CA2902872A1 - Biologically active molecules, conjugates thereof, and therapeutic uses - Google Patents

Biologically active molecules, conjugates thereof, and therapeutic uses Download PDF

Info

Publication number
CA2902872A1
CA2902872A1 CA2902872A CA2902872A CA2902872A1 CA 2902872 A1 CA2902872 A1 CA 2902872A1 CA 2902872 A CA2902872 A CA 2902872A CA 2902872 A CA2902872 A CA 2902872A CA 2902872 A1 CA2902872 A1 CA 2902872A1
Authority
CA
Canada
Prior art keywords
asparagine
alkyl
aryl
heteroaryl
heterocyclyl
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.)
Pending
Application number
CA2902872A
Other languages
English (en)
French (fr)
Inventor
Thomas Nittoli
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Regeneron Pharmaceuticals Inc
Original Assignee
Regeneron Pharmaceuticals 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 Regeneron Pharmaceuticals Inc filed Critical Regeneron Pharmaceuticals Inc
Publication of CA2902872A1 publication Critical patent/CA2902872A1/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D507/00—Heterocyclic compounds containing a condensed beta-lactam ring system, not provided for by groups C07D463/00, C07D477/00 or C07D499/00 - C07D505/00; Such ring systems being further condensed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K47/6801—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
    • A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
    • 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
    • A61K47/6835—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
    • A61K47/6855—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 breast cancer cell
    • 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
    • A61K47/6869—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 the reproductive system: ovaria, uterus, testes, prostate
    • 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
    • A61K47/6871—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 an enzyme
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Reproductive Health (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Communicable Diseases (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Cardiology (AREA)
  • Rheumatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
CA2902872A 2013-03-15 2014-03-14 Biologically active molecules, conjugates thereof, and therapeutic uses Pending CA2902872A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361792216P 2013-03-15 2013-03-15
US61/792,216 2013-03-15
PCT/US2014/029757 WO2014145090A1 (en) 2013-03-15 2014-03-14 Biologically active molecules, conjugates thereof, and therapeutic uses

Publications (1)

Publication Number Publication Date
CA2902872A1 true CA2902872A1 (en) 2014-09-18

Family

ID=50933481

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2902872A Pending CA2902872A1 (en) 2013-03-15 2014-03-14 Biologically active molecules, conjugates thereof, and therapeutic uses

Country Status (19)

Country Link
US (3) US10570151B2 (enExample)
EP (2) EP3964237A1 (enExample)
JP (3) JP6847388B2 (enExample)
KR (1) KR102306490B1 (enExample)
CN (1) CN105188766B (enExample)
AU (1) AU2014233385C1 (enExample)
BR (1) BR112015022585B1 (enExample)
CA (1) CA2902872A1 (enExample)
CL (1) CL2015002765A1 (enExample)
EA (1) EA038512B1 (enExample)
ES (1) ES2996807T3 (enExample)
IL (1) IL240418B (enExample)
MA (1) MA38496B2 (enExample)
MX (1) MX379256B (enExample)
MY (1) MY183572A (enExample)
PH (1) PH12015502131B1 (enExample)
SG (1) SG11201507481WA (enExample)
WO (1) WO2014145090A1 (enExample)
ZA (1) ZA201505813B (enExample)

