受容体に対する抗体 Download PDFInfo
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- 230000037439 somatic mutation Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000012451 transgenic animal system Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 101150057627 trxB gene Proteins 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 208000037964 urogenital cancer Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2869—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against hormone receptors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
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- C07K2317/52—Constant or Fc region; Isotype
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
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- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
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- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C07K2317/00—Immunoglobulins specific features
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- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
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- C07K2317/00—Immunoglobulins specific features
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- C07K2317/00—Immunoglobulins specific features
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Description
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、(荷電性/極性/芳香族)(荷電性/芳香族)XXXY(芳香族/脂肪族)(荷電性/中性)(中性/脂肪族)のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、N(Y/F)XXXY(Y/F)EXのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、N(Y/F)(中性)(荷電性)(中性)Y(Y/F)E(中性)のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、NFLESYFEAのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、N(Y/F)(荷電性)(中性)(荷電性)Y(Y/F)E(中性)のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、NYRGDYYETのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、H(芳香族)XXXYYNIのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、H(Y/F)(中性)(荷電性)(荷電性)YYNIのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、H(Y/F)(中性)(荷電性)(中性)YYNIのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、HYSKEYYNIのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、HFQRGYYNIのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、(Y/N)(芳香族)XXXYY(荷電性)(中性)のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、(Y/N)(芳香族)(中性)(中性)(中性)YYDVのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、(Y/N)(芳香族)(中性)(中性)(中性)YYEVのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、YFPLVYYDVのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、NYLPMYYEVのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、Y(荷電性)XXXY(中性)(中性)(中性)のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、YHVIQYLGPのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、HYSSRFFDV、NFKLMYYNV、NYRGDYYET、HFSRGYYDV、NFLESYFEA、NYLPMYYEV、HYIKVYYEA、HYSSRFFEV、NFRVMFFKA、HFQRGYYNI、HYSSRFFEV、YHVIQYLGP、HYSKEYYNI、YFPLVYYDV、DFTVPFYNA、NYDKKYFDV、YFPLVYYDVからなる群から選択されるアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR1は、KASQNVGTNVAのアミノ酸配列を有し、
CDR3は、CDR3配列を記載する前述の任意の実施形態のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR1は、SYYMSのアミノ酸配列を有し、
CDR3は、CDR3配列を記載する前述の任意の実施形態のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR2は、SASFRYSのアミノ酸配列を有し、
CDR3は、CDR3配列を記載する前述の任意の実施形態のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR2は、AINSNGGSTYYPDTVKGのアミノ酸配列を有し、
CDR3は、CDR3配列を記載する前述の任意の実施形態のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR1は、KASQNVGTNVAのアミノ酸配列を有し、
CDR2は、SASFRYSのアミノ酸配列を有し、
CDR3は、CDR3配列を記載する前述の任意の実施形態のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR1は、SYYMSのアミノ酸配列を有し、
CDR2は、AINSNGGSTYYPDTVKGのアミノ酸配列を有し、
CDR3は、CDR3配列を記載する前述の任意の実施形態のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4−リンカー−FR1a−CDR1a−FR2a−CDR2a−FR3a−CDR3a−FR4a
(式中、
FR1、FR2、FR3、FR4、FR1a、FR2a、FR3a、およびFR4aは、それぞれフレームワーク領域であり;
CDR1、CDR2、CDR3、CDR1a、CDR2a、CDR3aは、それぞれ相補性決定領域であり;
CDR1は、KASQNVGTNVAのアミノ酸配列を有し、
CDR2は、SASFRYSのアミノ酸配列を有し、
