CN102439036B - 双特异性egfr/igfir结合分子 - Google Patents

双特异性egfr/igfir结合分子 Download PDF

Info

Publication number
CN102439036B
CN102439036B CN200980155318.4A CN200980155318A CN102439036B CN 102439036 B CN102439036 B CN 102439036B CN 200980155318 A CN200980155318 A CN 200980155318A CN 102439036 B CN102439036 B CN 102439036B
Authority
CN
China
Prior art keywords
seq
amino acid
acid sequence
loop
egfr
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.)
Expired - Fee Related
Application number
CN200980155318.4A
Other languages
English (en)
Chinese (zh)
Other versions
CN102439036A (zh
Inventor
斯图尔特.伊曼纽尔
琳达.恩格尔
雷.坎普豪森
马丁.C.赖特
金格.C.拉克斯特劳
马科.戈塔蒂斯
琼.卡博尼
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.)
Bristol Myers Squibb Co
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of CN102439036A publication Critical patent/CN102439036A/zh
Application granted granted Critical
Publication of CN102439036B publication Critical patent/CN102439036B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
    • 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
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • 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
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07K14/475—Growth factors; Growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • 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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • 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
    • C07K2318/00—Antibody mimetics or scaffolds
    • C07K2318/20—Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Toxicology (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Endocrinology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN200980155318.4A 2008-11-24 2009-11-24 双特异性egfr/igfir结合分子 Expired - Fee Related CN102439036B (zh)

Applications Claiming Priority (11)

Application Number Priority Date Filing Date Title
US20016408P 2008-11-24 2008-11-24
US61/200,164 2008-11-24
US20028208P 2008-11-26 2008-11-26
US61/200,282 2008-11-26
US21296609P 2009-04-17 2009-04-17
US61/212,966 2009-04-17
US17827909P 2009-05-14 2009-05-14
US61/178,279 2009-05-14
US22733009P 2009-07-21 2009-07-21
US61/227,330 2009-07-21
PCT/US2009/065765 WO2010060095A1 (en) 2008-11-24 2009-11-24 Bispecific egfr/igfir binding molecules

Publications (2)

Publication Number Publication Date
CN102439036A CN102439036A (zh) 2012-05-02
CN102439036B true CN102439036B (zh) 2015-07-08

Family

ID=41667546

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200980155318.4A Expired - Fee Related CN102439036B (zh) 2008-11-24 2009-11-24 双特异性egfr/igfir结合分子

Country Status (21)

Country Link
US (5) US8343501B2 (enExample)
EP (2) EP3029064A1 (enExample)
JP (2) JP5823870B2 (enExample)
KR (1) KR20110098922A (enExample)
CN (1) CN102439036B (enExample)
AR (1) AR074399A1 (enExample)
AU (1) AU2009316271A1 (enExample)
BR (1) BRPI0922613A2 (enExample)
CA (1) CA2744405A1 (enExample)
CL (1) CL2011001214A1 (enExample)
CO (1) CO6382161A2 (enExample)
EA (1) EA022415B1 (enExample)
ES (1) ES2555381T3 (enExample)
IL (1) IL212715A0 (enExample)
MX (1) MX2011005257A (enExample)
NZ (2) NZ601693A (enExample)
PE (1) PE20110587A1 (enExample)
TN (1) TN2011000225A1 (enExample)
TW (1) TWI496582B (enExample)
WO (1) WO2010060095A1 (enExample)
ZA (1) ZA201103766B (enExample)