Families Citing this family (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8542802B2 (en) 2007-02-15 2013-09-24 Global Tel*Link Corporation System and method for three-way call detection
BR112015014712A2 (pt) 2012-12-21 2017-07-11 Abgenomics Int Inc ligadores de autoimolação hidrofílicos e seus conjugados
KR102306490B1 (ko) 2013-03-15 2021-09-28 리제너론 파아마슈티컬스, 인크. 생물학적 활성 분자, 그의 접합체 및 치료 용도
US9545451B2 (en) 2013-08-21 2017-01-17 Regeneron Pharmaceuticals, Inc. Anti-PRLR antibodies and methods for killing PRLR-expressing cells
TWI641620B (zh) 2013-08-21 2018-11-21 再生元醫藥公司 抗－ｐｒｌｒ抗體及其用途
EP3038624B1 (en) 2013-08-26 2024-09-25 Regeneron Pharmaceuticals, Inc. Pharmaceutical compositions comprising macrolide diastereomers, methods of their synthesis and therapeutic uses
MA39313B1 (fr) 2014-03-11 2018-12-31 Regeneron Pharma Anticorps anti-egfrviii et leurs utilisations dans le traitement de divers cancers
EP3148592A2 (en) 2014-06-02 2017-04-05 Regeneron Pharmaceuticals, Inc. Antibody-drug conjugates, their preparation and their therapeutic use
AU2015276821A1 (en) 2014-06-20 2017-01-12 Abgenomics International Inc. Anti-folate receptor aplha (FRA) antibody-drug conjugates and methods of using thereof
SG11201707148PA (en) * 2015-03-27 2017-10-30 Regeneron Pharma Maytansinoid derivatives, conjugates thereof, and methods of use
CN106243127B (zh) 2015-06-09 2021-01-26 凯惠科技发展(上海)有限公司 抗体药物偶联物、中间体、制备方法、药物组合物及应用
MY189159A (en) 2015-07-06 2022-01-29 Regeneron Pharma Multispecific antigen-binding molecules and uses thereof
IL260289B (en) 2016-01-08 2022-08-01 Bioalliance Cv Tetravalent anti-psgl-1 antibodies and uses thereof
PH12018501589B1 (en) * 2016-01-25 2022-08-10 Regeneron Pharma Maytansinoid derivatives, conjugates thereof, and methods of use
MA45328A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Compositions acide nucléique-polypeptide et utilisations de celles-ci
EP3448891A1 (en) 2016-04-28 2019-03-06 Regeneron Pharmaceuticals, Inc. Methods of making multispecific antigen-binding molecules
SMT202200173T1 (it) 2016-06-01 2022-05-12 Athira Pharma Inc Composti
PL3515946T3 (pl) 2016-09-23 2022-11-07 Regeneron Pharmaceuticals, Inc. Przeciwciała anty-muc16 (mucyna 16)
NZ751906A (en) 2016-09-23 2025-10-31 Regeneron Pharma Anti-steap2 antibodies, antibody-drug conjugates, and bispecific antigen-binding molecules that bind steap2 and cd3, and uses thereof
TWI782930B (zh) * 2016-11-16 2022-11-11 美商再生元醫藥公司 抗ｍｅｔ抗體，結合ｍｅｔ之雙特異性抗原結合分子及其使用方法
CN110382534B (zh) 2016-11-29 2023-05-09 里珍纳龙药品有限公司 治疗prlr阳性乳腺癌的方法
SG11201906200WA (en) 2017-01-06 2019-08-27 Avidity Biosciences Llc Nucleic acid-polypeptide compositions and methods of inducing exon skipping
AU2018227146B2 (en) 2017-02-28 2025-04-03 Daiichi Sankyo Company, Limited Method for treating EGFR-TKI-resistant non-small cell lung cancer by administration of anti-HER3 antibody-drug conjugate
TW201836647A (zh) 2017-04-06 2018-10-16 美商艾伯維有限公司 抗－ｐｒｌｒ抗體藥物軛合物（ａｄｃ）及其用途
JP7364471B2 (ja) 2017-05-18 2023-10-18 レゲネロン ファーマシューティカルス，インコーポレーテッド シクロデキストリンタンパク質薬物コンジュゲート
MY198804A (en) 2017-06-07 2023-09-28 Regeneron Pharma Compositions and methods for internalizing enzymes
KR102736878B1 (ko) 2017-06-23 2024-12-05 벨로스바이오 인코포레이티드 Ror1 항체 면역접합체
GB201711809D0 (en) 2017-07-21 2017-09-06 Governors Of The Univ Of Alberta Antisense oligonucleotide
CN111655268B (zh) 2017-10-04 2024-03-26 艾维迪提生物科学公司 核酸-多肽组合物及其用途
CA3080857A1 (en) * 2017-11-07 2019-05-16 Regeneron Pharmaceuticals, Inc. Hydrophilic linkers for antibody drug conjugates
IL319835A (en) 2017-12-06 2025-05-01 Avidity Biosciences Inc Compositions and methods for treating muscular dystrophy and myotonic dystrophy
JP7328990B2 (ja) 2018-04-30 2023-08-17 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Ｈｅｒ２及び／またはａｐｌｐ２に結合する抗体及び二重特異性抗原結合分子、ならびにそれらのコンジュゲート及び使用
CN112135624B (zh) 2018-05-17 2024-07-19 瑞泽恩制药公司 抗cd63抗体、缀合物和其用途
AU2019294510A1 (en) * 2018-06-26 2021-01-21 Immunogen, Inc. Immunoconjugates targeting ADAM9 and methods of use thereof
