DK2889624T3 - Reversibel kovalent binding af funktionelle molekyler - Google Patents

Reversibel kovalent binding af funktionelle molekyler Download PDF

Info

Publication number
DK2889624T3
DK2889624T3 DK15150363.8T DK15150363T DK2889624T3 DK 2889624 T3 DK2889624 T3 DK 2889624T3 DK 15150363 T DK15150363 T DK 15150363T DK 2889624 T3 DK2889624 T3 DK 2889624T3
Authority
DK
Denmark
Prior art keywords
group
formula
compound
moiety
groups
Prior art date
Application number
DK15150363.8T
Other languages
English (en)
Inventor
Mark Smith
Stephen Caddick
Vijay Chudasama
James Baker
Original Assignee
Ucl Business Plc
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
Priority claimed from GB0913967A external-priority patent/GB0913967D0/en
Priority claimed from GB0913965A external-priority patent/GB0913965D0/en
Priority claimed from GB0914321A external-priority patent/GB0914321D0/en
Application filed by Ucl Business Plc filed Critical Ucl Business Plc
Application granted granted Critical
Publication of DK2889624T3 publication Critical patent/DK2889624T3/da

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—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 organic compound
    • A61K47/545—Heterocyclic compounds
    • 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
    • A61K47/54—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 organic compound
    • A61K47/55—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 organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A61K47/551—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 organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid
    • 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
    • A61K47/56—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/14—Antitussive agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics
    • 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
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/40—2,5-Pyrrolidine-diones
    • C07D207/416—2,5-Pyrrolidine-diones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/44—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members
    • C07D207/444—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5
    • C07D207/456—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/655—Somatostatins
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pain & Pain Management (AREA)
  • Neurosurgery (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Pulmonology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Anesthesiology (AREA)
  • Food Science & Technology (AREA)

Claims (13)

