PL2552955T3 - Przeciwciała o zmodyfikowanym powinowactwie do FcRn, które wspomagają klirens antygenu - Google Patents

Przeciwciała o zmodyfikowanym powinowactwie do FcRn, które wspomagają klirens antygenu

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Publication number
PL2552955T3
PL2552955T3 PL11714860T PL11714860T PL2552955T3 PL 2552955 T3 PL2552955 T3 PL 2552955T3 PL 11714860 T PL11714860 T PL 11714860T PL 11714860 T PL11714860 T PL 11714860T PL 2552955 T3 PL2552955 T3 PL 2552955T3
Authority
PL
Poland
Prior art keywords
fcrn
antibodies
modified affinity
antigen clearance
support antigen
Prior art date
Application number
PL11714860T
Other languages
English (en)
Inventor
Tomoyuki Igawa
Shinya Ishii
Atsuhiko Maeda
Takashi Nakai
Original Assignee
Chugai Seiyaku Kabushiki Kaisha
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=44260244&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=PL2552955(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Chugai Seiyaku Kabushiki Kaisha filed Critical Chugai Seiyaku Kabushiki Kaisha
Publication of PL2552955T3 publication Critical patent/PL2552955T3/pl

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/283Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against Fc-receptors, e.g. CD16, CD32, CD64
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/06Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10Organic compounds
    • A61K49/14Peptides, e.g. proteins
    • A61K49/16Antibodies; Immunoglobulins; Fragments thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475Growth factors; Growth regulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503Immunoglobulin superfamily
    • C07K14/70535Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244Interleukins [IL]
    • C07K16/248IL-6
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/42Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C07K16/4208Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an idiotypic determinant on Ig
    • C07K16/4241Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an idiotypic determinant on Ig against anti-human or anti-animal Ig
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/545Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51Complete heavy chain or Fd fragment, i.e. VH + CH1
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/71Decreased effector function due to an Fc-modification
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/72Increased effector function due to an Fc-modification
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77Internalization into the cell
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/30Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Toxicology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Inorganic Chemistry (AREA)
  • Radiology & Medical Imaging (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Materials For Photolithography (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Slot Machines And Peripheral Devices (AREA)
  • Medicinal Preparation (AREA)
PL11714860T 2010-03-30 2011-03-30 Przeciwciała o zmodyfikowanym powinowactwie do FcRn, które wspomagają klirens antygenu PL2552955T3 (pl)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2010079667 2010-03-30
JP2010250830 2010-11-09
EP11714860.1A EP2552955B1 (en) 2010-03-30 2011-03-30 Antibodies with modified affinity to fcrn that promote antigen clearance
PCT/JP2011/001888 WO2011122011A2 (en) 2010-03-30 2011-03-30 Antibodies with modified affinity to fcrn that promote antigen clearance

Publications (1)

Publication Number Publication Date
PL2552955T3 true PL2552955T3 (pl) 2017-12-29

Family

ID=44260244

Family Applications (3)

Application Number Title Priority Date Filing Date
PL20160156.4T PL3702368T3 (pl) 2010-03-30 2011-03-30 Przeciwciała o zmodyfikowanym powinowactwie do FcRn, które wspomagają klierens antygenu
PL11714860T PL2552955T3 (pl) 2010-03-30 2011-03-30 Przeciwciała o zmodyfikowanym powinowactwie do FcRn, które wspomagają klirens antygenu
PL17154576.7T PL3181581T3 (pl) 2010-03-30 2011-03-30 Przeciwciała o zmodyfikowanym powinowactwie do FcRn, które wspomagają klierens antygenu

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PL20160156.4T PL3702368T3 (pl) 2010-03-30 2011-03-30 Przeciwciała o zmodyfikowanym powinowactwie do FcRn, które wspomagają klierens antygenu

Family Applications After (1)

Application Number Title Priority Date Filing Date
PL17154576.7T PL3181581T3 (pl) 2010-03-30 2011-03-30 Przeciwciała o zmodyfikowanym powinowactwie do FcRn, które wspomagają klierens antygenu

Country Status (21)

