ES2579987T3 - Polipéptidos interleuquina-2 mutantes - Google Patents

Polipéptidos interleuquina-2 mutantes Download PDF

Info

Publication number
ES2579987T3
ES2579987T3 ES12702045.1T ES12702045T ES2579987T3 ES 2579987 T3 ES2579987 T3 ES 2579987T3 ES 12702045 T ES12702045 T ES 12702045T ES 2579987 T3 ES2579987 T3 ES 2579987T3
Authority
ES
Spain
Prior art keywords
fab
mice
mutant
polypeptide
interleukin
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.)
Active
Application number
ES12702045.1T
Other languages
English (en)
Inventor
Oliver Ast
Peter Bruenker
Anne Freimoser-Grundschober
Sylvia Herter
Thomas U. Hofer
Ralf Hosse
Christian Klein
Ekkehard Moessner
Valeria G. Nicolini
Pablo Umana
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.)
Roche Glycart AG
Original Assignee
Roche Glycart AG
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 Roche Glycart AG filed Critical Roche Glycart AG
Application granted granted Critical
Publication of ES2579987T3 publication Critical patent/ES2579987T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against enzymes
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/55—IL-2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2013—IL-2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6813—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin the drug being a peptidic cytokine, e.g. an interleukin or interferon
    • 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
    • A61K47/6843—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 material from animals or humans
    • 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
    • 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
    • A61K47/6853—Carcino-embryonic antigens
    • 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
    • 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
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Toxicology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Oncology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Polipéptido interleuquina 2 (IL-2) mutante que comprende tres mutaciones de aminoácido que anulan o reducen la afinidad del polipéptido IL-2 mutante para el receptor de IL-2 de alta afinidad y conservan la afinidad del polipéptido IL-2 mutante para el receptor de IL-2 de afinidad intermedia, comparando cada uno con un polipéptido IL- 2 de tipo salvaje, en el que dichas tres mutaciones de aminoácido se encuentran en las posiciones correspondientes a los residuos 42, 45 y 72 de la IL-2 humana (SEC ID nº 1).

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
imagen7
imagen8
imagen9
imagen10
imagen11
imagen12
imagen13
imagen14
imagen15
imagen16
imagen17
imagen18
imagen19
imagen20
imagen21
imagen22
imagen23
imagen24
imagen25
imagen26
imagen27
imagen28
imagen29
imagen30
imagen31
imagen32
imagen33
imagen34
imagen35
imagen36
imagen37
imagen38
imagen39
imagen40
imagen41
imagen42
imagen43
imagen44
imagen45
imagen46
imagen47
imagen48
imagen49
imagen50
imagen51
imagen52
imagen53
imagen54
imagen55
imagen56
imagen57
imagen58
imagen59
imagen60
imagen61
imagen62
imagen63
imagen64
Grupo 7 (9 µg/g)
1 1 32 33 101208 94764 97986
1
5,5 34 35 35766 32359 34062
1
24 36 37 573 588 580
Fab-II2-Fab WT de 4G8
32 31779 37473
5
5,5 33 35 51143 53409
36
13562
1
1
38 39 73326 47953 60639
1
5,5 40 41 12168 14371 13269
Grupo 8 (4.5 µg/g)
1 24 42 43 494 487 490
Fab-II2-Fab mutante de 4G8
5 5,5 40 41 6561 15352 10957
38
608 721
5
24 39 42 543 1298
43
437
1
1
44 45 162970 129862 146416
1
5.5 46 47 20475 29125 24800
Grupo 9 (9 µg/g)
1 24 48 49 478 509 493
Fab-II2-Fab mutante de 4G8
5 5.5 46 47 20504 75557 48031
44
634 703
5
24 45 48 796 661
49
719
Estos datos demuestran que tanto Fab-IL-2 qm-Fab de 4G8 como Fab-IL-2 wt-Fab de 4G8 mostraban propiedades farmacocinéticas comparables con una exposición ligeramente superior para Fab-IL-2 qm-Fab de 4G8.
5 Mortalidad
En el grupo de 9 µg/g de Fab-IL-2 wt-Fab de 4G8 con diana en FAP, se produjo mortalidad relacionada con el tratamiento en un animal previamente a la necropsia, el día 5. Se observaron hipoactividad, piel fría y postura encorvada previamente a la muerte. Este animal probablemente murió debido a una combinación de infiltración
10 celular en el pulmón que se vio acompañada de edema y hemorragia y necrosis marcada de la médula ósea. Se resumen los datos de mortalidad en la Tabla 17.

TABLA 17. Mortalidad el día 5.
Grupo
Tipo Dosis (µg/kg) Muertos Sacrificio por toxicidad severa** Total
1
DPBS 0 0/5 0/5 0/5
2
Fab-IL-2 wt-Fab de 4G8 4,5 0/5 5/5 5/5
3
9 1/5* 4/5 4/5
4
Fab-IL-2 qm-Fab de 4G8 4,5 0/5 0/5 0/5
5
9 0/5 0/5 0/5
6
Fab-IL-2 wt-Fab de 4G8 4,5 1/6 5/6 6/6
7
9 2/6 4/6 6/6
8
Fab-IL-2 qm-Fab de 4G8 4,5 0/6 0/6 0/6
9
9
0/6 0/6 0/6
* progresando a necrosis ** el estudio se planificó para que durase siete días, pero todos los ratone tratados con el inmunoconjugado de IL-2 de tipo salvaje resultaron afectados marcadamente llegado el día 5 y se sacrificaron ya que no se esperaba
66
que sobreviviesen.
Observaciones clínicas Se registraron observaciones de hipoactividad, piel fría y postura encorvada en los animales que recibieron 4,5 y 9 µg/g/día de IL-2 wt. Se resumen las observaciones clínicas en la Tabla 18. TABLA 18. Observaciones clínicas el día 5.
Grupo
Tipo Dosis (µg/kg) Postura encorvada Hipoactivo Frío al tacto
1
DPBS 0 0/5 0/5 0/5
2
Fab-IL-2 wt-Fab de 4G8 4,5 4/5 4/5 5/5
3
9 5/5 5/5 5/5
4
Fab-IL-2 qm-Fab de 4G8 4,5 0/5 0/5 0/5
5
9 0/5 0/5 0/5
6
Fab-IL-2 wt-Fab de 4G8 4,5 6/6 2/6 2/6
7
9 6/6 5/6 6/6
8
Fab-IL-2 qm-Fab de 4G8 4,5 0/6 0/6 0/6
9
9
0/6 0/6 0/6
Peso corporal
10 Se observó una reducción moderada del peso corporal tras 5 días de tratamiento en animales que recibieron 4,5 y 9 (9% y 11%, respectivamente) µg/g/día de IL-2 wt. Se observó una ligera reducción del peso corporal tras 5 días de tratamiento en animales que habían recibido 4,5 ó 9 (2% y 1%, respectivamente) µg/g/día de IL-2 qm. También se observó una reducción moderada (9%) de peso corporal en los controles de vehículo tras 5 días de tratamiento. Sin
15 embargo, el porcentaje de reducción había sido de 5% si se hubiese excluido un valor potencialmente atípico (animal nº 3). La pérdida de peso corporal en el grupo de vehículo podría atribuirse a estrés.
Hematología
20 Se observó un recuento reducido de plaquetas en los animales que recibieron 4,5 (de ~4,5 veces) y 9 µg/g/día (de ~11 veces) Fab-IL-2 wt-Fab de 4G8, lo que se correlaciona con un número reducido de megacariocitos en la médula ósea, así como efectos sistémicos de consumo (fibrina) en el bazo y pulmón de estos animales (ver la sección de histopatología, posteriormente). Estos resultados indican que el recuento plaquetario reducido probablemente se debe a los efectos combinados del consumo y reducción de la producción/hiperplasia en la médula ósea debido al
25 incremento de la producción de linfocitos/células mieloides como efecto directo o indirecto de la IL-2.
Los resultados hematológicos de relación incierta con la administración de compuesto consistían de una reducción del recuento absoluto de linfocitos con Fab-IL-2 wt-Fab de 4G8 a las dosis de 4,5 (de ~5 veces) y de 9 µg/g (de ~3 veces) en comparación con el valor medio del grupo de control de vehículo. Estos resultados no presentan una clara 30 dependencia de la dosis, pero podrían considerarse secundarios a los efectos asociados al estrés en las observaciones vitales o una farmacología exagerada del compuesto (migración de los linfocitos al interior de los tejidos). No se produjeron cambios hematológicos relacionados con el tratamiento atribuibles a la administración de Fab-IL-2 qm-Fab de 4G8. Unos cuantos resultados hematológicos aislados eran estadísticamente diferentes de sus controles respectivos. Sin embargo, estos resultados eran de insuficiente magnitud para sugerir una relevancia
35 patológica.
Patología macroscópica e histopatología
Entre los resultados generales relacionados con el tratamiento se incluyen un agrandamiento del bazo, observado 40 en 5/5 y 4/5 de los ratones de los grupos de 4,5 y 9 µg/g de Fab-IL-2 wt-Fab de 4G8, respectivamente, y en 1/5 en los grupos de tratamiento de 4,5 y 9 µg/g de Fab-IL-2 qm-Fab de 4G8.
Se observaron resultados histopatológicos relacionados con el tratamiento en los grupos que recibieron 4,5 y 9 µg/g de Fab-IL-2 wt-Fab de 4G8 y que recibieron 4,5 y 9 µg/g de Fab-IL-2 qm-Fab de 4G8, en pulmón, médula ósea, 45 hígado, bazo y timo, con diferencias de incidencia, gradación de la severidad o naturaleza de los cambios, tal como se informa posteriormente.
Los resultados histopatológicos relacionados con el tratamiento en el pulmón consistían de infiltración mononuclear leve a marcada en 5/5 ratones de los grupos de 4,5 y 9 µg/g de Fab-IL-2 wt-Fab de 4G8 y marginalmente en 5/5 50 ratones de los grupos de 4,5 y 9 µg/g de Fab-IL-2 qm-Fab de 4G8. La infiltración monuclear consistía de linfocitos
67
imagen65
imagen66
imagen67
imagen68
5
10
15
20
25
30
35
40
45
IL-2 de tipo salvaje (wt) o mutante cuádruple (qm), en ratones Black 6 inmunocompetentes libres de tumor. Los ratones Black 6 hembra (Charles River, Alemania), de 8 a 9 semanas de edad al inicio del experimento, se mantuvieron bajo condiciones libres de patógenos específicos con ciclos diarios de 12 horas de luz/12 horas de oscuridad de acuerdo a directrices acordadas (GV-Solas, Felasa, TierschG). El protocolo del estudio experimental fue revisado y autorizado por el gobierno local (P 2008016). Tras la llegada, los animales se mantuvieron durante una semana para aclimatarse al nuevo entorno y para su observación. Se llevó a cabo un seguimiento continuo de su salud de manera periódica.
Los ratones recibieron inyecciones i.v. una vez al día durante 7 días de Fab-IL2 wt-Fab de 4G8 a dosis de 60, 80 y 100 µg/ratón o de Fab-IL2 qm-Fab de 4G8 a dosis de 100, 200, 400, 600 y 1.000 µg/ratón. Todos los ratones recibieron inyecciones i.v. de 200 µl de la solución apropiada. Con el fin de obtener la cantidad correcta de inmunoconjugado por cada 200 µl, las soluciones madre se diluyeron con PBS en caso necesario.
La figura 40 muestra que la MTD (dosis máxima tolerada) para Fab-IL2 qm-Fab era 10 veces mayor para Fab-IL2 wt-Fab, es decir 600 µg/ratón diariamente durante 7 días para Fab-IL2 qm-Fab frente a 60 µg/ratón diarios durante 7 días para Fab-IL2 wt-Fab.
TABLA 19
Compuesto
Dosis Tampón de formulación concentración (mg/ml)
60,
Fosfato potásico 25 mM, 3,32 (=solución madre)
Fab-IL-2 wt-Fab de
80, NaCl 125 mM,
4G8
100 µg Glicina 100 mM,
pH 6,7
Fab-IL-2 qm-Fab de 4G8
100, 200, 400, 600, 1.000 µg Fosfato potásico 25 mM, NaCl 125 mM, Glicina 100 mM, pH 6,7 4,25 (=solución madre)
Ejemplo 16
Farmacocinética de una única dosis de IgG-IL2 wt y qm dirigidos a FAP y sin diana
Se llevó a cabo un estudio farmacocinético (PK) de una sola dosis en ratones 129 inmunocompetentes libres de tumor para inmunoconjugados IgG-IL2 con diana en FAP que comrpendían IL-2 de tipo salvaje o mutante cuádruple e inmunoconjugados IgG-IL2 sin diana que comprendían IL-2 de tipo salvaje o mutante cuádruple.
Los ratones Black 129 hembra (Harlan, Reino Unido), de 8 a 9 semanas de edad al inicio del experimento, se mantuvieron bajo condiciones libres de patógenos específicos con ciclos diarios de 12 horas de luz/12 horas de oscuridad de acuerdo a directrices acordadas (GV-Solas, Felasa, TierschG). El protocolo del estudio experimental fue revisado y autorizado por el gobierno local (P 2008016). Tras su llegada, los animales se mantuvieron durante una semana para que se aclimatasen al nuevo entorno y para su observación. Se llevó a cabo un seguimiento continuo periódico de su estado de salud.
Los ratones recibieron inyecciones i.v. una vez con IgG-IL2 wt de 28H1 (2,5 mg/kg) con diana en FAP o IgG-IL2 qm de 28H1 (5 mg/kg) o IgG-IL2 wt DP47G2 sin diana (5 mg/kg) o IgG-IL2 qm DP47GS (5 mg/kg). Todos los ratones recibieron inyecciones i.v. de 200 µl de la solución apropiada. Con el fin de obtener la cantidad correcta de inmunoconjugado por cada 200 µl, las soluciones madre se diluyeron con PBS en caso necesario.
Se sangraron los ratones a las 1, 8, 24, 48, 72 y 96 horas y posteriormente cada 2 días durante 3 semanas. Se extrajeron los sueros y se almacenaron a -20ºC hasta la realización de los análisis ELISA. Se determinaron las concentraciones de inmunoconjugados en suero utilizando una ELISA para la cuantificación del anticuerpo de inmunoconjugado de IL-2 (Roche-Penzberg). Se midió la absorbancia utilizando una longitud de onda de medición de 405 nm y una longitud de onda de referencia de 492 nm (lector de microplacas regulable VersaMax, Molecular Devices). La figura 41 muestra la farmacocinética de dichos inmunoconjugados de IL-2. Los constructos IgG-IL2 tanto con diana en FAP (A) como sin dianas (B) presentaban una vida media en suero más prolongada (aproximadamente 30 horas) que los constructos IgG-IL2 wt correspondientes (aproximadamente 15 horas).
TABLA 20
imagen69
72
imagen70