1. Anvendelse af en forbindelse med formel (la) som et reagens til kobling af en forbindelse med formel Ri-H, der omfatter en første funktionel del med formel Fi, til en anden funktionel del med formel F2
(la) hvor: X og X'hver er oxygen; Y er en elektrofil fraspaltelig gruppe; R3 og R3’ sammen danner en gruppe med formel -N(R33')-N(R33·)-, hvor hver R33' er ens eller forskellige og er et hydrogenatom eller en gruppe med formel Y, Nu, -L(Z)n eller IG; Ri er en gruppe med formel -F1 eller -S-L-F-ι, og R1-H omfatter mindst en første SH-gruppe; R2 er et hydrogenatom eller en gruppe med formel Y, Nu, -L(Z)n eller IG; hver gruppe med formel Y er ens eller forskellige og er en elektrofil fraspaltelig gruppe; hver gruppe med formel Nu er ens eller forskellige og er en nukleofil valgt blandt -OH, -SH, -NH2 og -NH(Ci-6alkyl); hver gruppe med formel L er ens eller forskellige og er en linkergruppe; hver gruppe med formel Z er ens eller forskellige og er en reaktiv gruppe, der er bundet til en gruppe med formel L, der er i stand til at reagere med en forbindelse, der indeholder en anden funktionel del med formel F2, således at den anden funktionelle del bliver koblet til gruppen med formel L; n er 1, 2 eller 3; og hver gruppe med formel IG er ens eller forskellige og er en del, som er en Ci-2oalkylgruppe, en C2-2oalkenylgruppe eller en C2-2oalkynylgruppe, der er
usubstitueret eller substitueret med en eller flere substituenter valgt blandt halogenatomer og sulfonsyregrupper, og hvori (a) 0, 1 eller 2 carbonatomer er erstattet med grupper valgt blandt C6-ioarylen-, 5- til 10-leddede heteroarylen-, C3-7carbocyclylen- og 5- til 10-leddede heterocyclylengrupper, og (b) 0, 1 eller 2 -CH2-grupper er erstattet med grupper valgt blandt -O-, -S-, -S-S-, -C(O)- og -N(Ci-6alkyl)-grupper, hvor: (i) arylen-, heteroarylen-, carbocyclylen- og heterocyclylengrupperne er usubstitueret eller substitueret med en eller flere substituenter valgt blandt halogenatomer og Ci-6alkyl, Ci-6alkoxy, Ci-6alkylthiol, -N(Ci-6alkyl)(Ci-6alkyl), nitro og sulfonsyregrupper; og (ii) 0, 1 eller 2 carbonatomer i carbocyclylen- og heterocyclylengrupperne er erstattet med -C(O)-grupper; og enten: den ene af den første funktionelle del og den anden funktionelle del er et protein, som er et antistof eller antistoffragment, der er i stand til at binde til et specifikt antigen via en epitop på antigenet, og den anden af den første funktionelle del og den anden funktionelle del er et lægemiddel; eller den ene af den første funktionelle del og den anden funktionelle del er en polymer del valgt blandt peptider, proteiner, polysaccharider, polyethere, polyaminosyrer, polyvinylalkoholer, polyvinylpyrrolidoner, poly(meth)acrylsyre, polyurethaner og polyphosphazener, og den anden af den første funktionelle del og den anden funktionelle del er et lægemiddel; eller den ene af den første funktionelle del og den anden funktionelle del er et protein, som er et antistof eller antistoffragment, der er i stand til at binde til et specifikt antigen via en epitop på antigenet, og den anden af den første funktionelle del og den anden funktionelle del er en påviselig del valgt fra gruppen, der består af kromogene dele, fluorescerende dele, radioaktive dele og elektrokemisk aktive dele; hvor gruppen Ri bliver bundet til forbindelsen med formel (la) ved et nukleofilt angreb af den første SH-gruppe i forbindelsen med formel R1-H i 2-positionen af forbindelsen med formel (la), således at gruppen Y i 2-positionen erstattes med gruppen Ri.
2. Anvendelse ifølge krav 1, hvor: (A) : Y er et halogenatom eller en triflat-, tosylat-, mesylat-, N-hydroxysuccinimidyl-, N-hydroxysulfosuccinimidyl-, Ci-ealkylthiol-, 5- til 10-leddet heterocyclylthiol-, Ce-ioarylthiol-, C3-7carbocyclylthiol-, -OC(O)CH3-, -OC(O)CF3-, phenyloxy-, -NRxRyRz+ eller - PRxRyRz+ gruppe, hvori Rx, Ry og Rz er ens eller forskellige og er valgt blandt hydrogenatomer og Ci-oalkyl- og phenylgrupper; og/eller (B) : L er en del, der er en Ci-2oalkylengruppe, en C2-2oalkenylengruppe eller en C2-2oalkynylengruppe, der er usubstitueret eller substitueret med en eller flere substituenter valgt blandt halogenatomer og sulfonsyregrupper, og hvori (a) 0, 1 eller 2 carbonatomer er erstattet med grupper valgt blandt C6-ioarylen-, 5- til 10-leddede heteroarylen-, C3-7carbocyclylen og 5- til 10-leddede heterocyclylengrupper, og (b) 0, 1 eller 2 -Chb-grupper er erstattet med grupper valgt blandt -O-, -S-, -S-S-, -C(O)- og -N(Ci-6 alkyl)-grupper, hvor: (i) arylen-, heteroarylen-, carbocyclylen- og