DK1729795T3 - Albumin-fusionsproteiner - Google Patents
Albumin-fusionsproteiner Download PDFInfo
- Publication number
- DK1729795T3 DK1729795T3 DK05722848.8T DK05722848T DK1729795T3 DK 1729795 T3 DK1729795 T3 DK 1729795T3 DK 05722848 T DK05722848 T DK 05722848T DK 1729795 T3 DK1729795 T3 DK 1729795T3
- Authority
- DK
- Denmark
- Prior art keywords
- albumin fusion
- protein
- albumin
- fusion protein
- antibody
- Prior art date
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
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- 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
- C07K14/76—Albumins
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
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Claims (20)
1
1. Albumin-fusionsprotein omfattende to eller flere tandem-orienterede glucagon-lignende peptid 1 (GLP-l)-polypeptider, hvor albuminfusionsproteinet omfatter en aminosyresekvens udvalgt blandt: (a) aminosyresekvensen ifølge SEQ ID NO: 387; (b) en variant af (a), som er mindst 90 % identisk med aminosyresekvensen ifølge SEQ ID NO: 387, hvor varianten har GLP-1-aktivitet; eller (c) et fragment af (a) eller (b), hvor fragmentet har GLP-1-aktivitet; fusioneret på: (i) et albumin omfattende aminosyresekvensen ifølge SEQ ID NO:1; eller (ii) en albumin-variant, af hvilken aminosyresekvensen er mindst 90 % identisk med aminosyresekvensen ifølge SEQ ID NO:1; hvor albumin-fusionsproteinet omfatter den modificerede HSA/kex2-ledersekvens ifølge SEQ ID NO: 112.
2. Albumin-fusionsprotein ifølge krav 1, produceret ud fra en værtscelle omfattende et konstrukt, der eksprimerer albumin-fusionsproteinet, hvor kon-struktet er Construct ID 3610.
3. Albumin-fusionsprotein ifølge krav 1, omfattende aminosyresekvensen ifølge SEQ ID NO:387.
4. Albumin-fusionsprotein ifølge krav 1 omfattende aminosyresekvensen ifølge SEQ ID NO:319.
5. Albumin-fusionsprotein ifølge et hvilket som helst af kravene 1 til 4, hvor de mindst to tandem-orienterede GLP-1-polypeptider er fusionerede ved N-terminus eller ved C-terminus på albuminet, albumin-fragmentet eller albumin-varianten deraf.
6. Albumin-fusionsprotein ifølge et hvilket som helst af kravene 1 til 5, hvor albuminet er humant albumin. 2
7. Albumin-fusionsprotein ifølge et hvilket som helst af kravene 1 til 6, omfattende SEQ ID NO: 1.
8. Albumin-fusionsprotein ifølge et hvilket som helst af kravene 1 til 7, hvor de to eller flere tandem-orienterede GLP-1-polypeptider er genetisk fusionerede på albuminet, albumin-fragmentet eller albumin-varianten deraf.
9. Polynukleotid, der koder for albumin-fusionsproteinet ifølge et hvilket som helst af kravene 1 til 8.
10. Vektor, der omfatter en promoter, der er funktionsmæssigt forbundet med polynukleotidet ifølge krav 9.
11. Vektor ifølge krav 10, hvor promoteren er udvalgt blandt: (a) en Met25-promoter; (b) en cbh1-promoter; og (c) en cysD-promoter fra Aspergillus nidulans.
12. Isoleret værtscelle omfattende en vektor ifølge krav 10 eller 11.
13. Isoleret værtscelle ifølge krav 12, som er en gærcelle eller en pattedyrscelle.
14. Isoleret værtscelle ifølge krav 13, hvor værtscellen er en gærcelle udvalgt blandt S. cerevisiae, en K. lactis eller en P. Pastoris.
15. Isoleret værtscelle ifølge krav 13 eller 14, hvor gærcellen er glykosyle-ringsdeficient.
16. Isoleret værtscelle ifølge et hvilket som helst af kravene 13 til 15, hvor gæren er glykosylerings- og proteasedeficient.
17. Isoleret værtscelle ifølge krav 13, hvor pattedyrscellen er en CHO-celle, en COS-celle eller en NSO-celle. 3
18. Sammensætning omfattende albumin-fusionsproteinet ifølge et hvilket som helst af kravene 1 til 8 og en farmaceutisk acceptabel bærer.