Claims (1)

  1. imagen1
    imagen2
ES12702045.1T 2011-02-10 2012-02-07 Polipéptidos interleuquina-2 mutantes Active ES2579987T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP11153964 2011-02-10
EP11153964 2011-02-10
EP11164237 2011-04-29
EP11164237 2011-04-29
PCT/EP2012/051991 WO2012107417A1 (en) 2011-02-10 2012-02-07 Mutant interleukin-2 polypeptides

Publications (1)

Publication Number Publication Date
ES2579987T3 true ES2579987T3 (es) 2016-08-18

Family

ID=45560919

Family Applications (3)

Application Number Title Priority Date Filing Date
ES12702045.1T Active ES2579987T3 (es) 2011-02-10 2012-02-07 Polipéptidos interleuquina-2 mutantes
ES16164244.2T Active ES2694564T3 (es) 2011-02-10 2012-02-07 Polipéptidos de interleucina-2 mutantes
ES18191941T Active ES2883371T3 (es) 2011-02-10 2012-02-07 Polipéptidos de interleucina 2 mutantes

Family Applications After (2)

Application Number Title Priority Date Filing Date
ES16164244.2T Active ES2694564T3 (es) 2011-02-10 2012-02-07 Polipéptidos de interleucina-2 mutantes
ES18191941T Active ES2883371T3 (es) 2011-02-10 2012-02-07 Polipéptidos de interleucina 2 mutantes

Country Status (35)

Country Link
US (5) US9266938B2 (es)
EP (4) EP3075745B1 (es)
JP (2) JP5878182B2 (es)
KR (2) KR101852245B1 (es)
CN (3) CN103492411B (es)
AR (1) AR085335A1 (es)
AU (2) AU2012215573B2 (es)
BR (1) BR112013018932B1 (es)
CA (1) CA2824253C (es)
CL (1) CL2013001987A1 (es)
CO (1) CO6741186A2 (es)
CR (1) CR20130314A (es)
CY (1) CY1117842T1 (es)
DK (3) DK3075745T3 (es)
EA (1) EA033369B1 (es)
EC (1) ECSP13012815A (es)
ES (3) ES2579987T3 (es)
HR (3) HRP20160917T1 (es)
HU (3) HUE040326T2 (es)
IL (3) IL269687B (es)
LT (2) LT3489255T (es)
MA (1) MA35803B1 (es)
MX (2) MX356675B (es)
MY (1) MY190604A (es)
PE (2) PE20140303A1 (es)
PH (2) PH12013501657A1 (es)
PL (3) PL2673294T3 (es)
PT (3) PT2673294T (es)
RS (3) RS57767B1 (es)
SG (2) SG192673A1 (es)
SI (3) SI2673294T1 (es)
TW (2) TWI577801B (es)
UA (2) UA117294C2 (es)
WO (1) WO2012107417A1 (es)
ZA (1) ZA201305282B (es)