CDR3は、CDR3配列を記載する前述の任意の実施形態のアミノ酸配列またはQQYNSYPFTを有し、
CDR1aは、SYYMSのアミノ酸配列を有し、
CDR2aは、AINSNGGSTYYPDTVKGのアミノ酸配列を有し、
CDR3aは、CDR3配列を記載する前述の任意の実施形態のアミノ酸配列またはCDR3がCDR3配列を記載する前述の任意の実施形態のアミノ酸配列である場合にQQYNSYPFT(配列番号33)を有し、
FR1は、MADIVMTQSQKFMSTSVGDRVSVTC(配列番号25)のアミノ酸配列を有し、
FR2は、WYQQKPGQSPKALIY(配列番号26)のアミノ酸配列を有し、
FR3は、GVPDRFTGSGSGTDFTLTISNVQSEDLAEFFC(配列番号27)のアミノ酸配列を有し、
FR4は、FGSGTRLEIK(配列番号28)のアミノ酸配列を有し、
FR1aは、DVKLVESGGGLVKLGGSLKLSCAASGFTFS(配列番号29)のアミノ酸配列を有し、
FR2aは、WVRQTPEKRLELVA(配列番号30)のアミノ酸配列を有し、
FR3aは、RFTISRDNAKNTLYLQMSSLKSEDTAFYYCTR(配列番号31)のアミノ酸配列を有し、
FR4aは、WGAGTTVTVSS(配列番号32)のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、(荷電性/極性/芳香族)(芳香族)(荷電性/中性)(荷電性)(荷電性/中性)Y(芳香族)(荷電性)(中性)のアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、(荷電性/極性/芳香族)(F/Y)(荷電性/中性)(R/K)(荷電性/中性)(Y)(Y/F)(E/D)Vのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、およびFR4は、それぞれフレームワーク領域であり;
CDR1、CDR2、およびCDR3は、それぞれ相補性決定領域であり;
CDR3は、(H/N)(F/Y)(S/D)(R/K)(G/K)Y(Y/F)DVのアミノ酸配列を有する)によって定義される抗原結合部位を提供する。
− P2X7受容体の第1の単量体の一領域の形態である第1の領域、および
− 受容体の第2の単量体の一領域の形態である第2の領域
から形成され、第1および第2の領域が配列番号1に示す配列を有する受容体単量体の位置210にある残基のシス異性化により受容体内に形成され、第1および第2の領域が受容体内で互いに隣接して配列され、それによって抗P2X7抗体の抗原結合部位がエピトープを形成する第1および第2の領域に結合することが可能になる、エピトープに結合する。
MADIVMTQSQKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKALIYSASFRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEFFCQQYNSYPFTFGSGTRLEIKGGGGSGGGGSGGGGSDVKLVESGGGLVKLGGSLKLSCAASGFTFSSYYMSWVRQTPEKRLELVAAINSNGGSTYYPDTVKGRFTISRDNAKNTLYLQMSSLKSEDTAFYYCTRHYSSRFFDVWGAGTTVTVSS
MADIVMTQSQKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKALIYSASFRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEFFCQQYNSYPFTFGSGTRLEIKGGGGSGGGGSGGGGSDVKLVESGGGLVKLGGSLKLSCAASGFTFSSYYMSWVRQTPEKRLELVAAINSNGGSTYYPDTVKGRFTISRDNAKNTLYLQMSSLKSEDTAFYYCTRHYSSRFFDVWGAGTTVTVSSAAADYKDDDDKAAAHHHHHH
− 抗原結合部位、免疫グロブリン可変ドメイン、抗体、Fab、dab、scFv、二重特異性抗体、三重特異性抗体、融合タンパク質、コンジュゲート、または医薬組成物の形態の1つまたは複数を含む治療用組成物を収容する容器と、
− 使用説明書を含むラベルまたは添付文書と
を含むキットを提供する。