heterocyclylengrupperne er usubstitueret eller substitueret med en eller flere substituenter valgt blandt halogenatomer og C-i-oalkyl-, Ci-6alkoxy-, Ci-ealkylthiol-, -N(Ci-6alkyl)(Ci-6alkyl)-, nitro- og sulfonsyregrupper; og (ii) 0, 1 eller 2 carbonatomer i carbocyclylen- og heterocyclylengrupperne er erstattet med -C(O)-grupper; og/eller (C) : Zer: (a) en gruppe med formel -LG, -C(O)-LG, -C(S)-LG eller -C(NH)-LG, hvor LG er en elektrofil fraspaltelig gruppe; (b) en nukleofil Nu' valgt blandt -OH-, -SH-, -NH2-, -NH(Ci-6alkyl)- og -C(O)NHNH2-grupper; (c) en cyklisk del Cyc, der er modtagelig for en ringåbnende elektrofil reaktion med en nukleofil; (d) en gruppe med formel -S(O2)(Hal), hvor Hal er et halogenatom; (e) en gruppe med formel -N=C=O eller-N=C=S; (f) en gruppe med formel -S-S(IG'), hvor IG' er en gruppe med formel IG ifølge krav 2; (g) en gruppe AH, som er en C6-ioarylgruppe, der er substitueret med en eller flere halogenatomer; (h) en fotoreaktiv gruppe, der kan aktiveres ved eksponering for ultraviolet lys; (i) en gruppe med formel -C(O)H eller -C(O)(Ci-6alkyl); (j) en maleimidogruppe; (k) en gruppe med formel -C(O)CHCH2; (l) en gruppe med formel -C(O)C(N2)H eller -PhN2+, hvor Ph er en phenylgruppe; eller (m) en epoxidgruppe; og/eller (D) : IG er en del, som er en usubstitueret Ci-6alkylgruppe, C2-6alkenylgruppe eller C2-6alkynylgruppe, hvori (a) 0 eller 1 carbonatom er erstattet med en gruppe valgt blandt phenylen-, 5- til 6-leddede heteroarylen-, C5-6carbocyclylen- og 5- til 6-leddede heterocyclylengrupper, hvor phenylen-, heteroarylen-, carbocyclylen- og heterocyclylengrupperne er usubstitueret eller substitueret med en eller to substituenter valgt blandt halogenatomer og Ci-4alkyl- og Ci-4alkoxygrupper, og (b) 0, 1 eller 2 -CH2-grupper er erstattet med grupper valgt blandt -O-, -S- og - C(O)-grupper; og/eller (E) : n er 1; og/eller (F) : lægemidlet er et cytotoksisk middel.
3. Anvendelse ifølge krav 1 eller 2, hvor: Ri er en gruppe med formel -Fi; Fi er et peptid eller protein, der omfatter mindst en første cysteinrest; og gruppen Ri bliver bundet til forbindelsen med formel (la) ved et nukleofilt angreb af thiolgruppen i den første cysteinrest i 2-positionen af forbindelsen med formel (la), således at gruppen Y erstattes med thiolgruppen i den første cysteinrest i gruppen Ri; og hvor eventuelt: R2 er en gruppe med formel Y; Ri yderligere omfatter mindst en anden cysteinrest; og gruppen Ri bliver yderligere bundet til forbindelsen med formel (la) ved et nukleofilt angreb af thiolgruppen i den anden cysteinrest i 3-positionen af delen med formel (la), således at gruppen R2 erstattes med thiolgruppen i den anden cysteinrest i gruppen Ri.
4. Fremgangsmåde til fremstilling af et konjugat, hvilken fremgangsmåde omfatter (i) reaktion af en forbindelse med formel (la) med en forbindelse med formel R1-H til således fremstilling af en forbindelse med formel (II)
(ii) efterfølgende kobling af en del med formel F2 til forbindelsen med formel (il); hvor trin (i) inddrager binding af gruppen Ri ved et nukleofilt angreb af den første SH-gruppe i forbindelsen med formel R1-H i 2-positionen af forbindelsen med formel (la), således at gruppen Y i 2-positionen erstattes med gruppen Ri, og hvor X, X', Y, Ri, R2, R3, R3' og F2 alle er som defineret i et hvilket som helst af kravene 1 til 3.
5. Fremgangsmåde ifølge krav 4, hvor:
(A) : fremgangsmåden omfatter kobling af F2 til forbindelsen med formel (II) ved en elektrofil additionsreaktion af F2 over carbon-carbon-dobbeltbindingen mellem 2-positionen og 3-positionen i formel (II); eller (B) : R2 er en gruppe med formel Y, Nu eller -L(Z)n, og fremgangsmåden omfatter kobling af F2 til forbindelsen med formel (II) ved en reaktion mellem F2 og gruppen med formel Y, Nu eller-L(Z)n.
6. Fremgangsmåde til fremstilling af et konjugat, hvilken fremgangsmåde omfatter reaktion af en forbindelse med formel R1-H med en forbindelse med formel (Ila)
(Ha) hvor: R3a og R3a· sammen danner en gruppe med formel -N(R33a')-N(R33a·)-, hvor hver R33a· er ens eller forskellige og er en gruppe med formel R33' eller en gruppe med formel F2 eller -L(F2)m(Z)n-m; R2a er en gruppe med formel R2 eller en gruppe med formel F2 eller -L(F2)m(Z)n-m; m er et helt tal med en værdi fra nul til n; forbindelsen med formel (Ila) omfatter mindst én gruppe med formel F2; F2 er som defineret i krav 1; X, X', R3, R3, R33, R2, L, Z og n alle er som defineret i krav 1 eller 2; Ri er som defineret i krav 1 eller 3; og fremgangsmåden inddrager binding af gruppen Ri ved et nukleofilt angreb af den første SH-gruppe i forbindelsen med formel R1-H i 2-positionen af
