CN106938051A - 靶向于组织因子的抗体‑药物偶联物 - Google Patents
靶向于组织因子的抗体‑药物偶联物 Download PDFInfo
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- CN106938051A CN106938051A CN201710125244.6A CN201710125244A CN106938051A CN 106938051 A CN106938051 A CN 106938051A CN 201710125244 A CN201710125244 A CN 201710125244A CN 106938051 A CN106938051 A CN 106938051A
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K16/36—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
Abstract
Description
最初的残基 | 代表性的取代 | 优选的取代 |
Ala(A) | Val;Leu;Ile | Val |
Arg(R) | Lys;Gln;Asn | Lys |
Asn(N) | Gln;His;Lys;Arg | Gln |
Asp(D) | Glu | Glu |
Cys(C) | Ser | Ser |
Gln(Q) | Asn | Asn |
Glu(E) | Asp | Asp |
Gly(G) | Pro;Ala | Ala |
His(H) | Asn;Gln;Lys;Arg | Arg |
Ile(I) | Leu;Val;Met;Ala;Phe | Leu |
Leu(L) | Ile;Val;Met;Ala;Phe | Ile |
Lys(K) | Arg;Gln;Asn | Arg |
Met(M) | Leu;Phe;Ile | Leu |
Phe(F) | Leu;Val;Ile;Ala;Tyr | Leu |
Pro(P) | Ala | Ala |
Ser(S) | Thr | Thr |
Thr(T) | Ser | Ser |
Trp(W) | Tyr;Phe | Tyr |
Tyr(Y) | Trp;Phe;Thr;Ser | Phe |
Val(V) | Ile;Leu;Met;Phe;Ala | Leu |
序列编号 | SEQ ID NO.:9 | SEQ ID NO.:10 | SEQ ID NO.:11 | SEQ ID NO.:12 | SEQ ID NO.:13 |
SEQ ID NO.:14 | TF-mAb-H29 | TF-mAb-H30 | TF-mAb-H31 | TF-mAb-H32 | TF-mAb-H33 |
SEQ ID NO.:15 | TF-mAb-H34 | TF-mAb-H35 | TF-mAb-H36 | TF-mAb-H37 | TF-mAb-H38 |
SEQ ID NO.:16 | TF-mAb-H39 | TF-mAb-H40 | TF-mAb-H41 | TF-mAb-H42 | TF-mAb-H43 |
SEQ ID NO.:17 | TF-mAb-H44 | TF-mAb-H45 | TF-mAb-H46 | TF-mAb-H47 | TF-mAb-H48 |
抗体 | EC50(nM) | 抗体 | EC50(nM) |
TF-mAb-Ch | 0.0100 | TF-mAb-H39 | 0.0125 |
TF-mAb-H29 | 0.0178 | TF-mAb-H40 | 0.0131 |
TF-mAb-H30 | 0.0147 | TF-mAb-H41 | 0.0134 |
TF-mAb-H31 | 0.0145 | TF-mAb-H42 | 0.0128 |
TF-mAb-H32 | 0.0168 | TF-mAb-H43 | 0.0116 |
TF-mAb-H33 | 0.0189 | TF-mAb-H44 | 0.0120 |
TF-mAb-H34 | 0.0154 | TF-mAb-H45 | 0.0138 |
TF-mAb-H35 | 0.0105 | TF-mAb-H46 | 0.0119 |
TF-mAb-H36 | 0.0234 | TF-mAb-H47 | 0.0130 |
TF-mAb-H37 | 0.0173 | TF-mAb-H48 | 0.0153 |
TF-mAb-H38 | 0.0178 | IgG(阴性对照) | >6.67 |
Claims (10)
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EP17842668.0A EP3501548A4 (en) | 2016-08-22 | 2017-06-09 | ANTIBODY-ACTIVE SUBSTANCE CONJUGATE TISSUE FABRIC FACTOR |
PCT/CN2017/087779 WO2018036243A1 (zh) | 2016-08-22 | 2017-06-09 | 靶向于组织因子的抗体-药物偶联物 |
JP2019511435A JP7020655B2 (ja) | 2016-08-22 | 2017-06-09 | 組織因子標的化抗体薬物接合体 |
US16/326,886 US11534495B2 (en) | 2016-08-22 | 2017-06-09 | Tissue factor-targeted antibody-drug conjugate |
US18/050,240 US20230138930A1 (en) | 2016-08-22 | 2022-10-27 | Tissue factor-targeted antibody-drug conjugate |
