AR074399A1 - Moleculas biespecificas de union a egfr/igfir - Google Patents

Moleculas biespecificas de union a egfr/igfir

Info

Publication number
AR074399A1
AR074399A1 ARP090104530A ARP090104530A AR074399A1 AR 074399 A1 AR074399 A1 AR 074399A1 AR P090104530 A ARP090104530 A AR P090104530A AR P090104530 A ARP090104530 A AR P090104530A AR 074399 A1 AR074399 A1 AR 074399A1
Authority
AR
Argentina
Prior art keywords
seq
loop
acid sequence
amino acid
amino acids
Prior art date
Application number
ARP090104530A
Other languages
English (en)
Inventor
Stuart Emanuel
Linda Engle
Marco M Gottardis
Ray Camphausen
Joan Carboni
Martin Wright
Ginger Chao Rakestraw
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 AR074399A1 publication Critical patent/AR074399A1/es

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)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Toxicology (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Endocrinology (AREA)
  • Microbiology (AREA)
  • Mycology (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)

Abstract

Moléculas biespecíficas que comprenden un dominio de unión a EGFR y un dominio a IGFIR distinto para el uso en aplicaciones de diagnóstico, investigación y terapéuticas. Células que comprenden tales proteínas, a polinucleótidos que codifican tales proteínas o fragmentos de las mismas y a vectores que comprenden los polinucleótidos que codifican las proteínas innovadoras. Ejemplos de moléculas biespecíficas incluyen dímeros de proteína similar a anticuerpo basados en el décimo dominio de fibronectina de tipo III. Reivindicación 1: Un dímero de proteína similar a anticuerpo, caracterizado porque comprende a) un décimo dominio de fibronectina de tipo III (10Fn3) que se une a IGF-IR con una KD menor de 500 nM unido covalentemente o no covalentemente con b) un 10Fn3 que se une a EGFR con una KD menor de 500 nM; en el que el 10Fn3 de unión de IGF-IR comprende un bucle BC que tiene la secuencia de aminoácidos expuesta en los aminoácidos 21-30 de la SEC ID Ns 3, un bucle DE que tiene la secuencia de aminoácidos expuesta en los aminoácidos 51-56 de la SEC ID Ns 3 y un bucle FG que tiene la secuencia de aminoácidos expuesta en los aminoácidos 76-83 de la SEC ID Ns 3 y en el que el 10Fn3 de unión de EGFR comprende un bucle BC que tiene la secuencia de aminoácidos expuesta en los aminoácidos 21-30 de la SEC ID Ns 112, un bucle DE que tiene la secuencia de aminoácidos expuesta en los aminoácidos 51-56 de la SEC ID Ns 112 y un bucle FG que tiene la secuencia de aminoácidos expuesta en los aminoácidos 76-92 de la SEC ID Ns 112.
ARP090104530A 2008-11-24 2009-11-24 Moleculas biespecificas de union a egfr/igfir AR074399A1 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US20016408P 2008-11-24 2008-11-24
US20028208P 2008-11-26 2008-11-26
US21296609P 2009-04-17 2009-04-17
US17827909P 2009-05-14 2009-05-14
US22733009P 2009-07-21 2009-07-21

Publications (1)

Publication Number Publication Date
AR074399A1 true AR074399A1 (es) 2011-01-12

Family

ID=41667546

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP090104530A AR074399A1 (es) 2008-11-24 2009-11-24 Moleculas biespecificas de union a egfr/igfir

Country Status (21)

Country Link
US (5) US8343501B2 (es)
EP (2) EP3029064A1 (es)
JP (2) JP5823870B2 (es)
KR (1) KR20110098922A (es)
CN (1) CN102439036B (es)
AR (1) AR074399A1 (es)
AU (1) AU2009316271A1 (es)
BR (1) BRPI0922613A2 (es)
CA (1) CA2744405A1 (es)
CL (1) CL2011001214A1 (es)
CO (1) CO6382161A2 (es)
EA (1) EA022415B1 (es)
ES (1) ES2555381T3 (es)
IL (1) IL212715A0 (es)
MX (1) MX2011005257A (es)
NZ (2) NZ592782A (es)
PE (1) PE20110587A1 (es)
TN (1) TN2011000225A1 (es)
TW (1) TWI496582B (es)
WO (1) WO2010060095A1 (es)
ZA (1) ZA201103766B (es)