forbindelsen med formel (Ila), således at gruppen Y i 2-positionen erstattes med gruppen Ri.
7. Fremgangsmåde, der omfatter (i) tilvejebringelse af en forbindelse med formel (III) eller (Illa); og (ii) spaltning af bindingen mellem gruppen Ri og carbonatomet i 2-positionen af forbindelsen med formel (III) eller (Illa) (Ula) hvor: R3a og R3a· sammen danner en gruppe med formel -N(R33a')-N(R33a·)-, hvor hver R33a· er ens eller forskellige og er en gruppe med formel R33 eller en gruppe med formel F2 eller -L(F2)m(Z)n-m; R2a er en gruppe med formel R2 eller en gruppe med formel F2 eller -L(F2)m(Z)n-m; m er et helt tal med en værdi fra nul til n; Ri er som defineret i krav 1 eller 3; F2 er som defineret i krav 1; X, X', R3, R3, R33, R2, L, Z og n alle er som defineret i krav 1 eller 2; og hvor, når fremgangsmåden inddrager forbindelsen med formel (Illa):
Ri i forbindelsen med formel (Illa) omfatter mindst en første thiolgruppe og en anden thiolgruppe, hvor den første thiolgruppe er bundet til 2-positionen i forbindelsen med formel (Illa), og den anden thiolgruppe er bundet til 3-positionen i forbindelsen med formel (I I la); og trin (ii) yderligere inddrager spaltning af bindingen mellem gruppen Ri og carbonatomet i 3-positionen af delen med formel (Illa).
8. Forbindelse, hvilken forbindelse er: (A) en forbindelse med formel (Ila) ifølge krav 6; eller (B) en forbindelse med formel (III) ifølge krav 7, der omfatter mindst én gruppe med formel F2, og hvori R2a ikke er et hydrogenatom.
9. Forbindelse med formel (Illa) ifølge krav 7.
10. Forbindelse ifølge krav 9, der omfatter mindst én gruppe med formel F2.
11. Forbindelse ifølge krav 9 eller 10, hvor Ri er et peptid eller protein, der omfatter mindst to cyste in rester, hvilke cysteinrester fortrinsvis danner en intern disulfidbinding i peptidet eller proteinet, når peptidet eller proteinet ikke er bundet i forbindelsen med formel (Illa).
12. Fremgangsmåde, som er: (A) en fremgangsmåde til påvisning af, om et stof er til stede i en prøve, hvilken fremgangsmåde omfatter: tilvejebringelse af en forbindelse som defineret i (B) i krav 8 eller krav 10, hvor den ene af den første funktionelle del og den anden funktionelle del er en funktionel del, der er i stand til at generere et påviseligt signal, og den anden af den første funktionelle del og den anden funktionelle del er en funktionel del, der er i stand til at interagere med stoffet; inkubering af prøven med forbindelsen; og overvågning for et signal under betingelser, der åbner mulighed for generering af et påviseligt signal fra den funktionelle del, der er i stand til at generere et påviseligt signal; eller (B) en fremgangsmåde til identificering af, om et stof interagerer med en funktionel del med formel Ri, hvilken fremgangsmåde omfatter: fremstilling af et konjugat, der omfatter (a) den funktionelle del med formel Ri og (b) en påviselig del, der er i stand til at generere et signal, der kan modificeres ved hjælp af stoffet, ved udførelse af en fremgangsmåde ifølge et hvilket som helst af kravene 4 til 6; inkubering af konjugatet med stoffet; opnåelse af et signal fra den påviselige del; og sammenligning af signalet med et kontrolsignal, der kan opnås, når konjugatet ikke har været i kontakt med stoffet, til således bestemmelse af, om stoffet interagerer med konjugatet.
13. Fremgangsmåde ifølge et hvilket som helst af kravene 4 til 6, hvilken fremgangsmåde yderligere omfatter kobling af en eller flere yderligere funktionelle dele til konjugatet, hvor hver yderligere funktionelle del er ens eller forskellige og er valgt blandt en påviselig del, en enzymatisk aktiv del, en affinitetstag, en hapten, et immunogent bæremateriale, et antistof eller antistoffragment, et antigen, en ligand, en biologisk aktiv del, et liposom, en polymer del, en aminosyre, et peptid, et protein, en celle, et carbohydrat, et DNA og et RNA.
DK15150363.8T 2009-08-10 2010-08-09 Reversibel kovalent binding af funktionelle molekyler DK2889624T3 (da)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0913967A GB0913967D0 (en) 2009-08-10 2009-08-10 Functionalisation of solid substrates
GB0913965A GB0913965D0 (en) 2009-08-10 2009-08-10 Reversible covalent linkage of functional moieties
GB0914321A GB0914321D0 (en) 2009-08-14 2009-08-14 Thiol protecting group
EP12189317.6A EP2549276B1 (en) 2009-08-10 2010-08-09 Reversible covalent linkage of functional molecules