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EP (1) | EP3501548A4 (zh) |
JP (1) | JP7020655B2 (zh) |
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---|---|---|---|---|
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CN108452320A (zh) * | 2018-02-13 | 2018-08-28 | 和元生物技术(上海)股份有限公司 | 抗trailr2抗体-毒素-偶联物及其在抗肿瘤治疗中的药物用途 |
CN110141666A (zh) * | 2018-02-13 | 2019-08-20 | 和元生物技术(上海)股份有限公司 | 抗trailr2抗体-毒素-偶联物及其在抗肿瘤治疗中的药物用途 |
WO2019157973A1 (zh) * | 2018-02-13 | 2019-08-22 | 和元生物技术(上海)股份有限公司 | 抗trailr2抗体-毒素-偶联物及其在抗肿瘤治疗中的药物用途 |
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005025623A2 (en) * | 2003-07-28 | 2005-03-24 | Emory University | Ef-24-factor vii conjugates |
CN101195659A (zh) * | 2006-12-05 | 2008-06-11 | 复旦大学 | 高抗凝活性抗人组织因子单克隆抗体及其制备方法和应用 |
CN103119065A (zh) * | 2010-06-15 | 2013-05-22 | 根马布股份公司 | 针对组织因子的人抗体药物缀合物 |
WO2015075201A1 (en) * | 2013-11-21 | 2015-05-28 | Genmab A/S | Antibody-drug conjugate lyophilised formulation |
CN104892763A (zh) * | 2014-03-05 | 2015-09-09 | 中国科学院上海药物研究所 | 抗体-药物偶联物Pertuzumab-MCC-DM1、其与Trastuzumab的组合物及其应用 |
CN106467574A (zh) * | 2015-08-20 | 2017-03-01 | 复旦大学 | 靶向于组织因子的抗体、其制备方法和用途 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US5589173A (en) * | 1986-11-04 | 1996-12-31 | Genentech, Inc. | Method and therapeutic compositions for the treatment of myocardial infarction |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
WO1994005328A1 (en) * | 1992-08-28 | 1994-03-17 | The Scripps Research Institute | Inhibition of tumor metastasis via neutralization of tissue factor function |
US20060235209A9 (en) * | 1997-03-10 | 2006-10-19 | Jin-An Jiao | Use of anti-tissue factor antibodies for treating thromboses |
US7749498B2 (en) * | 1997-03-10 | 2010-07-06 | Genentech, Inc. | Antibodies for inhibiting blood coagulation and methods of use thereof |
US7579000B2 (en) * | 2002-05-01 | 2009-08-25 | Bayer Schering Pharma Ag | Tissue factor targeted antibodies as anticoagulants |
US7605235B2 (en) * | 2003-05-30 | 2009-10-20 | Centocor, Inc. | Anti-tissue factor antibodies and compositions |
NZ568762A (en) * | 2005-11-07 | 2011-11-25 | Scripps Research Inst | Use of an inhibitor of tissue factor signaling in the manufacture of a medcament for inhibiting or suppressing tissue factor/tissue factor VIIa signaling involving protease activated receptor 2 in a mammal |
UA109633C2 (uk) * | 2008-12-09 | 2015-09-25 | Антитіло людини проти тканинного фактора | |
US8722044B2 (en) * | 2011-03-15 | 2014-05-13 | Janssen Biotech, Inc. | Human tissue factor antibody and uses thereof |