JPWO2020059772A1 (ja) 2018-09-20 2021-08-30 第一三共株式会社 抗ｈｅｒ３抗体−薬物コンジュゲート投与によるｈｅｒ３変異がんの治療
IL319265A (en) 2018-12-21 2025-04-01 Avidity Biosciences Inc Anti-transferrin receptor antibodies and their uses
IL284623B2 (en) * 2019-01-07 2025-04-01 Astellas Pharma Inc A conjugate containing a ligand, a spacer, a peptide linker, and a biomolecule
CN113727757A (zh) 2019-02-21 2021-11-30 瑞泽恩制药公司 使用结合met的抗-met抗体和双特异性抗原结合分子治疗眼癌的方法
AU2020263487A1 (en) 2019-04-25 2021-12-16 Avidity Biosciences, Inc. Nucleic acid compositions and methods of multi-exon skipping
WO2020247818A1 (en) 2019-06-06 2020-12-10 Avidity Biosciences, Inc. Una amidites and uses thereof
US11578090B2 (en) 2019-06-06 2023-02-14 Avidity Biosciences, Inc. Nucleic acid-polypeptide compositions and uses thereof
US11896682B2 (en) 2019-09-16 2024-02-13 Regeneron Pharmaceuticals, Inc. Radiolabeled MET binding proteins for immuno-PET imaging and methods of use thereof
US11814428B2 (en) * 2019-09-19 2023-11-14 Regeneron Pharmaceuticals, Inc. Anti-PTCRA antibody-drug conjugates and uses thereof
AU2020381495A1 (en) 2019-11-15 2022-05-19 Seagen Inc. Methods of treating HER2 positive breast cancer with tucatinib in combination with an anti-HER2 antibody-drug conjugate
AU2021210987A1 (en) 2020-01-24 2022-08-04 Regeneron Pharmaceuticals, Inc. Protein-antiviral compound conjugates
WO2021174113A1 (en) 2020-02-28 2021-09-02 Regeneron Pharmaceuticals, Inc. Bispecific antigen binding molecules that bind her2, and methods of use thereof
US11555190B2 (en) 2020-03-19 2023-01-17 Avidity Biosciences, Inc. Compositions and methods of treating Facioscapulohumeral muscular dystrophy
WO2021195469A1 (en) 2020-03-27 2021-09-30 Avidity Biosciences, Inc. Compositions and methods of treating muscle dystrophy
IL319200A (en) 2020-04-16 2025-04-01 Regeneron Pharma Antibody-drug conjugates prepared using Diels-Alder compression methods
BR112023000711A2 (pt) 2020-07-17 2023-01-31 Daiichi Sankyo Co Ltd Método para produzir uma composição de conjugado de anticorpo-fármaco, e, composição de conjugado de anticorpo-fármaco
EP4232481A1 (en) 2020-10-22 2023-08-30 Regeneron Pharmaceuticals, Inc. Anti-fgfr2 antibodies and methods of use thereof
IL302814A (en) 2020-11-10 2023-07-01 Regeneron Pharma Selenium antibody conjugates
WO2022198231A1 (en) 2021-03-18 2022-09-22 Seagen Inc. Selective drug release from internalized conjugates of biologically active compounds
WO2022211075A1 (ja) 2021-03-31 2022-10-06 日本マイクロバイオファーマ株式会社 抗体薬物複合体の製造方法及びそれに用いる酵素
WO2022214499A2 (en) 2021-04-05 2022-10-13 Altheia Science S.R.L. Diagnosis and treatment of myeloid disorders and acute leukemias using novel tumor specific antigenscross-reference to related applications
KR20240055874A (ko) 2021-09-16 2024-04-29 어비디티 바이오사이언시스 인크. 안면견갑상완 근이영양증을 치료하는 조성물 및 방법
JP2025503504A (ja) 2021-12-23 2025-02-04 マイリキュール，インコーポレイテッド ポリヌクレオチドの送達のための組成物
US12071621B2 (en) 2022-04-05 2024-08-27 Avidity Biosciences, Inc. Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping
JP2025511758A (ja) 2022-04-05 2025-04-16 アルテイア サイエンス エッセ．エッレ．エッレ． 新規腫瘍特異的抗原を標的とする骨髄性障害および急性白血病の処置
EP4512410A1 (en) 2022-04-07 2025-02-26 Twinpig Biolab, Inc. Novel-peptide-based anticancer immunotherapeutic agent
EP4561636A1 (en) 2022-07-29 2025-06-04 Regeneron Pharmaceuticals, Inc. Compositions and methods for transferrin receptor (tfr)-mediated delivery to the brain and muscle
EP4619438A2 (en) 2022-11-14 2025-09-24 Regeneron Pharmaceuticals, Inc. Compositions and methods for fibroblast growth factor receptor 3-mediated delivery to astrocytes
WO2025006639A2 (en) 2023-06-27 2025-01-02 Avidity Biosciences, Inc. Compositions and methods of using prkag2-targeting antibody-oligonucleotide conjugates abstract
US12409230B2 (en) 2023-06-30 2025-09-09 Avidity Biosciences, Inc. Compositions comprising PLN-targeting anti-transferrin receptor antibody-polynucleotides and methods of use thereof to treat cardiomyopathy