Families Citing this family (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG149004A1 (en) 2003-12-05 2009-01-29 Bristol Myers Squibb Co Inhibitors of type 2 vascular endothelial growth factor receptors
AU2007325838B2 (en) 2006-11-22 2013-09-19 Bristol-Myers Squibb Company Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including IGF-IR
ES2533874T3 (es) 2007-10-31 2015-04-15 Medimmune, Llc Armazón proteico
JP2011517314A (ja) * 2008-02-14 2011-06-02 ブリストル−マイヤーズ スクイブ カンパニー Ｅｇｆｒに結合する操作されたタンパク質に基づく標的化された治療薬
US9296810B2 (en) 2008-05-02 2016-03-29 Novartis Ag Fibronectin-based binding molecules and uses thereof
EP2799448A1 (en) 2008-05-22 2014-11-05 Bristol-Myers Squibb Company Multivalent fibronectin based scaffold domain proteins
MX2011004550A (es) 2008-10-31 2011-07-20 Centocor Ortho Biotech Inc Composiciones de de supercóntigos a base de dominios de fibronectina tipo iii, métodos y usos.
TWI496582B (zh) 2008-11-24 2015-08-21 必治妥美雅史谷比公司 雙重專一性之ｅｇｆｒ／ｉｇｆｉｒ結合分子
US8067201B2 (en) 2009-04-17 2011-11-29 Bristol-Myers Squibb Company Methods for protein refolding
EP3434769B1 (en) 2009-10-30 2020-11-25 Novartis AG Universal fibronectin type iii bottom-side binding domain libraries
JP2013520426A (ja) 2010-02-18 2013-06-06 ブリストル−マイヤーズ スクイブ カンパニー Ｉｌ−２３に結合する、フィブロネクチンをベースとする足場ドメインタンパク質
AU2011240620A1 (en) 2010-04-13 2012-10-18 Medimmune, Llc Fibronectin type III domain-based multimeric scaffolds
CA2797274C (en) 2010-04-30 2024-01-23 Centocor Ortho Biotech Inc. Stabilized fibronectin domain compositions, methods and uses
TW201138808A (en) 2010-05-03 2011-11-16 Bristol Myers Squibb Co Serum albumin binding molecules
WO2011150133A2 (en) * 2010-05-26 2011-12-01 Bristol-Myers Squibb Company Fibronectin based scaffold proteins having improved stability
CA2804501C (en) 2010-07-06 2021-01-26 Novartis Ag Noro virus derived immunogenic compositions and methods
JP6092773B2 (ja) * 2010-07-30 2017-03-08 ノバルティス アーゲー フィブロネクチンクレードル分子及びそのライブラリ
CN103764162B (zh) * 2011-03-04 2017-03-08 夏尔人类遗传治疗公司 用于多肽组成物的肽连接物及其使用方法
US8580922B2 (en) 2011-03-04 2013-11-12 Shire Human Genetic Therapies, Inc. Peptide linkers for polypeptide compositions and methods for using same
SMT201700025T1 (it) 2011-04-13 2017-03-08 Bristol Myers Squibb Co Proteine di fusione ad fc comprendenti nuovi raccordi o arrangiamenti
EP3318880B1 (en) 2011-05-17 2020-12-16 Bristol-Myers Squibb Company Improved methods for the selection of binding proteins
WO2012158678A1 (en) 2011-05-17 2012-11-22 Bristol-Myers Squibb Company Methods for maintaining pegylation of polypeptides
MX358827B (es) 2011-09-27 2018-09-05 Janssen Biotech Inc Supercóntigos de proteína basados en repeticiones de fibronectina tipo iii con superficies de unión alternativas.
EP3753567A1 (en) 2011-10-11 2020-12-23 Viela Bio, Inc. Cd40l-specific tn3-derived scaffolds and methods of use thereof
CN104053670A (zh) 2011-10-31 2014-09-17 百时美施贵宝公司 具有降低的免疫原性的纤连蛋白结合域
WO2013177187A2 (en) 2012-05-22 2013-11-28 Massachusetts Institute Of Technology Synergistic tumor treatment with extended-pk il-2 and therapeutic agents
TWI641619B (zh) * 2012-06-25 2018-11-21 美商再生元醫藥公司 抗－ｅｇｆｒ抗體及其用途
FI3835310T3 (fi) 2012-09-13 2024-05-31 Bristol Myers Squibb Co Fibronektiinipohjaisia telinedomeeniproteiineja, jotka sitoutuvat myostatiiniin
US9695228B2 (en) * 2012-11-21 2017-07-04 Janssen Biotech, Inc. EGFR and c-Met fibronectin type III domain binding molecules
EP2951206A2 (en) * 2013-02-01 2015-12-09 Bristol-Myers Squibb Company Fibronectin based scaffold proteins
EP2953968B1 (en) 2013-02-06 2018-07-25 Bristol-Myers Squibb Company Fibronectin type iii domain proteins with enhanced solubility
EP3299378B1 (en) 2013-02-12 2019-07-31 Bristol-Myers Squibb Company High ph protein refolding methods
CA2926262C (en) 2013-10-14 2025-06-17 Janssen Biotech Inc CYSTEINE MODIFIED TYPE III FIBRONECTIN DOMAIN BINDING MOLECULES (FN3)
WO2015113494A1 (zh) * 2014-01-28 2015-08-06 北京韩美药品有限公司 双功能融合蛋白及其制备方法和用途
ES2913840T3 (es) 2014-03-20 2022-06-06 Bristol Myers Squibb Co Dominios de tipo III de fibronectina de unión a seroalbúmina