19. Fremgangsmåde til fremstilling af et albumin-fusionsprotein, omfattende: (a) at transformere en værtscelle omfattende mindst en vektor ifølge krav 10 eller 11; (b) at dyrke værtscellen under betingelser, der er egnede til ekspression af albumin-fusionsproteinet; og (c) at isolere albumin-fusionsproteinet.
20. Fremgangsmåde ifølge krav 19, hvor det isolerede albuminfusionsprotein gennemgår yderligere behandling til fjernelse af ledersekvensen.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54227404P | 2004-02-09 | 2004-02-09 | |
| US54990104P | 2004-03-05 | 2004-03-05 | |
| US55690604P | 2004-03-29 | 2004-03-29 | |
| US63660304P | 2004-12-17 | 2004-12-17 | |
| PCT/US2005/004041 WO2005077042A2 (en) | 2004-02-09 | 2005-02-09 | Albumin fusion proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK1729795T3 true DK1729795T3 (da) | 2016-04-11 |
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ID=34865403
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK05722848.8T DK1729795T3 (da) | 2004-02-09 | 2005-02-09 | Albumin-fusionsproteiner |
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| PL (1) | PL1729795T3 (da) |
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Families Citing this family (181)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9526733D0 (en) | 1995-12-30 | 1996-02-28 | Delta Biotechnology Ltd | Fusion proteins |
| ES2484966T3 (es) | 2000-04-12 | 2014-08-12 | Novozymes Biopharma Dk A/S | Proteínas de fusión de albúmina |
| US20050100991A1 (en) * | 2001-04-12 | 2005-05-12 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| WO2003060071A2 (en) | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| EP1463752A4 (en) | 2001-12-21 | 2005-07-13 | Human Genome Sciences Inc | ALBUMIN FUSION PROTEINS |
| US20080194481A1 (en) | 2001-12-21 | 2008-08-14 | Human Genome Sciences, Inc. | Albumin Fusion Proteins |
| US20060002935A1 (en) | 2002-06-28 | 2006-01-05 | Domantis Limited | Tumor Necrosis Factor Receptor 1 antagonists and methods of use therefor |
| WO2004096113A2 (en) * | 2003-04-28 | 2004-11-11 | Medical Instill Technologies, Inc. | Container with valve assembly for filling and dispensing substances, and apparatus and method for filling |
| PL1729795T3 (pl) * | 2004-02-09 | 2016-08-31 | Human Genome Sciences Inc | Białka fuzyjne albuminy |
| CN101724071A (zh) | 2004-10-08 | 2010-06-09 | 杜门蒂斯有限公司 | 抗肿瘤坏死因子受体1的单域抗体及其使用方法 |
| BRPI0614761A2 (pt) * | 2005-08-12 | 2009-05-19 | Human Genome Sciences Inc | proteìnas de fusão de albumina |
| US7855279B2 (en) * | 2005-09-27 | 2010-12-21 | Amunix Operating, Inc. | Unstructured recombinant polymers and uses thereof |
| US20090099031A1 (en) * | 2005-09-27 | 2009-04-16 | Stemmer Willem P | Genetic package and uses thereof |
| JP2009509535A (ja) * | 2005-09-27 | 2009-03-12 | アムニクス， インコーポレイテッド | タンパク様薬剤およびその使用 |
| US7846445B2 (en) * | 2005-09-27 | 2010-12-07 | Amunix Operating, Inc. | Methods for production of unstructured recombinant polymers and uses thereof |
| PL1965823T3 (pl) | 2005-11-04 | 2017-08-31 | Glaxosmithkline Llc | Sposoby podawania środków hipoglikemicznych |
| US20080280328A1 (en) * | 2005-11-18 | 2008-11-13 | Novozymes A/S | Glucoamylase Variants |
| EP1816201A1 (en) | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
| MX2008013119A (es) | 2006-04-11 | 2008-10-21 | Novartis Ag | Inhibidores de hcv/vih y sus usos. |