− 抗原結合部位、免疫グロブリン可変ドメイン、抗体、Fab、dab、scFv、二重特異性抗体、三重特異性抗体、融合タンパク質、またはコンジュゲートの形態の1つまたは複数を含む診断用組成物を収容する容器と、
− 使用説明書を含むラベルまたは添付文書と
を含むキットを提供する。
目的:ここに記載する実験では、生細胞上に発現されたP2X7受容体に結合する抗体の生成および精製を詳述する。具体的には、この実験では、配列番号4(2F6)に示した配列を有する抗体の生成および精製を説明する。
目的:IgMおよびマウスIgG2aを含めた2F6抗体形態が生細胞の表面上の非機能性受容体に結合するか否かを決定すること。さらに、2F6抗体形態が非機能性P2X7受容体を発現する細胞、例えば癌細胞の特性を阻害するか否かを決定すること。
目的:癌細胞表面上に発現されたP2X7三量体内の隣接した単量体にまたがるユニークでアクセス可能な複合エピトープに向けられた抗体が、死癌細胞上に残存する標的と比較して、生癌細胞の表面上の標的に優先的に結合することができるか否かを明確にすること。
目的:マウス異種移植腫瘍における2F6 hIgG1の治療効果を決定し、同じ標的に対して産生され、親和性精製された高親和性ヒツジポリクローナル抗体と比較した。
4T1マウス乳腺腫瘍細胞を培養するための試薬は以下の供給業者から入手した。RPMI1640細胞培養培地、FCS、Glutamax、HBSS、およびペニシリン−ストレプトマイシンは、Invitrogen Australia(Mt Waverley,VIC,Australia)から、トリパンブルーは、Sigma−Aldrich(Castle Hill,NSW,Australia)から入手した。Matrigel(商標)は、BD Biosciences (North Ryde,NSW,Australia)から入手した。
目的:ここに記載の実験は、結合定数の増大を示す抗体形態(すなわちscFv/Fab)を開発して、リンパ球などの任意の正常細胞上の機能性受容体への非結合および癌細胞上の非機能性P2X7受容体への特異的結合の両方を改善すること、したがって、WT組換え2F6モノクローナルが達成する濃度より低い抗体濃度で癌細胞増殖の阻害を得ることにあった。
目的:親和性成熟Fabが生細胞上に発現された非機能性P2X7受容体に対する特異性を示したか否かを決定すること。
Claims (24)
- 非機能性P2X7受容体に結合するための抗体もしくは抗体断片であって、
FR1a−CDR1a−FR2a−CDR2a−FR3a−CDR3a−FR4a−リンカー−FR1−CDR1−FR2−CDR2−FR3−CDR3−FR4
(式中、
FR1、FR2、FR3、FR4、FR1a、FR2a、FR3a、およびFR4aは、それぞれフレームワーク領域であり;
CDR1、CDR2、CDR3、CDR1a、CDR2a、およびCDR3aは、それぞれ相補性決定領域であり;
CDR3は、HYSSRFFDV、NYRGDYYET、HFSRGYYDV、NFLESYFEA、NYLPMYYEV、HYSSRFFEV、NFRVMFFKA、HFQRGYYNI、YHVIQYLGP、HYSKEYYNI、およびYFPLVYYDVからなる群から選択されるアミノ酸配列を有し、
CDR1は、SYYMSのアミノ酸配列を有し、
CDR2は、AINSNGGSTYYPDTVKGのアミノ酸配列を有し、
CDR1aは、KASQNVGTNVAのアミノ酸配列を有し、
CDR2aは、SASFRYSのアミノ酸配列を有し、
CDR3aは、QQYNSYPFTのアミノ酸配列を有する)を含む、抗体もしくは抗体断片。 - CDR3がHFSRGYYDVのアミノ酸配列を有する、請求項1に記載の抗体もしくは抗体断片。
- CDR3がHFQRGYYNIのアミノ酸配列を有する、請求項1に記載の抗体もしくは抗体断片。
- CDR3がHYSKEYYNIのアミノ酸配列を有する、請求項1に記載の抗体もしくは抗体断片。
- FR1がDVKLVESGGGLVKLGGSLKLSCAASGFTFSのアミノ酸配列を有する、請求項1から4のいずれか一項に記載の抗体もしくは抗体断片。
- FR2がWVRQTPEKRLELVAのアミノ酸配列を有する、請求項1から5のいずれか一項に記載の抗体もしくは抗体断片。
- FR3がRFTISRDNAKNTLYLQMSSLKSEDTAFYYCTRのアミノ酸配列を有する、請求項1から6のいずれか一項に記載の抗体もしくは抗体断片。
- FR4がWGAGTTVTVSSのアミノ酸配列を有する、請求項1から7のいずれか一項に記載の抗体もしくは抗体断片。