EP3180018B1 (en) 2014-08-12 2019-07-24 Massachusetts Institute Of Technology Synergistic tumor treatment with il-2 and integrin-binding-fc-fusion protein
US20170216403A1 (en) 2014-08-12 2017-08-03 Massachusetts Institute Of Technology Synergistic tumor treatment with il-2, a therapeutic antibody, and an immune checkpoint blocker
MX385081B (es) 2014-11-25 2025-03-14 Bristol Myers Squibb Co Métodos y composiciones para radioetiquetado con 18f de productos biológicos.
EP3702367B1 (en) 2014-11-25 2024-05-15 Bristol-Myers Squibb Company Novel pd-l1 binding polypeptides for imaging
CA2972800A1 (en) 2015-01-02 2016-07-07 Dyax Corp. Bispecific antibodies against plasma kallikrein and factor xii
US10913802B2 (en) 2015-07-21 2021-02-09 Dyax Corp. Monoclonal antibody inhibitor of factor XIIA
ES2781207T3 (es) 2015-09-23 2020-08-31 Bristol Myers Squibb Co Dominios de fibronectina de tipo iii de unión a seroalbúmina con velocidad de disociación rápida
WO2017210335A1 (en) 2016-06-01 2017-12-07 Bristol-Myers Squibb Company Imaging methods using 18f-radiolabeled biologics
WO2017210302A1 (en) 2016-06-01 2017-12-07 Bristol-Myers Squibb Company Pet imaging with pd-l1 binding polypeptides
EP3471750A4 (en) 2016-06-21 2020-02-26 Janssen Biotech, Inc. Cysteine engineered fibronectin type iii domain binding molecules
EP3554535A4 (en) 2016-12-14 2020-10-21 Janssen Biotech, Inc. PD-L1 BINDING FIBRONECTIN TYPE III DOMAINS
US10626165B2 (en) 2016-12-14 2020-04-21 Janssen Biotech, Inc. CD8a-binding fibronectin type III domains
EP3554561B1 (en) 2016-12-14 2023-06-28 Janssen Biotech, Inc. Cd137 binding fibronectin type iii domains
US10350266B2 (en) 2017-01-10 2019-07-16 Nodus Therapeutics, Inc. Method of treating cancer with a multiple integrin binding Fc fusion protein
US10603358B2 (en) 2017-01-10 2020-03-31 Nodus Therapeutics Combination tumor treatment with an integrin-binding-Fc fusion protein and immune stimulator
US12331103B2 (en) 2017-06-16 2025-06-17 Protelica, Inc. Fibronectin binding domain chimeric antigen receptors and methods of use thereof
EP3684811A2 (en) 2017-08-17 2020-07-29 Massachusetts Institute of Technology Multiple specificity binders of cxc chemokines and uses thereof
KR101943081B1 (ko) * 2017-08-31 2019-01-29 (주)케어젠 주름 개선 활성을 나타내는 펩타이드 및 이의 용도
US20220275043A1 (en) 2018-07-17 2022-09-01 Massachusetts Institute Of Technology Soluble multimeric immunoglobulin-scaffold based fusion proteins and uses thereof
JP7557882B2 (ja) 2018-09-28 2024-09-30 マサチューセッツ インスティテュート オブ テクノロジー コラーゲンに局在化される免疫調節分子およびその方法
US12410260B2 (en) * 2019-01-11 2025-09-09 The University Of North Carolina At Chapel Hill Highly modular biepitopic and bispecific CAR-T cells for cancer immunotherapy
KR101959020B1 (ko) * 2019-01-14 2019-03-18 (주)케어젠 주름 개선 활성을 나타내는 펩타이드 및 이의 용도
US11235032B2 (en) 2019-01-23 2022-02-01 Massachusetts Institute Of Technology Combination immunotherapy dosing regimen for immune checkpoint blockade
WO2021076543A1 (en) 2019-10-14 2021-04-22 Aro Biotherapeutics Company Epcam binding fibronectin type iii domains
US11781138B2 (en) 2019-10-14 2023-10-10 Aro Biotherapeutics Company FN3 domain-siRNA conjugates and uses thereof
EP4045061A4 (en) 2019-10-14 2024-04-17 ARO Biotherapeutics Company FIBRONECTIN TYPE III DOMAINS BINDING TO CD137
CA3176448A1 (en) 2020-03-31 2021-10-07 Repertoire Immune Medicines, Inc. Barcodable exchangeable peptide-mhc multimer libraries
WO2022087154A1 (en) 2020-10-20 2022-04-28 Repertoire Immune Medicines, Inc. Mhc class ii peptide multimers and uses thereof
AU2022258584A1 (en) 2021-04-14 2023-10-12 Aro Biotherapeutics Company Fn3 domain-sirna conjugates and uses thereof
EP4323409A4 (en) 2021-04-14 2025-04-16 ARO Biotherapeutics Company CD71-BINDING FIBRONECTIN TYPE III DOMAINS
US20250326844A1 (en) 2022-04-07 2025-10-23 Repertoire Immune Medicines, Inc. T cell receptor multimers and uses thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008066752A2 (en) * 2006-11-22 2008-06-05 Adnexus, A Bristol-Myers Squibb R & D Company Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including igf-ir