Families Citing this family (293)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5992710A (ja) * 1982-11-16 1984-05-29 関西電力株式会社 直接水冷線路の立坑部の布設方法
WO2011028952A1 (en) 2009-09-02 2011-03-10 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
AU2011283694B2 (en) 2010-07-29 2017-04-13 Xencor, Inc. Antibodies with modified isoelectric points
CA2806021C (en) 2010-08-13 2019-05-21 Roche Glycart Ag Anti-fap antibodies and methods of use
SG192673A1 (en) 2011-02-10 2013-09-30 Roche Glycart Ag Mutant interleukin-2 polypeptides
PE20141017A1 (es) 2011-03-02 2014-08-25 Roche Glycart Ag Anticuerpos del cea
EA201892619A1 (ru) 2011-04-29 2019-04-30 Роше Гликарт Аг Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2
WO2012164083A1 (en) 2011-06-01 2012-12-06 Actogenix N.V. Polycistronic expression system for bacteria
WO2013026839A1 (en) 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use
US12466897B2 (en) 2011-10-10 2025-11-11 Xencor, Inc. Heterodimeric human IgG1 polypeptides with isoelectric point modifications
US10851178B2 (en) 2011-10-10 2020-12-01 Xencor, Inc. Heterodimeric human IgG1 polypeptides with isoelectric point modifications
MY175687A (en) * 2012-08-07 2020-07-06 Roche Glycart Ag Composition comprising two antibodies engineered to have reduced and increased effector function
US20140044675A1 (en) 2012-08-10 2014-02-13 Roche Glycart Ag Interleukin-2 fusion proteins and uses thereof
RU2015117393A (ru) 2012-10-08 2016-12-10 Роше Гликарт Аг Лишенные fc антитела, содержащие два Fab-фрагмента, и способы их применения
RU2015125639A (ru) * 2012-11-30 2017-01-10 Роше Гликарт Аг Удаление раковых клеток с помощью циркулирующих вирус-специфических цитотоксических т-клеток с использованием направленных против раковых клеток многофункциональных белков, содержащих молекулу гкгс класса i
WO2014096015A1 (en) 2012-12-21 2014-06-26 F. Hoffmann-La Roche Ag Disulfide-linked multivalent mhc class i comprising multi-function proteins
US10968276B2 (en) 2013-03-12 2021-04-06 Xencor, Inc. Optimized anti-CD3 variable regions
US10131710B2 (en) 2013-01-14 2018-11-20 Xencor, Inc. Optimized antibody variable regions
US10487155B2 (en) 2013-01-14 2019-11-26 Xencor, Inc. Heterodimeric proteins
KR102211837B1 (ko) 2013-01-14 2021-02-03 젠코어 인코포레이티드 신규한 이형이량체 단백질
US9605084B2 (en) 2013-03-15 2017-03-28 Xencor, Inc. Heterodimeric proteins
US11053316B2 (en) 2013-01-14 2021-07-06 Xencor, Inc. Optimized antibody variable regions
US9701759B2 (en) 2013-01-14 2017-07-11 Xencor, Inc. Heterodimeric proteins
WO2014113510A1 (en) 2013-01-15 2014-07-24 Xencor, Inc. Rapid clearance of antigen complexes using novel antibodies
EP2961773B1 (en) 2013-02-26 2019-03-20 Roche Glycart AG Bispecific t cell activating antigen binding molecules
LT2961771T (lt) * 2013-02-26 2020-03-10 Roche Glycart Ag Bispecifinės t ląstelę aktyvinančios antigeną surišančios molekulės, specifinės cd3 ir cea antigenams
US9580486B2 (en) * 2013-03-14 2017-02-28 Amgen Inc. Interleukin-2 muteins for the expansion of T-regulatory cells
US10858417B2 (en) 2013-03-15 2020-12-08 Xencor, Inc. Heterodimeric proteins
US10106624B2 (en) 2013-03-15 2018-10-23 Xencor, Inc. Heterodimeric proteins
EP2970486B1 (en) 2013-03-15 2018-05-16 Xencor, Inc. Modulation of t cells with bispecific antibodies and fc fusions
US10519242B2 (en) 2013-03-15 2019-12-31 Xencor, Inc. Targeting regulatory T cells with heterodimeric proteins
UA118028C2 (uk) 2013-04-03 2018-11-12 Рош Глікарт Аг Біспецифічне антитіло, специфічне щодо fap і dr5, антитіло, специфічне щодо dr5, і спосіб їх застосування
HRP20200250T1 (hr) 2013-08-08 2020-05-29 The Scripps Research Institute Metoda site-specifično enzimsko obilježavanje nukleinskih kiselina in vitro ugradnjom neprirodnih nukleotida
PT3102595T (pt) * 2014-02-06 2019-01-11 Hoffmann La Roche Proteínas de fusão de interleucina-2 e suas utilizações
GB201403775D0 (en) 2014-03-04 2014-04-16 Kymab Ltd Antibodies, uses & methods
EP3699195A3 (en) 2014-03-28 2020-11-04 Xencor, Inc. Bispecific antibodies that bind to cd38 and cd3
TWI638047B (zh) 2014-04-09 2018-10-11 史基普研究協會 藉由核酸三磷酸酯轉運子將非天然或經修飾的核苷三磷酸酯輸入至細胞中
DK3166973T3 (da) 2014-07-10 2020-04-06 Univ Zuerich Immunstimulerende monoklonale antistoffer mod human interleukin-2
PT3172227T (pt) * 2014-07-21 2019-12-06 Delinia Inc Moléculas que ativam seletivamente células t reguladoras para o tratamento de doenças autoimuneis
EP3177643B1 (en) 2014-08-04 2019-05-08 F.Hoffmann-La Roche Ag Bispecific t cell activating antigen binding molecules
AU2015301936B2 (en) 2014-08-11 2019-03-07 Delinia, Inc. Modified IL-2 variants that selectively activate regulatory T cells for the treatment of autoimmune diseases
DK3186283T3 (da) * 2014-08-29 2020-03-02 Hoffmann La Roche Kombinationsbehandling med tumormålrettede IL-2- immuncytokinervarianter og antistoffer mod humant PD-L1
EP3224275B1 (en) 2014-11-14 2020-03-04 F.Hoffmann-La Roche Ag Antigen binding molecules comprising a tnf family ligand trimer
EP4141032B1 (en) 2014-11-20 2024-05-29 F. Hoffmann-La Roche AG Combination therapy of t cell activating bispecific antigen binding molecules and pd-1 axis binding antagonists
DK3221357T3 (da) 2014-11-20 2020-08-10 Hoffmann La Roche Fælles letkæder og fremgangsmåder til anvendelse
PT3221356T (pt) 2014-11-20 2020-10-29 Hoffmann La Roche Moléculas de ligação ao antigénio biespecíficas ativadoras das células t contra folr1 e cd3
PE20171324A1 (es) 2014-11-26 2017-09-11 Xencor Inc Anticuerpos heterodimericos que se unen a cd3 y a antigenos tumorales
US10259887B2 (en) 2014-11-26 2019-04-16 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
EP3223907A2 (en) 2014-11-26 2017-10-04 Xencor, Inc. Heterodimeric antibodies that bind cd3 and cd38
EP3233192B1 (en) 2014-12-15 2021-04-14 Washington University Compositions and methods for targeted cytokine delivery
WO2016105450A2 (en) 2014-12-22 2016-06-30 Xencor, Inc. Trispecific antibodies
US10227411B2 (en) 2015-03-05 2019-03-12 Xencor, Inc. Modulation of T cells with bispecific antibodies and FC fusions
EP3973980A1 (en) 2015-03-31 2022-03-30 F. Hoffmann-La Roche AG Antigen binding molecules comprising a trimeric tnf family ligand
AR106188A1 (es) 2015-10-01 2017-12-20 Hoffmann La Roche Anticuerpos anti-cd19 humano humanizados y métodos de utilización
PE20180484A1 (es) 2015-10-02 2018-03-07 Hoffmann La Roche Moleculas biespecificas de union a antigeno activadoras de celulas t
US10526413B2 (en) 2015-10-02 2020-01-07 Hoffmann-La Roche Inc. Bispecific antibodies specific for OX40
WO2017055404A1 (en) 2015-10-02 2017-04-06 F. Hoffmann-La Roche Ag Bispecific antibodies specific for pd1 and tim3
WO2017077382A1 (en) 2015-11-06 2017-05-11 Orionis Biosciences Nv Bi-functional chimeric proteins and uses thereof
RU2018124307A (ru) 2015-12-04 2020-01-14 Новартис Аг Антительно-цитокиновые привитые композиции и способы применения для иммунорегуляции
CA3007030A1 (en) 2015-12-07 2017-06-15 Xencor, Inc. Heterodimeric antibodies that bind cd3 and psma
IL313608A (en) 2015-12-09 2024-08-01 Hoffmann La Roche Antibody against CD20 type II to reduce the formation of antibodies against drugs
EP3178848A1 (en) 2015-12-09 2017-06-14 F. Hoffmann-La Roche AG Type ii anti-cd20 antibody for reducing formation of anti-drug antibodies
WO2017106767A1 (en) 2015-12-18 2017-06-22 The Scripps Research Institute Production of unnatural nucleotides using a crispr/cas9 system
KR20180097615A (ko) 2016-01-08 2018-08-31 에프. 호프만-라 로슈 아게 Pd-1 축 결합 길항물질 및 항-cea/항-cd3 이중특이성 항체를 사용하는 cea-양성 암의 치료 방법
WO2017122130A1 (en) 2016-01-11 2017-07-20 Novartis Ag Immune-stimulating humanized monoclonal antibodies against human interleukin-2, and fusion proteins thereof
US10905727B2 (en) 2016-01-14 2021-02-02 Intrexon Actobiotics N.V. Compositions and methods for the treatment of type 1 diabetes
US20170204154A1 (en) * 2016-01-20 2017-07-20 Delinia, Inc. Molecules that selectively activate regulatory t cells for the treatment of autoimmune diseases
CN116769054A (zh) 2016-02-05 2023-09-19 奥里尼斯生物科学私人有限公司 双特异性信号传导剂及其用途
AU2017213659B2 (en) * 2016-02-05 2024-04-18 Washington University Compositions and methods for targeted cytokine delivery
EP3426278B1 (en) 2016-03-07 2024-01-03 Vib Vzw Cd20 binding single domain antibodies
