CA3072099A1 - Engineered antibody fc variants for enhanced serum half life - Google Patents

Engineered antibody fc variants for enhanced serum half life Download PDF

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Publication number
CA3072099A1
CA3072099A1 CA3072099A CA3072099A CA3072099A1 CA 3072099 A1 CA3072099 A1 CA 3072099A1 CA 3072099 A CA3072099 A CA 3072099A CA 3072099 A CA3072099 A CA 3072099A CA 3072099 A1 CA3072099 A1 CA 3072099A1
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CA
Canada
Prior art keywords
polypeptide
domain
antibody
binding
fcrn
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CA3072099A
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English (en)
French (fr)
Inventor
George Georgiou
Chang-Han Lee
Tae Hyun Kang
Original Assignee
Research Development Foundation
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Application filed by Research Development Foundation filed Critical Research Development Foundation
Publication of CA3072099A1 publication Critical patent/CA3072099A1/en
Pending legal-status Critical Current

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Classifications

    • 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
    • C07K16/2803—Immunoglobulins [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
    • C07K16/283—Immunoglobulins [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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • 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
    • C07K16/32—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • 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
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41—Glycosylation, sialylation, or fucosylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/524—CH2 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/526—CH3 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/72—Increased effector function due to an Fc-modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/75—Agonist effect on antigen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
CA3072099A 2017-08-11 2018-08-11 Engineered antibody fc variants for enhanced serum half life Pending CA3072099A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201762544622P 2017-08-11 2017-08-11
US62/544,622 2017-08-11
PCT/US2018/046398 WO2019033087A1 (en) 2017-08-11 2018-08-11 MODIFIED FC ANTIBODY VARIANTS FOR ENHANCED SERIAL HALF LIFE

Publications (1)

Publication Number Publication Date
CA3072099A1 true CA3072099A1 (en) 2019-02-14

Family

ID=65272701

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3072099A Pending CA3072099A1 (en) 2017-08-11 2018-08-11 Engineered antibody fc variants for enhanced serum half life

Country Status (9)

Country Link
US (3) US11059892B2 (enExample)
EP (1) EP3665195A4 (enExample)
JP (3) JP7191087B2 (enExample)
KR (1) KR102867311B1 (enExample)
CN (1) CN111032688A (enExample)
AU (1) AU2018314257B2 (enExample)
CA (1) CA3072099A1 (enExample)
IL (1) IL272561B2 (enExample)
WO (1) WO2019033087A1 (enExample)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4017529A4 (en) * 2019-08-22 2024-03-13 Cidara Therapeutics, Inc. FIELDS FC VARIANTS AND THEIR USES
EP4225787A4 (en) * 2020-05-21 2024-10-23 Zydus Lifesciences Limited FC VARIANT AND PRODUCTION THEREOF
JP7659628B2 (ja) * 2020-11-11 2025-04-09 ギリアード サイエンシーズ， インコーポレイテッド ｇｐ１２０ ＣＤ４結合部位指向性抗体による治療に感受性のＨＩＶ患者を特定する方法
KR20230152032A (ko) 2021-02-03 2023-11-02 모차르트 쎄라퓨틱스 인코포레이티드 결합제 및 이를 사용하는 방법
EP4319820A1 (en) 2021-04-10 2024-02-14 Profoundbio Us Co. Folr1 binding agents, conjugates thereof and methods of using the same
JP7742892B2 (ja) 2021-04-23 2025-09-22 ジェンマブ エー／エス 抗ｃｄ７０抗体、そのコンジュゲートおよびこれを使用する方法
TW202320857A (zh) 2021-07-06 2023-06-01 美商普方生物製藥美國公司 連接子、藥物連接子及其結合物及其使用方法
WO2023076876A1 (en) 2021-10-26 2023-05-04 Mozart Therapeutics, Inc. Modulation of immune responses to viral vectors
US20250188186A1 (en) * 2021-12-10 2025-06-12 Board Of Regents, The University Of Texas System Ph-selective antibody fc domains
WO2024030956A2 (en) 2022-08-03 2024-02-08 Mozart Therapeutics, Inc. Cd39-specific binding agents and methods of using the same
WO2024044477A1 (en) 2022-08-26 2024-02-29 Gilead Sciences, Inc. Dosing and scheduling regimen for broadly neutralizing antibodies
CN121194993A (zh) 2023-05-24 2025-12-23 莫扎特治疗公司 Cd8特异性结合蛋白及其应用方法
TW202509078A (zh) 2023-07-07 2025-03-01 美商維里迪恩醫療股份有限公司 治療慢性甲狀腺眼病之方法
WO2025072406A1 (en) 2023-09-26 2025-04-03 Profoundbio Us Co. Ptk7 binding agents, conjugates thereof and methods of using the same
WO2025117639A1 (en) 2023-11-27 2025-06-05 Profoundbio Us Co. Antibodies and methods for ptk7 detection
TW202547866A (zh) 2024-01-10 2025-12-16 丹麥商珍美寶股份有限公司 Ｓｌｉｔｒｋ６結合劑、其共軛物及使用彼之方法
WO2025170982A2 (en) 2024-02-06 2025-08-14 Paragon Therapeutics, Inc. Il-23 antibody compositions and methods of use
WO2025171006A1 (en) * 2024-02-06 2025-08-14 Paragon Therapeutics, Inc. Il-23 binding protein compositions and methods of use
US20250381289A1 (en) 2024-02-29 2025-12-18 Genmab A/S Egfr and c-met bispecific binding agents, conjugates thereof and methods of using the same
WO2025222129A2 (en) 2024-04-19 2025-10-23 Mozart Therapeutics, Inc. Engineered cytokines and targeted cytokine delivery
WO2026090160A2 (en) 2024-10-22 2026-04-30 Gilead Sciences, Inc. Cd4-targeted il-15 molecules and methods of use

