AU2017228468B2 - Process for the preparation of an antibody-rifamycin conjugate - Google Patents

Process for the preparation of an antibody-rifamycin conjugate Download PDF

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Publication number
AU2017228468B2
AU2017228468B2 AU2017228468A AU2017228468A AU2017228468B2 AU 2017228468 B2 AU2017228468 B2 AU 2017228468B2 AU 2017228468 A AU2017228468 A AU 2017228468A AU 2017228468 A AU2017228468 A AU 2017228468A AU 2017228468 B2 AU2017228468 B2 AU 2017228468B2
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AU
Australia
Prior art keywords
iii
antibody
amino
rifamycin
oxidants
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
AU2017228468A
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English (en)
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AU2017228468A1 (en
Inventor
Stephan Bachmann
Serena Maria FANTASIA
Michael Jansen
Stefan Koenig
Xin Linghu
Sebastian Rieth
Nathaniel L. SEGRAVES
Andreas Zogg
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Genentech Inc
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Genentech Inc
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Publication of AU2017228468B2 publication Critical patent/AU2017228468B2/en
Ceased legal-status Critical Current
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    • 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
    • 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
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/27—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups
    • C07C205/35—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C205/36—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
    • C07C205/37—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/74—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C215/76—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton of the same non-condensed six-membered aromatic ring
    • C07C215/78—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton of the same non-condensed six-membered aromatic ring containing at least two hydroxy groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Gram-positive bacteria
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Gram-positive bacteria
    • C07K16/1271—Micrococcaceae (F); Staphylococcaceae (F), e.g. Staphylococcus (G)
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77—Internalization into the cell

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Peptides Or Proteins (AREA)
  • Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
AU2017228468A 2016-03-04 2017-03-03 Process for the preparation of an antibody-rifamycin conjugate Ceased AU2017228468B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662303556P 2016-03-04 2016-03-04
US62/303,556 2016-03-04
PCT/US2017/020711 WO2017152083A1 (en) 2016-03-04 2017-03-03 Process for the preparation of an antibody-rifamycin conjugate

Publications (2)

Publication Number Publication Date
AU2017228468A1 AU2017228468A1 (en) 2018-07-26
AU2017228468B2 true AU2017228468B2 (en) 2019-12-05

Family

ID=58361102

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2017228468A Ceased AU2017228468B2 (en) 2016-03-04 2017-03-03 Process for the preparation of an antibody-rifamycin conjugate

Country Status (13)

Country Link
US (2) US10336683B2 (enExample)
EP (1) EP3423457B1 (enExample)
JP (2) JP6705904B2 (enExample)
KR (1) KR102204805B1 (enExample)
CN (1) CN108713020A (enExample)
AR (1) AR107800A1 (enExample)
AU (1) AU2017228468B2 (enExample)
BR (1) BR112018014355A2 (enExample)
CA (1) CA3012046C (enExample)
IL (1) IL260465B (enExample)
MX (1) MX2018010491A (enExample)
SG (1) SG11201807537RA (enExample)
WO (1) WO2017152083A1 (enExample)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102204805B1 (ko) 2016-03-04 2021-01-20 제넨테크, 인크. 항체-리파마이신 접합체의 제조 방법
CN108047250B (zh) * 2018-02-12 2020-08-14 丹诺医药(苏州）有限公司 一种利福霉素-硝基咪唑偶联分子的应用
CN110687218B (zh) * 2018-08-07 2021-04-23 中国科学院大连化学物理研究所 液相色谱测定苯并噁嗪利福霉素的方法
CN110687217B (zh) * 2018-08-07 2021-04-23 中国科学院大连化学物理研究所 液相色谱测定利福霉素s的方法
PH12021551476A1 (en) * 2018-12-21 2022-04-25 Regeneron Pharma Rifamycin analogs and antibody-drug conjugates thereof
EP4387618A4 (en) * 2021-08-20 2025-07-09 Univ Rutgers DUAL-TARGETED RNA POLYMERASE INHIBITORS: CONJUGATES OF BENZOXAZINO- AND SPIRO-RIFAMYCINS WITH N-AROYL- N-ARYL-PHENYLALANINAMIDES
CN114436864A (zh) * 2022-02-17 2022-05-06 浙江鼎龙科技股份有限公司 一种2-甲基-5氨基苯酚的制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140356375A1 (en) * 2013-05-31 2014-12-04 Genentech, Inc. Anti-wall teichoic antibodies and conjugates