| US7966746B2 (en) * | 2006-04-24 | 2011-06-28 | Medical Instill Technologies, LLC | Needle penetrable and laser resealable lyophilization method |
| AU2007258609B2 (en) | 2006-06-07 | 2013-01-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| PE20121528A1 (es) * | 2006-09-13 | 2012-12-12 | Smithkline Beecham Corp | Metodos para administrar agentes hipoglucemiantes de larga duracion |
| EP2068905A4 (en) * | 2006-09-14 | 2009-12-30 | Human Genome Sciences Inc | ALBUM INFUSION PROTEINS |
| WO2008052043A2 (en) * | 2006-10-24 | 2008-05-02 | Cogenesys, Inc. | Opioid receptor agonist fusion proteins |
| EP2727936B1 (en) | 2006-11-22 | 2016-09-07 | Bristol-Myers Squibb Company | Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including IGF-IR |
| EP2450369A1 (en) | 2007-01-30 | 2012-05-09 | Epivax, Inc. | Regulatory t cell epitopes, compositions and uses thereof |
| ATE516814T1 (de) | 2007-02-02 | 2011-08-15 | Bristol Myers Squibb Co | 10fn3 domain zur behandlung von krankheiten begleitet von unerwünschter angiogenese |
| KR20100018040A (ko) | 2007-06-06 | 2010-02-16 | 도만티스 리미티드 | 프로테아제 내성 폴리펩티드를 선택하는 방법 |
| WO2009012502A1 (en) * | 2007-07-19 | 2009-01-22 | The Arizona Board Of Regents, A Body Corporate Of The State Of Arizona Acting For And On Behalf Of Arizona State University | Self- anchoring mems intrafascicular neural electrode |
| EP2185701A4 (en) * | 2007-08-15 | 2011-03-02 | Amunix Operating Inc | COMPOSITIONS AND METHODS FOR ENHANCING THE PRODUCTION OF RECOMBINANT POLYPEPTIDES |
| JP2011509920A (ja) * | 2007-09-05 | 2011-03-31 | サノフィ−アベンティス | 虚血又は再灌流事象によって引き起こされる心臓の障害又は間接的な後遺症の治療又は予防のための尿酸オキシダーゼの使用 |
| EP2050764A1 (en) | 2007-10-15 | 2009-04-22 | sanofi-aventis | Novel polyvalent bispecific antibody format and uses thereof |
| GB0723712D0 (en) * | 2007-12-04 | 2008-01-16 | Apitope Technology Bristol Ltd | Peptides |
| EP2072527A1 (en) | 2007-12-21 | 2009-06-24 | Altonabiotec AG | Fusion polypeptides comprising a SHBG dimerization component and uses thereof |
| WO2009116557A1 (ja) * | 2008-03-21 | 2009-09-24 | 富士フイルム株式会社 | 薬剤含有組成物 |
| WO2009142773A2 (en) | 2008-05-22 | 2009-11-26 | Bristol-Myers Squibb Company | Multivalent fibronectin based scaffold domain proteins |
| WO2009144927A1 (ja) * | 2008-05-27 | 2009-12-03 | 富士フイルム株式会社 | 薬剤含有組成物 |
| WO2010068735A1 (en) | 2008-12-10 | 2010-06-17 | Glaxosmithkline Llc. | Pharmaceutical compositions |
| US8716448B2 (en) | 2009-02-03 | 2014-05-06 | Amunix Operating Inc. | Coagulation factor VII compositions and methods of making and using same |
| SI2393828T1 (sl) | 2009-02-03 | 2017-01-31 | Amunix Operating Inc. | Podaljšani rekombinantni polipetidi in sestavki, ki jih obsegajo |
| US8703717B2 (en) | 2009-02-03 | 2014-04-22 | Amunix Operating Inc. | Growth hormone polypeptides and methods of making and using same |
| US8680050B2 (en) * | 2009-02-03 | 2014-03-25 | Amunix Operating Inc. | Growth hormone polypeptides fused to extended recombinant polypeptides and methods of making and using same |
| EP2396347B1 (en) | 2009-02-11 | 2017-04-12 | Albumedix A/S | Albumin variants and conjugates |
| WO2010094720A2 (en) | 2009-02-19 | 2010-08-26 | Glaxo Group Limited | Improved anti-tnfr1 polypeptides, antibody variable domains & antagonists |