Families Citing this family (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2004296376B2 (en) 2003-12-05 2010-03-04 Bristol-Myers Squibb Company Inhibitors of type 2 vascular endothelial growth factor receptors
US8470332B2 (en) 2006-11-22 2013-06-25 Bristol-Myers Squibb Company Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including IGF-IR
EP2215246B1 (en) 2007-10-31 2015-01-07 MedImmune, LLC Protein scaffolds
MX2010008874A (es) 2008-02-14 2010-09-22 Bristol Myers Squibb Co Terapeuticos dirigidos a base de proteinas manipuladas que se unen al receptor de factor de crecimiento epidermico.
EP3173424A1 (en) 2008-05-02 2017-05-31 Novartis Ag Improved fibronectin-based binding molecules and uses thereof
AR071874A1 (es) 2008-05-22 2010-07-21 Bristol Myers Squibb Co Proteinas de dominio de armazon basadas en fibronectina multivalentes
AU2009308935B2 (en) 2008-10-31 2015-02-26 Janssen Biotech, Inc. 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
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
EP2536757B1 (en) 2010-02-18 2015-03-25 Bristol-Myers Squibb Company Fibronectin based scaffold domain proteins that bind il-23
BR112012026003B1 (pt) 2010-04-13 2022-03-15 Medimmune, Llc Estrutura multimérica recombinante específica trail r2, seu uso, bem como composição
PT2571531T (pt) 2010-04-30 2016-08-31 Janssen Biotech Inc Composições do domínio da fibronectina estabilizadas, métodos e utilizações
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
US20130171185A1 (en) * 2010-07-06 2013-07-04 Ethan Settembre Norovirus derived immunogenic compositions and methods
EP3222631A3 (en) * 2010-07-30 2017-11-22 Novartis AG Fibronectin cradle molecules and libraries thereof
US8580922B2 (en) 2011-03-04 2013-11-12 Shire Human Genetic Therapies, Inc. Peptide linkers for polypeptide compositions and methods for using same
WO2012122042A2 (en) * 2011-03-04 2012-09-13 Shire Human Genetic Therapies, Inc. Peptide linkers for polypeptide compositions and methods for using same
PL2697257T3 (pl) 2011-04-13 2017-04-28 Bristol-Myers Squibb Company Białka fuzyjne fc o nowatorskim układzie lub zawierające nowatorskie łączniki
WO2012158678A1 (en) 2011-05-17 2012-11-22 Bristol-Myers Squibb Company Methods for maintaining pegylation of polypeptides
EP2710382B1 (en) 2011-05-17 2017-10-18 Bristol-Myers Squibb Company Improved methods for the selection of binding proteins
KR102142385B1 (ko) 2011-09-27 2020-08-10 얀센 바이오테크 인코포레이티드 대체 결합 표면을 가진 피브로넥틴 유형 iii 반복체 기반의 단백질 스캐폴드
SG11201400567QA (en) 2011-10-11 2014-05-29 Medimmune Llc Cd40l-specific tn3-derived scaffolds and methods of use thereof
US9522951B2 (en) 2011-10-31 2016-12-20 Bristol-Myers Squibb Company Fibronectin binding domains with reduced immunogenicity
US9844582B2 (en) 2012-05-22 2017-12-19 Massachusetts Institute Of Technology Synergistic tumor treatment with extended-PK IL-2 and therapeutic agents
TW201843172A (zh) * 2012-06-25 2018-12-16 美商再生元醫藥公司 抗－ｅｇｆｒ抗體及其用途
DK3835310T3 (da) 2012-09-13 2024-06-03 Bristol Myers Squibb Co Fibronektinbaserede skeletdomæneproteiner, der binder til myostatin