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB877732A (en) 1958-08-12 1961-09-20 Lepetit Spa The antibiotic rifomycin, its components and methods of preparing same
US4690919A (en) 1984-01-04 1987-09-01 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Benzoxazinorifamycin derivative, process for preparing the same and antibacterial agent containing the same
JPS63183587A (ja) 1985-02-05 1988-07-28 Kanegafuchi Chem Ind Co Ltd ベンゾキサジノリフアマイシン誘導体
CA1304363C (en) 1988-11-01 1992-06-30 Takehiko Yamane 3'-hydroxybenzoxazinorifamycin derivative, process for preparing the same and antibacterial agent containing the same
US6322788B1 (en) 1998-08-20 2001-11-27 Stanley Arthur Kim Anti-bacterial antibodies and methods of use
DK1545613T3 (da) 2002-07-31 2011-11-14 Seattle Genetics Inc Auristatinkonjugater og deres anvendelse til behandling af cancer, en autoimmun sygdom eller en infektiøs sygdom
CN1894259A (zh) 2003-08-22 2007-01-10 活跃生物工艺学公司 利福霉素类似物及其应用
EP2478912B1 (en) 2003-11-06 2016-08-31 Seattle Genetics, Inc. Auristatin conjugates with anti-HER2 or anti-CD22 antibodies and their use in therapy
CN1918172B (zh) 2003-12-23 2011-09-14 活跃生物工艺学公司 利福霉素类似物及其用途
US7265107B2 (en) 2004-03-10 2007-09-04 Cumbre Pharmaceuticals Inc. Rifamycin C-11 oxime cyclo derivatives effective against drug-resistant microbes
DK1791565T3 (en) 2004-09-23 2016-08-01 Genentech Inc Cysteingensplejsede antibodies and conjugates
CN101395259A (zh) 2005-12-14 2009-03-25 活跃生物药物学有限公司 利福霉素类似物及其应用
WO2008008480A2 (en) 2006-07-12 2008-01-17 Cumbre Pharmaceuticals Inc. Nitroheteroaryl-containing rifamycin derivatives
DK2121920T3 (da) 2007-03-01 2011-11-21 Symphogen As Fremgangsmåde til kloning af sammenhørende antistoffer
CL2008001334A1 (es) 2007-05-08 2008-09-22 Genentech Inc Anticuerpo anti-muc16 disenado con cisteina; conjugado que lo comprende; metodo de produccion; formulacion farmaceutica que lo comprende; y su uso para tratar el cancer.
NZ584514A (en) 2007-10-19 2012-07-27 Genentech Inc Cysteine engineered anti-tenb2 antibodies and antibody drug conjugates
WO2009064792A1 (en) 2007-11-16 2009-05-22 Cumbre Pharmaceuticals Inc. Quinolone carboxylic acid-substituted rifamycin derivatives
WO2009086277A1 (en) * 2007-12-20 2009-07-09 Envivo Pharmaceuticals, Inc. Tetrasubstituted benzenes
WO2010019511A2 (en) 2008-08-13 2010-02-18 Targanta Therapeutics Corp. Phosphonated rifamycins and uses thereof for the prevention and treatment of bone and joint infections
CA2799540A1 (en) 2010-06-08 2011-12-15 Genentech, Inc. Cysteine engineered antibodies and conjugates
WO2013168965A2 (ko) 2012-05-07 2013-11-14 목암생명공학연구소 포도상구균 감염 예방용 백신 조성물
JP6371758B2 (ja) 2013-03-12 2018-08-08 全薬工業株式会社 抗ブドウ球菌抗体、その製造方法並びにその使用
MX369022B (es) 2013-05-31 2019-10-25 Genentech Inc Anticuerpos anti-ácido teicoico de la pared celular y conjugados.
RU2687044C2 (ru) 2013-05-31 2019-05-06 Дженентек, Инк. Антитела против стеночной тейхоевой кислоты и их конъюгаты
HK1243931A1 (zh) * 2014-12-03 2018-07-27 F. Hoffmann-La Roche Ag 抗金黄色葡萄球菌抗体利福霉素缀合物及其用途
RU2017118792A (ru) * 2014-12-03 2019-01-09 Дженентек, Инк. Конъюгаты антитела к staphylococcus aureus с рифамицином и их применение
KR102204805B1 (ko) 2016-03-04 2021-01-20 제넨테크, 인크. 항체-리파마이신 접합체의 제조 방법

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140356375A1 (en) * 2013-05-31 2014-12-04 Genentech, Inc. Anti-wall teichoic antibodies and conjugates

Also Published As

Publication number Publication date
EP3423457A1 (en) 2019-01-09
US10336683B2 (en) 2019-07-02
JP2019510740A (ja) 2019-04-18
US20190270695A1 (en) 2019-09-05
EP3423457B1 (en) 2021-02-17
CA3012046A1 (en) 2017-09-08
WO2017152083A1 (en) 2017-09-08
KR102204805B1 (ko) 2021-01-20
US10689325B2 (en) 2020-06-23
MX2018010491A (es) 2018-11-09
CA3012046C (en) 2020-11-10
JP2020090506A (ja) 2020-06-11
AR107800A1 (es) 2018-06-06
KR20180118173A (ko) 2018-10-30
CN108713020A (zh) 2018-10-26
JP6705904B2 (ja) 2020-06-03
SG11201807537RA (en) 2018-09-27
US20170252457A1 (en) 2017-09-07
BR112018014355A2 (pt) 2018-12-18
AU2017228468A1 (en) 2018-07-26
IL260465B (en) 2020-11-30

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