CO2019006565A2 - Novedoso conjugado de amanitina - Google Patents

Novedoso conjugado de amanitina

Info

Publication number
CO2019006565A2
CO2019006565A2 CONC2019/0006565A CO2019006565A CO2019006565A2 CO 2019006565 A2 CO2019006565 A2 CO 2019006565A2 CO 2019006565 A CO2019006565 A CO 2019006565A CO 2019006565 A2 CO2019006565 A2 CO 2019006565A2
Authority
CO
Colombia
Prior art keywords
conjugate
novel
amatoxin
amino acid
binding moiety
Prior art date
Application number
CONC2019/0006565A
Other languages
English (en)
Inventor
Torsten Hechler
Michael Kulke
Christian Lutz
Andreas Pahl
CHRISTOPH MüLLER
Werner Simon
Anikó Pálfi
Original Assignee
Heidelberg Pharma Res Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Heidelberg Pharma Res Gmbh filed Critical Heidelberg Pharma Res Gmbh
Publication of CO2019006565A2 publication Critical patent/CO2019006565A2/es

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/50—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
    • 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
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • A61K47/6831—Fungal toxins, e.g. alpha sarcine, mitogillin, zinniol or restrictocin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/50—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
    • 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
    • A61K47/6851—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 determinant of a tumour cell
    • A61K47/6867—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 determinant of a tumour cell the tumour determinant being from a cell of a blood cancer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/50—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
    • 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
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/50—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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/37—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi
    • 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
    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Toxicology (AREA)
  • Cell Biology (AREA)
  • Mycology (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

La invención se refiere a un conjugado que comprende (a) una amatoxina que comprende un aminoácido 4 con una posición 6'-desoxi; y (ii) un aminoácido 8 con una posición S-desoxi; (b) un resto de unión a BCMA que comprende (i) los dominios variables del anticuerpo humanizado J22.9-ISY, y (ii) una región constante de cadena pesada que comprende una mutación D265C; y (c) un enlazador escindible por la proteasa que enlaza dicha amatoxina y dicho resto de unión a diana. La invención se refiere además a una composición farmacéutica que comprende dicho conjugado, particularmente, para el uso en el tratamiento del mieloma múltiple.
CONC2019/0006565A 2016-12-23 2019-06-20 Novedoso conjugado de amanitina CO2019006565A2 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP16206849 2016-12-23
PCT/EP2017/084431 WO2018115466A1 (en) 2016-12-23 2017-12-22 Amanitin antibody conjugates

Publications (1)

Publication Number Publication Date
CO2019006565A2 true CO2019006565A2 (es) 2019-09-18

Family

ID=57680140

Family Applications (1)

Application Number Title Priority Date Filing Date
CONC2019/0006565A CO2019006565A2 (es) 2016-12-23 2019-06-20 Novedoso conjugado de amanitina

Country Status (14)