US9695228B2 (en) 2012-11-21 2017-07-04 Janssen Biotech, Inc. EGFR and c-Met fibronectin type III domain binding molecules
WO2014120891A2 (en) 2013-02-01 2014-08-07 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
WO2015057545A2 (en) 2013-10-14 2015-04-23 Janssen Biotech, Inc. Cysteine engineered fibronectin type iii domain binding molecules
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
KR102472862B1 (ko) 2014-03-20 2022-12-05 브리스톨-마이어스 스큅 컴퍼니 혈청 알부민-결합 피브로넥틴 유형 iii 도메인
DK3180018T3 (da) 2014-08-12 2019-10-28 Massachusetts Inst Technology Synergistisk tumorbehandling med IL-2 og integrinbindende Fc-fusionsprotein
US20170224777A1 (en) 2014-08-12 2017-08-10 Massachusetts Institute Of Technology Synergistic tumor treatment with il-2, a therapeutic antibody, and a cancer vaccine
ES2822990T3 (es) 2014-11-25 2021-05-05 Bristol Myers Squibb Co Novedosos polipéptidos de unión a PD-L1 para obtención de imágenes
ES2941895T3 (es) 2014-11-25 2023-05-26 Bristol Myers Squibb Co Métodos y composiciones para radioetiquetado con 18F del dominio de fibronectina tipo (III)
JP6744313B2 (ja) * 2015-01-02 2020-08-26 ダイアックス コーポレーション 血漿カリクレインおよび第ｘｉｉ因子に対する二重特異性抗体
EP4011916A1 (en) 2015-07-21 2022-06-15 Takeda Pharmaceutical Company Limited A 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
JP7016323B2 (ja) 2016-06-01 2022-02-21 ブリストル－マイヤーズ スクイブ カンパニー Ｐｄ－ｌ１結合ポリペプチドを用いるｐｅｔ造影
EP3471750A4 (en) 2016-06-21 2020-02-26 Janssen Biotech, Inc. CYSTEINE-MODIFIED TYPE III FIBRONECTIN BINDING MOLECULES
WO2018111978A1 (en) 2016-12-14 2018-06-21 Janssen Biotech, Inc. Cd137 binding fibronectin type iii domains
CA3046963A1 (en) 2016-12-14 2018-06-21 Janssen Biotech, Inc. Cd8a-binding fibronectin type iii domains
US10597438B2 (en) 2016-12-14 2020-03-24 Janssen Biotech, Inc. PD-L1 binding fibronectin type III domains
EP3568150A4 (en) 2017-01-10 2020-12-02 Xcella Biosciences, Inc. POLYTHERAPY FOR TUMOR TREATMENT WITH INTEGRIN-BOUND FC FUSION PROTEIN AND IMMUNE MODULATOR
US10350266B2 (en) 2017-01-10 2019-07-16 Nodus Therapeutics, Inc. Method of treating cancer with a multiple integrin binding Fc fusion protein
US20220002384A1 (en) * 2017-06-16 2022-01-06 Protelica, Inc. Fibronectin binding domain chimeric antigen receptors and methods of use thereof
WO2019036605A2 (en) 2017-08-17 2019-02-21 Massachusetts Institute Of Technology MULTIPLE SPECIFICITY BINDING AGENTS 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
CN112771071A (zh) 2018-09-28 2021-05-07 麻省理工学院 胶原蛋白定位的免疫调节分子及其方法
WO2020146706A2 (en) * 2019-01-11 2020-07-16 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
US11781138B2 (en) 2019-10-14 2023-10-10 Aro Biotherapeutics Company FN3 domain-siRNA conjugates and uses thereof
WO2021076546A1 (en) 2019-10-14 2021-04-22 Aro Biotherapeutics Company Cd71 binding fibronectin type iii domains
AU2021248941A1 (en) 2020-03-31 2022-11-17 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
BR112023021325A2 (pt) 2021-04-14 2023-12-19 Aro Biotherapeutics Company Domínios de fibronectina tipo iii de ligação a cd71
WO2023196995A1 (en) 2022-04-07 2023-10-12 Repertoire Immune Medicines, Inc. T cell receptor multimers and uses thereof