Publications (1)

Publication Number Publication Date
DK2889624T3 true DK2889624T3 (da) 2018-12-10

Family

ID=42668730

Family Applications (2)

Application Number Title Priority Date Filing Date
DK15150363.8T DK2889624T3 (da) 2009-08-10 2010-08-09 Reversibel kovalent binding af funktionelle molekyler
DK12189317.6T DK2549276T3 (da) 2009-08-10 2010-08-09 Reversibel, kovalent binding af funktionelle molekyler

Family Applications After (1)

Application Number Title Priority Date Filing Date
DK12189317.6T DK2549276T3 (da) 2009-08-10 2010-08-09 Reversibel, kovalent binding af funktionelle molekyler

Country Status (11)

Country Link
US (6) US9295729B2 (da)
EP (5) EP2464974A1 (da)
JP (3) JP2013501765A (da)
CN (1) CN102597773B (da)
AU (2) AU2010283632B2 (da)
BR (1) BR112012003089A2 (da)
CA (3) CA2770626A1 (da)
DK (2) DK2889624T3 (da)
ES (2) ES2699312T3 (da)
IL (2) IL218010A (da)
WO (3) WO2011018613A1 (da)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102317315A (zh) 2009-02-11 2012-01-11 诺维信生物制药丹麦公司 白蛋白变体和缀合物
DK2889624T3 (da) 2009-08-10 2018-12-10 Ucl Business Plc Reversibel kovalent binding af funktionelle molekyler
JP2013509170A (ja) 2009-10-30 2013-03-14 ノボザイムス バイオファーマ デーコー アクティーゼルスカブ アルブミン変異体
WO2011124718A1 (en) 2010-04-09 2011-10-13 Novozymes A/S Albumin derivatives and variants
EP2780364A2 (en) 2011-11-18 2014-09-24 Eleven Biotherapeutics, Inc. Proteins with improved half-life and other properties
KR20140139480A (ko) * 2011-12-05 2014-12-05 이제니카 바이오테라퓨틱스, 인크. 항체-약물 접합체 및 관련 화합물, 조성물, 및 방법
EP2814512A1 (en) 2012-02-16 2014-12-24 UCL Business Plc. Lysosome-cleavable linker
EP2822597A1 (en) * 2012-03-09 2015-01-14 UCL Business Plc. Chemical modification of antibodies
KR20140136934A (ko) 2012-03-16 2014-12-01 노보자임스 바이오파마 디케이 에이/에스 알부민 변이체
BR112015010318A2 (pt) 2012-11-08 2017-08-22 Albumedix As Variantes de albumina
MX2015006868A (es) 2012-11-30 2015-10-05 Novartis Ag Metodos para la elaboracion de conjugados a partir de proteinas que contienen disulfuro.
BR112015022585B1 (pt) 2013-03-15 2023-04-04 Regeneron Pharmaceuticals, Inc Composto, composição farmacêutica, conjugado droga-anticorpo, e, uso dos mesmos
WO2014197866A1 (en) 2013-06-06 2014-12-11 Igenica Biotherapeutics, Inc. Modified antibodies 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
AU2014311361B2 (en) 2013-08-26 2018-11-29 Regeneron Pharmaceuticals, Inc. Pharmaceutical compositions comprising macrolide diastereomers, methods of their synthesis and therapeutic uses
AU2014356126B2 (en) 2013-11-26 2017-01-05 Novartis Ag Methods for oxime conjugation to ketone-modified polypeptides
CA2940685C (en) 2014-03-11 2023-10-24 Regeneron Pharmaceuticals, Inc. Anti-egfrviii antibodies and uses thereof
US10406198B2 (en) 2014-05-23 2019-09-10 Novartis Ag Methods for making conjugates from disulfide-containing proteins
CN105294832B (zh) * 2014-08-11 2020-11-06 浙江海洋学院 一种缢蛏活性三肽及其制备方法和应用
EP3218009B1 (en) 2014-10-14 2021-04-07 Polytherics Limited Process for the conjugation of a peptide or protein with a reagent comprising a leaving group including a portion of peg
US10342441B2 (en) 2015-02-27 2019-07-09 Qualcomm Incorporated Estimating heart rate by tracking optical signal frequency components
WO2016160615A1 (en) 2015-03-27 2016-10-06 Regeneron Pharmaceuticals, Inc. Maytansinoid derivatives, conjugates thereof, and methods of use
CN104910312B (zh) * 2015-05-28 2019-03-15 江苏省原子医学研究所 一种提高染料荧光强度的线性聚合物及其制备方法和应用
WO2017007796A1 (en) 2015-07-06 2017-01-12 Regeneron Pharmaceuticals, Inc. Multispecific antigen-binding molecules and uses thereof
CA2989966C (en) 2015-08-20 2024-04-30 Albumedix A/S Albumin variants and conjugates
WO2017089607A1 (en) 2015-11-27 2017-06-01 Heidelberg Pharma Gmbh Derivatives of gamma-amanitin
CA3007644A1 (en) 2015-12-11 2017-06-15 Regeneron Pharmaceuticals, Inc. Methods for reducing or preventing growth of tumors resistant to egfr and/or erbb3 blockade
MA43094B1 (fr) 2016-01-25 2020-10-28 Regeneron Pharma Dérivés de maytansinoïde, leurs conjugués, et procédés d'utilisation
EP3222292A1 (en) 2016-03-03 2017-09-27 Heidelberg Pharma GmbH Amanitin conjugates
US11352446B2 (en) 2016-04-28 2022-06-07 Regeneron Pharmaceuticals, Inc. Methods of making multispecific antigen-binding molecules
US20190328900A1 (en) 2016-07-01 2019-10-31 Glaxosmithkline Intellectual Property Development Limited Antibody-drug conjugates and therapeutic methods using the same
