ES2555381T3 - Moléculas biespecíficas de unión a EGFR/IGFIR - Google Patents
Moléculas biespecíficas de unión a EGFR/IGFIR Download PDFInfo
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- ES2555381T3 ES2555381T3 ES09760433.4T ES09760433T ES2555381T3 ES 2555381 T3 ES2555381 T3 ES 2555381T3 ES 09760433 T ES09760433 T ES 09760433T ES 2555381 T3 ES2555381 T3 ES 2555381T3
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- 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
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Families Citing this family (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0417302A (pt) | 2003-12-05 | 2007-03-06 | Compound Therapeutics Inc | inibidores de receptores de fator de crescimento endotelial vascular do tipo 2 |
| 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 |
| AU2008319298B2 (en) | 2007-10-31 | 2014-07-31 | Medimmune, Llc | Protein scaffolds |
| AU2009213141A1 (en) | 2008-02-14 | 2009-08-20 | Bristol-Myers Squibb Company | Targeted therapeutics based on engineered proteins that bind EGFR |
| AU2009242038B2 (en) | 2008-05-02 | 2013-05-30 | 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 |
| PT2356269T (pt) | 2008-10-31 | 2016-09-13 | Janssen Biotech Inc | Composições, métodos e usos de scaffolds baseados em domínios de fibronectina tipo iii |
| 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 |
| WO2011051333A1 (en) | 2009-10-30 | 2011-05-05 | Novartis Ag | Universal fibronectin type iii bottom-side binding domain libraries |
| BR112012019881A2 (pt) | 2010-02-18 | 2017-06-27 | Bristol Myers Squibb Co | proteínas de domínio estrutural baseadas na fibronectina que ligam-se à il-23 |
| BR112012026003B1 (pt) | 2010-04-13 | 2022-03-15 | Medimmune, Llc | Estrutura multimérica recombinante específica trail r2, seu uso, bem como composição |
| ES2730693T3 (es) | 2010-04-30 | 2019-11-12 | Janssen Biotech Inc | Composiciones del dominio de fibronectina estabilizados, métodos y usos |
| TW201138808A (en) | 2010-05-03 | 2011-11-16 | Bristol Myers Squibb Co | Serum albumin binding molecules |
| JP6023703B2 (ja) * | 2010-05-26 | 2016-11-09 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 改善された安定性を有するフィブロネクチンをベースとする足場タンパク質 |
| EP2591097A1 (en) * | 2010-07-06 | 2013-05-15 | Novartis AG | Norovirus derived immunogenic compositions and methods |
| EP3222631A3 (en) | 2010-07-30 | 2017-11-22 | Novartis AG | Fibronectin cradle molecules and libraries thereof |
| WO2012122042A2 (en) * | 2011-03-04 | 2012-09-13 | Shire Human Genetic Therapies, Inc. | Peptide linkers for polypeptide compositions and methods for using same |
| US8580922B2 (en) | 2011-03-04 | 2013-11-12 | Shire Human Genetic Therapies, Inc. | Peptide linkers for polypeptide compositions and methods for using same |
| SI2697257T1 (sl) | 2011-04-13 | 2017-02-28 | Bristol-Myers Squibb Company | FC fuzijski proteini, ki vsebujejo nove linkerje ali razmestitve |
| WO2012158678A1 (en) | 2011-05-17 | 2012-11-22 | Bristol-Myers Squibb Company | Methods for maintaining pegylation of polypeptides |
| ES2848531T3 (es) | 2011-05-17 | 2021-08-10 | Bristol Myers Squibb Co | Métodos mejorados para la selección de proteínas de unión |
| EP3540100B8 (en) | 2011-09-27 | 2022-11-02 | Janssen Biotech, Inc. | Fibronectin type iii repeat based protein scaffolds with alternative binding surfaces |
| SG10201707813YA (en) | 2011-10-11 | 2017-11-29 | Medimmune Llc | Cd40l-specific tn3-derived scaffolds and methods of use thereof |