- FR1aがMADIVMTQSQKFMSTSVGDRVSVTCのアミノ酸配列を有する、請求項1から8のいずれか一項に記載の抗体もしくは抗体断片。
- FR2aがWYQQKPGQSPKALIYのアミノ酸配列を有する、請求項1から9のいずれか一項に記載の抗体もしくは抗体断片。
- FR3aがGVPDRFTGSGSGTDFTLTISNVQSEDLAEFFCのアミノ酸配列を有する、請求項1から9のいずれか一項に記載の抗体もしくは抗体断片。
- FR4aがFGSGTRLEIKのアミノ酸配列を有する、請求項1から9のいずれか一項に記載の抗体もしくは抗体断片。
- リンカーが、15個のアミノ酸残基のアミノ酸配列を有する、請求項1から12のいずれか一項に記載に記載の抗体もしくは抗体断片。
- リンカーが、GGGGSGGGGSGGGGSのアミノ酸配列を有する、請求項13に記載の抗体もしくは抗体断片。
- Fab、Fab’、F(ab’)2、scFv、二重特異性抗体、三重特異性抗体、直鎖状抗体、単鎖抗体、および多重特異性抗体断片からなる群より選択される、請求項1から14のいずれか一項に記載の抗体もしくは抗体断片。
- 二価または二重特異性である、請求項1から15のいずれか一項に記載の抗体もしくは抗体断片。
- 非機能性P2X7受容体の発現に関連した癌の処置のための医薬の製造のための、請求項1から16のいずれか一項に記載の抗体もしくは抗体断片の使用であって、
癌が、乳腺腫瘍、結腸直腸腫瘍、腺癌、中皮腫、膀胱腫瘍、前立腺腫瘍、胚細胞腫瘍、肝細胞腫/コロンジオ(cholongio)、カルシノーマ、神経内分泌腫瘍、下垂体腫瘍、小20円形細胞腫瘍、扁平上皮癌、黒色腫、非定型的線維黄色腫、精上皮腫、非精上皮腫、間質ライディッヒ細胞腫、セルトリ細胞腫、皮膚腫瘍、腎腫瘍、精巣腫瘍、脳腫瘍、卵巣腫瘍、胃腫瘍、口腔腫瘍、膀胱腫瘍、骨腫瘍、頸部腫瘍、食道腫瘍、喉頭腫瘍、肝臓腫瘍、肺腫瘍、膣腫瘍、およびウィルムス腫瘍からなる群より選択される使用。 - 癌が、腺癌、腺腫、腺線維腫、腺リンパ腫、アドントーマ(adontoma)、AIDS関連癌、聴神経腫、急性リンパ性白血病、急性骨髄性白血病、腺嚢癌腫、副腎皮質癌、原発性骨髄線維症、脱毛症、胞状軟部肉腫、エナメル上皮腫、角化血管腫、好酸球性血管リンパ球増殖症、硬化性血管腫、血管腫症、アプドーマ、肛門癌、血管肉腫、再生不良性貧血、星状細胞腫、毛細血管拡張性運動失調、基底細胞癌(皮膚)、膀胱癌、骨癌、腸癌、脳幹神経膠腫、脳およびCNS腫瘍、乳癌、鰓腫、CNS腫瘍、カルチノイド腫瘍、子宮頸癌、小児期脳腫瘍、小児期癌、小児期白血病、小児期軟部組織肉腫、軟骨肉腫、絨毛癌、慢性リンパ球性白血病、慢性骨髄性白血病、結腸直腸癌、皮膚T細胞リンパ腫、癌腫、癌肉腫、子宮頚部異形成、葉状嚢肉腫、セメント腫、脊索腫、分離腫、軟骨肉腫、軟骨芽細胞腫、頭蓋咽頭腫、胆管細胞腫、コレステリン腫、円柱腫、嚢胞腺癌、嚢腺腫、隆起性皮膚繊維肉腫、繊維形成性小円形細胞腫、腺管癌、未分化胚細胞腫、内分泌癌、子宮内膜癌、上衣細胞腫、食道癌、ユーイング肉腫、肝外胆管癌、眼癌、眼黒色腫、網膜芽細胞腫、卵管癌、ファンコーニ貧血、繊維腫、繊維肉腫、胆嚢癌、胃癌、消化管癌、消化管カルチノイド腫瘍、尿生殖器癌、胚細胞腫瘍、妊娠性絨毛疾患、神経膠腫、婦人科癌、巨細胞腫、神経節神経腫、神経膠腫、グロムス血管腫、顆粒層細胞腫、半陰陽性卵巣腫瘍、血液学的悪性疾患、毛様細胞性白血病、頭頸部癌、肝細胞癌、遺伝性乳癌、組織球増殖症、ホジキン病、ヒトパピローマウイルス、胞状奇胎、高カルシウム血症、下咽頭癌、過誤腫、血管内皮腫、血管腫、血管周囲細胞腫、血管肉腫、血管肉腫、組織球障害、組織球増殖性悪性疾患、組織球腫、肝細胞腫、汗腺腫、ホンドロ肉腫(hondrosarcoma)、免疫増殖性小(immunoproliferative small)、オポーマ(opoma)、オントラオーキュラー黒色腫(ontraocular