EA201990781A9 (ru) 2016-09-23 2019-11-27 Анти-steap2 антитела, конъюгаты антитело-лекарственное средство и биспецифические антигенсвязывающие молекулы, которые связывают steap2 и cd3, и их применение
US10941208B2 (en) 2016-09-23 2021-03-09 Regeneron Pharmaceuticals, Inc. Anti-MUC16 antibodies
JOP20190086A1 (ar) 2016-10-21 2019-04-18 Novartis Ag مشتقات نافثيريدينون جديدة واستخدامها في معالجة عدم انتظام ضربات القلب
JP7330101B2 (ja) 2016-11-08 2023-08-21 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 ステロイド及びそのタンパク質コンジュゲート
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
US10864279B2 (en) 2016-12-16 2020-12-15 Industrial Technology Research Institute Linker-drug and antibody-drug conjugate (ADC) employing the same
US11491231B2 (en) * 2017-03-31 2022-11-08 University of Pittsburgh—of the Commonwealth System of Higher Education Peptide-oligonucleotide chimeras (POCs) as programmable biomolecular constructs for the assembly of morphologically-tunable soft materials
MX2019013690A (es) 2017-05-18 2020-01-27 Regeneron Pharma Conjugados de farmaco-proteina con ciclodextrina.
EP3661938A1 (en) 2017-08-07 2020-06-10 Heidelberg Pharma Research GmbH Novel method for synthesizing amanitins
AU2018314668B2 (en) 2017-08-07 2022-06-02 Heidelberg Pharma Research Gmbh Novel method for synthesizing amanitins
CN111432844B (zh) 2017-09-22 2023-10-27 海德堡医药研究有限责任公司 靶向psma的鹅膏蕈碱缀合物
CA3086926A1 (en) 2018-01-08 2019-07-11 Regeneron Pharmaceuticals, Inc. Steroids and antibody-conjugates thereof
AU2019246389A1 (en) 2018-03-28 2020-08-27 Ascendis Pharma Oncology Division A/S IL-2 conjugates
CA3093083A1 (en) 2018-03-28 2019-10-03 Ascendis Pharma A/S Conjugates
WO2019212965A1 (en) 2018-04-30 2019-11-07 Regeneron Pharmaceuticals, Inc. Antibodies, and bispecific antigen-binding molecules that bind her2 and/or aplp2, conjugates, and uses thereof
JP2021523147A (ja) 2018-05-09 2021-09-02 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 抗ｍｓｒ１抗体及びその使用方法
SG11202011232VA (en) 2018-05-17 2020-12-30 Regeneron Pharma Anti-cd63 antibodies, conjugates, and uses thereof
GB2575793A (en) * 2018-07-20 2020-01-29 Montanuniv Leoben Resin composition suitable for printing and printing methods
CN109293683A (zh) * 2018-09-05 2019-02-01 河南师范大学 一种还原响应型喜树碱二聚体及基于该喜树碱二聚体的还原敏感的药物传递系统
CN111433188B (zh) * 2018-12-17 2023-08-01 荣昌生物制药(烟台)股份有限公司 一种用于抗体药物偶联物的连接子及其应用
US11666658B2 (en) 2018-12-21 2023-06-06 Regeneran Pharmaceuticals, Inc. Rifamycin analogs and antibody-drug conjugates thereof
US20220040319A1 (en) 2019-02-21 2022-02-10 Regeneron Pharmaceuticals, Inc. Methods of treating ocular cancer using anti-met antibodies and bispecific antigen binding molecules that bind met
CN114340684A (zh) 2019-09-16 2022-04-12 瑞泽恩制药公司 用于免疫pet成像的放射性标记的met结合蛋白
US11814428B2 (en) 2019-09-19 2023-11-14 Regeneron Pharmaceuticals, Inc. Anti-PTCRA antibody-drug conjugates and uses thereof
IL295312A (en) 2020-02-28 2022-10-01 Regeneron Pharma Bispecific antigen binding molecules that bind her2 and methods of using them
EP4135775A1 (en) 2020-04-16 2023-02-22 Regeneron Pharmaceuticals, Inc. Diels-alder conjugation methods
KR20230019889A (ko) 2020-06-03 2023-02-09 아센디스 파마 온콜로지 디비전 에이/에스 Il-2 서열 및 이의 용도
MX2023000544A (es) 2020-07-13 2023-02-13 Regeneron Pharma Conjugados de proteina-farmaco que comprenden analogos de camptotecina y metodos de uso de los mismos.
CN116615251A (zh) 2020-09-14 2023-08-18 瑞泽恩制药公司 包含glp1肽模拟物的抗体-药物缀合物及其用途
MX2023004434A (es) 2020-10-22 2023-05-08 Regeneron Pharma Anticuerpos anti-fgfr2 y metodos para usarlos.
CN114031719B (zh) * 2021-11-26 2023-11-07 珠海宏昌电子材料有限公司 双马来酰亚胺-三嗪树脂及其制备方法和应用
US20230287138A1 (en) 2022-01-12 2023-09-14 Regneron Pharmaceuticals, Inc. Protein-drug conjugates comprising camptothecin analogs and methods of use thereof
CN114377723B (zh) * 2022-01-22 2022-12-13 海南大学 一种二氧化钛及其可见光催化产氢
US20230330254A1 (en) 2022-03-11 2023-10-19 Regeneron Pharmaceuticals, Inc. Anti-glp1r antibody-tethered drug conjugates comprising glp1 peptidomimetics and uses thereof
WO2024020164A2 (en) 2022-07-21 2024-01-25 Firefly Bio, Inc. Glucocorticoid receptor agonists and conjugates thereof
WO2024081151A1 (en) * 2022-10-11 2024-04-18 Ohio State Innovation Foundation Detection of an amphiphile using visual inspection of a ligand-modified substrate