Family Cites Families (148)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US4002531A (en) 1976-01-22 1977-01-11 Pierce Chemical Company Modifying enzymes with polyethylene glycol and product produced thereby
USRE30985E (en) 1978-01-01 1982-06-29 Serum-free cell culture media
US4560655A (en) 1982-12-16 1985-12-24 Immunex Corporation Serum-free cell culture medium and process for making same
US4657866A (en) 1982-12-21 1987-04-14 Sudhir Kumar Serum-free, synthetic, completely chemically defined tissue culture media
US4767704A (en) 1983-10-07 1988-08-30 Columbia University In The City Of New York Protein-free culture medium
GB8516415D0 (en) 1985-06-28 1985-07-31 Celltech Ltd Culture of animal cells
US4927762A (en) 1986-04-01 1990-05-22 Cell Enterprises, Inc. Cell culture medium with antioxidant
US5770697A (en) 1986-11-04 1998-06-23 Protein Polymer Technologies, Inc. Peptides comprising repetitive units of amino acids and DNA sequences encoding the same
US6018030A (en) 1986-11-04 2000-01-25 Protein Polymer Technologies, Inc. Peptides comprising repetitive units of amino acids and DNA sequences encoding the same
US5641648A (en) 1986-11-04 1997-06-24 Protein Polymer Technologies, Inc. Methods for preparing synthetic repetitive DNA
US5514581A (en) 1986-11-04 1996-05-07 Protein Polymer Technologies, Inc. Functional recombinantly prepared synthetic protein polymer
US4863457A (en) 1986-11-24 1989-09-05 Lee David A Drug delivery device
US4997652A (en) 1987-12-22 1991-03-05 Visionex Biodegradable ocular implants
WO1990003430A1 (en) 1988-09-23 1990-04-05 Cetus Corporation Cell culture medium for enhanced cell growth, culture longevity and product expression
CA2053317C (en) 1989-04-19 1996-03-12 Shmuel Zalipsky Active carbonates of polyalkylene oxides for modification of polypeptides
FR2646437B1 (fr) 1989-04-28 1991-08-30 Transgene Sa Nouvelles sequences d'adn, leur application en tant que sequence codant pour un peptide signal pour la secretion de proteines matures par des levures recombinantes, cassettes d'expression, levures transformees et procede de preparation de proteines correspondant
US5164188A (en) 1989-11-22 1992-11-17 Visionex, Inc. Biodegradable ocular implants
WO1992002536A1 (en) 1990-08-02 1992-02-20 The Regents Of The University Of Colorado Systematic polypeptide evolution by reverse translation
JP3051145B2 (ja) 1990-08-28 2000-06-12 住友製薬株式会社 新規なポリエチレングリコール誘導体修飾ペプチド
US5122469A (en) 1990-10-03 1992-06-16 Genentech, Inc. Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins
KR0185215B1 (ko) 1990-11-30 1999-05-01 요시다 쇼오지 서방성 안구삽입용 약제
US5773574A (en) 1990-12-03 1998-06-30 The Scripps Research Institute Polypeptides for promoting cell attachment
US5235041A (en) 1990-12-28 1993-08-10 Protein Polymer Technologies, Inc. Purification of structurally ordered recombinant protein polymers
US5792742A (en) 1991-06-14 1998-08-11 New York University Fibrin-binding peptide fragments of fibronectin
AU2313392A (en) 1991-08-01 1993-03-02 University Research Corporation Systematic polypeptide evolution by reverse translation
NZ255041A (en) 1992-07-13 1996-11-26 Bionebraska Inc Preparation of a recombinant single copy polypeptide or portion thereof modified with a terminal alpha amino carbon reactive group and reactive side chain groups involving biologically added protective groups
EP0669836B1 (en) 1992-11-13 1996-07-03 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human b lymphocyte restricted differentiation antigen for treatment of b cell lymphoma
WO1994017097A1 (en) 1993-01-19 1994-08-04 Regents Of The University Of Minnesota Synthetic fibronectin fragments as inhibitors of retroviral infections
WO1994018921A1 (en) 1993-02-26 1994-09-01 Santen Pharmaceutical Co., Ltd. Biodegradable sclera plug
US5643575A (en) 1993-10-27 1997-07-01 Enzon, Inc. Non-antigenic branched polymer conjugates
AU8124694A (en) 1993-10-29 1995-05-22 Affymax Technologies N.V. In vitro peptide and antibody display libraries
US5443505A (en) 1993-11-15 1995-08-22 Oculex Pharmaceuticals, Inc. Biocompatible ocular implants
US5516522A (en) 1994-03-14 1996-05-14 Board Of Supervisors Of Louisiana State University Biodegradable porous device for long-term drug delivery with constant rate release and method of making the same
US5824784A (en) 1994-10-12 1998-10-20 Amgen Inc. N-terminally chemically modified protein compositions and methods
US5932462A (en) 1995-01-10 1999-08-03 Shearwater Polymers, Inc. Multiarmed, monofunctional, polymer for coupling to molecules and surfaces