JP7015244B2 (ja) 2016-03-22 2022-02-02 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト プロテアーゼ活性化ｔ細胞二重特異性分子
EP3455245A2 (en) 2016-05-13 2019-03-20 Orionis Biosciences NV Therapeutic targeting of non-cellular structures
WO2017194783A1 (en) 2016-05-13 2017-11-16 Orionis Biosciences Nv Targeted mutant interferon-beta and uses thereof
CN109478421B (zh) 2016-05-25 2024-07-09 豪夫迈·罗氏有限公司 剂量方案设计相关的材料与方法
JP7010854B2 (ja) 2016-06-14 2022-01-26 ゼンコア インコーポレイテッド 二重特異性チェックポイント阻害剤抗体
RU2769282C2 (ru) 2016-06-20 2022-03-30 Кимаб Лимитед Анти-PD-L1 и IL-2 цитокины
US9567399B1 (en) 2016-06-20 2017-02-14 Kymab Limited Antibodies and immunocytokines
US20190218257A1 (en) 2016-06-24 2019-07-18 The Scripps Research Institute Novel nucleoside triphosphate transporter and uses thereof
CN109715663B (zh) 2016-06-28 2022-11-25 Xencor股份有限公司 结合生长抑素受体2的异源二聚抗体
US10696722B2 (en) 2016-08-10 2020-06-30 Ajou University Industry-Academic Cooperation Foundation Heterodimeric Fc-fused cytokine and pharmaceutical composition comprising the same
US10793632B2 (en) 2016-08-30 2020-10-06 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
AU2017335771A1 (en) 2016-09-28 2019-02-28 Musc Foundation For Research Development Antibodies that bind interleukin-2 and uses thereof
US10882918B2 (en) 2016-09-30 2021-01-05 Hoffmann-La Roche Inc. Bispecific T cell activating antigen binding molecules
MY203000A (en) 2016-10-14 2024-06-01 Xencor Inc Il15/il15r� heterodimeric fc-fusion proteins
WO2018073365A1 (en) 2016-10-19 2018-04-26 F. Hoffmann-La Roche Ag Method for producing an immunoconjugate
WO2018077893A1 (en) 2016-10-24 2018-05-03 Orionis Biosciences Nv Targeted mutant interferon-gamma and uses thereof
EP3534947A1 (en) 2016-11-03 2019-09-11 Kymab Limited Antibodies, combinations comprising antibodies, biomarkers, uses & methods
EP3538548A4 (en) * 2016-11-08 2020-08-19 Delinia, Inc. IL-2 VARIANTS FOR THE TREATMENT OF AUTOIMMUNE DISEASES
CU24483B1 (es) * 2016-11-15 2020-04-02 Ct Inmunologia Molecular Método para incrementar los niveles de secreción de la interleucina-2
AU2017380981B2 (en) 2016-12-19 2025-01-30 F. Hoffmann-La Roche Ag Combination therapy with targeted 4-1BB (CD137) agonists
GB201621806D0 (en) 2016-12-21 2017-02-01 Philogen Spa Immunocytokines with progressive activation mechanism
ES2973548T3 (es) 2016-12-22 2024-06-20 Cue Biopharma Inc Polipéptidos multiméricos moduladores de linfocitos T y métodos para su uso
KR102642385B1 (ko) 2017-02-06 2024-03-04 오리오니스 바이오사이언시스 엔브이 표적화된 키메라 단백질 및 이의 용도
CN110573172A (zh) 2017-02-06 2019-12-13 奥里尼斯生物科学有限公司 靶向的工程化干扰素及其用途
EP3596108A4 (en) 2017-03-15 2020-12-23 Pandion Operations, Inc. TARGETED IMMUNOTOLERANCE
US20200010528A1 (en) 2017-03-15 2020-01-09 Cue Biopharma, Inc. Methods for modulating an immune response
JP7148539B2 (ja) * 2017-04-03 2022-10-05 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 免疫抱合体
MY201482A (en) * 2017-04-03 2024-02-26 Hoffmann La Roche Immunoconjugates of an anti-pd-1 antibody with a mutant il-2 or with il-15
JP6997209B2 (ja) 2017-04-04 2022-02-04 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト Ｃｄ４０およびｆａｐに特異的に結合することができる新規な二重特異性抗原結合分子
EP4516809A3 (en) 2017-04-05 2025-09-03 F. Hoffmann-La Roche AG Bispecific antibodies specifically binding to pd1 and lag3
CN110709513B (zh) * 2017-04-11 2023-10-03 豪夫迈·罗氏有限公司 具有热稳定性增加的突变型逆转录酶以及涉及其的产物、方法和用途
CN110505883A (zh) 2017-04-13 2019-11-26 豪夫迈·罗氏有限公司 供治疗癌症的方法中使用的白介素-2免疫缀合物,cd40激动剂,和任选地pd-1轴结合拮抗剂
JOP20190271A1 (ar) 2017-05-24 2019-11-21 Novartis Ag بروتينات مطعّمة بسيتوكين- الجسم المضاد وطرق الاستخدام للاضطرابات المتعلقة بالمناعة
MY206158A (en) * 2017-05-24 2024-12-02 Novartis Ag Antibody-cytokine engrafted proteins and methods of use in the treatment of cancer
US10676516B2 (en) 2017-05-24 2020-06-09 Pandion Therapeutics, Inc. Targeted immunotolerance
WO2018215938A1 (en) * 2017-05-24 2018-11-29 Novartis Ag Antibody-cytokine engrafted proteins and methods of use
WO2019006472A1 (en) 2017-06-30 2019-01-03 Xencor, Inc. TARGETED HETETRODIMERIC FUSION PROTEINS CONTAINING IL-15 / IL-15RA AND ANTIGEN-BINDING DOMAINS
JP7325341B2 (ja) 2017-07-11 2023-08-14 シンソークス，インク． 非天然ヌクレオチドの組み込み及びその方法
KR20240141853A (ko) * 2017-08-03 2024-09-27 신톡스, 인크. 자가면역 질환의 치료를 위한 사이토카인 접합체
JP2021502100A (ja) 2017-11-08 2021-01-28 ゼンコア インコーポレイテッド 新規抗ｐｄ−１配列を用いた二重特異性および単一特異性抗体
US10981992B2 (en) 2017-11-08 2021-04-20 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
KR102777151B1 (ko) 2017-11-21 2025-03-05 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 인터루킨-2의 부분 효능제
USRE50550E1 (en) 2017-12-06 2025-08-26 Pandion Operations, Inc. IL-2 muteins and uses thereof
US10946068B2 (en) 2017-12-06 2021-03-16 Pandion Operations, Inc. IL-2 muteins and uses thereof
US10174092B1 (en) 2017-12-06 2019-01-08 Pandion Therapeutics, Inc. IL-2 muteins
IL275426B2 (en) 2017-12-19 2025-03-01 Xencor Inc Engineered il-2 fc fusion proteins
WO2019129053A1 (zh) * 2017-12-26 2019-07-04 南京金斯瑞生物科技有限公司 以抗体Fc区为骨架的融合蛋白二聚体及其应用
SG11202006101WA (en) 2017-12-29 2020-07-29 Scripps Research Inst Unnatural base pair compositions and methods of use
US12247060B2 (en) 2018-01-09 2025-03-11 Marengo Therapeutics, Inc. Calreticulin binding constructs and engineered T cells for the treatment of diseases
EP3743448A4 (en) 2018-01-26 2021-11-03 Orionis Biosciences, Inc. XCR1 BINDING AGENTS AND USES THEREOF
KR102877915B1 (ko) 2018-02-05 2025-10-29 오리오니스 바이오사이언시즈 인코포레이티드 섬유아세포 결합제 및 이의 용도
IL325995A (en) 2018-02-08 2026-03-01 Genentech Inc Bispecific antigen binding molecules and methods of use
EP3762406A2 (en) * 2018-03-09 2021-01-13 Askgene Pharma, Inc. Cytokine prodrugs
TWI841551B (zh) 2018-03-13 2024-05-11 瑞士商赫孚孟拉羅股份公司 使用靶向4-1bb (cd137)之促效劑的組合療法
EP3765517A1 (en) 2018-03-14 2021-01-20 Elstar Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
PE20210313A1 (es) * 2018-03-28 2021-02-12 Bristol Myers Squibb Co Proteinas de fusion interleucina-2/receptor alfa de interleucina-2 y metodos de uso
CN111918665B (zh) * 2018-03-28 2024-11-26 阿森迪斯药物肿瘤股份有限公司 Il-2缀合物
CA3096052A1 (en) 2018-04-04 2019-10-10 Xencor, Inc. Heterodimeric antibodies that bind fibroblast activation protein
EP3781598A1 (en) 2018-04-18 2021-02-24 Xencor, Inc. Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains
SG11202010163QA (en) 2018-04-18 2020-11-27 Xencor Inc Pd-1 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and pd-1 antigen binding domains and uses thereof
CA3105448A1 (en) 2018-07-03 2020-01-09 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
MX2021000801A (es) 2018-07-24 2021-04-12 BioNTech SE Agonistas de il2.
WO2020023702A1 (en) 2018-07-25 2020-01-30 AskGene Pharma, Inc. Novel il-21 prodrugs and methods of use thereof
JP7241161B2 (ja) 2018-08-01 2023-03-16 イミュニティーバイオ、インコーポレイテッド 細胞免疫療法の安定した遺伝子改変のための、ホーミング受容体又はサイトカインとキメラ抗原受容体とを含むクアドリシストロニックシステム
CA3111576A1 (en) * 2018-09-11 2020-03-19 Ambrx, Inc. Interleukin-2 polypeptide conjugates and their uses
US11492384B2 (en) 2018-09-17 2022-11-08 Gi Innovation, Inc. Fusion protein comprising IL-2 protein and CD80 protein, and use thereof
AR114732A1 (es) 2018-09-18 2020-10-07 Hoffmann La Roche Utilización de un inhibidor de catepsina s contra la formación de anticuerpos antifármaco
EP3854805A4 (en) * 2018-09-21 2022-08-24 Innovent Biologics (Suzhou) Co., Ltd. NOVEL INTERLEUKIN 2 AND ITS USE
CA3098930A1 (en) * 2018-09-21 2020-03-26 Innovent Biologics (Suzhou) Co., Ltd. Novel interleukin-2 and use thereof
US20220002370A1 (en) * 2018-09-27 2022-01-06 Xilio Development, Inc. Masked cytokine polypeptides
AU2019355971B2 (en) 2018-10-03 2025-05-08 Xencor, Inc. IL-12 heterodimeric Fc-fusion proteins
SG11202104136YA (en) * 2018-10-23 2021-05-28 Dragonfly Therapeutics Inc Heterodimeric fc-fused proteins
TWI840433B (zh) 2018-10-29 2024-05-01 大陸商北京強新生物科技有限公司 新穎合理設計的蛋白質組合物
US12410225B2 (en) 2018-11-08 2025-09-09 Orionis Biosciences, Inc Modulation of dendritic cell lineages
EP3901167A4 (en) * 2018-12-21 2022-11-16 Hanmi Pharm. Co., Ltd. NOVEL IMMUNOSUPRESSIVE INTERLEUKIN 2
WO2020127369A1 (en) 2018-12-21 2020-06-25 Ose Immunotherapeutics Bifunctional molecule directed against human pd-1
UA128001C2 (uk) 2018-12-21 2024-03-06 Ф. Хоффманн-Ля Рош Аг Націлені на пухлину агоністичні cd28-антигензв'язувальні молекули
KR20210107714A (ko) * 2018-12-21 2021-09-01 지앙수 헨그루이 메디슨 컴퍼니 리미티드 인간 인터류킨-2 변이체 또는 이의 유도체