Family Cites Families (87)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4307016A (en) 1978-03-24 1981-12-22 Takeda Chemical Industries, Ltd. Demethyl maytansinoids
JPS5566585A (en) 1978-11-14 1980-05-20 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
CA2026147C (en) 1989-10-25 2006-02-07 Ravi J. Chari Cytotoxic agents comprising maytansinoids and their therapeutic use
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
US5714586A (en) 1995-06-07 1998-02-03 American Cyanamid Company Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US20070258987A1 (en) 2000-11-28 2007-11-08 Seattle Genetics, Inc. Recombinant Anti-Cd30 Antibodies and Uses Thereof
EP1258255A1 (en) 2001-05-18 2002-11-20 Boehringer Ingelheim International GmbH Conjugates of an antibody to CD44 and a maytansinoid
US6441163B1 (en) 2001-05-31 2002-08-27 Immunogen, Inc. Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
WO2003074551A2 (en) * 2002-03-01 2003-09-12 The Administrators Of The Tulane Educational Fund Conjugates of therapeutic or cytotoxic agents and biologically active peptides
US20090068178A1 (en) 2002-05-08 2009-03-12 Genentech, Inc. Compositions and Methods for the Treatment of Tumor of Hematopoietic Origin
US20110250133A1 (en) 2003-01-13 2011-10-13 Bracco Imaging S.P.A. Gastrin releasing peptide compounds
US8088387B2 (en) 2003-10-10 2012-01-03 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
US7276497B2 (en) 2003-05-20 2007-10-02 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
KR101531400B1 (ko) 2003-06-27 2015-06-26 암젠 프레몬트 인코포레이티드 상피 성장 인자 수용체의 결실 돌연변이체 지향 항체 및 그용도
GB0316294D0 (en) 2003-07-11 2003-08-13 Polytherics Ltd Conjugated biological molecules and their preparation
TW200539855A (en) 2004-03-15 2005-12-16 Wyeth Corp Calicheamicin conjugates
JP4806680B2 (ja) 2004-05-19 2011-11-02 メダレックス インコーポレイテッド 自己犠牲リンカー及び薬剤複合体
AU2005249490B2 (en) * 2004-06-01 2010-07-29 Genentech, Inc. Antibody drug conjugates and methods
EP1817341A2 (en) 2004-11-29 2007-08-15 Seattle Genetics, Inc. Engineered antibodies and immunoconjugates
WO2006062779A2 (en) 2004-12-09 2006-06-15 Centocor, Inc. Anti-integrin immunoconjugates, methods and uses
PL2135881T3 (pl) * 2005-06-20 2012-02-29 Genentech Inc Przeciwciała wiążące się z antygenem TAT10772 związanym z nowotworem, do diagnozowania i leczenia nowotworu
CN101287498B (zh) 2005-06-20 2013-03-27 Psma开发有限公司 Psma抗体-药物缀合物
CA2617953C (en) 2005-08-09 2013-12-17 Millennium Pharmaceuticals, Inc. Method of acylating maytansinol with chiral amino acids
EP2399609B1 (en) * 2005-08-24 2015-03-18 ImmunoGen, Inc. Process for preparing maytansinoid antibody conjugates
US7750116B1 (en) 2006-02-18 2010-07-06 Seattle Genetics, Inc. Antibody drug conjugate metabolites
RU2483080C2 (ru) 2006-10-27 2013-05-27 Дженентек, Инк. Антитела и иммуноконъюгаты и их применение
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
WO2008122039A2 (en) 2007-04-02 2008-10-09 The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Selenocysteine mediated hybrid antibody molecules
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.
