ECSP19078277A - Nuevos ligadores peptídicos y conjugados de criptoficina y su preparación - Google Patents

Nuevos ligadores peptídicos y conjugados de criptoficina y su preparación

Info

Publication number
ECSP19078277A
ECSP19078277A ECSENADI201978277A ECDI201978277A ECSP19078277A EC SP19078277 A ECSP19078277 A EC SP19078277A EC SENADI201978277 A ECSENADI201978277 A EC SENADI201978277A EC DI201978277 A ECDI201978277 A EC DI201978277A EC SP19078277 A ECSP19078277 A EC SP19078277A
Authority
EC
Ecuador
Prior art keywords
conjugates
cryptophyphin
preparation
disclosure
chemical group
Prior art date
Application number
ECSENADI201978277A
Other languages
English (en)
Spanish (es)
Inventor
Marie-Priscille Brun
Philippe Hubert
Herve Bouchard
Original Assignee
Sanofi Sa
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 Sanofi Sa filed Critical Sanofi Sa
Publication of ECSP19078277A publication Critical patent/ECSP19078277A/es

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/15Depsipeptides; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/62Medicinal 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
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/62Medicinal 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
    • A61K47/65Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817Toxins
    • A61K47/6829Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6889Conjugates 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K11/00Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06017Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06052Val-amino acid

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Toxicology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
ECSENADI201978277A 2017-05-10 2019-10-31 Nuevos ligadores peptídicos y conjugados de criptoficina y su preparación ECSP19078277A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP17305531 2017-05-10
PCT/EP2018/061989 WO2018206635A1 (en) 2017-05-10 2018-05-09 Peptidic linkers and cryptophycin conjugates, useful in therapy, and their preparation

Publications (1)

Publication Number Publication Date
ECSP19078277A true ECSP19078277A (es) 2019-11-30

Family

ID=58873750

Family Applications (1)

Application Number Title Priority Date Filing Date
ECSENADI201978277A ECSP19078277A (es) 2017-05-10 2019-10-31 Nuevos ligadores peptídicos y conjugados de criptoficina y su preparación

Country Status (21)

Country Link
US (5) US20180369401A1 (https=)
EP (1) EP3621658A1 (https=)
JP (2) JP2020519610A (https=)
KR (1) KR102722886B1 (https=)
CN (1) CN110831633A (https=)
AR (1) AR111781A1 (https=)
AU (2) AU2018265333C1 (https=)
BR (1) BR112019023336A2 (https=)
CA (1) CA3062977A1 (https=)
CO (1) CO2019012108A2 (https=)
EA (1) EA201992667A1 (https=)
EC (1) ECSP19078277A (https=)
IL (1) IL270507B2 (https=)
MA (1) MA50764A (https=)
MX (1) MX2019013421A (https=)
MY (1) MY204075A (https=)
PH (1) PH12019550230A1 (https=)
TN (1) TN2019000303A1 (https=)
TW (1) TWI778059B (https=)
UY (1) UY37728A (https=)
WO (1) WO2018206635A1 (https=)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11951165B2 (en) 2016-12-30 2024-04-09 Vaxcyte, Inc. Conjugated vaccine carrier proteins
ES3024474T3 (en) 2016-12-30 2025-06-04 Vaxcyte Inc Polypeptide-antigen conjugates with non-natural amino acids
EP3621658A1 (en) 2017-05-10 2020-03-18 Sanofi Peptidic linkers and cryptophycin conjugates, useful in therapy, and their preparation
CN111154133B (zh) * 2020-01-03 2022-07-12 万华化学集团股份有限公司 一种环氧树脂发泡剂,环氧树脂组合物及环氧发泡材料的制备方法和用途
CN114053426B (zh) * 2020-07-30 2024-06-18 成都科岭源医药技术有限公司 一种双药链接组装单元及双药靶向接头-药物偶联物
CN115105607B (zh) * 2021-03-22 2024-12-20 成都科岭源医药技术有限公司 一种用于adc的双药-接头的制备方法及其用途
KR20240150807A (ko) 2022-02-22 2024-10-16 아라리스 바이오테크 아게 2개 이상의 페이로드를 포함하는 펩티드 링커
CN115212315A (zh) * 2022-08-03 2022-10-21 联宁(苏州)生物制药有限公司 一种抗体偶联药物中间体及含有其的抗体偶联药物
WO2025082990A1 (en) 2023-10-15 2025-04-24 Araris Biotech Ag Antibody-drug conjugates using two different types of topoisomerase i inhibitors
WO2026013234A1 (en) 2024-07-10 2026-01-15 Araris Biotech Ag Triple-payload antibody-drug conjugates (adcs)