SG11202106700WA (en) * 2019-01-07 2021-07-29 Inhibrx Inc Polypeptides comprising modified il-2 polypeptides and uses thereof
TW202038994A (zh) * 2019-01-14 2020-11-01 美商醫格耐免疫治療公司 重組痘瘡病毒及其使用方法
EP3923974A4 (en) 2019-02-06 2023-02-08 Synthorx, Inc. IL-2 CONJUGATES AND METHODS OF USE THEREOF
GB2599228B (en) 2019-02-21 2024-02-07 Marengo Therapeutics Inc Multifunctional molecules that bind to T cell related cancer cells and uses thereof
CN119039441A (zh) 2019-02-21 2024-11-29 马伦戈治疗公司 与nkp30结合的抗体分子及其用途
CA3132185A1 (en) 2019-03-01 2020-09-10 Xencor, Inc. Heterodimeric antibodies that bind enpp3 and cd3
CN111647068A (zh) * 2019-03-04 2020-09-11 江苏恒瑞医药股份有限公司 一种人白细胞介素2变体或其衍生物
JP7773372B2 (ja) 2019-03-28 2025-11-19 オリオニス バイオサイエンシズ，インコーポレイテッド 線維芽細胞活性化タンパク質結合物質およびその使用
CN111944008A (zh) * 2019-05-14 2020-11-17 上海盖浦生物科技有限公司 一种突变蛋白的方法以及得到的突变体蛋白
CN111944036B (zh) * 2019-05-14 2024-09-06 上海盖浦生物科技有限公司 一种增殖免疫细胞的突变体蛋白
BR112021023345A2 (pt) 2019-05-20 2022-02-01 Pandion Operations Inc Imunotolerância com alvo em madcam
IL288210B2 (en) 2019-05-20 2026-03-01 Cytune Pharma Dosing regimens of IL-2/IL-15 beta-gamma receptor agonists for the treatment of cancer or infectious diseases
CA3141626A1 (en) 2019-06-12 2020-12-17 AskGene Pharma, Inc. Novel il-15 prodrugs and methods of use thereof
AU2020291535A1 (en) 2019-06-14 2022-01-20 The Scripps Research Institute Reagents and methods for replication, transcription, and translation in semi-synthetic organisms
WO2020252421A2 (en) * 2019-06-14 2020-12-17 Cugene, Inc. Novel interleukin-2 variants and bifunctional fusion molecules thereof
TW202115105A (zh) * 2019-06-24 2021-04-16 德商拜恩迪克Ｒｎａ製藥有限公司 Ｉｌ２激動劑
JP2022538139A (ja) 2019-07-02 2022-08-31 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 変異体インターロイキン－２及び抗ｃｄ８抗体を含む免疫複合体
AR119382A1 (es) * 2019-07-12 2021-12-15 Hoffmann La Roche Anticuerpos de pre-direccionamiento y métodos de uso
BR112022000928A2 (pt) 2019-07-19 2022-03-08 Seneca Therapeutics Inc Terapia oncolítica do vírus seneca valley de segunda geração: composições e métodos da mesma
BR112022001320A2 (pt) * 2019-07-25 2022-04-12 Univ Chicago Composições e métodos compreendendo agentes terapêuticos ativados por protease
PH12022550165A1 (en) 2019-07-26 2023-05-08 Visterra Inc Interleukin-2 agents and uses thereof
CA3148505A1 (en) * 2019-08-12 2021-02-18 AskGene Pharma, Inc. Novel il-2 fusion molecules
KR20220044534A (ko) * 2019-08-13 2022-04-08 엘피스 바이오파마슈티컬즈 조작된 인터류킨-2 수용체 베타 효능제
JP2022544405A (ja) 2019-08-15 2022-10-18 アイジーエム バイオサイエンシズ インコーポレイテッド 免疫刺激性多量体型結合分子
US12234271B2 (en) 2019-09-10 2025-02-25 Synthorx, Inc. Il-2 conjugates and methods of use to treat autoimmune diseases
US20220378933A1 (en) * 2019-09-19 2022-12-01 Proviva Therapeutics (Hong Kong) Limited Il-2 compositions and methods of use thereof
CA3156035A1 (en) 2019-09-27 2021-04-01 Intrexon Actobiotics Nv D/B/A Precigen Actobio Treatment of celiac disease
MX2022005330A (es) * 2019-11-05 2022-05-26 Regeneron Pharma Moleculas de union multiespecificas con scfv en el extremo nterminal.
AU2020389422B2 (en) 2019-11-20 2024-08-08 Gi Cell, Inc. Medium composition for culturing T cells and method for culturing T cells using same
KR102351020B1 (ko) 2019-11-20 2022-01-14 주식회사 지아이셀 자연살해세포 배양용 조성물 및 이를 이용한 자연살해세포 제조방법
IL291909A (en) 2019-11-20 2022-06-01 Gi Cell Inc Regulatory t cell culture composition and use thereof
IL293364B2 (en) * 2019-11-27 2026-04-01 Gi Innovation Inc Pharmaceutical preparation for the treatment of cancer containing fusion proteins containing IL-2 protein and 80CD protein and immune checkpoint inhibitors
US20230014358A1 (en) * 2019-11-27 2023-01-19 Gi Cell, Inc. Composition for anticancer treatment, comprising nk cells and fusion protein which comprises il-2 protein and cd80 protein
IL292935A (en) 2019-11-27 2022-07-01 Gi Cell Inc A compound for anti-cancer treatment, which includes nk cells and a fusion protein including il-2 protein and cd80 protein
CN114437198A (zh) 2019-12-17 2022-05-06 北京志道生物科技有限公司 白介素-2衍生物
IL293471A (en) 2019-12-17 2022-08-01 Amgen Inc Dual interleukin-2 / tnf receptor agonist for use in medicine
WO2021127487A2 (en) 2019-12-20 2021-06-24 Regeneron Pharmaceuticals, Inc. Novel il2 agonists and methods of use thereof
AU2020416273A1 (en) 2020-01-03 2022-07-28 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
WO2021140435A1 (en) * 2020-01-09 2021-07-15 Pfizer Inc. Recombinant vaccinia virus
US11633488B2 (en) 2020-01-10 2023-04-25 Bright Peak Therapeutics Ag Modified IL-2 polypeptides and uses thereof
CA3165927A1 (en) 2020-01-11 2021-07-15 AskGene Pharma, Inc. Novel masked cytokines and methods of use thereof
WO2021146436A2 (en) 2020-01-14 2021-07-22 Synthekine, Inc. Biased il2 muteins methods and compositions
KR20220141299A (ko) 2020-01-14 2022-10-19 신테카인, 인크. Il2 오르토로그 및 사용 방법
US11230699B2 (en) 2020-01-28 2022-01-25 Immunitybio, Inc. Chimeric antigen receptor-modified NK-92 cells targeting EGFR super-family receptors
EP4107187A4 (en) 2020-02-21 2024-07-03 Pandion Operations, Inc. TISSUE-TARGETED IMMUNOTOLERANCE WITH A CD39 EFFECTOR
TWI839476B (zh) * 2020-02-26 2024-04-21 大陸商北京泰德製藥股份有限公司 介白素-2多肽共軛物及其用途
CA3169095A1 (en) * 2020-03-05 2021-09-10 Kenan Christopher GARCIA Designed il-2 variants
KR20210117208A (ko) * 2020-03-18 2021-09-28 (주)지아이이노베이션 Il-2 단백질 및 cd80 단백질 단편 또는 이의 변이체를 포함하는 융합단백질 및 이의 용도
KR102440962B1 (ko) 2020-03-18 2022-09-07 ㈜지아이이노베이션 Il-2 단백질 및 cd80 단백질을 포함하는 융합단백질 및 항암제를 포함하는 암 치료용 약학 조성물
JP7697959B2 (ja) 2020-03-18 2025-06-24 ジーアイ イノベーション， インコーポレイテッド Ｉｌ－２タンパク質とｃｄ８０タンパク質を含む融合タンパク質製剤
JP2023518434A (ja) * 2020-03-19 2023-05-01 イノベント バイオロジクス（スーチョウ）カンパニー，リミティド インターロイキン２変異体およびその使用
AU2021237518B2 (en) * 2020-03-19 2024-08-15 Fortvita Biologics (Singapore) Pte.Ltd. Interleukin-2 mutant and use thereof
TW202204388A (zh) * 2020-04-01 2022-02-01 美商艾希利歐發展股份有限公司 經遮蔽之il-2細胞激素及其裂解產物
AU2021256936A1 (en) 2020-04-15 2022-07-21 F. Hoffmann-La Roche Ag Immunoconjugates
EP4139341A1 (en) 2020-04-21 2023-03-01 Regeneron Pharmaceuticals, Inc. Il-2 variants with reduced binding to il-2 receptor alpha and uses thereof
MX2022013112A (es) * 2020-04-22 2023-01-16 Dragonfly Therapeutics Inc Fórmulacion, regimen de dosificación y proceso de manufactura de proteínas heterodiméricas fusionadas con fc.
PE20231648A1 (es) 2020-04-22 2023-10-17 Merck Sharp And Dohme Llc CONJUGADOS DE INTERLEUCINA 2 HUMANA SESGADOS AL DIMERO DEL RECEPTOR DE INTERLEUCINA 2 byc Y CONJUGADOS CON UN POLIMERO HIDROSOLUBLE NO PEPTIDICO
JP2023527690A (ja) 2020-05-11 2023-06-30 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 改変ｐｂｍｃと免疫抱合体との併用療法
WO2021231376A2 (en) 2020-05-12 2021-11-18 Cue Biopharma, Inc. Multimeric t-cell modulatory polypeptides and methods of use thereof
IL298136A (en) 2020-05-13 2023-01-01 Bonum Therapeutics Inc Preparations of protein complexes and methods of using them
CN113667004B (zh) * 2020-05-14 2026-04-24 上海盖浦生物科技有限公司 一种白介素2突变体
WO2021231976A1 (en) 2020-05-14 2021-11-18 Xencor, Inc. Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3
KR20230019889A (ko) 2020-06-03 2023-02-09 아센디스 파마 온콜로지 디비전 에이/에스 Il-2 서열 및 이의 용도
KR102373965B1 (ko) 2020-06-05 2022-03-15 (주)지아이이노베이션 Ｉｌ-２ 단백질 및 ｃｄ８０ 단백질을 포함하는 융합단백질을 포함하는 방사선 치료 증진용 약학적 조성물
WO2021255155A1 (en) 2020-06-19 2021-12-23 F. Hoffmann-La Roche Ag Antibodies binding to cd3 and cd19
PE20230470A1 (es) 2020-06-19 2023-03-14 Hoffmann La Roche Moleculas de union al dominio fc de activacion inmunitaria
EP4174088A4 (en) 2020-06-30 2024-01-24 GI Innovation, Inc. FUSION PROTEIN COMPRISING AN ANTI-LAG-3 AND IL-2 ANTIBODY AND USE THEREOF
US20230242607A1 (en) * 2020-07-09 2023-08-03 Eutilex Co., Ltd. Il-2 variants
KR20220014531A (ko) * 2020-07-29 2022-02-07 (주)메디톡스 헤테로이량체 Ｆｃ 융합 단백질, 및 관련 조성물, 용도 및 방법
TW202221031A (zh) 2020-07-30 2022-06-01 英商阿法克塔生命科學有限公司 血清半衰期延長之pd-l1抑制多肽
CA3192204A1 (en) 2020-08-19 2022-02-24 Xencor, Inc. Anti-cd28 and/or anti-b7h3 compositions
IL301027A (en) * 2020-09-04 2023-05-01 Shandong Simcere Biopharmaceutical Co Ltd Mutant AI 2 and its application
WO2022056014A1 (en) 2020-09-09 2022-03-17 Cue Biopharma, Inc. Mhc class ii t-cell modulatory multimeric polypeptides for treating type 1 diabetes mellitus (t1d) and methods of use thereof
CN117500518A (zh) * 2020-09-18 2024-02-02 地方独立行政法人 宫城县立医院机构 Il-2突变蛋白及包含其的药物