US5559000A (en) 1995-01-18 1996-09-24 The Scripps Research Institute Encoded reaction cassette
US5869079A (en) 1995-06-02 1999-02-09 Oculex Pharmaceuticals, Inc. Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents
US6369116B1 (en) 1995-06-02 2002-04-09 Oculex Pharmaceuticals, Inc. Composition and method for treating glaucoma
DE19646372C1 (de) 1995-11-11 1997-06-19 Evotec Biosystems Gmbh Genotyp und Phänotyp koppelnde Verbindung
GB9618960D0 (en) 1996-09-11 1996-10-23 Medical Science Sys Inc Proteases
US5922676A (en) 1996-09-20 1999-07-13 The Burnham Institute Methods of inhibiting cancer by using superfibronectin
WO1998016636A1 (en) 1996-10-17 1998-04-23 Mitsubishi Chemical Corporation Molecule that homologizes genotype and phenotype and utilization thereof
WO1998031794A1 (fr) 1997-01-17 1998-07-23 Toa Gosei Co., Ltd. Polypeptide liant le facteur vegf
US6261804B1 (en) 1997-01-21 2001-07-17 The General Hospital Corporation Selection of proteins using RNA-protein fusions
PT1712623E (pt) 1997-01-21 2011-12-21 Gen Hospital Corp Selecção de proteínas utilizando fusões de arn-proteína
WO1998048837A1 (en) * 1997-04-30 1998-11-05 Enzon, Inc. Polyalkylene oxide-modified single chain polypeptides
CA2293632C (en) 1997-06-12 2011-11-29 Research Corporation Technologies, Inc. Artificial antibody polypeptides
US6159722A (en) 1997-12-03 2000-12-12 Boehringer Mannheim Gmbh Chimeric serine proteases
CA2323638A1 (en) 1998-04-03 1999-10-14 Phylos, Inc. Addressable protein arrays
US20030045681A1 (en) 1998-05-11 2003-03-06 Anthony J. Zelano Specific binding molecules for scintigraphy, conjugates containing them and therapeutic method for treatment of angiogenesis
JP4108827B2 (ja) 1998-05-28 2008-06-25 大日本印刷株式会社 無機質系化粧板
CA2342967A1 (en) 1998-12-08 2000-06-15 Biovation Limited Modifying protein immunogenicity
ATE439592T1 (de) 1998-12-10 2009-08-15 Bristol Myers Squibb Co Proteingerüste für antikörper-nachahmer und andere bindende proteine
US7115396B2 (en) 1998-12-10 2006-10-03 Compound Therapeutics, Inc. Protein scaffolds for antibody mimics and other binding proteins
US6818418B1 (en) * 1998-12-10 2004-11-16 Compound Therapeutics, Inc. Protein scaffolds for antibody mimics and other binding proteins
GB9827228D0 (en) 1998-12-10 1999-02-03 Univ Nottingham Cancer detection method and reagents
US6416758B1 (en) 1999-04-28 2002-07-09 Board Of Regents, The University Of Texax System Antibody conjugate kits for selectively inhibiting VEGF
DE60034566T2 (de) 1999-07-27 2008-01-03 Adnexus Therapeutics, Inc., Waltham Peptidakzeptor ligationsverfahren
US6399857B1 (en) 1999-09-22 2002-06-04 Paradigm Genetics, Inc. Modified nucleotide sequence encoding a LexA DNA binding domain optimized for arabidopsis species
CA2404528A1 (en) 2000-03-31 2001-10-04 Institut Pasteur Peptides blocking vascular endothelial growth factor (vegf)-mediated angiogenesis, polynucleotides encoding said peptides and methods of use thereof
US20030104520A1 (en) 2000-06-15 2003-06-05 Ellington Andrew D. Regulatable, catalytically active nucleic acids
JP4578768B2 (ja) 2000-07-11 2010-11-10 リサーチ コーポレイション テクノロジーズ，インコーポレイテッド 人工抗体ポリペプチド
EP1324779B1 (en) 2000-09-29 2011-07-20 Schering Corporation Pegylated interleukin-10
AU1325102A (en) 2000-10-16 2002-04-29 Phylos Inc Protein scaffolds for antibody mimics and other binding proteins
US7598352B2 (en) 2000-11-17 2009-10-06 University Of Rochester Method of identifying polypeptide monobodies which bind to target proteins and use thereof
AU3649502A (en) 2000-11-29 2002-06-11 Oculex Pharm Inc Methods for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor
US6509027B2 (en) 2001-02-12 2003-01-21 Supergen, Inc. Injectable pharmaceutical composition comprising coated particles of camptothecin
WO2002081497A2 (en) 2001-04-04 2002-10-17 University Of Rochester αξβ3 INTEGRIN-BINDING POLYPEPTIDE MONOBODIES AND THEIR USE
AU2002256371B2 (en) 2001-04-26 2008-01-10 Amgen Mountain View Inc. Combinatorial libraries of monomer domains
US20030004561A1 (en) 2001-06-28 2003-01-02 Steve Bigus Peeling sheath for self-expanding stent
AU2002342672A1 (en) 2001-09-11 2003-03-24 Nascacell Gmbh Method for screening for inhibitors of protein/protein interaction and corresponding ribozymes
US20080193445A1 (en) * 2002-01-18 2008-08-14 Liliane Goetsch Novel anti-IGF-IR antibodies and uses thereof
SG161101A1 (en) 2002-02-22 2010-05-27 Schering Corp Pharmaceutical formulations of antineoplastic agents, in particular temozolomide processes of making and using the same
EP1916001B1 (en) 2002-03-04 2011-05-25 Imclone LLC Human antibodies specific to KDR and uses thereof