| EP2419120A4 (en) * | 2009-04-08 | 2016-01-06 | Univ California | HUMAN PROTEIN CONCERNS WITH CONTROLLED SERUM PHARMACOKINETICS |
| US20110182850A1 (en) | 2009-04-10 | 2011-07-28 | Trixi Brandl | Organic compounds and their uses |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| KR101286721B1 (ko) * | 2009-06-05 | 2013-07-16 | 한국과학기술연구원 | 폴리-시스테인 펩티드 융합 재조합 알부민 및 이의 제조방법 |
| JP5839597B2 (ja) * | 2009-06-08 | 2016-01-06 | アムニクス オペレーティング インコーポレイテッド | グルコース調節ポリペプチド並びにその作成及び使用方法 |
| US9849188B2 (en) | 2009-06-08 | 2017-12-26 | Amunix Operating Inc. | Growth hormone polypeptides and methods of making and using same |
| WO2011006914A2 (en) | 2009-07-16 | 2011-01-20 | Glaxo Group Limited | Antagonists, uses & methods for partially inhibiting tnfr1 |
| WO2011012609A2 (en) | 2009-07-29 | 2011-02-03 | Glaxo Group Limited | Ligands that bind tgf-beta receptor rii |
| EP2493504B1 (en) | 2009-10-27 | 2015-10-07 | Glaxo Group Limited | Stable anti-tnfr1 polypeptides, antibody variable domains and antagonists |
| AU2010313497B2 (en) | 2009-10-30 | 2013-08-01 | Boehringer Ingelheim International Gmbh | Dosage regimens for HCV combination therapy comprising BI201335, interferon alpha and ribavirin |
| BR112012009450A2 (pt) | 2009-10-30 | 2017-05-23 | Novozymes Biopharma Dk As | variantes de albumina |
| EP2535057A2 (en) | 2010-02-09 | 2012-12-19 | Proyecto de Biomedicina Cima, S.L. | Compositions for the treatment of infectious and tumoural diseases |
| MX2012009050A (es) | 2010-02-18 | 2012-09-07 | Squibb Bristol Myers Co | Proteinas de dominio de andamiaje de fibronectina que se unen a interleucina 23 (il-23). |
| US8557961B2 (en) | 2010-04-02 | 2013-10-15 | Amunix Operating Inc. | Alpha 1-antitrypsin compositions and methods of making and using same |
| EP2556087A1 (en) | 2010-04-09 | 2013-02-13 | Novozymes Biopharma DK A/S | Albumin derivatives and variants |
| MA34209B1 (fr) | 2010-04-13 | 2013-05-02 | Bristol Myers Squibb Co | Protéines à domaine de squelette basé sur la fibronectine qui se lient à pcsk9 |
| JP2013525491A (ja) | 2010-05-04 | 2013-06-20 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 心血管障害を治療または予防し心血管保護を提供する方法 |
| WO2011150133A2 (en) | 2010-05-26 | 2011-12-01 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins having improved stability |
| EP2585065A1 (en) | 2010-06-24 | 2013-05-01 | Panmed Ltd. | Treatment of hepatitis c virus related diseases using hydroxychloroquine or a combination of hydroxychloroquine and an anti-viral agent |
| WO2012013597A1 (de) * | 2010-07-28 | 2012-02-02 | Justus-Liebig-Universität Giessen | Stoffe und deren verwendung zur beeinflussung natriuretischer peptidrezeptoren |
| KR20130120481A (ko) | 2010-10-08 | 2013-11-04 | 노파르티스 아게 | 술파미드 ｎｓ3 억제제의 비타민 ｅ 제제 |
| US9260496B2 (en) | 2010-12-22 | 2016-02-16 | Bristol-Myers Squibb Company | Fibronectin based scaffold domain proteins that bind IL-23 |
| EA201391012A1 (ru) | 2011-01-06 | 2014-01-30 | Глэксо Груп Лимитед | Лиганды, связывающиеся с рецепторами tgf-бета типа ii |
| EP3539991A1 (en) * | 2011-01-07 | 2019-09-18 | Chugai Seiyaku Kabushiki Kaisha | Method for improving physical properties of antibody |
| WO2012115772A2 (en) | 2011-02-25 | 2012-08-30 | Medtronic, Inc. | Therapy for kidney disease and/or heart failure |
| DK2681245T3 (da) | 2011-03-03 | 2018-08-13 | Zymeworks Inc | Multivalent heteromultimert scaffold-design og konstruktioner |