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA667583A (en) * 1963-07-30 Druey Jean Tetrahydro-dioxopyridazines and process for their preparation
US2861093A (en) * 1956-09-24 1958-11-18 Eastman Kodak Co Reaction products of dialkyl phosphorothiolothionates and mucohalic acids
BE725964A (da) * 1967-12-23 1969-05-29
DE2032709A1 (en) * 1970-07-02 1972-01-20 Badische Anilin- & Soda-Fabrik Ag, 6700 Ludwigshafen 2-halo-3-mercapto-maleicaldehydeacids as photo-hardeners - from mucohaloacids and mercaptans with bases in inert solvents
JPS5440556B2 (da) 1973-03-13 1979-12-04
GB1544686A (en) * 1977-07-12 1979-04-25 Ici Ltd Disperse anthraquinone dyestuffs
DE3513715A1 (de) 1985-04-17 1986-10-23 Bayer Ag, 5090 Leverkusen Polycarbonate mit dichlormaleinimid-endgruppen, ihre herstellung und modifizierung
US4680272A (en) 1985-10-23 1987-07-14 University Of California Method for detecting molecules containing amine or thiol groups
JPS63145282A (ja) 1986-12-08 1988-06-17 Taiyo Yakuhin Kogyo Kk ピリダジン誘導体
AU650953B2 (en) 1991-03-21 1994-07-07 Novartis Ag Inhaler
PT100941A (pt) * 1991-10-11 1993-10-29 Ciba Geigy Ag Herbicidas a base de eteres ou tioeteres pirimidinilicos ou triazinilicos, e processo para a sua preparacao
US5414074A (en) 1992-09-25 1995-05-09 University Of Michigan Synthesis of C-glycosylated compounds with the use of a mild, iodine-catalyzed reaction
DE4310141A1 (de) * 1993-03-29 1994-10-06 Boehringer Mannheim Gmbh Homobidentale trifunktionelle Linker
GB9801210D0 (en) 1998-01-21 1998-03-18 Merck Sharp & Dohme Therapeutic agents
DE19843873A1 (de) 1998-09-25 2000-03-30 Univ Halle Wittenberg Verfahren zur Bestimmung von Proteaseaktivitäten auf Zelloberflächen
US7442764B2 (en) 1999-06-07 2008-10-28 Mirns Bio Corporation Reversible modification of amine-containing compounds
GB2352085A (en) 1999-07-15 2001-01-17 Univ Bristol Integrated semiconductor optical devices
DE10032335A1 (de) 2000-07-04 2002-01-17 Cognis Deutschland Gmbh Dimethylbenzol-Derivate
WO2002063299A1 (en) * 2001-02-05 2002-08-15 Graffinity Pharmaceuticals Ag Low affinity screening method
ES2330089T3 (es) 2001-08-17 2009-12-04 Mitsui Chemicals Agro, Inc. Derivado de 3-fenoxi-4-piridazinol y composicion herbicida que lo contiene.
EP1578527A1 (en) * 2002-09-13 2005-09-28 Ciphergen Biosystems, Inc. Preparation and use of mixed mode solid substrates for chromatography adsorbents and biochip arrays
US20090074885A1 (en) 2003-09-08 2009-03-19 Roche Madison Inc. Reversible Hydrophobic Modification of Drugs for Improved Delivery to Cells
EP1722781A4 (en) 2004-02-22 2010-07-21 Us Gov Health & Human Serv ANTITUMOR PHOSPHATASE INHIBITORS BASED ON MALEIIMIDE
US7390570B2 (en) 2004-05-13 2008-06-24 The Yokohama Rubber Co., Ltd. Maleimide terminated rubber and curable composition produced by using the maleimide terminated rubber
CN103893778A (zh) 2005-08-19 2014-07-02 恩多塞特公司 多药物配体缀合物
US20070248950A1 (en) * 2006-04-19 2007-10-25 Analytical Biological Services, Inc. Supported polydiacetylene 3-D arrays for flourescent or phosphorescent detection
GB0716783D0 (en) 2007-08-29 2007-10-10 Ucl Business Plc New Process
EA020005B1 (ru) 2008-08-07 2014-07-30 Ипсен Фарма С.А.С. Аналоги глюкозазависимого инсулинотропного полипептида
EP2915538A3 (en) 2008-08-07 2015-10-14 Ipsen Pharma S.A.S. Truncated analogues of glucose-dependent insulinotropic polypeptide
KR101593158B1 (ko) * 2008-08-07 2016-02-12 입센 파마 에스.에이.에스. Ｎ-말단이 변형된 포도당 의존적인 인슐린 분비 자극성 폴리펩타이드(ｇｉｐ)의 유사체
DK2889624T3 (da) 2009-08-10 2018-12-10 Ucl Business Plc Reversibel kovalent binding af funktionelle molekyler
EP2814512A1 (en) * 2012-02-16 2014-12-24 UCL Business Plc. Lysosome-cleavable linker