AU2003243436A1 (en) 2002-06-06 2003-12-22 Shohei Koide Reconstituted polypeptides
CN102584997A (zh) 2002-11-08 2012-07-18 埃博灵克斯股份有限公司 针对肿瘤坏死因子-α的单结构域抗体及其用途
US7053701B2 (en) 2003-11-04 2006-05-30 Vice Michael W Power amplifier output stage with multiple power states and improved efficiency
EP2302229B1 (en) 2003-11-17 2016-06-08 Telezygology Inc. Shape memory releasable fastening system
SG149004A1 (en) * 2003-12-05 2009-01-29 Bristol Myers Squibb Co Inhibitors of type 2 vascular endothelial growth factor receptors
US20080220049A1 (en) 2003-12-05 2008-09-11 Adnexus, A Bristol-Myers Squibb R&D Company Compositions and methods for intraocular delivery of fibronectin scaffold domain proteins
US20070059336A1 (en) 2004-04-30 2007-03-15 Allergan, Inc. Anti-angiogenic sustained release intraocular implants and related methods
WO2005110374A1 (en) 2004-04-30 2005-11-24 Allergan, Inc. Intraocular drug delivery systems containing a therapeutic component, a cyclodextrin, and a polymeric component
US20060182783A1 (en) 2004-04-30 2006-08-17 Allergan, Inc. Sustained release intraocular drug delivery systems
US20050244469A1 (en) 2004-04-30 2005-11-03 Allergan, Inc. Extended therapeutic effect ocular implant treatments
JP2008512352A (ja) 2004-07-17 2008-04-24 イムクローン システムズ インコーポレイティド 新規な四価の二重特異性抗体
US7597884B2 (en) * 2004-08-09 2009-10-06 Alios Biopharma, Inc. Hyperglycosylated polypeptide variants and methods of use
BRPI0516308A2 (pt) 2004-10-04 2010-06-15 Qlt Usa Inc composição fluida, métodos de tratamento de uma doença ou disfunção, métodos de liberação local ou sistêmica de um agente biológico, implantes, método de formação de um implante, kit de agente biológico e usos de uma composição fluida
EP1838307A1 (en) 2004-12-02 2007-10-03 Schering Corporation Methods of using temozolomide formulation intrathecally in the treatment of cancers
BRPI0519897A2 (pt) 2005-02-23 2009-08-18 Merrimack Pharmaceuticals Inc método para modular a atividade ou atividades biológicas de moléculas alvo em uma célula alvo, agente de ligação biespecìfico, composição, uso de um agente de ligação biespecìfico, e, kit
FR2888850B1 (fr) 2005-07-22 2013-01-11 Pf Medicament Nouveaux anticorps anti-igf-ir et leurs applications
US7612181B2 (en) * 2005-08-19 2009-11-03 Abbott Laboratories Dual variable domain immunoglobulin and uses thereof
US7887273B2 (en) 2005-09-15 2011-02-15 Newfrey Llc Blind rivet and method
US20070072933A1 (en) 2005-09-26 2007-03-29 Peyman Gholam A Delivery of an ocular agent
US8097438B2 (en) * 2005-10-07 2012-01-17 The Regents Of The University Of California Nucleic acids encoding modified cytochrome P450 enzymes and methods of use thereof
CN101394834A (zh) 2005-10-18 2009-03-25 阿勒根公司 用糖皮质激素衍生物选择性渗透后段组织来治疗眼睛
WO2007053807A2 (en) 2005-10-31 2007-05-10 Wisconsin Alumni Research Foundation Calcitriol for treating intraocular diseases associated with angiogenesis
EP1945767B1 (de) 2005-11-09 2010-04-07 MorphoSys AG Identifizierung und charakterisierung von funktionsblockierenden anti-ed-b-fibronektin antikörpern
EP3269381B1 (en) * 2005-11-23 2020-10-07 Acceleron Pharma, Inc. Activin-actriia antagonists in use for promoting bone growth
EP2397148A3 (en) 2006-02-02 2012-04-25 Allergan, Inc. Compositions and methods for the treatment of ophthalmic disease
JP5161796B2 (ja) * 2006-02-24 2013-03-13 シエシー ファルマセウティチィ ソシエタ ペル アチオニ 抗アミロイド免疫原性組成物、方法、および使用
EP2013229A2 (en) * 2006-04-21 2009-01-14 Transgene S.A. Hpv-18-based papillomavirus vaccine
US20070269422A1 (en) 2006-05-17 2007-11-22 Ablynx N.V. Serum albumin binding proteins with long half-lives
JP5638804B2 (ja) 2006-08-04 2014-12-10 アストラゼネカ アクチボラグ ＥｒｂＢ２に対する抗体
WO2008031098A1 (en) 2006-09-09 2008-03-13 The University Of Chicago Binary amino acid libraries for fibronectin type iii polypeptide monobodies
WO2008048970A2 (en) * 2006-10-16 2008-04-24 The Arizona Board Of Regents, A Body Corporate Of The State Of Arizona Acting For And On Behalf Of Arizona State University Synthetic antibodies
US8476243B2 (en) * 2006-12-29 2013-07-02 Transderm, Inc. Methods and compositions for treating keratin hyperproliferative disorders
ATE516814T1 (de) 2007-02-02 2011-08-15 Bristol Myers Squibb Co 10fn3 domain zur behandlung von krankheiten begleitet von unerwünschter angiogenese
MX2009009379A (es) 2007-03-02 2009-09-14 Amgen Inc Metodos y composiciones para tratar enfermedades tumorales.
US11078262B2 (en) 2007-04-30 2021-08-03 Allergan, Inc. High viscosity macromolecular compositions for treating ocular conditions
US8420779B2 (en) 2007-05-22 2013-04-16 Amgen Inc. Compositions and methods for producing bioactive fusion proteins