| RU2650784C2 (ru) | 2011-05-05 | 2018-04-17 | Альбумедикс А/С | Варианты альбумина |
| EP2750697A4 (en) | 2011-09-02 | 2015-03-25 | Medtronic Inc | CHIMERIC NATRIURETIC PEPTIDE COMPOSITIONS AND METHOD FOR THE PRODUCTION THEREOF |
| WO2013067029A2 (en) | 2011-10-31 | 2013-05-10 | Bristol-Myers Squibb Company | Fibronectin binding domains with reduced immunogenicity |
| WO2013075066A2 (en) | 2011-11-18 | 2013-05-23 | Eleven Biotherapeutics, Inc. | Proteins with improved half-life and other properties |
| DK2822577T3 (da) | 2012-02-15 | 2019-04-01 | Bioverativ Therapeutics Inc | Rekombinante faktor viii-proteiner |
| EP3564260B1 (en) | 2012-02-15 | 2022-10-19 | Bioverativ Therapeutics Inc. | Factor viii compositions and methods of making and using same |
| JP6355563B2 (ja) | 2012-02-27 | 2018-07-11 | アムニクス オペレーティング インコーポレイテッド | Ｘｔｅｎ共役組成物およびそれを製造する方法 |
| WO2013138338A2 (en) | 2012-03-12 | 2013-09-19 | Massachusetts Institute Of Technology | Methods for treating tissue damage associated with ischemia with apoliporotein d |
| JP2015509980A (ja) | 2012-03-14 | 2015-04-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｈｃｖ−ｈｉｖ同時感染患者集団のｈｃｖ感染症を治療するための併用療法 |
| WO2013135896A1 (en) | 2012-03-16 | 2013-09-19 | Novozymes Biopharma Dk A/S | Albumin variants |
| JP2015512900A (ja) | 2012-03-28 | 2015-04-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 特別な患者の遺伝子亜型分集団のｈｃｖ感染症を治療するための併用療法 |
| WO2013177187A2 (en) | 2012-05-22 | 2013-11-28 | Massachusetts Institute Of Technology | Synergistic tumor treatment with extended-pk il-2 and therapeutic agents |
| AU2013289881B2 (en) | 2012-07-13 | 2018-01-18 | Zymeworks Bc Inc. | Multivalent heteromultimer scaffold design and constructs |
| WO2014029752A1 (en) | 2012-08-22 | 2014-02-27 | Glaxo Group Limited | Anti lrp6 antibodies |
| PT3835310T (pt) | 2012-09-13 | 2024-05-20 | Bristol Myers Squibb Co | Proteínas de domínio de estrutura à base de fibronectina que ligam à miostatina |
| WO2014072481A1 (en) | 2012-11-08 | 2014-05-15 | Novozymes Biopharma Dk A/S | Albumin variants |
| US20140205566A1 (en) | 2012-11-30 | 2014-07-24 | Novartis Ag | Cyclic nucleuoside derivatives and uses thereof |
| WO2014120891A2 (en) | 2013-02-01 | 2014-08-07 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins |
| CA2903739A1 (en) | 2013-03-06 | 2014-09-12 | Glaxosmithkline Llc | Host cells and methods of use |
| USRE48805E1 (en) * | 2013-03-06 | 2021-11-02 | Vision Global Holdings Ltd. | Method for cancer targeting treatment and detection of arginine using albumin-binding arginine deiminase fusion protein |
| US9255262B2 (en) * | 2013-03-06 | 2016-02-09 | Vision Global Holdings Ltd. | Albumin-binding arginine deminase and the use thereof |
| WO2014165093A2 (en) | 2013-03-13 | 2014-10-09 | Bristol-Myers Squibb Company | Fibronectin based scaffold domains linked to serum albumin or a moiety binding thereto |
| EP3712177A1 (en) | 2013-03-15 | 2020-09-23 | GlaxoSmithKline Intellectual Property Development Limited | Anti-lag-3 binding proteins |
| RU2646098C2 (ru) | 2013-04-30 | 2018-03-01 | Интас Фармасьютикалс Лтд | Новый способ клонирования, экспрессии и очистки для получения ранибизумаба |
| KR102111078B1 (ko) | 2013-07-04 | 2020-05-18 | 노파르티스 아게 | O-만노실트랜스퍼라제 결핍 사상균 세포 및 이의 이용 방법 |
| TWI667255B (zh) | 2013-08-14 | 2019-08-01 | 美商生物化學醫療公司 | 因子ｖｉｉｉ－ｘｔｅｎ融合物及其用途 |