Also Published As

Publication number Publication date
US20190142950A1 (en) 2019-05-16
WO2011018611A1 (en) 2011-02-17
JP5954789B2 (ja) 2016-07-20
EP2549276A2 (en) 2013-01-23
BR112012003089A2 (pt) 2016-08-16
EP2889624B1 (en) 2018-10-03
EP2464654A2 (en) 2012-06-20
AU2016262736B2 (en) 2018-05-10
JP2013501764A (ja) 2013-01-17
WO2011018613A1 (en) 2011-02-17
EP2464654B1 (en) 2014-10-08
WO2011018612A3 (en) 2011-04-14
EP2464974A1 (en) 2012-06-20
AU2010283632B2 (en) 2016-08-25
US10174094B2 (en) 2019-01-08
AU2010283632A2 (en) 2012-03-08
US20160176942A1 (en) 2016-06-23
CN102597773B (zh) 2015-07-15
US20120190579A1 (en) 2012-07-26
IL218010A0 (en) 2012-04-30
US9295729B2 (en) 2016-03-29
US10548982B2 (en) 2020-02-04
AU2016262736A1 (en) 2016-12-15
EP2889624A3 (en) 2015-09-30
CN102597773A (zh) 2012-07-18
EP2889624A2 (en) 2015-07-01
US20120190124A1 (en) 2012-07-26
ES2537623T3 (es) 2015-06-10
IL218010A (en) 2016-05-31
IL245506A0 (en) 2016-06-30
EP2549276A3 (en) 2013-03-20
AU2010283632A1 (en) 2012-03-08
JP2013501766A (ja) 2013-01-17
US20200108150A1 (en) 2020-04-09
US10933142B2 (en) 2021-03-02
WO2011018612A2 (en) 2011-02-17
ES2699312T3 (es) 2019-02-08
CA2770617A1 (en) 2011-02-17
CA2770620A1 (en) 2011-02-17
JP2013501765A (ja) 2013-01-17
US20120190814A1 (en) 2012-07-26
DK2549276T3 (da) 2015-06-08
CA2770617C (en) 2018-02-20
CA2770626A1 (en) 2011-02-17
EP2464972A1 (en) 2012-06-20
IL245506A (en) 2017-09-28
EP2549276B1 (en) 2015-02-25

Similar Documents

Publication Publication Date Title
DK2889624T3 (da) Reversibel kovalent binding af funktionelle molekyler
TWI792596B (zh) 新穎脂肪酸及其於共軛至生物分子之用途
JP6086528B2 (ja) 長期のインビボ有効性を有する成長ホルモン
JP5252458B2 (ja) 新規タンパク質コンジュゲート及びその製造方法
BRPI0607248A2 (pt) conjugado de um polipeptìdeo e um oligossacarìdeo, composição farmacêutica, uso do conjugado, e, processo para a preparação de um conjugado
Wu et al. Manipulation of glutathione-mediated degradation of thiol–maleimide conjugates
JP2008543297A (ja) トランスグルタミナーゼを介した成長ホルモンのコンジュゲート
JP2013518038A (ja) ｉｎ−ｖｉｖｏにおける効力が延長された成長ホルモン
AU2018309724A1 (en) Modified DDAH polypeptides comprising a pharmacokinetic enhancing moiety, improved pharmacology and their uses
Freidel Design, synthesis and application of novel disulfide-intercalation agents for the site-selective modification of peptides and proteins