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4554101A (en) 1981-01-09 1985-11-19 New York Blood Center, Inc. Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity
US5824311A (en) 1987-11-30 1998-10-20 Trustees Of The University Of Pennsylvania Treatment of tumors with monoclonal antibodies against oncogene antigens
US4870287A (en) 1988-03-03 1989-09-26 Loma Linda University Medical Center Multi-station proton beam therapy system
US5801029A (en) 1993-02-16 1998-09-01 Onyx Pharmaceuticals, Inc. Cytopathic viruses for therapy and prophylaxis of neoplasia
US5801005A (en) 1993-03-17 1998-09-01 University Of Washington Immune reactivity to HER-2/neu protein for diagnosis of malignancies in which the HER-2/neu oncogene is associated
GB9506466D0 (en) 1994-08-26 1995-05-17 Prolifix Ltd Cell cycle regulated repressor and dna element
US5702892A (en) 1995-05-09 1997-12-30 The United States Of America As Represented By The Department Of Health And Human Services Phage-display of immunoglobulin heavy chain libraries
US5760395A (en) 1996-04-18 1998-06-02 Universities Research Assoc., Inc. Method and apparatus for laser-controlled proton beam radiology
US5739169A (en) 1996-05-31 1998-04-14 Procept, Incorporated Aromatic compounds for inhibiting immune response
US6737056B1 (en) * 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
US7094571B2 (en) 2000-10-27 2006-08-22 The Board Of Regents Of The University Of Texas System Combinatorial protein library screening by periplasmic expression
US7419783B2 (en) 2001-11-05 2008-09-02 Research Development Foundation Engineering of leader peptides for the secretion of recombinant proteins in bacteria
US7317091B2 (en) 2002-03-01 2008-01-08 Xencor, Inc. Optimized Fc variants
JP2005520569A (ja) 2002-03-23 2005-07-14 リサーチ　ディベロップメント　ファンデーション バクテリア内で複数のジスルフィド結合を有する蛋白質の分泌とその利用
US7611866B2 (en) 2002-07-15 2009-11-03 Board Of Regents, The University Of Texas System Selection of bacterial inner-membrane anchor polypeptides
US9051373B2 (en) * 2003-05-02 2015-06-09 Xencor, Inc. Optimized Fc variants
EP2385069A3 (en) 2003-11-12 2012-05-30 Biogen Idec MA Inc. Neonatal Fc rReceptor (FcRn)- binding polypeptide variants, dimeric Fc binding proteins and methods related thereto
WO2007024249A2 (en) 2004-11-10 2007-03-01 Macrogenics, Inc. Engineering fc antibody regions to confer effector function
US8546543B2 (en) * 2004-11-12 2013-10-01 Xencor, Inc. Fc variants that extend antibody half-life