| EP2773659A2 (en) | 2011-10-31 | 2014-09-10 | Bristol-Myers Squibb Company | Fibronectin binding domains with reduced immunogenicity |
| 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 |
| RS65556B1 (sr) | 2012-09-13 | 2024-06-28 | Bristol Myers Squibb Co | Proteini domena skele na bazi fibronektina koji vezuju miostatin |
| 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 |
| ES2814558T3 (es) | 2013-02-06 | 2021-03-29 | Bristol Myers Squibb Co | Proteínas de dominio de fibronectina tipo III con solubilidad mejorada |
| ES2751735T3 (es) | 2013-02-12 | 2020-04-01 | Bristol Myers Squibb Co | Métodos de replegado de proteínas a elevado pH |
| US10196446B2 (en) | 2013-10-14 | 2019-02-05 | Janssen Biotech, Inc. | Cysteine engineered fibronectin type III domain binding molecules |
| CN105916883B (zh) * | 2014-01-28 | 2019-12-03 | 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 |
| EP3129401B1 (en) | 2014-03-20 | 2019-06-12 | Bristol-Myers Squibb Company | Serum albumin-binding fibronectin type iii domains |
| WO2016025645A1 (en) | 2014-08-12 | 2016-02-18 | Massachusetts Institute Of Technology | Synergistic tumor treatment with il-2, a therapeutic antibody, and an immune checkpoint blocker |
| CA2957717C (en) | 2014-08-12 | 2021-10-19 | Massachusetts Institute Of Technology | Synergistic tumor treatment with il-2 and integrin-binding-fc-fusion protein |
| EP4218832A3 (en) | 2014-11-25 | 2023-08-23 | Bristol-Myers Squibb Company | Methods and compositions for 18f-radiolabeling of the fibronectin type (iii) domain |
| ES2822990T3 (es) | 2014-11-25 | 2021-05-05 | Bristol Myers Squibb Co | Novedosos polipéptidos de unión a PD-L1 para obtención de imágenes |
| CA2972800A1 (en) | 2015-01-02 | 2016-07-07 | Dyax Corp. | Bispecific antibodies against plasma kallikrein and factor xii |
| EP3325516B1 (en) | 2015-07-21 | 2021-12-15 | Takeda Pharmaceutical Company Limited | A monoclonal antibody inhibitor of factor xiia |
| CN108290941A (zh) | 2015-09-23 | 2018-07-17 | 百时美施贵宝公司 | 快解离速率的血清白蛋白结合性纤连蛋白iii型结构域 |
| US10994033B2 (en) | 2016-06-01 | 2021-05-04 | Bristol-Myers Squibb Company | Imaging methods using 18F-radiolabeled biologics |
| EP3463486A1 (en) | 2016-06-01 | 2019-04-10 | Bristol-Myers Squibb Company | Pet imaging with pd-l1 binding polypeptides |
| MX2018016185A (es) | 2016-06-21 | 2019-03-28 | Janssen Biotech Inc | Moléculas de unión al dominio de fibronectina tipo iii diseñadas de cisteína. |
| WO2018111976A1 (en) | 2016-12-14 | 2018-06-21 | Janssen Biotech, Inc. | Pd-l1 binding fibronectin type iii domains |
| AU2017378226A1 (en) | 2016-12-14 | 2019-06-20 | 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 |
| EP3568150A4 (en) | 2017-01-10 | 2020-12-02 | Xcella Biosciences, Inc. | POLYTHERAPY FOR TUMOR TREATMENT WITH INTEGRIN-BOUND FC FUSION PROTEIN AND IMMUNE MODULATOR |
| CN111065407A (zh) | 2017-06-16 | 2020-04-24 | 普罗特利卡公司 | 纤连蛋白结合结构域嵌合抗原受体及其使用方法 |
| 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 |
| SG11202100935TA (en) | 2018-09-28 | 2021-02-25 | Massachusetts Inst Technology | Collagen-localized immunomodulatory molecules and methods thereof |
| 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 |
| US12491255B2 (en) | 2019-10-14 | 2025-12-09 | Aro Biotherapeutics Company | EPCAM binding fibronectin type III domains |
| WO2021076574A2 (en) | 2019-10-14 | 2021-04-22 | 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 |
| WO2021202727A2 (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 |