melanoma)、島細胞癌、カポジ肉腫、腎臓癌、ランゲルハンス細胞組織球増殖症、喉頭癌、平滑筋肉腫、白血病、リ・フラウメニ症候群、口唇癌、脂肪肉腫、肝臓癌、肺癌、リンパ水腫、リンパ腫、ホジキンリンパ腫、非ホジキンリンパ腫、レイゴミオ肉腫(leigomyosarcoma)、白血病、白血肉腫、ライディッヒ細胞腫、脂肪肉腫、平滑筋腫、平滑筋肉腫、リンパ管腫、リンパ管細胞腫、リンパ管腫、リンパギオミオーマ(lymphagiomyoma)、リンパ管肉腫、男性乳癌、悪性腎横紋筋肉腫様腫瘍、髄芽細胞腫、黒色腫、メルケル細胞癌、中皮腫、転移性癌、口腔癌、多発性内分泌腺腫症、菌状息肉腫、骨髄異形成症候群、骨髄腫、骨髄増殖性障害、悪性カルチノイド症候群カルチノイド心疾患、髄芽細胞腫、髄膜腫、黒色腫、間葉細胞腫、中腎腫、中皮腫、筋芽細胞腫、筋腫、筋肉腫、粘液腫、粘液肉腫、鼻腔癌、鼻咽頭癌、腎芽細胞腫、神経芽細胞腫、神経繊維腫症、ナイメーヘン染色体不安定症候群、非黒色腫皮膚癌、非小細胞肺癌(nsclc)、神経鞘腫、神経芽細胞腫、神経上皮腫、神経線維腫症、神経繊維腫、神経腫、新生物、眼癌、食道癌、口腔癌、中咽頭癌、骨肉腫、造瘻術卵巣癌、膵臓癌、副鼻腔癌、副甲状腺癌、耳下腺癌、陰茎癌、末梢性神経外胚葉性腫瘍、下垂体癌、真性赤血球増加症、前立腺癌、骨腫、骨肉腫、卵巣癌、乳頭腫、傍神経節腫、非クロム親和性傍神経節腫、松果体腫、形質細胞腫、癌原遺伝子、稀な癌および関連疾患、腎細胞癌、網膜芽細胞腫、横紋筋肉腫、ロートムント・トムソン症候群、細網内皮症、横紋筋腫、唾液腺癌、肉腫、神経鞘腫、セザリー症候群、皮膚癌、小細胞肺癌(sclc)、小腸癌、軟部組織肉腫、脊髄腫瘍、扁平上皮癌(皮膚)、胃癌、滑膜肉腫、肉腫、セルトリ細胞腫、滑膜腫、精巣癌、胸腺癌、甲状腺癌、移行上皮癌(膀胱)、移行上皮癌(腎盂/尿管)、栄養膜癌、奇形腫、卵胞膜細胞腫、胸腺腫、栄養膜腫瘍、尿道癌、尿路系癌、ウロプラキン(uroplakin)、子宮肉腫、子宮癌、膣癌、外陰部癌、ワルデンストレームマクログロブリン血症、およびウィルムス腫瘍からなる群より選択される請求項17に記載の使用。
- 癌または非機能性P2X7受容体の発現に関連した炎症性症状の診断のための医薬の製造のための、請求項1から18のいずれか一項に記載の抗体もしくは抗体断片の使用であって、
癌が、乳腺腫瘍、結腸直腸腫瘍、腺癌、中皮腫、膀胱腫瘍、前立腺腫瘍、胚細胞腫瘍、肝細胞腫/コロンジオ(cholongio)、カルシノーマ、神経内分泌腫瘍、下垂体腫瘍、小20円形細胞腫瘍、扁平上皮癌、黒色腫、非定型的線維黄色腫、精上皮腫、非精上皮腫、間質ライディッヒ細胞腫、セルトリ細胞腫、皮膚腫瘍、腎腫瘍、精巣腫瘍、脳腫瘍、卵巣腫瘍、胃腫瘍、口腔腫瘍、膀胱腫瘍、骨腫瘍、頸部腫瘍、食道腫瘍、喉頭腫瘍、肝臓腫瘍、肺腫瘍、膣腫瘍、およびウィルムス腫瘍からなる群より選択される使用。 - 癌が、腺癌、腺腫、腺線維腫、腺リンパ腫、アドントーマ(adontoma)、AIDS関連癌、聴神経腫、急性リンパ性白血病、急性骨髄性白血病、腺嚢癌腫、副腎皮質癌、原発性骨髄線維症、脱毛症、胞状軟部肉腫、エナメル上皮腫、角化血管腫、好酸球性血管リンパ球増殖症、硬化性血管腫、血管腫症、アプドーマ、肛門癌、血管肉腫、再生不良性貧血、星状細胞腫、毛細血管拡張性運動失調、基底細胞癌(皮膚)、膀胱癌、骨癌、腸癌、脳幹神経膠腫、脳およびCNS腫瘍、乳癌、鰓腫、CNS腫瘍、カルチノイド腫瘍、子宮頸癌、小児期脳腫瘍、小児期癌、小児期白血病、小児期軟部組織肉腫、軟骨肉腫、絨毛癌、慢性リンパ球性白血病、慢性骨髄性白血病、結腸直腸癌、皮膚T細胞リンパ腫、癌腫、癌肉腫、子宮頚部異形成、葉状嚢肉腫、セメント腫、脊索腫、分離腫、軟骨肉腫、軟骨芽細胞腫、頭蓋咽頭腫、胆管細胞腫、コレステリン腫、円柱腫、嚢胞腺癌、嚢腺腫、隆起性皮膚繊維肉腫、繊維形成性小円形細胞腫、腺管癌、未分化胚細胞腫、内分泌癌、子宮内膜癌、上衣細胞腫、食道癌、ユーイング肉腫、肝外胆管癌、眼癌、眼黒色腫、網膜芽細胞腫、卵管癌、ファンコーニ貧血、繊維腫、繊維肉腫、胆嚢癌、胃癌、消化管癌、消化管カルチノイド腫瘍、尿生殖器癌、胚細胞腫瘍、妊娠性絨毛疾患、神経膠腫、婦人科癌、巨細胞腫、神経節神経腫、神経膠腫、グロムス血管腫、顆粒層細胞腫、半陰陽性卵巣腫瘍、血液学的悪性疾患、毛様細胞性白血病、頭頸部癌、肝細胞癌、遺伝性乳癌、組織球増殖症、ホジキン病、ヒトパピローマウイルス、胞状奇胎、高カルシウム血症、下咽頭癌、過誤腫、血管内皮腫、血管腫、血管周囲細胞腫、血管肉腫、血管肉腫、組織球障害、組織球増殖性悪性疾患、組織球腫、肝細胞腫、汗腺腫、ホンドロ肉腫(hondrosarcoma)、免疫増殖性小(immunoproliferative small)、オポーマ(opoma)、オントラオーキュラー黒色腫(ontraocular