Country Link
US (1) US11446388B2 (es)
EP (1) EP3558390A1 (es)
JP (1) JP7038717B2 (es)
KR (1) KR102455175B1 (es)
CN (1) CN110099698B (es)
AU (1) AU2017380099A1 (es)
BR (1) BR112019012937A2 (es)
CA (1) CA3044508A1 (es)
CL (1) CL2019001740A1 (es)
CO (1) CO2019006565A2 (es)
MX (1) MX2019007604A (es)
RU (1) RU2755728C2 (es)
WO (1) WO2018115466A1 (es)
ZA (1) ZA201903062B (es)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20230082055A (ko) 2016-06-17 2023-06-08 마젠타 테라퓨틱스 인코포레이티드 세포의 고갈을 위한 조성물 및 방법
JOP20190156B1 (ar) 2016-12-23 2023-09-17 Bayer Pharma AG أميدات عطرية لحمض الكربوكسيليك بصفتها مضادات لمستقبلة البراديكينين b1
WO2018134787A2 (en) 2017-01-20 2018-07-26 Magenta Therapeutics, Inc. Compositions and methods for the depletion of cd137+ cells
AU2018317611B2 (en) * 2017-08-18 2022-03-10 Baili-Bio (Chengdu) Pharmaceutical Co., Ltd. Non-natural amatoxin-type antibody conjugate
EP3773740A1 (en) * 2018-04-13 2021-02-17 Heidelberg Pharma Research GmbH Targeted amatoxin conjugate for the treatment of solid tumors
JP2022512629A (ja) * 2018-10-23 2022-02-07 マジェンタ セラピューティクス インコーポレイテッド Ｆｃサイレンス化抗体薬物コンジュゲート（ＡＤＣ）及びその使用
JP2022530026A (ja) 2019-04-24 2022-06-27 ハイデルベルク ファルマ リサーチ ゲゼルシャフト ミット ベシュレンクテル ハフツング アマトキシン抗体薬物複合体及びその使用
CN114144201A (zh) * 2019-05-23 2022-03-04 海德堡医药研究有限责任公司 含可裂解连接基的抗体药物缀合物
AR120218A1 (es) * 2019-10-15 2022-02-02 Heidelberg Pharma Res Gmbh Conjugados de amatoxina y anticuerpo específico de linfocitos b
JP2023502745A (ja) * 2019-11-21 2023-01-25 アンナチュラル・プロダクツ・インコーポレイテッド 細胞透過性環状ペプチドおよびその使用
CA3195572A1 (en) 2020-11-04 2022-05-12 Heidelberg Pharma Research Gmbh Composition comprising a combination of immune checkpoint inhibitor and antibody-amatoxin conjugate for use in cancer therapy
WO2022187591A1 (en) 2021-03-05 2022-09-09 Go Therapeutics, Inc. Anti-glyco-cd44 antibodies and their uses
AR125130A1 (es) 2021-03-19 2023-06-14 Heidelberg Pharma Res Gmbh Conjugados de amatoxina y anticuerpo específicos de linfocitos b
CA3228178A1 (en) 2021-08-05 2023-02-09 Go Therapeutics, Inc. Anti-glyco-muc4 antibodies and their uses
WO2023194539A1 (en) 2022-04-07 2023-10-12 Heidelberg Pharma Research Gmbh Methods of improving the therapeutic index of amatoxin-antibody conjugates
CN114839284B (zh) * 2022-04-14 2024-03-26 中国疾病预防控制中心职业卫生与中毒控制所 非疾病诊断目的的鹅膏毒肽检测方法
EP4353220A1 (en) 2022-10-12 2024-04-17 Pierre Fabre Medicament Use of a liquid aqueous composition for solubilization and stabilization of an antibody-drug conjugate
US20240165257A1 (en) 2022-11-01 2024-05-23 Heidelberg Pharma Research Gmbh Anti-gucy2c antibody and uses thereof

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1690935A3 (en) 1990-01-12 2008-07-30 Abgenix, Inc. Generation of xenogeneic antibodies
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
EP1859811B1 (en) * 2006-05-27 2011-08-24 Faulstich, Heinz, Dr. Use of conjugates of amatoxins or phallotoxins with macromolecules for tumor and inflammation therapy
JP2012523383A (ja) 2009-04-08 2012-10-04 ファウルシュティヒ，ハインツ がんの治療のためのアマトキシンと複合体形成した標的結合部分
WO2010115629A2 (en) * 2009-04-08 2010-10-14 Deutsches Krebsforschungszentrum Amatoxin-armed therapeutic cell surface binding components designed for tumour therapy
CA2758230A1 (en) 2009-04-09 2010-10-14 Aqua Rehab Inc. Device and method for sealing a junction between a main pipe and a lateral pipe connected thereto
US20130028917A1 (en) 2010-04-15 2013-01-31 Spirogen Developments Sàrl Pyrrolobenzodiazepines and conjugates thereof
EP2436398B1 (en) * 2010-09-30 2013-01-23 Heidelberg Pharma GmbH Amatoxin-conjugates with improved linkers
EP2497499A1 (en) 2011-03-10 2012-09-12 Heidelberg Pharma GmbH Amatoxin-conjugates with improved linkages
EP2684865A1 (en) 2012-07-13 2014-01-15 Heidelberg Pharma GmbH Methods for synthesizing amatoxin building block and amatoxins
EP3508503B1 (en) 2012-11-01 2022-11-02 Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft Antibody against cd269 (bcma)
US9243058B2 (en) * 2012-12-07 2016-01-26 Amgen, Inc. BCMA antigen binding proteins
EP2774624A1 (en) 2013-03-04 2014-09-10 Heidelberg Pharma GmbH Amatoxin derivatives
JP6321687B2 (ja) * 2014-03-10 2018-05-09 ハイデルベルク ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング アマトキシン誘導体
NZ725701A (en) 2014-04-30 2023-09-29 Max Delbrueck Centrum Fuer Molekulare Medizin Helmholtz Gemeinschaft Humanized antibodies against cd269 (bcma)
MX2017005268A (es) 2014-10-24 2017-07-26 Dupont Nutrition Biosci Aps Tripeptidil peptidasas tolerantes a prolina y usos de las mismas.
LT3268047T (lt) * 2015-03-09 2023-11-10 Heidelberg Pharma Research Gmbh Amatoksino-antikūno konjugatai
EP3222292A1 (en) * 2016-03-03 2017-09-27 Heidelberg Pharma GmbH Amanitin conjugates
MX2018015684A (es) 2016-06-17 2019-08-29 Magenta Therapeutics Inc Composiciones y metodos para el agotamiento de celulas cd117.