| BR112023021318A2 (pt) | 2021-04-14 | 2023-12-19 | Aro Biotherapeutics Company | Conjugados de domínio fn3-sirna e usos dos mesmos |
| CA3214552A1 (en) | 2021-04-14 | 2022-10-20 | Russell C. Addis | Cd71 binding fibronectin type iii domains |
| CA3245061A1 (en) | 2022-04-07 | 2023-10-12 | Repertoire Immune Medicines, Inc. | T-CELL RECEIVER MULTIMERS AND THEIR USES |
Family Cites Families (149)
| 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 |
| 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 |
| 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 |
| 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 |
| HUT64022A (en) | 1989-04-19 | 1993-11-29 | Enzon Inc | Process for producing active polyalkileneoxide carbonates for the 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 |
| 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 |
| JPH07509128A (ja) | 1992-07-13 | 1995-10-12 | バイオネブラスカ・インコーポレーテッド | 組換型ポリペプチドの修飾方法 |
| EP1005870B1 (en) | 1992-11-13 | 2009-01-21 | Biogen Idec Inc. | Therapeutic application of chimeric 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 |
| KR100313268B1 (ko) | 1993-02-26 | 2002-11-22 | 산텐 세이야꾸 가부시키가이샤 | 생체분해성공막플러그 |
| 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 |
| EP0962527B1 (en) | 1996-10-17 | 2004-08-04 | Mitsubishi Chemical Corporation | Molecule that homologizes genotype and phenotype and utilization thereof |
| JP3837748B2 (ja) | 1997-01-17 | 2006-10-25 | 東亞合成株式会社 | Ｖｅｇｆ結合性ポリペプチド |
| CA2278786C (en) | 1997-01-21 | 2010-07-20 | The General Hospital Corporation | Selection of proteins using rna-protein fusions |
| US6261804B1 (en) | 1997-01-21 | 2001-07-17 | The General Hospital Corporation | Selection of proteins using RNA-protein fusions |
| JP2002505574A (ja) | 1997-04-30 | 2002-02-19 | エンゾン，インコーポレイテッド | ポリアルキレンオキシド修飾された単鎖ポリペプチド |
| EP1958962A3 (en) | 1997-06-12 | 2013-05-01 | Novartis International Pharmaceutical Ltd. | 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 |
| ES2278463T3 (es) | 1998-12-08 | 2007-08-01 | Biovation Limited | Metodo para reducir la inmunogenicidad de proteinas. |
| 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 |
| ATE439592T1 (de) | 1998-12-10 | 2009-08-15 | Bristol Myers Squibb Co | Proteingerüste für antikörper-nachahmer und andere bindende proteine |
| GB9827228D0 (en) | 1998-12-10 | 1999-02-03 | Univ Nottingham | Cancer detection method and reagents |
| 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 |
| EP1196637B1 (en) | 1999-07-27 | 2007-04-25 | Adnexus Therapeutics, Inc. | Peptide acceptor ligation methods |
| US6399857B1 (en) | 1999-09-22 | 2002-06-04 | Paradigm Genetics, Inc. | Modified nucleotide sequence encoding a LexA DNA binding domain optimized for arabidopsis species |
| EP1268544A2 (en) | 2000-03-31 | 2003-01-02 | Institut Pasteur | Peptides blocking vascular endothelial growth factor (vegf)-mediated angiogenesis, polynucleotides encoding said peptides and methods of use thereof |
| AU2001268481A1 (en) | 2000-06-15 | 2001-12-24 | Board Of Regents, The University Of Texas System | Regulatable, catalytically active nucleic acids |
| CA2416219C (en) | 2000-07-11 | 2016-10-11 | Research Corporation Technologies, Inc. | Artificial antibody polypeptides |
| ES2367891T3 (es) | 2000-09-29 | 2011-11-10 | Schering Corporation | Interleucina-10 pegilada. |
| 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 |
| 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 |
| NZ534378A (en) | 2002-02-22 | 2006-10-27 | Schering Corp | Pharmaceutical formulations of antineoplastic agents, in particular temozolomide, processes of making and using the same |