CN114369153A (zh) * 2020-10-18 2022-04-19 北京志道生物科技有限公司 一种白介素-2突变体
CN118598976A (zh) * 2020-10-18 2024-09-06 北京志道生物科技有限公司 经修饰的il-2分子及其用途
TW202406932A (zh) 2020-10-22 2024-02-16 美商基利科學股份有限公司 介白素2-Fc融合蛋白及使用方法
EP4232068A1 (en) 2020-10-26 2023-08-30 Cytune Pharma IL-2/IL-15RBetaGamma AGONIST FOR TREATING NON-MELANOMA SKIN CANCER
WO2022090203A1 (en) 2020-10-26 2022-05-05 Cytune Pharma IL-2/IL-15Rβү AGONIST FOR TREATING SQUAMOUS CELL CARCINOMA
JP2023548311A (ja) 2020-10-29 2023-11-16 ブリストル－マイヤーズ スクイブ カンパニー 疾患の治療のための融合タンパク質
CN114437228B (zh) * 2020-10-30 2024-02-06 中国科学院生物物理研究所 一种il-2与抗体亚单位构成的双功能融合蛋白
US20230398183A1 (en) 2020-11-13 2023-12-14 Jiangsu Hengrui Pharmaceuticals Co., Ltd. Pharmaceutical composition comprising human interleukin 2 variant or derivative thereof and use thereof
CN112724259B (zh) * 2020-11-16 2022-12-20 天津林达生物科技有限公司 人血清白蛋白与白介素2的融合蛋白及其用途
WO2022115865A2 (en) 2020-11-25 2022-06-02 Xilio Development, Inc. Tumor-specific cleavable linkers
KR20230117122A (ko) 2020-12-04 2023-08-07 에프. 호프만-라 로슈 아게 pH 의존성 돌연변이체 인터류킨-2 폴리펩티드
US12098178B2 (en) 2020-12-04 2024-09-24 Visterra, Inc. Methods of using interleukin-2 agents
WO2022148853A1 (en) 2021-01-11 2022-07-14 F. Hoffmann-La Roche Ag Immunoconjugates
EP4281549A4 (en) * 2021-01-19 2025-05-07 Seneca Therapeutics, Inc. ONCOLYTIC THERAPY COMPOSITIONS CONTAINING SENECA VALLEY VIRUS AND METHODS THEREFOR
WO2022189377A1 (en) 2021-03-09 2022-09-15 F. Hoffmann-La Roche Ag Combination therapy of pd-1-targeted il-2 variant immunoconjugates and fap/4-1bb binding molecules
US11739144B2 (en) 2021-03-09 2023-08-29 Xencor, Inc. Heterodimeric antibodies that bind CD3 and CLDN6
EP4304724A1 (en) 2021-03-09 2024-01-17 F. Hoffmann-La Roche AG Combination therapy of pd-1-targeted il-2 variant immunoconjugate and anti-tyrp1/anti-cd3 bispecific antibodies
EP4305065A1 (en) 2021-03-10 2024-01-17 Xencor, Inc. Heterodimeric antibodies that bind cd3 and gpc3
WO2022200525A1 (en) 2021-03-26 2022-09-29 Innate Pharma Multispecific proteins comprising an nkp46-binding site, a cancer antgienge binding site fused to a cytokine for nk cell engaging
EP4314032A1 (en) 2021-03-30 2024-02-07 F. Hoffmann-La Roche AG Protease-activated polypeptides
IL304365B2 (en) * 2021-03-31 2025-04-01 Hanmi Pharmaceutical Co Ltd A novel conjugate of an IL2 immunostimulatory analog and method of preparation thereof
MX2023011964A (es) 2021-04-09 2024-01-08 Ose Immunotherapeutics Nuevo andamio para moléculas bifuncionales con propiedades mejoradas.
CN113321722A (zh) * 2021-04-13 2021-08-31 苏州复融生物技术有限公司 白介素2突变体及其应用
CA3213632A1 (en) 2021-04-30 2022-11-03 F. Hoffmann-La Roche Ag Dosing for combination treatment with anti-cd20/anti-cd3 bispecific antibody and anti-cd79b antibody drug conjugate
WO2022258691A1 (en) 2021-06-09 2022-12-15 Innate Pharma Multispecific proteins binding to nkg2d, a cytokine receptor, a tumour antigen and cd16a
BR112023025331A2 (pt) 2021-06-09 2024-02-27 Innate Pharma Proteína multiespecífica, composição farmacêutica, célula recombinante, ácido nucleico ou conjunto de ácidos nucleicos, uso de uma proteína ou composição, métodos ou uso
KR20240019786A (ko) 2021-06-09 2024-02-14 이나뜨 파르마 에스.에이. Cd20, nkp46, cd16에 결합하고 il-2에 접합된 다중특이적 항체
WO2022258678A1 (en) 2021-06-09 2022-12-15 Innate Pharma Multispecific proteins binding to nkp30, a cytokine receptor, a tumour antigen and cd16a
TW202317623A (zh) 2021-06-14 2023-05-01 美商再生元醫藥公司 基於il2之治療劑及其使用方法
WO2022266467A2 (en) 2021-06-17 2022-12-22 Dana-Farber Cancer Institute, Inc. Recombinant histone polypeptide and uses thereof
WO2023281480A1 (en) 2021-07-09 2023-01-12 Bright Peak Therapeutics Ag Conjugates of checkpoint inhibitors with il-2, and uses thereof
US20230201364A1 (en) 2021-07-09 2023-06-29 Bright Peak Therapeutics Ag Antibody conjugates and manufacture thereof
US20230201365A1 (en) 2021-07-09 2023-06-29 Bright Peak Therapeutics Ag Modified cd20 antibodies and uses thereof
EP4366781A1 (en) 2021-07-09 2024-05-15 Bright Peak Therapeutics AG Checkpoint inhibitors conjugated to il-2, and uses thereof
EP4357357A4 (en) * 2021-07-30 2025-01-08 Dracoterpin Biomedicine LLC HUMAN INTERLEUKIN-2 VARIANT AND ITS USE
KR20240043797A (ko) 2021-08-13 2024-04-03 싸이튠 파마 암 치료용 IL-2/IL-15Rβγ 작용제와 항체-약물 접합체 조합
AU2022332499A1 (en) 2021-08-24 2024-03-21 Jiangsu Hengrui Pharmaceuticals Co., Ltd. Fap/cd40 binding molecule and medicinal use thereof
EP4405487A4 (en) * 2021-09-26 2025-12-03 Wuxi Biologics Ireland Ltd IL-2 VARIANTS AND THEIR FUSING PROTEINS
IL312005A (en) 2021-10-14 2024-06-01 Hoffmann La Roche New interleukin-7 immunoconjugates
CN118139648A (zh) 2021-10-14 2024-06-04 豪夫迈·罗氏有限公司 用于治疗癌症的替代的PD1-IL7v免疫缀合物
CU24763B1 (es) 2021-12-21 2025-07-09 Ct Inmunologia Molecular Proteínas de fusión compuestas por un anticuerpo y una muteína agonista de interleucina 2
KR20230095612A (ko) * 2021-12-22 2023-06-29 한미약품 주식회사 신규 면역 억제 인터루킨 2 (Interleukin 2) 아날로그
EP4463135A2 (en) 2022-01-10 2024-11-20 Sana Biotechnology, Inc. Methods of ex vivo dosing and administration of lipid particles or viral vectors and related systems and uses
US20230303650A1 (en) * 2022-01-21 2023-09-28 Aetio Biotherapy, Inc. Immunoconjugates of Interlukin-2 Mutant Polypeptides with Antibodies
KR20230121685A (ko) * 2022-02-11 2023-08-21 주식회사 카나프테라퓨틱스 Il-12 및 항-fap 항체를 포함하는 융합단백질 및 항암제를 포함하는 암 치료용 약학 조성물
JP7829127B2 (ja) * 2022-02-21 2026-03-13 シーティーセルズ、インコーポレイテッド 抗原結合ドメインおよびサイトカイン三量体ドメインを含む融合タンパク質
WO2023161857A1 (en) 2022-02-23 2023-08-31 Bright Peak Therapeutics Ag Bifunctional cytokine compositions
CN116769013A (zh) * 2022-03-10 2023-09-19 广东菲鹏制药股份有限公司 白细胞介素2突变体以及含有其的复合物
WO2023193015A1 (en) 2022-04-01 2023-10-05 Sana Biotechnology, Inc. Cytokine receptor agonist and viral vector combination therapies
US20240076343A1 (en) 2022-06-16 2024-03-07 Cephalon Llc Anti-pd-1 antibody-attenuated il-2 immunoconjugates and uses thereof
TW202409069A (zh) * 2022-07-01 2024-03-01 大陸商北京星奇原生物科技有限公司 Ｉｌ－２多肽和使用方法
EP4556493A1 (en) 2022-07-11 2025-05-21 Genuv Inc. Cytokine fusion protein
US11773160B1 (en) 2022-08-05 2023-10-03 Anaveon AG Immune-stimulating IL-2 fusion proteins
TWI875131B (zh) * 2022-08-16 2025-03-01 國立陽明交通大學 介白素-2變異體及其於治療癌症的用途
JP2025534285A (ja) 2022-09-29 2025-10-15 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト プロテアーゼ活性化ポリペプチド
CN116041539B (zh) * 2022-10-31 2023-07-21 山东博安生物技术股份有限公司 Il-2突变体免疫缀合物
WO2024119193A2 (en) 2022-12-02 2024-06-06 AskGene Pharma, Inc. Mutant il-2 polypeptides and il-2 prodrugs
US20240417436A1 (en) 2023-01-11 2024-12-19 Bright Peak Therapeutics Ag Conditionally activated immunocytokines and methods of use
US20240376170A1 (en) 2023-01-11 2024-11-14 Bright Peak Therapeutics Ag Conditionally activated proteins and methods of use
CR20250288A (es) 2023-01-20 2025-08-29 Hoffmann La Roche POLIPÉPTIDOS DE DOMINIO Fc -VARIANTE DE IL2 RECOMBINANTES Y POLITERAPIA CON POLIPÉPTIDOS DE UNIÓN AL ANTÍGENO ANCLADOS A LA MEMBRANA
KR20250153216A (ko) 2023-02-24 2025-10-24 상하이 맙젠 바이오텍 리미티드 Fap/cd40 결합 분자의 약학적 조성물 및 이의 의약적 용도
TW202436358A (zh) 2023-03-01 2024-09-16 大陸商江蘇恆瑞醫藥股份有限公司 Ｆａｐ／４－１ｂｂ／ｃｄ４０結合分子及其醫藥用途
EP4694916A1 (en) 2023-04-14 2026-02-18 SOTIO Biotech Inc. Engineered immune cells for treating cancer in combination with il-2/il-15 receptor ?? agonists
AU2024273454A1 (en) 2023-05-16 2025-11-27 F. Hoffmann-La Roche Ag Pd-1-regulated il-2 immunocytokine and uses thereof
WO2024251884A1 (en) 2023-06-09 2024-12-12 Innate Pharma Nk cell engager proteins comprising anti-cd20 and ant-nkp46 antibody, linked to il-2 in treatment of r/r b-nhl
TW202508641A (zh) 2023-08-16 2025-03-01 大陸商上海邁晉生物醫藥科技有限公司 一種包含免疫綴合物的醫藥組成物及其用途
US20250195677A1 (en) 2023-12-19 2025-06-19 Cephalon Llc Uses for attenuated il-2 immunoconjugates
WO2025202147A1 (en) 2024-03-27 2025-10-02 F. Hoffmann-La Roche Ag Interleukin-7 immunoconjugates
WO2025242835A1 (en) 2024-05-22 2025-11-27 Ose Immunotherapeutics Molecules comprising masking linkers and uses thereof for the treatment of cancer
WO2025242836A1 (en) 2024-05-22 2025-11-27 Ose Immunotherapeutics Molecules comprising masking linkers and uses thereof for the treatment of auto-immune or inflammatory diseases and disorders
WO2026083295A1 (en) 2024-10-16 2026-04-23 Bright Peak Therapeutics Ag Trispecific compositions comprising il-2, vegf binding domains, and pd-1 binding domains