Family Cites Families (149)

* 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
US5514581A (en) 1986-11-04 1996-05-07 Protein Polymer Technologies, Inc. Functional recombinantly prepared synthetic protein polymer
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
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
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
EP0435911B1 (en) 1988-09-23 1996-03-13 Cetus Oncology Corporation Cell culture medium for enhanced cell growth, culture longevity and product expression
ES2247656T3 (es) 1989-04-19 2006-03-01 Enzon, Inc. Un proceso para formar un polipeptido modificado que comprende un polipeptido y un oxido de polialquileno.
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
AU8498091A (en) 1990-08-02 1992-03-02 Regents Of The University Of Colorado, The 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
WO1993003172A1 (en) 1991-08-01 1993-02-18 University Research Corporation Systematic polypeptide evolution by reverse translation
DE69332377T2 (de) 1992-07-13 2003-07-03 Bionebraska, Inc. Verfahren zur modifizierung rekombinanter polypeptide
DE69329503T2 (de) 1992-11-13 2001-05-03 Idec Pharma Corp Therapeutische Verwendung von chimerischen und markierten Antikörpern, die gegen ein Differenzierung-Antigen gerichtet sind, dessen Expression auf menschliche B Lymphozyt beschränkt ist, für die Behandlung von B-Zell-Lymphoma
WO1994017097A1 (en) 1993-01-19 1994-08-04 Regents Of The University Of Minnesota Synthetic fibronectin fragments as inhibitors of retroviral infections
ATE195065T1 (de) 1993-02-26 2000-08-15 Santen Pharmaceutical Co Ltd Biologisch abbaubarer sklerastopfen
US5643575A (en) 1993-10-27 1997-07-01 Enzon, Inc. Non-antigenic branched polymer conjugates
WO1995011922A1 (en) 1993-10-29 1995-05-04 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 (fr) 1996-10-17 1998-04-23 Mitsubishi Chemical Corporation Molecule permettant d'homologuer un genotype et un phenotype, et utilisation de celle-ci
US6348333B1 (en) 1997-01-17 2002-02-19 Toa Gosei Co., Ltd. VEGF-binding KDR polypeptide
DE69835143T2 (de) 1997-01-21 2007-06-06 The General Hospital Corp., Boston Selektion von proteinen mittels rns-protein fusionen
US6261804B1 (en) 1997-01-21 2001-07-17 The General Hospital Corporation Selection of proteins using RNA-protein fusions
EP0979102A4 (en) * 1997-04-30 2005-11-23 Enzon Inc DETAILED POLYPEPTIDE MODIFIED BY POLYALKYLENE OXIDE
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
ATE340870T1 (de) 1998-04-03 2006-10-15 Compound Therapeutics Inc Adressierbare 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
EP1051432B1 (en) 1998-12-08 2007-01-24 Biovation Limited Method for reducing immunogenicity of proteins
US7115396B2 (en) * 1998-12-10 2006-10-03 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
WO2000034784A1 (en) 1998-12-10 2000-06-15 Phylos, 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
CA2372053C (en) 1999-04-28 2008-09-02 Board Of Regents, The University Of Texas System Compositions and methods for cancer treatment by selectively inhibiting vegf
DK1870417T3 (da) 1999-07-27 2012-07-16 Bristol Myers Squibb Co Peptidacceptor-ligeringsmetoder
US6399857B1 (en) 1999-09-22 2002-06-04 Paradigm Genetics, Inc. Modified nucleotide sequence encoding a LexA DNA binding domain optimized for arabidopsis species
US20050019826A1 (en) 2000-03-31 2005-01-27 Roselyne Tournaire Peptides blocking vascular endothelial growth factor(vegf)-mediated angiogenesis, polynucleotides encoding said pepetides and methods of use thereof
EP1364009A2 (en) 2000-06-15 2003-11-26 Board of Regents, The University of Texas System Regulatable, catalytically active nucleic acids
AU2001277867B2 (en) 2000-07-11 2006-12-07 Research Corporation Technologies, Inc. Artificial antibody polypeptides