| DK1487856T3 (da) | 2002-03-04 | 2010-10-18 | Imclone Llc | KDR-specifikke humane antistoffer og deres anvendelse |
| WO2003104418A2 (en) | 2002-06-06 | 2003-12-18 | Research Corporation Technologies, Inc. | Reconstituted polypeptides |
| ES2551682T3 (es) | 2002-11-08 | 2015-11-23 | Ablynx N.V. | Anticuerpos de dominio simple dirigidos contra factor de necrosis tumoral-alfa y usos para los mismos |
| US7053701B2 (en) | 2003-11-04 | 2006-05-30 | Vice Michael W | Power amplifier output stage with multiple power states and improved efficiency |
| EP2302230B1 (en) | 2003-11-17 | 2017-01-11 | Telezygology Inc. | Shape memory fastener assembly |
| BRPI0417302A (pt) | 2003-12-05 | 2007-03-06 | Compound Therapeutics Inc | inibidores de receptores de fator de crescimento endotelial vascular do tipo 2 |
| 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 |
| 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 |
| US20070059336A1 (en) | 2004-04-30 | 2007-03-15 | Allergan, Inc. | Anti-angiogenic sustained release intraocular implants and related methods |
| EP1786918A4 (en) | 2004-07-17 | 2009-02-11 | Imclone Systems Inc | NEW BISPECIFIC ANTIBODY TETRAVALENT |
| US7597884B2 (en) * | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
| JP2008520547A (ja) | 2004-10-04 | 2008-06-19 | キューエルティー ユーエスエー，インコーポレイテッド． | 眼部送達のためのポリマー送達処方 |
| WO2006060464A1 (en) | 2004-12-02 | 2006-06-08 | Schering Corporation | Methods of using temozolomide formulation intrathecally in the treatment of cancers |
| RU2007135216A (ru) | 2005-02-23 | 2009-03-27 | Мерримак Фармасьютикалз, Инк. (Us) | Биспецифические связывающие агенты для модулирования биологической активности |
| 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 |
| EP1931770A4 (en) * | 2005-10-07 | 2009-11-25 | Univ California | NUCLEIC ACIDS CODING FOR MODIFIED CYTOCHROM P450 ENZYME AND METHOD OF USE THEREOF |
| EP1937210B1 (en) | 2005-10-18 | 2017-05-31 | 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 |
| EA201692543A1 (ru) * | 2005-11-23 | 2017-08-31 | Акселерон Фарма Инк. | Антагонисты активина-actriia и их применение для стимулирования роста кости |
| 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 |
| JP2009534331A (ja) * | 2006-04-21 | 2009-09-24 | トランジェーヌ、ソシエテ、アノニム | Ｈｐｖ‐１８を主体とするパピローマウイルスワクチン |
| US20070269422A1 (en) | 2006-05-17 | 2007-11-22 | Ablynx N.V. | Serum albumin binding proteins with long half-lives |
| ES2613957T3 (es) | 2006-08-04 | 2017-05-29 | Medimmune Limited | Anticuerpos contra ERBB2 |
| 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 |
| 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 |
| US8476243B2 (en) * | 2006-12-29 | 2013-07-02 | Transderm, Inc. | Methods and compositions for treating keratin hyperproliferative disorders |
| WO2008097497A2 (en) | 2007-02-02 | 2008-08-14 | Adnexus, A Bristol-Myers Squibb R & D Company | Vegf pathway blockade |
| ES2707551T3 (es) | 2007-03-02 | 2019-04-04 | Amgen Inc | Métodos y composiciones para tratar enfermedades tumorales |
| US11078262B2 (en) | 2007-04-30 | 2021-08-03 | Allergan, Inc. | High viscosity macromolecular compositions for treating ocular conditions |
| JP5591691B2 (ja) | 2007-05-22 | 2014-09-17 | アムジエン・インコーポレーテツド | 生物活性を有する融合タンパク質を作製するための組成物及び方法 |
| 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 |
| US8680019B2 (en) | 2007-08-10 | 2014-03-25 | Protelica, Inc. | Universal fibronectin Type III binding-domain libraries |