Family Cites Families (85)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2388385B1 (fr) 1977-04-18 1982-01-08 Hitachi Metals Ltd Piece d'ornement fixee par des aimants permanents
US4518584A (en) 1983-04-15 1985-05-21 Cetus Corporation Human recombinant interleukin-2 muteins
US4604377A (en) 1984-03-28 1986-08-05 Cetus Corporation Pharmaceutical compositions of microbially produced interleukin-2
US5116943A (en) 1985-01-18 1992-05-26 Cetus Corporation Oxidation-resistant muteins of Il-2 and other protein
US5206344A (en) 1985-06-26 1993-04-27 Cetus Oncology Corporation Interleukin-2 muteins and polymer conjugation thereof
JP2524586B2 (ja) 1985-06-26 1996-08-14 シタス コーポレイション ポリマ−接合を利用する医薬組成物用蛋白質の可溶化
US4766106A (en) 1985-06-26 1988-08-23 Cetus Corporation Solubilization of proteins for pharmaceutical compositions using polymer conjugation
US6548640B1 (en) 1986-03-27 2003-04-15 Btg International Limited Altered antibodies
JP3101690B2 (ja) 1987-03-18 2000-10-23 エス・ビィ・２・インコーポレイテッド 変性抗体の、または変性抗体に関する改良
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
US5959177A (en) 1989-10-27 1999-09-28 The Scripps Research Institute Transgenic plants expressing assembled secretory antibodies
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
EP1400536A1 (en) 1991-06-14 2004-03-24 Genentech Inc. Method for making humanized antibodies
GB9114948D0 (en) 1991-07-11 1991-08-28 Pfizer Ltd Process for preparing sertraline intermediates
US5565332A (en) 1991-09-23 1996-10-15 Medical Research Council Production of chimeric antibodies - a combinatorial approach
FI941572A7 (fi) 1991-10-07 1994-05-27 Oncologix Inc Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenete lmä
CA2372813A1 (en) 1992-02-06 1993-08-19 L.L. Houston Biosynthetic binding protein for cancer marker
US5229109A (en) 1992-04-14 1993-07-20 Board Of Regents, The University Of Texas System Low toxicity interleukin-2 analogues for use in immunotherapy
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
DE19607751A1 (de) 1996-02-29 1997-09-04 Henkel Kgaa Neue Aminophenol-Derivate und deren Verwendung
KR20060079258A (ko) 1996-10-18 2006-07-05 제넨테크, 인크. 항-ＥｒｂＢ２ 항체
US6040498A (en) 1998-08-11 2000-03-21 North Caroline State University Genetically engineered duckweed
DK1034298T3 (da) 1997-12-05 2012-01-30 Scripps Research Inst Humanisering af murint antistof
ATE375365T1 (de) 1998-04-02 2007-10-15 Genentech Inc Antikörper varianten und fragmente davon
DK1071700T3 (da) 1998-04-20 2010-06-07 Glycart Biotechnology Ag Glykosylerings-modifikation af antistoffer til forbedring af antistofafhængig cellulær cytotoksicitet
US6455677B1 (en) 1998-04-30 2002-09-24 Boehringer Ingelheim International Gmbh FAPα-specific antibody with improved producibility
EP0953639A1 (en) 1998-04-30 1999-11-03 Boehringer Ingelheim International GmbH FAPalpha-specific antibody with improved producibility
US6955807B1 (en) * 1998-05-15 2005-10-18 Bayer Pharmaceuticals Corporation IL-2 selective agonists and antagonists
DZ2788A1 (fr) 1998-05-15 2003-12-01 Bayer Ag Agonistes et antagonistes selectifs à IL-2.
EP1156823B1 (en) 1999-02-12 2008-10-29 The Scripps Research Institute Methods for treatment of tumors and metastases using a combination of anti-angiogenic and immuno therapies
ES2248127T3 (es) 1999-10-04 2006-03-16 Medicago Inc. Metodo para regular la transcripcion de genes foraneos en presencia de nigtrogeno.
US7125978B1 (en) 1999-10-04 2006-10-24 Medicago Inc. Promoter for regulating expression of foreign genes
EP1268550A2 (en) 2000-03-17 2003-01-02 Boehringer Ingelheim Pharma KG Human fap-alpha-specific antibodies
JP4936299B2 (ja) 2000-08-21 2012-05-23 メレクシス・テクノロジーズ・ナムローゼフェンノートシャップ 磁場方向検出センサ
US7396917B2 (en) 2000-12-05 2008-07-08 Alexion Pharmaceuticals, Inc. Rationally designed antibodies
DE60236735D1 (de) 2001-04-13 2010-07-29 Biogen Idec Inc Antikörper gegen vla-1
NZ571596A (en) 2001-08-03 2010-11-26 Glycart Biotechnology Ag Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
WO2003015697A2 (en) 2001-08-13 2003-02-27 University Of Southern California Interleukin-2 mutants with reduced toxicity
DK1454138T3 (da) * 2001-12-04 2012-02-13 Merck Patent Gmbh Immunocytokiner med moduleret selektivitet
US7432063B2 (en) 2002-02-14 2008-10-07 Kalobios Pharmaceuticals, Inc. Methods for affinity maturation
WO2004055056A1 (en) * 2002-12-17 2004-07-01 Merck Patent Gmbh Humanized antibody (h14.18) of the mouse 14.18 antibody binding to gd2 and its fusion with il-2
EP2248892B1 (en) 2003-01-22 2015-04-22 Roche Glycart AG Fusion constructs and use of same to produce antibodies with increased FC receptor binding affinity and effector function
TWI353991B (en) * 2003-05-06 2011-12-11 Syntonix Pharmaceuticals Inc Immunoglobulin chimeric monomer-dimer hybrids
JP2007515185A (ja) 2003-12-22 2007-06-14 カイロン コーポレイション 免疫応答障害に対する処置ストラテジーのための診断法としてのＦｃレセプター多型の使用
US20060234205A1 (en) * 2004-03-05 2006-10-19 Chiron Corporation In vitro test system for predicting patient tolerability of therapeutic agents
CN1930300A (zh) * 2004-03-05 2007-03-14 希龙公司 预测患者治疗药物耐受性的体外试验系统
EP1740615B1 (en) 2004-03-31 2014-11-05 Genentech, Inc. Humanized anti-tgf-beta antibodies
CA2607954A1 (en) * 2005-05-11 2006-11-16 Philogen S.P.A. Conjugate for targeting of drug
EP1806365A1 (en) 2006-01-05 2007-07-11 Boehringer Ingelheim International GmbH Antibody molecules specific for fibroblast activation protein and immunoconjugates containing them
CA2648484A1 (en) 2006-05-08 2007-11-15 Philogen Spa Antibody-targeted cytokines for therapy
AU2007271398B2 (en) 2006-07-06 2013-06-20 Merck Patent Gmbh Compositions and methods for enhancing the efficacy of IL-2 mediated immune responses
AR062223A1 (es) 2006-08-09 2008-10-22 Glycart Biotechnology Ag Moleculas de adhesion al antigeno que se adhieren a egfr, vectores que los codifican, y sus usos de estas
ES2368868T3 (es) 2006-09-20 2011-11-23 Mt-Biomethan Gmbh Procedimiento y dispositivo para la separación de metano y dióxido de carbono de biogás.
WO2008065372A2 (en) * 2006-11-28 2008-06-05 Nautilus Biotech, S.A. Modified erythropoietin polypeptides and uses thereof for treatment
AU2009233925B2 (en) 2006-12-05 2014-03-13 Ibc Pharmaceuticals, Inc. Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technology
EP2158318A2 (en) * 2007-05-14 2010-03-03 Biogen Idec MA, Inc. Single-chain fc (scfc) regions, binding polypeptides comprising same, and methods related thereto
JP2010534469A (ja) 2007-07-25 2010-11-11 アストラゼネカ アクチボラグ Ｋｄｒ指向性標的化結合物質およびその使用
EP2018877A1 (en) 2007-07-27 2009-01-28 The Procter and Gamble Company Absorbent article comprising water-absorbing polymeric particles and method for the production thereof
WO2009061853A2 (en) 2007-11-05 2009-05-14 Massachusetts Institute Of Technology Mutant interleukin-2 (il-2) polypeptides
AU2008343589A1 (en) 2007-12-19 2009-07-09 Centocor Ortho Biotech Inc. Design and generation of human de novo pIX phage display libraries via fusion to pIX or pVII, vectors, antibodies and methods
JP6157046B2 (ja) 2008-01-07 2017-07-05 アムジェン インコーポレイテッド 静電的ステアリング（ｅｌｅｃｔｒｏｓｔａｔｉｃｓｔｅｅｒｉｎｇ）効果を用いた抗体Ｆｃヘテロ二量体分子を作製するための方法
ATE548052T1 (de) 2008-01-17 2012-03-15 Philogen Spa Kombination aus einem anti-edb-fibronectin- antikörper-il-2-fusionsprotein und einem b-zellen bindenden molekül, b-zellen-vorläufern und/oder deren krebserregendem gegenspieler
DK2285416T3 (da) 2008-05-13 2012-09-10 Molmed Spa Konjugat til behandlingen af mesotheliom
AU2010206840B2 (en) * 2009-01-21 2015-02-05 Amgen Inc. Compositions and methods of treating inflammatory and autoimmune diseases
CN104119438A (zh) 2009-01-29 2014-10-29 米迪缪尼有限公司 延长体内半衰期的人抗il-6抗体及其在治疗肿瘤、自身免疫性疾病和炎症性疾病中的应用
EP2411416A1 (en) * 2009-03-24 2012-02-01 The Government of the United States of America as represented by The Secretary of the Department of Health and Human Services Anti-mesothelin antibodies
WO2010117448A2 (en) 2009-04-05 2010-10-14 Provenance Biopharmaceuticals Corp. Chimeric immunocytokines and methods of use thereof
EP2448599A1 (en) 2009-06-30 2012-05-09 Philogen S.p.A. Immunocytokines in combination with anti-erbb antibodies for the treatment of cancer
JP5764127B2 (ja) 2009-08-17 2015-08-12 ロシュ グリクアート アーゲー 標的化イムノコンジュゲート
KR101528013B1 (ko) 2009-08-31 2015-06-16 로슈 글리카트 아게 친화성-성숙된 인간화된 항-ｃｅａ 단일클론 항체
CA2773515C (en) 2009-09-29 2015-04-28 Roche Glycart Ag Bispecific death receptor agonistic antibodies
CA2806021C (en) 2010-08-13 2019-05-21 Roche Glycart Ag Anti-fap antibodies and methods of use
CU23923B1 (es) 2010-11-12 2013-07-31 Ct De Inmunología Molecular Polipéptidos derivados de la il-2 con actividad agonista
SG192673A1 (en) 2011-02-10 2013-09-30 Roche Glycart Ag Mutant interleukin-2 polypeptides
PE20141017A1 (es) 2011-03-02 2014-08-25 Roche Glycart Ag Anticuerpos del cea
ES2692268T5 (en) 2011-03-29 2025-02-26 Roche Glycart Ag Antibody fc variants
EA201892619A1 (ru) 2011-04-29 2019-04-30 Роше Гликарт Аг Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2
MY175687A (en) 2012-08-07 2020-07-06 Roche Glycart Ag Composition comprising two antibodies engineered to have reduced and increased effector function
PE20150645A1 (es) 2012-08-08 2015-05-11 Roche Glycart Ag Proteinas de fusion de interleuquina 10 y usos de las mismas
US20140044675A1 (en) 2012-08-10 2014-02-13 Roche Glycart Ag Interleukin-2 fusion proteins and uses thereof
UA118028C2 (uk) 2013-04-03 2018-11-12 Рош Глікарт Аг Біспецифічне антитіло, специфічне щодо fap і dr5, антитіло, специфічне щодо dr5, і спосіб їх застосування
WO2014180754A1 (en) 2013-05-07 2014-11-13 F. Hoffmann-La Roche Ag Trimeric antigen binding molecules
DK3186283T3 (da) 2014-08-29 2020-03-02 Hoffmann La Roche Kombinationsbehandling med tumormålrettede IL-2- immuncytokinervarianter og antistoffer mod humant PD-L1