JP2010528285A (ja) 2007-05-23 2010-08-19 ベンタナ・メデイカル・システムズ・インコーポレーテツド 免疫組織化学およびｉｎｓｉｔｕハイブリダーゼーションのためのポリマー担体
KR20160125535A (ko) 2008-03-18 2016-10-31 제넨테크, 인크. 항-ｈｅｒ２ 항체-약물 접합체와 화학요법제의 병용물, 및 사용 방법
JP5752592B2 (ja) * 2008-04-11 2015-07-22 シアトル ジェネティックス， インコーポレイテッド 膵臓癌、卵巣癌、および他の癌の検出および処置
RU2503687C2 (ru) 2008-04-30 2014-01-10 Иммьюноджен, Инк. Сшивающие реагенты и их применение
RU2487877C2 (ru) * 2008-04-30 2013-07-20 Иммьюноджен, Инк. Высокоэффективные конъюгаты и гидрофильные сшивающие агенты (линкеры)
DK2374481T3 (en) 2008-07-21 2016-02-01 Polytherics Ltd New reagents and methods for the conjugation of biological molecules
US9005598B2 (en) 2009-03-04 2015-04-14 Polytherics Limited Conjugated proteins and peptides
BRPI1012676A2 (pt) * 2009-04-01 2016-04-05 Genentech Inc anticorpos anti-fcrh5 e imunoconjugados e métodos de uso
CN102597773B (zh) 2009-08-10 2015-07-15 Ucl商业有限公司 功能性分子的可逆的共价连接
TW201117814A (en) 2009-10-02 2011-06-01 Sanofi Aventis New maytansinoids and the use of said maytansinoids to prepare conjugates with an antibody
AR078470A1 (es) 2009-10-02 2011-11-09 Sanofi Aventis Anticuerpos que se unen especificamente al receptor epha2
KR20120080611A (ko) 2009-10-06 2012-07-17 이뮤노젠 아이엔씨 효능 있는 접합체 및 친수성 링커
MY173390A (en) * 2009-10-23 2020-01-22 Takeda Pharmaceuticals Co Anti-gcc antibody molecules and related compositions and methods
US8501692B2 (en) 2009-12-14 2013-08-06 The Regents Of The University Of Michigan Compositions and methods for altering cocaine esterase activity
RS52983B (sr) 2010-04-15 2014-02-28 Spirogen Sárl Pirolobenzodiazepini i njihovi konjugati
US20130244905A1 (en) 2010-07-06 2013-09-19 Ed Grabczyk Reporter for RNA Polymerase II Termination
RS55495B1 (sr) 2010-08-02 2017-04-28 Regeneron Pharma Miševi koji stvaraju vezujuće proteine koji sadrže vl domene
BR112013005070B1 (pt) 2010-09-01 2018-04-03 Bayer Intellectual Property Gmbh Compostos n-(tetrazol-5-il)- e n-(triazol-5-il) arilcarboxamidas, composição herbicida, seus usos como herbicidas e método para controlar plantas indesejadas
JP5828902B2 (ja) 2010-10-29 2015-12-09 イミュノジェン， インコーポレイテッド 非拮抗性ｅｇｆｒ結合分子およびその免疫複合体
CA2816681A1 (en) 2010-11-03 2012-05-10 Immunogen, Inc. Cytotoxic agents comprising new ansamitocin derivatives
CA2816426A1 (en) * 2010-11-17 2012-06-07 Genentech, Inc. Alaninyl maytansinol antibody conjugates
CN103732256A (zh) 2011-05-16 2014-04-16 皇家飞利浦有限公司 生物正交药物活化
EP3170821B1 (en) 2011-05-27 2021-09-15 Ambrx, Inc. Compositions containing, methods involving, and uses of non-natural amino acid linked dolastatin derivatives
US8815226B2 (en) 2011-06-10 2014-08-26 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
EA029797B1 (ru) * 2011-06-21 2018-05-31 Иммуноджен, Инк. Новые производные майтанзиноида с пептидным линкером и их конъюгаты
JP6399930B2 (ja) 2011-10-14 2018-10-03 シアトル ジェネティクス，インコーポレーテッド ピロロベンゾジアゼピンおよび標的コンジュゲート
JP6170497B2 (ja) 2011-10-14 2017-07-26 メドイミューン・リミテッドＭｅｄＩｍｍｕｎｅ Ｌｉｍｉｔｅｄ ピロロベンゾジアゼピン
CA2850373C (en) 2011-10-14 2019-07-16 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
WO2013053872A1 (en) 2011-10-14 2013-04-18 Spirogen Sàrl Synthesis method and intermediates useful in the preparation of pyrrolobenzodiazepines