US8367805B2 (en) 2004-11-12 2013-02-05 Xencor, Inc. Fc variants with altered binding to FcRn
BRPI0517837A (pt) 2004-11-12 2008-10-21 Xencor Inc variantes fc com ligação alterada a fcrn
CA2595169A1 (en) 2005-01-12 2006-07-20 Xencor, Inc. Antibodies and fc fusion proteins with altered immunogenicity
WO2008106982A2 (en) 2007-03-07 2008-09-12 Aarhus Universitet Pig model for atherosclerosis
DK2155789T3 (da) 2007-05-01 2013-10-21 Res Dev Foundation Immunoglobulin-Fc-biblioteker
US8043621B2 (en) 2007-05-10 2011-10-25 Ramot At Tel Aviv University Ltd. Recombinant fusion protein and polynucleotide construct for immunotoxin production
CN102549016B (zh) 2009-06-30 2015-05-06 研究发展基金会 免疫球蛋白fc多肽
TWI667257B (zh) 2010-03-30 2019-08-01 中外製藥股份有限公司 促進抗原消失之具有經修飾的ＦｃＲｎ親和力之抗體
GB201112429D0 (en) * 2011-07-19 2011-08-31 Glaxo Group Ltd Antigen-binding proteins with increased FcRn binding
US20150050269A1 (en) 2011-09-30 2015-02-19 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule promoting disappearance of antigens having plurality of biological activities
TW201817744A (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
CN104010659A (zh) 2011-12-19 2014-08-27 洛克菲勒大学 非唾液酸化的抗炎多肽
EP3892638A1 (en) * 2012-05-30 2021-10-13 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule for eliminating aggregated antigens
EP3142700B1 (en) * 2014-05-16 2021-03-03 Medimmune, LLC Molecules with altered neonate fc receptor binding having enhanced therapeutic and diagnostic properties
JP6034332B2 (ja) 2014-05-30 2016-11-30 トヨタ自動車株式会社 組換え微生物及び当該組換え微生物を用いた物質製造方法
EP3215528B1 (en) * 2014-11-06 2019-08-07 F.Hoffmann-La Roche Ag Fc-region variants with modified fcrn-binding and methods of use
TWI901940B (zh) 2017-08-03 2025-10-21 美商安進公司 介白素-21突變蛋白及治療方法

Also Published As

Publication number Publication date
CN111032688A (zh) 2020-04-17
EP3665195A4 (en) 2021-05-19
AU2018314257A1 (en) 2020-02-13
KR20200035972A (ko) 2020-04-06
JP2022145845A (ja) 2022-10-04
IL272561B2 (en) 2026-05-01
JP7583767B2 (ja) 2024-11-14
IL272561A (en) 2020-03-31
US20210347891A1 (en) 2021-11-11
AU2018314257B2 (en) 2025-03-27
US11059892B2 (en) 2021-07-13
KR102867311B1 (ko) 2025-10-01
JP2020530296A (ja) 2020-10-22
JP7191087B2 (ja) 2022-12-16
US11958904B2 (en) 2024-04-16
EP3665195A1 (en) 2020-06-17
US20240270852A1 (en) 2024-08-15
JP2025013474A (ja) 2025-01-24
WO2019033087A1 (en) 2019-02-14
IL272561B1 (en) 2026-01-01
US20190048078A1 (en) 2019-02-14

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