melanoma)、島細胞癌、カポジ肉腫、腎臓癌、ランゲルハンス細胞組織球増殖症、喉頭癌、平滑筋肉腫、白血病、リ・フラウメニ症候群、口唇癌、脂肪肉腫、肝臓癌、肺癌、リンパ水腫、リンパ腫、ホジキンリンパ腫、非ホジキンリンパ腫、レイゴミオ肉腫(leigomyosarcoma)、白血病、白血肉腫、ライディッヒ細胞腫、脂肪肉腫、平滑筋腫、平滑筋肉腫、リンパ管腫、リンパ管細胞腫、リンパ管腫、リンパギオミオーマ(lymphagiomyoma)、リンパ管肉腫、男性乳癌、悪性腎横紋筋肉腫様腫瘍、髄芽細胞腫、黒色腫、メルケル細胞癌、中皮腫、転移性癌、口腔癌、多発性内分泌腺腫症、菌状息肉腫、骨髄異形成症候群、骨髄腫、骨髄増殖性障害、悪性カルチノイド症候群カルチノイド心疾患、髄芽細胞腫、髄膜腫、黒色腫、間葉細胞腫、中腎腫、中皮腫、筋芽細胞腫、筋腫、筋肉腫、粘液腫、粘液肉腫、鼻腔癌、鼻咽頭癌、腎芽細胞腫、神経芽細胞腫、神経繊維腫症、ナイメーヘン染色体不安定症候群、非黒色腫皮膚癌、非小細胞肺癌(nsclc)、神経鞘腫、神経芽細胞腫、神経上皮腫、神経線維腫症、神経繊維腫、神経腫、新生物、眼癌、食道癌、口腔癌、中咽頭癌、骨肉腫、造瘻術卵巣癌、膵臓癌、副鼻腔癌、副甲状腺癌、耳下腺癌、陰茎癌、末梢性神経外胚葉性腫瘍、下垂体癌、真性赤血球増加症、前立腺癌、骨腫、骨肉腫、卵巣癌、乳頭腫、傍神経節腫、非クロム親和性傍神経節腫、松果体腫、形質細胞腫、癌原遺伝子、稀な癌および関連疾患、腎細胞癌、網膜芽細胞腫、横紋筋肉腫、ロートムント・トムソン症候群、細網内皮症、横紋筋腫、唾液腺癌、肉腫、神経鞘腫、セザリー症候群、皮膚癌、小細胞肺癌(sclc)、小腸癌、軟部組織肉腫、脊髄腫瘍、扁平上皮癌(皮膚)、胃癌、滑膜肉腫、肉腫、セルトリ細胞腫、滑膜腫、精巣癌、胸腺癌、甲状腺癌、移行上皮癌(膀胱)、移行上皮癌(腎盂/尿管)、栄養膜癌、奇形腫、卵胞膜細胞腫、胸腺腫、栄養膜腫瘍、尿道癌、尿路系癌、ウロプラキン(uroplakin)、子宮肉腫、子宮癌、膣癌、外陰部癌、ワルデンストレームマクログロブリン血症、およびウィルムス腫瘍からなる群より選択される請求項19に記載の使用。
- 癌腫が、ウォーカー癌、基底細胞癌、基底扁平上皮細胞癌、ブラウン・ペアス癌、腺管癌、エーリッヒ腫瘍、クレブス2癌、メルケル細胞癌、ムチン様癌、非小細胞肺癌、燕麦細胞癌、乳頭様癌、硬性癌、細気管支癌、気管支原性癌、扁平上皮細胞癌、および移行性細胞癌からなる群より選択される請求項18または20に記載の使用。
- 白血病が、b細胞、混合細胞、ヌル細胞、t細胞、t細胞慢性、htlv−ii関連、リンパ管肉腫、リンパ球性急性、リンパ球性慢性、肥満細胞、および骨髄性からなる群より選択される請求項18または20に記載の使用。
- 新生物が、骨、乳房、消化系、結腸直腸、および肝臓からなる群より選択される請求項18または20に記載の使用。
- 肉腫が、ユーイング実験的肉腫、カポジ肉腫、および肥満細胞肉腫からなる群より選択される請求項18または20に記載の使用。
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EP2201026B1 (en) | 2007-09-14 | 2017-01-04 | Biosceptre (Aust) Pty Ltd | Novel p2x7 epitopes |
US8293491B2 (en) | 2007-09-14 | 2012-10-23 | Biosceptre International Limited | Purinergic (P2X) receptors in extra-cellular body fluid |
KR101701300B1 (ko) | 2008-07-04 | 2017-02-01 | 바이오셉터 (어스트) 피티와이 엘티디 | 항p2x7 펩티드 및 에피토프 |
JP5936067B2 (ja) | 2009-08-20 | 2016-06-15 | バイオセプター・(オーストラリア)・ピーティーワイ・リミテッド | 抗p2x7受容体抗体およびその断片 |
ES2667003T3 (es) | 2009-12-24 | 2018-05-09 | Biosceptre (Aust) Pty Ltd | Anticuerpos para receptores P2X7 oligoméricos no funcionales |
US9562094B2 (en) | 2010-09-10 | 2017-02-07 | Biosceptre (Aust) Pty Ltd | Companion animal treatments |
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