WO2013068874A1 (en) 2011-11-11 2013-05-16 Pfizer Inc. Antibody-drug conjugates
JP2015500205A (ja) 2011-11-16 2015-01-05 アムジエン・インコーポレーテツド 上皮成長因子欠失変異体ｖｉｉｉ関連障害の治療方法
SG11201402686UA (en) 2011-12-05 2014-06-27 Igenica Inc Antibody-drug conjugates and related compounds, compositions, and methods
GB201210770D0 (en) 2012-06-18 2012-08-01 Polytherics Ltd Novel conjugation reagents
IN2014DN10428A (enExample) 2012-06-19 2015-08-21 Polytherics Ltd
RS64329B1 (sr) * 2012-10-23 2023-08-31 Synaffix Bv Modifikovano antitelo, konjugat antitela i postupak za njihovo pripremanje
NO2789793T3 (enExample) 2012-10-24 2018-01-27
AU2012395148B2 (en) 2012-11-24 2016-10-27 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
TW201425336A (zh) 2012-12-07 2014-07-01 Amgen Inc Ｂｃｍａ抗原結合蛋白質
CN103333179B (zh) 2012-12-21 2017-06-16 百奥泰生物科技(广州)有限公司 类美登素衍生物及其制备方法和用途
CN103254213B (zh) 2012-12-21 2015-02-25 百奥泰生物科技(广州)有限公司 类美登素酯的制备方法及用于所述方法的组合物
KR102306490B1 (ko) 2013-03-15 2021-09-28 리제너론 파아마슈티컬스, 인크. 생물학적 활성 분자, 그의 접합체 및 치료 용도
CN103254311B (zh) 2013-05-09 2015-05-13 齐鲁制药有限公司 一种制备抗体-美登素类生物碱药物偶联物的方法
WO2014194030A2 (en) 2013-05-31 2014-12-04 Immunogen, Inc. Conjugates comprising cell-binding agents and cytotoxic agents
WO2014197866A1 (en) 2013-06-06 2014-12-11 Igenica Biotherapeutics, Inc. Modified antibodies and related compounds, compositions, and methods of use
WO2014197854A1 (en) 2013-06-06 2014-12-11 Igenica Biotherapeutics, Inc. Novel linkers for antibody-drug conjugates and related compounds, compositions, and methods of use
WO2014197871A2 (en) 2013-06-06 2014-12-11 Igenica Biotherapeutics, Inc. Antibody-drug conjugates, compositions and methods of use
NZ714765A (en) 2013-06-06 2021-12-24 Pf Medicament Anti-c10orf54 antibodies and uses thereof
US9545451B2 (en) 2013-08-21 2017-01-17 Regeneron Pharmaceuticals, Inc. Anti-PRLR antibodies and methods for killing PRLR-expressing cells
EP3038624B1 (en) 2013-08-26 2024-09-25 Regeneron Pharmaceuticals, Inc. Pharmaceutical compositions comprising macrolide diastereomers, methods of their synthesis and therapeutic uses
WO2015081281A1 (en) 2013-11-26 2015-06-04 Segway Orthopaedics, Inc. Surgical blade with viewing aperture
US9493413B2 (en) 2013-11-27 2016-11-15 Redwood Bioscience, Inc. Hydrazinyl-pyrrolo compounds and methods for producing a conjugate
CN105793268B (zh) 2013-12-02 2019-03-15 香港浸会大学 具有两个稠合大环的抗癌性美登木素类化合物
EP3148592A2 (en) 2014-06-02 2017-04-05 Regeneron Pharmaceuticals, Inc. Antibody-drug conjugates, their preparation and their therapeutic use
SG11201707148PA (en) 2015-03-27 2017-10-30 Regeneron Pharma Maytansinoid derivatives, conjugates thereof, and methods of use
PH12018501589B1 (en) 2016-01-25 2022-08-10 Regeneron Pharma Maytansinoid derivatives, conjugates thereof, and methods of use
NZ751906A (en) 2016-09-23 2025-10-31 Regeneron Pharma Anti-steap2 antibodies, antibody-drug conjugates, and bispecific antigen-binding molecules that bind steap2 and cd3, and uses thereof
US11814428B2 (en) 2019-09-19 2023-11-14 Regeneron Pharmaceuticals, Inc. Anti-PTCRA antibody-drug conjugates and uses thereof

