SG11201700365TA - Methods of conjugating an agent to a thiol moiety in a protein that contains at least one trisulfide bond - Google Patents

Methods of conjugating an agent to a thiol moiety in a protein that contains at least one trisulfide bond

Info

Publication number
SG11201700365TA
SG11201700365TA SG11201700365TA SG11201700365TA SG11201700365TA SG 11201700365T A SG11201700365T A SG 11201700365TA SG 11201700365T A SG11201700365T A SG 11201700365TA SG 11201700365T A SG11201700365T A SG 11201700365TA SG 11201700365T A SG11201700365T A SG 11201700365TA
Authority
SG
Singapore
Prior art keywords
conjugating
protein
agent
methods
thiol moiety
Prior art date
Application number
SG11201700365TA
Other languages
English (en)
Inventor
Jayme Franklin
xin xin Lin
Jeffrey Gorrell
Timothy Tully
Matthew Hutchinson
Charity Tucker Bechtel
Original Assignee
Genentech Inc
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 Genentech Inc filed Critical Genentech Inc
Publication of SG11201700365TA publication Critical patent/SG11201700365TA/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07—Tetrapeptides
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • A61K47/68031—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
    • 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
    • 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
    • A61K47/6849—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
    • C07K1/1133—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by redox-reactions involving cystein/cystin side chains
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Cell Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
SG11201700365TA 2014-07-24 2015-07-17 Methods of conjugating an agent to a thiol moiety in a protein that contains at least one trisulfide bond SG11201700365TA (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201462028679P 2014-07-24 2014-07-24
PCT/US2015/040931 WO2016014360A1 (en) 2014-07-24 2015-07-17 Methods of conjugating an agent to a thiol moiety in a protein that contains at least one trisulfide bond

Publications (1)

Publication Number Publication Date
SG11201700365TA true SG11201700365TA (en) 2017-02-27

Family

ID=55163580

Family Applications (2)

Application Number Title Priority Date Filing Date
SG11201700365TA SG11201700365TA (en) 2014-07-24 2015-07-17 Methods of conjugating an agent to a thiol moiety in a protein that contains at least one trisulfide bond
SG10202102467RA SG10202102467RA (en) 2014-07-24 2015-07-17 Methods of conjugating an agent to a thiol moiety in a protein that contains at least one trisulfide bond

Family Applications After (1)

Application Number Title Priority Date Filing Date
SG10202102467RA SG10202102467RA (en) 2014-07-24 2015-07-17 Methods of conjugating an agent to a thiol moiety in a protein that contains at least one trisulfide bond

Country Status (15)

Country Link
US (2) US11370838B2 (https=)
EP (1) EP3172219A4 (https=)
JP (3) JP6956630B2 (https=)
KR (1) KR102463267B1 (https=)
CN (1) CN106536540A (https=)
AR (1) AR101304A1 (https=)
AU (2) AU2015294389B2 (https=)
BR (1) BR112017001403A2 (https=)
CA (1) CA2955007C (https=)
IL (1) IL250148B2 (https=)
MX (2) MX2017001022A (https=)
MY (1) MY198629A (https=)
RU (2) RU2021106673A (https=)
SG (2) SG11201700365TA (https=)
WO (1) WO2016014360A1 (https=)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG11201700365TA (en) * 2014-07-24 2017-02-27 Genentech Inc Methods of conjugating an agent to a thiol moiety in a protein that contains at least one trisulfide bond
JP7148524B2 (ja) * 2017-02-08 2022-10-05 ファイザー・インク キャップされたおよびキャップされていない抗体システインのための大規模産生プロセス、ならびに治療的タンパク質コンジュゲーションにおけるその使用