ES2719584T3 (es) | 2014-04-11 | 2019-07-11 | Medimmune Llc | Compuestos conjugados que comprenden anticuerpos modificados por ingeniería genética con cisteína |
WO2018036117A1 (zh) | 2016-08-22 | 2018-03-01 | 复旦大学 | 靶向于组织因子的抗体、其制备方法和用途 |
CN110575547B (zh) | 2018-06-07 | 2021-07-30 | 中国科学院上海药物研究所 | 靶向于tf的抗体-药物偶联物及其制法和用途 |
-
2017
- 2017-03-03 CN CN201710125244.6A patent/CN106938051B/zh active Active
- 2017-06-09 US US16/326,886 patent/US11534495B2/en active Active
- 2017-06-09 JP JP2019511435A patent/JP7020655B2/ja active Active
- 2017-06-09 EP EP17842668.0A patent/EP3501548A4/en active Pending
- 2017-06-09 WO PCT/CN2017/087779 patent/WO2018036243A1/zh unknown
-
2022
- 2022-10-27 US US18/050,240 patent/US20230138930A1/en active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005025623A2 (en) * | 2003-07-28 | 2005-03-24 | Emory University | Ef-24-factor vii conjugates |
CN101195659A (zh) * | 2006-12-05 | 2008-06-11 | 复旦大学 | 高抗凝活性抗人组织因子单克隆抗体及其制备方法和应用 |
CN103119065A (zh) * | 2010-06-15 | 2013-05-22 | 根马布股份公司 | 针对组织因子的人抗体药物缀合物 |
WO2015075201A1 (en) * | 2013-11-21 | 2015-05-28 | Genmab A/S | Antibody-drug conjugate lyophilised formulation |
CN104892763A (zh) * | 2014-03-05 | 2015-09-09 | 中国科学院上海药物研究所 | 抗体-药物偶联物Pertuzumab-MCC-DM1、其与Trastuzumab的组合物及其应用 |
CN106467574A (zh) * | 2015-08-20 | 2017-03-01 | 复旦大学 | 靶向于组织因子的抗体、其制备方法和用途 |
Non-Patent Citations (4)
Title |
---|
ESTHER C.W. BREIJ ET AL: "An Antibody–Drug Conjugate That Targets Tissue Factor Exhibits Potent Therapeutic Activity against a Broad Range of Solid Tumors", 《AMERICAN ASSOCIATION FOR CANCER RESEARCH》 * |
XUESAI ZHANG ET A: "Pathological expression of tissue factor confers promising antitumor response to a novel therapeutic antibody SC1 in triple negative breast cancer and pancreatic adenocarcinoma", 《ONCOTARGET》 * |
YOSHIKATSU KOGA ET AL: "Antitumor effect of antitissue factor antibody-MMAE conjugate in human pancreatic tumor xenografts", 《INTERNATIONAL JOURNAL OF CANCER》 * |
曹睿,等: "肿瘤靶向治疗抗体药物的研究进展", 《中国生化药物杂志》 * |
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WO2022179571A1 (en) * | 2021-02-25 | 2022-09-01 | Shanghai Allygen Biologics Co., Ltd. | Targeting conjugates comprising targeting moiety binding fragments and uses thereof |
Also Published As
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EP3501548A4 (en) | 2020-06-17 |
JP7020655B2 (ja) | 2022-02-16 |
EP3501548A1 (en) | 2019-06-26 |
US20230138930A1 (en) | 2023-05-04 |
US20190201543A1 (en) | 2019-07-04 |
WO2018036243A1 (zh) | 2018-03-01 |
CN106938051B (zh) | 2019-10-11 |
JP2019528079A (ja) | 2019-10-10 |
US11534495B2 (en) | 2022-12-27 |
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