EP2295450B1 (en) 2000-09-29 2015-01-28 Merck Sharp & Dohme Corp. Pegylated interleukin-10
AU2002213251B2 (en) 2000-10-16 2007-06-14 Bristol-Myers Squibb Company 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
US6699493B2 (en) 2000-11-29 2004-03-02 Oculex Pharmaceuticals, Inc. Method 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
ATE472609T1 (de) 2001-04-26 2010-07-15 Amgen Mountain View Inc Kombinatorische bibliotheken von monomerdomänen
US20030004561A1 (en) 2001-06-28 2003-01-02 Steve Bigus Peeling sheath for self-expanding stent
WO2003022858A2 (de) 2001-09-11 2003-03-20 Nascacell Gmbh Verfahren zum screenen von inhibitoren für die protein-protein-wechselwirkung sowie ribozyme hierzu
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
JP2005526506A (ja) 2002-03-04 2005-09-08 イムクローン システムズ インコーポレイティド Ｋｄｒに特異的なヒト抗体及びその利用
AU2003243436A1 (en) 2002-06-06 2003-12-22 Shohei Koide Reconstituted polypeptides
ES2466716T3 (es) 2002-11-08 2014-06-11 Ablynx N.V. Anticuerpos de un solo dominio estabilizados
US7053701B2 (en) 2003-11-04 2006-05-30 Vice Michael W Power amplifier output stage with multiple power states and improved efficiency
CN102400990B (zh) 2003-11-17 2014-08-20 远程接合技术公司 固定器组件
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
AU2004296376B2 (en) 2003-12-05 2010-03-04 Bristol-Myers Squibb Company Inhibitors of type 2 vascular endothelial growth factor receptors
US20050244469A1 (en) 2004-04-30 2005-11-03 Allergan, Inc. Extended therapeutic effect ocular implant treatments
US20050244472A1 (en) 2004-04-30 2005-11-03 Allergan, Inc. Intraocular drug delivery systems containing excipients with reduced toxicity and related methods
US20060182783A1 (en) 2004-04-30 2006-08-17 Allergan, Inc. Sustained release intraocular drug delivery systems
US20070059336A1 (en) 2004-04-30 2007-03-15 Allergan, Inc. Anti-angiogenic sustained release intraocular implants and related methods
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
AU2005294382A1 (en) 2004-10-04 2006-04-20 Qlt Usa, Inc. Ocular delivery of polymeric delivery formulations
US20060122162A1 (en) 2004-12-02 2006-06-08 Schering Corporation Methods of using temozolomide formulation intrathecally in the treatment of cancers
CA2599606A1 (en) 2005-02-23 2006-08-31 Merrimack Pharmaceuticals, Inc. Bispecific binding agents for modulating biological activity
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
BRPI0616883A2 (pt) * 2005-10-07 2011-07-05 Univ California ácidos nucléicos que codificam enzima modificada de citocromo p450 e métodos de uso dos mesmos
CA2602577C (en) 2005-10-18 2015-03-31 Allergan, Inc. Ocular therapy using glucocorticoid derivatives selectively penetrating posterior segment tissues
US20070099879A1 (en) 2005-10-31 2007-05-03 Wisconsin Alumni Research Foundation (Warf) Method of using calcitriol for treating intraocular diseases associated with angiogenesis
DE502005009389D1 (de) 2005-11-09 2010-05-20 Morphosys Ag Identifizierung und charakterisierung von funktionsblockierenden anti-ed-b-fibronektin antikörpern
CN105001320A (zh) * 2005-11-23 2015-10-28 阿塞勒隆制药公司 Activin-ActRIIa拮抗剂及其促进骨骼生长的应用
EP1993584B1 (en) 2006-02-02 2012-05-30 Allergan, Inc. Inhibitors of CXCR4 activity for use in the treatment of ocular disorders
CA2638841A1 (en) * 2006-02-24 2007-08-30 Chiesi Farmaceutici S.P.A. Anti-amyloid immunogenic compositions, methods and uses
MX2008013489A (es) * 2006-04-21 2008-10-30 Transgene Sa Vacuna de virus de papiloma basado en hpv-18 (virus de papiloma humano 18).
US20070269422A1 (en) 2006-05-17 2007-11-22 Ablynx N.V. Serum albumin binding proteins with long half-lives
EP2511301B1 (en) 2006-08-04 2017-12-06 MedImmune Limited Human antibodies to erbb 2
WO2008031098A1 (en) 2006-09-09 2008-03-13 The University Of Chicago Binary amino acid libraries for fibronectin type iii polypeptide monobodies