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
JPS5896026A (ja) 1981-10-30 1983-06-07 Nippon Chemiphar Co Ltd 新規ウロキナ−ゼ誘導体およびその製造法ならびにそれを含有する血栓溶解剤
DE3380726D1 (en) 1982-06-24 1989-11-23 Japan Chem Res Long-acting composition
US4766106A (en) 1985-06-26 1988-08-23 Cetus Corporation Solubilization of proteins for pharmaceutical compositions using polymer conjugation
JP2665353B2 (ja) * 1988-09-10 1997-10-22 住商ファーマインターナショナル株式会社 双特異性抗体の製造法
JPH0278699A (ja) 1988-09-12 1990-03-19 Green Cross Corp:The ベンゾイルウレア系化合物・アルブミン複合体
JPH02218700A (ja) * 1989-02-17 1990-08-31 Nippon Kayaku Co Ltd 双特異性抗体及びそれを用いる養子免疫療法
US5622929A (en) 1992-01-23 1997-04-22 Bristol-Myers Squibb Company Thioether conjugates
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
ZA955789B (en) 1994-07-15 1996-03-11 Novo Nordisk As A method of converting a hydrophobic derivative of a polypeptide into the native form
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
JPH11124395A (ja) 1997-10-16 1999-05-11 Seiwa Kasei Kk システイン導入ペプチドおよびその製造方法
SE9802454D0 (sv) 1998-07-08 1998-07-08 Pharmacia & Upjohn Ab Production of peptides
EP1183357A2 (en) 1999-05-20 2002-03-06 Scios Inc. Vascular endothelial growth factor dimers
CA2434045A1 (en) 2000-10-31 2002-08-15 The Regents Of The University Of Colorado, A Body Corporate Improved protein disaggregation and refolding using high pressure
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
US20040048315A1 (en) 2002-08-28 2004-03-11 Pharmacia Corporation Method for the preparation of growth hormone and antagonist thereof having lower levels of isoform impurities thereof
JP5356648B2 (ja) 2003-02-20 2013-12-04 シアトル ジェネティックス， インコーポレイテッド 抗ｃｄ７０抗体−医薬結合体、ならびに癌および免疫障害の処置のためのそれらの使用
ES2383300T3 (es) 2003-11-13 2012-06-20 Hanmi Holdings Co., Ltd Fragmento Fc de IgG para un vehículo de fármacos y procedimiento para su preparación
JP4942643B2 (ja) * 2004-03-02 2012-05-30 シアトル ジェネティックス， インコーポレイテッド 部分的に付加された抗体およびそれらの結合体化方法
NZ579482A (en) * 2004-06-01 2011-02-25 Genentech Inc Antibody drug conjugates and methods
ATE463503T1 (de) * 2004-12-29 2010-04-15 Novo Nordisk Healthcare Ag Verfahren zur verhinderung der bildung von trisulfidderivaten von polypeptiden
EP2032606B1 (en) * 2006-05-30 2013-11-27 Genentech, Inc. Antibodies and immunoconjugates and uses therefor
US20080220448A1 (en) 2006-09-01 2008-09-11 Blincko Stuart J Antigenic protein conjugates and process for preparing same
JP5394246B2 (ja) 2007-03-30 2014-01-22 ジェネンテック， インコーポレイテッド 抗体及びイムノコンジュゲートとこれらの使用方法
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.
EP2176295B1 (en) 2007-07-16 2014-11-19 Genentech, Inc. Humanized anti-cd79b antibodies and immunoconjugates and methods of use
PE20090943A1 (es) 2007-07-16 2009-08-05 Genentech Inc Anticuerpos anti-cd79b e inmunoconjugados
EP2249967B1 (en) * 2008-01-31 2019-03-13 Ingevity South Carolina, LLC Oxidized and maleated derivative composition
KR101607346B1 (ko) 2008-01-31 2016-03-29 제넨테크, 인크. 항-ｃｄ７９ｂ 항체 및 면역접합체 및 사용 방법
EP2483289B2 (en) * 2009-10-02 2025-03-26 Biogen MA Inc. Methods of preventing and removing trisulfide bonds
PL2542576T3 (pl) * 2010-03-02 2016-10-31 Sposoby badań przesiewowych przeciwciał
JP2014500248A (ja) * 2010-11-05 2014-01-09 コヴェックス・テクノロジーズ・アイルランド・リミテッド 抗糖尿病化合物
WO2012158551A1 (en) * 2011-05-13 2012-11-22 Biogen Idec Ma Inc. Methods of preventing and removing trisulfide bonds
SG11201401422VA (en) * 2011-10-27 2014-09-26 Genmab As Production of heterodimeric proteins
JP2015502397A (ja) * 2011-12-23 2015-01-22 ファイザー・インク 部位特異的コンジュゲーションのための操作された抗体定常領域、ならびにそのための方法および使用
US9056910B2 (en) * 2012-05-01 2015-06-16 Genentech, Inc. Anti-PMEL17 antibodies and immunoconjugates
EP2861261A2 (en) * 2012-06-19 2015-04-22 Polytherics Limited Process for preparation of antibody conjugates and antibody conjugates
SG11201700365TA (en) * 2014-07-24 2017-02-27 Genentech Inc Methods of conjugating an agent to a thiol moiety in a protein that contains at least one trisulfide bond

Also Published As

Publication number Publication date
JP6956630B2 (ja) 2021-11-02
US20220372141A1 (en) 2022-11-24
SG10202102467RA (en) 2021-04-29
WO2016014360A1 (en) 2016-01-28
RU2021106673A (ru) 2021-11-25
AU2021209196B2 (en) 2023-02-02
MY198629A (en) 2023-09-11
KR20170028435A (ko) 2017-03-13
AU2015294389B2 (en) 2021-04-29
AU2021209196A1 (en) 2021-08-19
AU2015294389A1 (en) 2017-02-23
MX2017001022A (es) 2017-12-20
IL250148B2 (en) 2023-03-01
IL250148A0 (en) 2017-03-30
CN106536540A (zh) 2017-03-22
IL250148B (en) 2022-11-01
JP2023052645A (ja) 2023-04-11
US20170209593A1 (en) 2017-07-27
US11370838B2 (en) 2022-06-28
CA2955007C (en) 2023-04-11
JP7219256B2 (ja) 2023-02-07
BR112017001403A2 (pt) 2017-11-21
CA2955007A1 (en) 2016-01-28
AR101304A1 (es) 2016-12-07
KR102463267B1 (ko) 2022-11-03
RU2744978C2 (ru) 2021-03-17
RU2017105428A3 (https=) 2018-08-29
RU2017105428A (ru) 2018-08-29
JP2017526652A (ja) 2017-09-14
JP2021046419A (ja) 2021-03-25
MX2022012589A (es) 2022-11-09
EP3172219A4 (en) 2018-04-04
EP3172219A1 (en) 2017-05-31

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