Also Published As

Publication number Publication date
PL2673294T3 (pl) 2016-11-30
EA201300896A1 (ru) 2014-02-28
HK1217020A1 (zh) 2016-12-16
KR101667096B1 (ko) 2016-10-18
SG10201604160WA (en) 2016-07-28
PH12017500954B1 (en) 2020-06-03
CN105440123B (zh) 2020-10-09
EP3075745B1 (en) 2018-09-05
AU2012215573B2 (en) 2015-11-26
PH12017500954A1 (en) 2017-11-27
EA033369B1 (ru) 2019-10-31
HUE055284T2 (hu) 2021-11-29
BR112013018932B1 (pt) 2020-11-17
EP3489255B1 (en) 2021-06-16
MA35803B1 (fr) 2014-12-01
JP5878182B2 (ja) 2016-03-08
EP3075745A1 (en) 2016-10-05
HRP20160917T1 (hr) 2016-09-23
CA2824253A1 (en) 2012-08-16
UA113729C2 (xx) 2017-03-10
UA117294C2 (uk) 2018-07-10
US10184009B2 (en) 2019-01-22
MX356675B (es) 2018-06-08
LT3489255T (lt) 2021-08-25
EP3489255A1 (en) 2019-05-29
AU2015249085A1 (en) 2015-11-12
ES2694564T3 (es) 2018-12-21
SI3489255T1 (sl) 2021-11-30
CY1117842T1 (el) 2017-05-17
PE20140303A1 (es) 2014-03-22
PT3075745T (pt) 2018-11-14
TW201237165A (en) 2012-09-16
CL2013001987A1 (es) 2014-01-31
CN103492411B (zh) 2016-12-07
IL252230B (en) 2019-10-31
PL3075745T3 (pl) 2019-07-31
ECSP13012815A (es) 2013-10-31
AU2015249085B2 (en) 2017-12-14
KR20150092367A (ko) 2015-08-12
CO6741186A2 (es) 2013-08-30
PT2673294T (pt) 2016-07-07
DK3075745T3 (en) 2018-11-26
JP2015229676A (ja) 2015-12-21
IL252230A0 (en) 2017-07-31
SG192673A1 (en) 2013-09-30
US20190077881A1 (en) 2019-03-14
US9266938B2 (en) 2016-02-23
PL3489255T3 (pl) 2021-11-22
ES2883371T3 (es) 2021-12-07
EP3971206A1 (en) 2022-03-23
BR112013018932A2 (pt) 2017-05-02
HUE029139T2 (hu) 2017-02-28
SI2673294T1 (sl) 2016-08-31
PH12013501657A1 (en) 2013-10-07
MX2013009226A (es) 2013-12-06
US20120244112A1 (en) 2012-09-27
MX340671B (es) 2016-07-20
CN103492411A (zh) 2014-01-01
US20190322765A1 (en) 2019-10-24
ZA201305282B (en) 2016-07-27
JP6155300B2 (ja) 2017-06-28
TWI577801B (zh) 2017-04-11
US11111312B2 (en) 2021-09-07
CN112210000A (zh) 2021-01-12
EP2673294A1 (en) 2013-12-18
NZ611749A (en) 2015-08-28
KR20130118363A (ko) 2013-10-29
RS62238B1 (sr) 2021-09-30
IL269687A (en) 2019-11-28
AU2012215573A1 (en) 2013-05-02
US20160208017A1 (en) 2016-07-21
HRP20181736T1 (hr) 2018-12-28
US20180142037A1 (en) 2018-05-24
PT3489255T (pt) 2021-08-13
TWI666027B (zh) 2019-07-21
KR101852245B1 (ko) 2018-04-25
RS57767B1 (sr) 2018-12-31
SI3075745T1 (sl) 2018-12-31
CA2824253C (en) 2019-09-17
JP2014506793A (ja) 2014-03-20
HRP20211318T1 (hr) 2021-11-26
HUE040326T2 (hu) 2019-03-28
AR085335A1 (es) 2013-09-25
MY190604A (en) 2022-04-27
RS54802B1 (sr) 2016-10-31
TW201718029A (zh) 2017-06-01
CR20130314A (es) 2013-08-09
WO2012107417A1 (en) 2012-08-16
US10323098B2 (en) 2019-06-18
CN105440123A (zh) 2016-03-30
PE20181077A1 (es) 2018-07-05
IL269687B (en) 2022-08-01
IL227095B (en) 2018-06-28
DK3489255T3 (da) 2021-08-23
EP2673294B1 (en) 2016-04-27
LT3075745T (lt) 2018-11-26
DK2673294T3 (en) 2016-05-30
NZ710742A (en) 2017-04-28

Similar Documents

Publication Publication Date Title
ES2579987T3 (es) Polipéptidos interleuquina-2 mutantes
ES2924039T3 (es) Acidos nucleicos, péptidos y métodos
ES2643465T3 (es) Polipéptidos inmunomoduladores derivados de IL-2 y su uso terapéutico contra el cáncer e infecciones crónicas
ES2543915T3 (es) Polipéptidos derivados de la IL-2 con actividad agonista para la terapia del cáncer e infecciones crónicas
ES2509883T3 (es) Antagonistas de glucagón
MX2009004147A (es) Vacunas de peptido para canceres que expresan polipeptidos mphosph1 o depdc1.
ES2333772T3 (es) Polipeptidos homologos de il-17 y il-17r y sus utilizaciones terapeuticas.
MX2009009022A (es) Vacunas de peptídicas para cánceres que expresan antígenos asociados con tumores.
ES2328717T3 (es) Peptido antagonista de interleuquina-15.
HRP20200428T1 (hr) Sastavi alfa-galaktozidaze
ES2694418T3 (es) Análogos de insulina de cadena sencilla de acción prolongada
CA2946402A1 (en) Single-chain trail-receptor agonist proteins
AU2022209272B2 (en) Stable modulators of gamma-c-cytokine activity
PE20090763A1 (es) Polipetidos, dominios variables de anticuerpos y antagonistas
CR20120415A (es) Polipéptidos agonistas que se enlazan a dr5
HRP20150664T1 (hr) Antikancerogeni fuzijski protein
FI3712264T3 (fi) Kystationiini-beta-syntaasientsyymi homokystinurian hoitoon
MX2020008096A (es) Peptidos de la cadena b de la relaxina lipidados modificados y su uso terapeutico.
US20230338473A1 (en) Antagonistic peptide targeting il-2, il-9, and il-15 signaling for the treatment of cytokinerelease syndrome and cytokine storm associated disorders
ES2282666T3 (es) Antagonistas de quimiocinas cxc de union a cxcr3.
CU24508B1 (es) Composición farmacéutica que comprende péptido tipo apl
ES2987275T3 (es) Péptido antagonista de la actividad de la interleucina-15
HRP20250746T1 (hr) Peptidni spojevi i njihova terapijska upotreba
ES2927910T3 (es) Composiciones y métodos para inhibir interacciones de CD279
KR102397510B1 (ko) 난소 기능 보존용 펩티드 및 이를 포함하는 조성물