US20110143953A1 (en) * 2006-10-16 2011-06-16 Arizona Board Of Regents, A Body Corporate Of The State Of Arizona Synthetic Antibodies
US8470332B2 (en) 2006-11-22 2013-06-25 Bristol-Myers Squibb Company Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including IGF-IR
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
US20100166747A1 (en) 2007-03-02 2010-07-01 Beltran Pedro J Methods and compositions for treating tumor diseases
US11078262B2 (en) 2007-04-30 2021-08-03 Allergan, Inc. High viscosity macromolecular compositions for treating ocular conditions
CA2687141C (en) 2007-05-22 2014-04-01 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
AU2008287426B2 (en) 2007-08-10 2014-06-26 Protelica, Inc. Universal fibronectin type III binding-domain libraries
EP2197476A2 (en) 2007-08-20 2010-06-23 Bristol-Myers Squibb Company Use of vegfr-2 inhibitors for treating metastatic cancer
EP3241846B1 (en) 2007-10-04 2022-02-23 ZymoGenetics, Inc. B7 family member zb7h6 and related compositions and methods
EP2215246B1 (en) 2007-10-31 2015-01-07 MedImmune, LLC Protein scaffolds
EP2217274A1 (en) 2007-11-28 2010-08-18 Bristol-Myers Squibb Company Combination vegfr2 therapy with mtor inhibitors
JP2011507529A (ja) 2007-12-19 2011-03-10 セントコア・オーソ・バイオテツク・インコーポレーテツド Ｍ１３ファージのｐＩＸへの融合を介する代替の足場タンパク質融合ファージ提示
CA2710835A1 (en) 2007-12-27 2009-07-09 Novartis Ag Improved fibronectin-based binding molecules and their use
MX2010008874A (es) 2008-02-14 2010-09-22 Bristol Myers Squibb Co Terapeuticos dirigidos a base de proteinas manipuladas que se unen al receptor de factor de crecimiento epidermico.
EP3173424A1 (en) 2008-05-02 2017-05-31 Novartis Ag Improved fibronectin-based binding molecules and uses thereof
AR071874A1 (es) 2008-05-22 2010-07-21 Bristol Myers Squibb Co Proteinas de dominio de armazon basadas en fibronectina multivalentes
AU2009308935B2 (en) 2008-10-31 2015-02-26 Janssen Biotech, Inc. Fibronectin type III domain based scaffold compositions, methods and uses
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
EP2379718B2 (en) 2008-12-16 2020-12-30 Novartis AG Yeast display systems
US20100210511A1 (en) * 2009-02-11 2010-08-19 Bristol-Myers Squibb Company Combination VEGFR2 Therapy with Temozolomide
JP5873335B2 (ja) 2009-02-12 2016-03-01 ヤンセン バイオテツク，インコーポレーテツド フィブロネクチンｉｉｉ型ドメインに基づくスカフォールド組成物、方法及び使用
US8067201B2 (en) * 2009-04-17 2011-11-29 Bristol-Myers Squibb Company Methods for protein refolding
WO2011020033A2 (en) 2009-08-13 2011-02-17 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
WO2011100700A2 (en) 2010-02-12 2011-08-18 University Of Rochester Antigenic mimics of discontinuous epitopes of pathogen recognized by broadly neutralizing antibodies
EP2536757B1 (en) 2010-02-18 2015-03-25 Bristol-Myers Squibb Company Fibronectin based scaffold domain proteins that bind il-23
BR112012026003B1 (pt) 2010-04-13 2022-03-15 Medimmune, Llc Estrutura multimérica recombinante específica trail r2, seu uso, bem como composição
DK2558491T3 (en) 2010-04-13 2018-10-15 Bristol Myers Squibb Co Fibronectin-based Scaffold domain proteins that bind PCSK9
PT2571531T (pt) 2010-04-30 2016-08-31 Janssen Biotech Inc Composições do domínio da fibronectina estabilizadas, métodos e utilizações
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
EP3222631A3 (en) 2010-07-30 2017-11-22 Novartis AG Fibronectin cradle molecules and libraries thereof
WO2012088006A1 (en) 2010-12-22 2012-06-28 Bristol-Myers Squibb Company Fibronectin based scaffold domain proteins that bind il-23
PL2697257T3 (pl) 2011-04-13 2017-04-28 Bristol-Myers Squibb Company Białka fuzyjne fc o nowatorskim układzie lub zawierające nowatorskie łączniki
EP2710382B1 (en) 2011-05-17 2017-10-18 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
KR102142385B1 (ko) 2011-09-27 2020-08-10 얀센 바이오테크 인코포레이티드 대체 결합 표면을 가진 피브로넥틴 유형 iii 반복체 기반의 단백질 스캐폴드

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