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4040907A (en) * 1974-06-20 1977-08-09 Syva Company Iodothyronine enzyme conjugates
WO1995017093A1 (en) 1993-12-21 1995-06-29 University Of Hawaii New cryptophycins
PT934065E (pt) * 1996-08-30 2006-10-31 Univ Hawaii Compostos farmaceuticos
US20020128185A1 (en) 1998-02-25 2002-09-12 Chuan Shih Pharmaceutical compounds
US7230101B1 (en) 2002-08-28 2007-06-12 Gpc Biotech, Inc. Synthesis of methotrexate-containing heterodimeric molecules
US20050175619A1 (en) 2004-02-05 2005-08-11 Robert Duffy Methods of producing antibody conjugates
EP2010475A2 (en) 2006-04-27 2009-01-07 Intezyne Technologies Incorporated Heterofunctional poly(ethylene glycol) containing acid-labile amino protecting groups and uses thereof
ES2673822T3 (es) 2006-07-18 2018-06-25 Sanofi Anticuerpo antagonista contra EphA2 para el tratamiento de cáncer
BRPI0812970A2 (pt) * 2007-06-25 2019-09-24 Endocyte Inc conjugados contendo espaçadores hidrofílicos
FR2947269B1 (fr) * 2009-06-29 2013-01-18 Sanofi Aventis Nouveaux composes anticancereux
US8953557B2 (en) 2009-06-30 2015-02-10 Alcatel Lucent Roaming method for a mobile terminal in WLAN, related access controller and access point device
TW201116297A (en) 2009-10-02 2011-05-16 Sanofi Aventis Antibodies that specifically bind to the EphA2 receptor
WO2015057876A1 (en) * 2013-10-15 2015-04-23 Sorrento Therapeutics Inc. Drug-conjugates with a targeting molecule and two different drugs
ES2826398T3 (es) 2013-10-15 2021-05-18 Seagen Inc Enlazadores-fármacos pegilados para una mejor farmacocinética de los conjugados ligando-fármaco
EP3068443B1 (en) * 2013-11-12 2019-04-10 Centre for Probe Development and Commercialization Residualizing linkers and uses thereof
US10736974B2 (en) 2014-10-22 2020-08-11 The Johns Hopkins University Scaffolds and multifunctional intermediates for imaging PSMA and cancer therapy
JP2018506509A (ja) * 2014-12-09 2018-03-08 アッヴィ・インコーポレイテッド 細胞透過性Bcl−xL阻害剤との抗体薬物コンジュゲート
JP2018515457A (ja) * 2015-04-21 2018-06-14 アッヴィ・ステムセントルクス・エル・エル・シー カリケアマイシン構築物および使用方法
TWI714661B (zh) 2015-11-05 2021-01-01 法商賽諾菲公司 新穎念珠藻素化合物及接合物、其製備與其治療用途
CN108066772B (zh) * 2016-11-14 2021-07-13 中国科学院上海药物研究所 靶向tacstd2的抗体与药物偶联体(adc)分子
EP3621658A1 (en) 2017-05-10 2020-03-18 Sanofi Peptidic linkers and cryptophycin conjugates, useful in therapy, and their preparation