Country Link
US (6) US20130131319A1 (pl)
EP (4) EP3181581B1 (pl)
JP (8) JP5415624B2 (pl)
KR (6) KR102468436B1 (pl)
CN (2) CN102918057B (pl)
AU (1) AU2011233390B2 (pl)
BR (1) BR112012024710B1 (pl)
CA (1) CA2794860C (pl)
DK (1) DK2552955T3 (pl)
ES (3) ES2989715T3 (pl)
HR (3) HRP20241623T1 (pl)
HU (3) HUE033812T2 (pl)
LT (1) LT2552955T (pl)
MX (1) MX2012011338A (pl)
PL (3) PL3702368T3 (pl)
PT (2) PT2552955T (pl)
RU (1) RU2745989C9 (pl)
SG (2) SG10201703798YA (pl)
SI (2) SI2552955T1 (pl)
TW (2) TWI667257B (pl)
WO (1) WO2011122011A2 (pl)

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EP3604330A1 (en) 2011-02-25 2020-02-05 Chugai Seiyaku Kabushiki Kaisha Fcgammariib-specific fc antibody
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KR20140076593A (ko) * 2011-09-30 2014-06-20 추가이 세이야쿠 가부시키가이샤 항원의 소실을 촉진시키는 항원 결합 분자
TW201817745A (zh) 2011-09-30 2018-05-16 日商中外製藥股份有限公司 具有促進抗原清除之FcRn結合域的治療性抗原結合分子
JP6322411B2 (ja) * 2011-09-30 2018-05-09 中外製薬株式会社 複数の生理活性を有する抗原の消失を促進する抗原結合分子
US10556949B2 (en) 2011-09-30 2020-02-11 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule inducing immune response to target antigen
BR112014013081A2 (pt) * 2011-11-30 2020-10-20 Chugai Seiyaku Kabushiki Kaisha veículo contendo fármaco em célula para formação de um complexo imune
KR102041412B1 (ko) * 2011-12-30 2019-11-11 한미사이언스 주식회사 면역글로불린 Fc 단편 유도체
JP6226752B2 (ja) 2012-02-09 2017-11-08 中外製薬株式会社 抗体のFc領域改変体
SI2814587T1 (en) 2012-02-15 2018-08-31 F. Hoffmann-La Roche Ag Affinity chromatography based on the Fc receptor
TW202500756A (zh) 2012-02-24 2025-01-01 日商中外製藥股份有限公司 經FcγRIIB促進抗原消失之抗原結合分子
SMT201800395T1 (it) 2012-03-16 2018-09-13 Regeneron Pharma Anticorpi a catena leggera ingegnerizzati con istidina e roditori modificati geneticamente per la generazione degli stessi
US20140013456A1 (en) 2012-03-16 2014-01-09 Regeneron Pharmaceuticals, Inc. Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same
PT2825037T (pt) 2012-03-16 2019-08-07 Regeneron Pharma Animais não humanos que expressam sequências de imunoglobulinas sensíveis ao ph
RU2014141536A (ru) 2012-03-16 2016-05-10 Регенерон Фармасьютикалз, Инк. Мыши, которые продуцируют антигенсвязывающие белки с зависимыми от величины ph характеристиками связывания
MX382840B (es) * 2012-04-27 2025-03-13 Bioatla Llc Regiones de anticuerpo modificado y sus usos.
EP3892638A1 (en) 2012-05-30 2021-10-13 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule for eliminating aggregated antigens
SG10202006507XA (en) * 2012-05-30 2020-08-28 Chugai Pharmaceutical Co Ltd Target-tissue-specific antigen-binding molecule
TWI855488B (zh) 2012-08-24 2024-09-11 日商中外製藥股份有限公司 FcγRIIb特異性Fc區域變異體
EP3597747B1 (en) 2012-08-24 2023-03-15 Chugai Seiyaku Kabushiki Kaisha Mouse fcgammarii-specific fc antibody
ES2876009T3 (es) 2012-12-27 2021-11-11 Chugai Pharmaceutical Co Ltd Polipéptido heterodimerizado
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SG10201803449VA (en) 2013-09-27 2018-05-30 Chugai Pharmaceutical Co Ltd Method for producing polypeptide heteromultimer
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