| US8470966B2 (en) | 2007-08-10 | 2013-06-25 | Protelica, Inc. | Universal fibronectin type III binding-domain libraries |
| WO2009025806A2 (en) | 2007-08-20 | 2009-02-26 | Adnexus, A Bristol-Myers Squibb R & D Company | Use of vegfr-2 inhibitors for treating metastatic cancer |
| ES2629440T5 (es) | 2007-10-04 | 2020-11-20 | Zymogenetics Inc | zB7H6 miembro de la familia B7 y composiciones y métodos relacionados |
| AU2008319298B2 (en) | 2007-10-31 | 2014-07-31 | Medimmune, Llc | Protein scaffolds |
| EP2217274A1 (en) | 2007-11-28 | 2010-08-18 | Bristol-Myers Squibb Company | Combination vegfr2 therapy with mtor inhibitors |
| WO2009086116A2 (en) | 2007-12-19 | 2009-07-09 | Centocor, Inc. | Alternative scaffold protein fusions phage display via fusion to plx of m13 phage |
| WO2009083804A2 (en) | 2007-12-27 | 2009-07-09 | Novartis Ag | Improved fibronectin-based binding molecules and their use |
| AU2009213141A1 (en) | 2008-02-14 | 2009-08-20 | Bristol-Myers Squibb Company | Targeted therapeutics based on engineered proteins that bind EGFR |
| AU2009242038B2 (en) | 2008-05-02 | 2013-05-30 | 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 |
| PT2356269T (pt) | 2008-10-31 | 2016-09-13 | Janssen Biotech Inc | Composições, métodos e usos de scaffolds baseados em domínios de fibronectina tipo iii |
| 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 |
| CA2746840A1 (en) | 2008-12-16 | 2010-06-24 | Novartis Ag | Yeast display systems |
| WO2010093771A1 (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 |
| WO2011051333A1 (en) | 2009-10-30 | 2011-05-05 | 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 |
| EP2533807A2 (en) | 2010-02-12 | 2012-12-19 | University Of Rochester | Antigenic mimics of discontinuous epitopes of pathogen recognized by broadly neutralizing antibodies |
| BR112012019881A2 (pt) | 2010-02-18 | 2017-06-27 | Bristol Myers Squibb Co | proteínas de domínio estrutural baseadas na fibronectina que ligam-se à il-23 |
| EA022983B1 (ru) | 2010-04-13 | 2016-04-29 | Бристол-Майерс Сквибб Компани | Белки на основе структурного домена фибронектина, связывающие pcsk9 |
| BR112012026003B1 (pt) | 2010-04-13 | 2022-03-15 | Medimmune, Llc | Estrutura multimérica recombinante específica trail r2, seu uso, bem como composição |
| ES2730693T3 (es) | 2010-04-30 | 2019-11-12 | Janssen Biotech Inc | Composiciones del dominio de fibronectina estabilizados, métodos y usos |
| TW201138808A (en) | 2010-05-03 | 2011-11-16 | Bristol Myers Squibb Co | Serum albumin binding molecules |
| JP6023703B2 (ja) * | 2010-05-26 | 2016-11-09 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 改善された安定性を有するフィブロネクチンをベースとする足場タンパク質 |
| EP3222631A3 (en) | 2010-07-30 | 2017-11-22 | Novartis AG | Fibronectin cradle molecules and libraries thereof |
| US9260496B2 (en) | 2010-12-22 | 2016-02-16 | Bristol-Myers Squibb Company | Fibronectin based scaffold domain proteins that bind IL-23 |
| SI2697257T1 (sl) | 2011-04-13 | 2017-02-28 | Bristol-Myers Squibb Company | FC fuzijski proteini, ki vsebujejo nove linkerje ali razmestitve |
| WO2012158678A1 (en) | 2011-05-17 | 2012-11-22 | Bristol-Myers Squibb Company | Methods for maintaining pegylation of polypeptides |
| ES2848531T3 (es) | 2011-05-17 | 2021-08-10 | Bristol Myers Squibb Co | Métodos mejorados para la selección de proteínas de unión |
| EP3540100B8 (en) | 2011-09-27 | 2022-11-02 | Janssen Biotech, Inc. | Fibronectin type iii repeat based protein scaffolds with alternative binding surfaces |
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