Also Published As

Publication number Publication date
US20190328899A1 (en) 2019-10-31
KR20190100190A (ko) 2019-08-28
CN110099698B (zh) 2023-02-17
ZA201903062B (en) 2023-08-30
JP7038717B2 (ja) 2022-03-18
MX2019007604A (es) 2019-08-16
RU2019119442A3 (es) 2021-03-04
JP2020504736A (ja) 2020-02-13
CL2019001740A1 (es) 2019-12-06
KR102455175B1 (ko) 2022-10-17
US11446388B2 (en) 2022-09-20
RU2755728C2 (ru) 2021-09-20
BR112019012937A2 (pt) 2019-12-10
WO2018115466A1 (en) 2018-06-28
CN110099698A (zh) 2019-08-06
AU2017380099A1 (en) 2019-06-13
RU2019119442A (ru) 2020-12-21
EP3558390A1 (en) 2019-10-30
CA3044508A1 (en) 2018-06-28

Similar Documents

Publication Publication Date Title
CO2019006565A2 (es) Novedoso conjugado de amanitina
BR112019012354A2 (pt) anticorpos apenas de cadeia pesada anti-bcma
CY1124834T1 (el) Αναστολεις της αλληλεπιδρασης της μηνινης-mll
CY1123977T1 (el) Anti-pd-1 και anti-lag3 αντισωματα για την θεραπεια του καρκινου
CL2020000263A1 (es) Conjugado de anticuerpo monoclonal contra bcma-fármaco.
PE20181805A1 (es) Composiciones y anticuerpos anti-tim-3
PH12018501419A1 (en) Pharmaceutical composition comprising bispecific antibody constructs
CL2023000895A1 (es) Receptores quiméricos de dll3 y métodos para su uso
CO2017000754A2 (es) Anticuerpo monoclonal anti-ctla4 o fragmento de unión a antígeno del mismo, y una composición farmacéutica del mismo
CO2018011195A2 (es) Composiciones que comprenden una coformulación de anticuerpos anti-pd-l1 y anti-ctla-4
PE20170665A1 (es) Anticuerpos anti-tau humanizados
CY1125025T1 (el) 2-φορμυλ-3-υδροξυφαινυλοξυμεθυλ ενωσεις ικανες ρυθμισης αιμοσφαιρινης
CO2020010345A2 (es) Dominios variables de anticuerpos que se dirigen al receptor nkg2d
PE20171180A1 (es) Anticuerpos anti-pd-1 y sus metodos de uso
NZ734892A (en) Amatoxin-antibody conjugates
AR117913A2 (es) Conjugado fármaco-anticuerpo, composición farmacéutica y sus usos
CL2023002105A1 (es) Dominios variables de anticuerpo que se dirigen a cd33 y sus usos
MX2022006461A (es) Anticuerpos anti-axl, fragmentos de anticuerpos y sus inmunoconjugados y usos de los mismos.
PE20210167A1 (es) Proteinas de union multiespecificas y mejoras con estas
BR112021019334A2 (pt) Anticorpos de cadeia pesada que se ligam ao psma
MX2020012679A (es) Compuestos de amino-pirazincarboxamida, conjugados, y usos de los mismos.
BR112019000693A2 (pt) composições de muc1- car e métodos para uso
EA202091161A1 (ru) Конъюгаты антител против cd22 с майтанзином, их комбинации и способы применения
PE20201171A1 (es) Anticuerpos de cadena pesada que se unen a cd22
MX2022009915A (es) Anticuerpos anti-ror2, fragmentos de anticuerpos, sus inmunoconjugados y usos de los mismos.