US8470966B2 (en) 2007-08-10 2013-06-25 Protelica, Inc. Universal fibronectin type III binding-domain libraries
US8680019B2 (en) 2007-08-10 2014-03-25 Protelica, Inc. Universal fibronectin Type III binding-domain libraries
JP5781762B2 (ja) 2007-08-10 2015-09-24 プロテリックス、インク ユニバーサルｉｉｉ型フィブロネクチン結合ドメインのライブラリ
US20100285000A1 (en) * 2007-08-20 2010-11-11 Bristol-Myers Squibb Company Use of vegfr-2 inhibitors for treating metastatic cancer
JP5496897B2 (ja) 2007-10-04 2014-05-21 ザイモジェネティクス， インコーポレイテッド Ｂ７ファミリーメンバーのｚＢ７Ｈ６ならびに関連する組成物および方法
ES2533874T3 (es) 2007-10-31 2015-04-15 Medimmune, Llc Armazón proteico
EP2217274A1 (en) 2007-11-28 2010-08-18 Bristol-Myers Squibb Company Combination vegfr2 therapy with mtor inhibitors
EP2238247A2 (en) 2007-12-19 2010-10-13 Centocor Ortho Biotech Inc. Alternative scaffold protein fusions phage display via fusion to plx of m13 phage
US20100322930A1 (en) 2007-12-27 2010-12-23 Frank Kolbinger Fibronectin-based binding molecules and their use
JP2011517314A (ja) 2008-02-14 2011-06-02 ブリストル−マイヤーズ スクイブ カンパニー Ｅｇｆｒに結合する操作されたタンパク質に基づく標的化された治療薬
US9296810B2 (en) 2008-05-02 2016-03-29 Novartis Ag Fibronectin-based binding molecules and uses thereof
EP2799448A1 (en) 2008-05-22 2014-11-05 Bristol-Myers Squibb Company Multivalent fibronectin based scaffold domain proteins
MX2011004550A (es) 2008-10-31 2011-07-20 Centocor Ortho Biotech Inc Composiciones de de supercóntigos a base de dominios de fibronectina tipo iii, métodos y usos.
US8415291B2 (en) 2008-10-31 2013-04-09 Centocor Ortho Biotech Inc. Anti-TNF alpha fibronectin type III domain based scaffold compositions, methods and uses
TWI496582B (zh) 2008-11-24 2015-08-21 必治妥美雅史谷比公司 雙重專一性之ｅｇｆｒ／ｉｇｆｉｒ結合分子
CN102245771B (zh) 2008-12-16 2013-04-10 诺瓦提斯公司 酵母展示系统
US20100210511A1 (en) * 2009-02-11 2010-08-19 Bristol-Myers Squibb Company Combination VEGFR2 Therapy with Temozolomide
AU2010213892B2 (en) 2009-02-12 2014-10-23 Janssen Biotech, Inc. Fibronectin type III domain based scaffold compositions, methods and uses
US8067201B2 (en) * 2009-04-17 2011-11-29 Bristol-Myers Squibb Company Methods for protein refolding
US20120270797A1 (en) 2009-08-13 2012-10-25 Massachusetts Institute Of Technology Engineered proteins including mutant fibronectin domains
EP3434769B1 (en) 2009-10-30 2020-11-25 Novartis AG Universal fibronectin type iii bottom-side binding domain libraries
WO2011051466A1 (en) 2009-11-02 2011-05-05 Novartis Ag Anti-idiotypic fibronectin-based binding molecules and uses thereof
US20110123545A1 (en) 2009-11-24 2011-05-26 Bristol-Myers Squibb Company Combination of vegfr2 and igf1r inhibitors for the treatment of proliferative diseases
WO2011092233A1 (en) 2010-01-29 2011-08-04 Novartis Ag Yeast mating to produce high-affinity combinations of fibronectin-based binders
US8961977B2 (en) 2010-02-12 2015-02-24 University Of Rochester Antigenic mimics of discontinuous epitopes of pathogen recognized by broadly neutralizing antibodies
JP2013520426A (ja) 2010-02-18 2013-06-06 ブリストル−マイヤーズ スクイブ カンパニー Ｉｌ−２３に結合する、フィブロネクチンをベースとする足場ドメインタンパク質
AU2011240620A1 (en) 2010-04-13 2012-10-18 Medimmune, Llc Fibronectin type III domain-based multimeric scaffolds
CN105175532B (zh) 2010-04-13 2023-01-17 百时美施贵宝公司 结合pcsk9的基于纤连蛋白的支架域蛋白质
CA2797274C (en) 2010-04-30 2024-01-23 Centocor Ortho Biotech Inc. Stabilized fibronectin domain compositions, methods and uses
TW201138808A (en) 2010-05-03 2011-11-16 Bristol Myers Squibb Co Serum albumin binding molecules
WO2011150133A2 (en) * 2010-05-26 2011-12-01 Bristol-Myers Squibb Company Fibronectin based scaffold proteins having improved stability
JP6092773B2 (ja) 2010-07-30 2017-03-08 ノバルティス アーゲー フィブロネクチンクレードル分子及びそのライブラリ
US9260496B2 (en) 2010-12-22 2016-02-16 Bristol-Myers Squibb Company Fibronectin based scaffold domain proteins that bind IL-23
SMT201700025T1 (it) 2011-04-13 2017-03-08 Bristol Myers Squibb Co Proteine di fusione ad fc comprendenti nuovi raccordi o arrangiamenti
EP3318880B1 (en) 2011-05-17 2020-12-16 Bristol-Myers Squibb Company Improved methods for the selection of binding proteins
WO2012158678A1 (en) 2011-05-17 2012-11-22 Bristol-Myers Squibb Company Methods for maintaining pegylation of polypeptides
MX358827B (es) 2011-09-27 2018-09-05 Janssen Biotech Inc Supercóntigos de proteína basados en repeticiones de fibronectina tipo iii con superficies de unión alternativas.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008066752A2 (en) * 2006-11-22 2008-06-05 Adnexus, A Bristol-Myers Squibb R & D Company Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including igf-ir