Also Published As

Publication number Publication date
MA38496A1 (fr) 2018-06-29
MA38496B2 (fr) 2021-01-29
PH12015502131B1 (en) 2022-03-23
AU2014233385B2 (en) 2019-03-07
IL240418A0 (en) 2015-09-24
BR112015022585A2 (pt) 2017-10-24
ES2996807T3 (en) 2025-02-13
JP2019135239A (ja) 2019-08-15
NZ710814A (en) 2020-10-30
EA201500905A1 (ru) 2017-02-28
EP2968593B1 (en) 2024-11-20
PH12015502131A1 (en) 2016-01-25
US20160030591A1 (en) 2016-02-04
US20220332729A1 (en) 2022-10-20
KR102306490B1 (ko) 2021-09-28
EA038512B1 (ru) 2021-09-08
WO2014145090A1 (en) 2014-09-18
US20200277306A1 (en) 2020-09-03
CN105188766A (zh) 2015-12-23
US10570151B2 (en) 2020-02-25
ZA201505813B (en) 2023-01-25
CL2015002765A1 (es) 2016-06-24
EP3964237A1 (en) 2022-03-09
CN105188766B (zh) 2019-07-12
MX2015011348A (es) 2016-01-15
BR112015022585B1 (pt) 2023-04-04
AU2014233385C1 (en) 2019-09-19
SG11201507481WA (en) 2015-10-29
HK1212890A1 (en) 2016-06-24
US11345715B2 (en) 2022-05-31
KR20150128932A (ko) 2015-11-18
MY183572A (en) 2021-02-26
JP6847388B2 (ja) 2021-03-31
JP2016521256A (ja) 2016-07-21
MX379256B (es) 2025-03-10
IL240418B (en) 2020-11-30
US12378258B2 (en) 2025-08-05
EP2968593A1 (en) 2016-01-20
JP2021105007A (ja) 2021-07-26
AU2014233385A1 (en) 2015-09-17

Similar Documents

Publication Publication Date Title
US12378258B2 (en) Biologically active molecules, conjugates thereof, and therapeutic uses
CA2950155C (en) Biologically active molecule conjugates, reagents and methods of manufacture, and therapeutic uses
TWI709412B (zh) 自行穩定之接合劑共軛物
ES2983109T3 (es) Conjugados enlazadores autoestabilizantes
IL297167A (en) Charging variant connectors
CN103648532A (zh) 具有肽连接子的新型美登木素生物碱衍生物及其偶联物
JP6423804B2 (ja) 細胞結合剤及び細胞毒性剤を含む複合体
HK40066743A (en) Biologically active molecules, conjugates thereof, and therapeutic uses
HK1212890B (en) Biologically active molecules, conjugates thereof, and therapeutic uses
NZ710814B2 (en) Biologically active molecules, conjugates thereof, and therapeutic uses

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20190314

EEER Examination request

Effective date: 20190314

EEER Examination request

Effective date: 20190314

EEER Examination request

Effective date: 20190314

EEER Examination request

Effective date: 20190314

EEER Examination request

Effective date: 20190314

EEER Examination request

Effective date: 20190314

EEER Examination request

Effective date: 20190314

EEER Examination request

Effective date: 20190314