Also Published As

Publication number Publication date
EP3621658A1 (en) 2020-03-18
MY204075A (en) 2024-08-06
WO2018206635A1 (en) 2018-11-15
AU2022204711A1 (en) 2022-07-21
CA3062977A1 (en) 2018-11-15
MA50764A (fr) 2020-03-18
AU2018265333A1 (en) 2019-11-28
AU2022204711B2 (en) 2024-01-04
TWI778059B (zh) 2022-09-21
US20210228726A1 (en) 2021-07-29
JP2023085475A (ja) 2023-06-20
MX2019013421A (es) 2020-02-05
BR112019023336A2 (pt) 2020-06-16
CO2019012108A2 (es) 2020-02-28
TN2019000303A1 (en) 2021-05-07
IL270507A (https=) 2019-12-31
KR20200005580A (ko) 2020-01-15
CN110831633A (zh) 2020-02-21
UY37728A (es) 2019-01-02
TW201907957A (zh) 2019-03-01
IL270507B1 (en) 2023-04-01
KR102722886B1 (ko) 2024-10-29
EA201992667A1 (ru) 2020-03-10
AU2018265333C1 (en) 2025-04-24
US20200093934A1 (en) 2020-03-26
AU2018265333B2 (en) 2022-07-21
US20180369401A1 (en) 2018-12-27
IL270507B2 (en) 2023-08-01
US11007275B2 (en) 2021-05-18
PH12019550230A1 (en) 2020-07-06
US11998611B2 (en) 2024-06-04
AR111781A1 (es) 2019-08-21
US20200054760A1 (en) 2020-02-20
US20250205348A1 (en) 2025-06-26
AU2022204711B9 (en) 2025-01-23
AU2022204711C1 (en) 2025-04-24
JP2020519610A (ja) 2020-07-02

Similar Documents

Publication Publication Date Title
ECSP19078277A (es) Nuevos ligadores peptídicos y conjugados de criptoficina y su preparación
TR201909093T4 (tr) Hidroksi içeren FXR (NR1H4) modüle edici bileşikleri.
PY1909256A (es) Derivados de tetrahidroquinazolina útiles como agentes anticáncer
ECSP18034035A (es) Compuestos de criptoficina novedosos y productos conjugados, su preparación y su uso terapéutico
BR112017005393A2 (pt) composto de fórmula i, método de preparação de um conjugado de fórmula a, conjugado de fórmula a1, composição compreendendo uma mistura dos compostos de conjugado de anticorpo-fármaco, composição farmacêutica, e uso de um conjugado ou de uma composição
MX2020004804A (es) Compuestos de modulacion de fxr (nr1h4).
MX2018015443A (es) Compuestos moduladores de fxr (nr1h4).
CL2018000106A1 (es) Moléculas de anticuerpo que se unen a cd45
AR119018A1 (es) Inhibidores de proteína quinasas dependientes de adn
TR201906401T4 (tr) Yeni fxr (nr1h4) modüle edici bileşikler.
CL2012003054A1 (es) Anticuerpos contra la angiopoyetina 2 humana (ang-2); composicion farmaceutica que contiene dicho anticuerpo; uso del anticuerpo para preparar medicamento destinado a la prevencion de metastasis; acido nucleico que codifica dicho anticuerpo; vector de expresión.
BRPI1011043B8 (pt) fenilureias e fenilamidas substituídas como ligantes de receptor de vaniloide, seus usos e seu processo de preparação, e composição farmacêutica
BR112015011456A2 (pt) compostos de aminopirimidina como inibidores de egfr mutantes contendo t790m
DOP2010000357A (es) Derivados de indazoles sustituidos con fenilo o piridinilo
BR112012024822B8 (pt) Composto, uso de um composto e composição farmacêutica
BR112019005246A2 (pt) composto com a fórmula i, composto com a fórmula ii, composto com a fórmula iii, composição farmacêutica, método de tratamento de câncer
AR076398A1 (es) Formulacion
HN2012000217A (es) Compuestos derivados de amido espirociclicos y sales farmaceuticamente aceptable de los mismos.
AR077972A1 (es) Anticuerpos contra cdcp1 destinados al tratamiento del cancer
BR112018073490A2 (pt) 6.7.beta-epóxidos esteroides como intermediários químicos
MX2016001519A (es) Derivados de 25-oh vitamina d para determinacion de metabolitos de vitamina d.
MX2018002514A (es) Citotoxinas modificadas y su uso terapeutico.
BR112016011778A2 (pt) Pirazol fluorofenila, seus usos, e composição farmacêutica
ECSP22021881A (es) Composición farmacéutica acuosa de anticuerpo anti-pd1 prolgolimab y su uso
BR112016002752A8 (pt) Anticorpo ou seus fragmentos funcionais que pode especificamente se ligar ao her2, polinucleotídeo isolado, combinação dos polinucleotídeos isolados, vetor de expressão, conjugado, conjugado com a fórmula geral ab-(l-u)n, composição farmacêutica e uso do anticorpo ou seus fragmentos funcionais