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Simultaneous blockade of both the epidermal growth factor receptor and the insulin-like growth factor receptor signaling pathways in cancer cells with a fully human recombinant bispecific antibody;LU D et al;《Journal of Biological Chemistry》;20040123;第2856-2865页 *

Also Published As

Publication number Publication date
AU2009316271A1 (en) 2010-05-27
JP5823870B2 (ja) 2015-11-25
TW201026332A (en) 2010-07-16
AR074399A1 (es) 2011-01-12
JP2012509900A (ja) 2012-04-26
EP2350126A1 (en) 2011-08-03
US8343501B2 (en) 2013-01-01
NZ592782A (en) 2012-09-28
US10183987B2 (en) 2019-01-22
US10954286B2 (en) 2021-03-23
US20130157948A1 (en) 2013-06-20
US9017655B2 (en) 2015-04-28
WO2010060095A1 (en) 2010-05-27
IL212715A0 (en) 2011-07-31
TWI496582B (zh) 2015-08-21
CL2011001214A1 (es) 2011-09-16
EA201100669A1 (ru) 2012-05-30
US20100179094A1 (en) 2010-07-15
EP3029064A1 (en) 2016-06-08
US20190153069A1 (en) 2019-05-23
BRPI0922613A2 (pt) 2019-09-24
PE20110587A1 (es) 2011-08-31
CN102439036A (zh) 2012-05-02
US20150259398A1 (en) 2015-09-17
US9771411B2 (en) 2017-09-26
ES2555381T3 (es) 2015-12-30
KR20110098922A (ko) 2011-09-02
EA022415B1 (ru) 2015-12-30
CA2744405A1 (en) 2010-05-27
NZ601693A (en) 2014-02-28
JP2016000731A (ja) 2016-01-07
MX2011005257A (es) 2011-05-31
US20180037631A1 (en) 2018-02-08
TN2011000225A1 (en) 2012-12-17
EP2350126B1 (en) 2015-11-04
CO6382161A2 (es) 2012-02-15
ZA201103766B (en) 2012-10-31

Similar Documents

Publication Publication Date Title
CN102439036B (zh) 双特异性egfr/igfir结合分子
US10781247B2 (en) Targeted therapeutics based on engineered proteins that bind EGFR
US10774130B2 (en) Method of treating cancer by administering multivalent fibronectin based scaffold domain proteins
CN101636410A (zh) 基于酪氨酸激酶受体（包括igf-ir）的工程化蛋白质的靶向治疗剂
AU2013202605A1 (en) Bispecific egfr/igfir binding molecules

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20150708

Termination date: 20171124