| EP3035950A4 (en) * | 2013-08-14 | 2017-05-03 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Glycosylated pacap/vip analogues with enhanced cns penetration for treatment of neurodegenerative diseases |
| CN105377882B (zh) * | 2014-03-06 | 2020-05-05 | 葛兰素史密斯克莱有限责任公司 | 宿主细胞和使用方法 |
| EP3157947A1 (en) | 2014-06-23 | 2017-04-26 | Novartis AG | Hsa-gdf-15 fusion polypeptide and use thereof |
| AU2015293949B2 (en) | 2014-07-21 | 2019-07-25 | Teknologian Tutkimuskeskus Vtt Oy | Production of glycoproteins with mammalian-like N-glycans in filamentous fungi |
| 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 |
| EP3646879B1 (en) | 2014-08-12 | 2024-04-03 | Massachusetts Institute Of Technology | Synergistic tumor treatment with integrin-binding-fc-fusion protein and an immune checkpoint inhibitor |
| US9616114B1 (en) | 2014-09-18 | 2017-04-11 | David Gordon Bermudes | Modified bacteria having improved pharmacokinetics and tumor colonization enhancing antitumor activity |
| EA037590B1 (ru) | 2014-11-25 | 2021-04-19 | Бристол-Майерс Сквибб Компани | Связывающиеся с pd-l1 полипептиды на основе 10fn3 домена для визуализации |
| EP4218832A3 (en) | 2014-11-25 | 2023-08-23 | Bristol-Myers Squibb Company | Methods and compositions for 18f-radiolabeling of the fibronectin type (iii) domain |
| EP3967755B1 (en) | 2014-12-19 | 2024-03-27 | Inozyme Pharma, Inc. | Soluble npp1 for use in a method for treating pseudoxanthoma elasticum |
| SG11201708441RA (en) | 2015-04-24 | 2017-11-29 | Viiv Healthcare Uk (No 5) Ltd | Polypeptides targeting hiv fusion |
| EP3331608A4 (en) | 2015-08-03 | 2019-05-01 | Bioverativ Therapeutics Inc. | FUSION XI FUSION PROTEINS AND METHODS OF MAKING AND USING THE SAME |
| BR112018003179A2 (pt) | 2015-08-20 | 2018-09-25 | Albumedix As | conjugados e variantes de albumina |
| PE20181275A1 (es) | 2015-08-28 | 2018-08-03 | Amunix Operating Inc | Ensamble de polipeptido quimerico y metodos para hacer y usar el mismo |
| CN108699145A (zh) | 2015-09-02 | 2018-10-23 | 伊缪泰普有限公司 | 抗lag-3抗体 |
| SI3348635T1 (sl) * | 2015-09-08 | 2021-08-31 | Jcr Pharmaceuticals Co., Ltd. | Novi mutant humanega serumskega albumina |
| EP3351561A4 (en) * | 2015-09-18 | 2019-05-15 | University of Miyazaki | PROLONGED ACTION ADRENOMEDULLIN DERIVATIVE |
| KR20180057657A (ko) | 2015-09-23 | 2018-05-30 | 브리스톨-마이어스 스큅 컴퍼니 | 글리피칸-3-결합 피브로넥틴 기반 스캐폴드 분자 |
| CN110317264B (zh) * | 2015-11-10 | 2022-10-11 | 孙嘉琳 | 一种抗肿瘤蛋白内皮抑素的衍生物 |
| EP3393494A1 (en) | 2015-12-22 | 2018-10-31 | Novartis Ag | Methods of treating or ameliorating metabolic disorders using growth differentiation factor 15 (gdf-15) |
| EP3393496B1 (en) | 2015-12-23 | 2023-10-11 | The Johns Hopkins University | Long-acting glp-1r agonist as a therapy of neurological and neurodegenerative conditions |
| WO2017159540A1 (ja) * | 2016-03-14 | 2017-09-21 | Ｊｃｒファーマ株式会社 | 血清アルブミン－２０ｋ成長ホルモン融合タンパク質 |
| WO2017210335A1 (en) | 2016-06-01 | 2017-12-07 | Bristol-Myers Squibb Company | Imaging methods using 18f-radiolabeled biologics |
| EP3471747A1 (en) | 2016-06-16 | 2019-04-24 | Alexion Pharmaceuticals, Inc. | Methods of treating myointimal proliferation |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| 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 |
| US10767164B2 (en) | 2017-03-30 | 2020-09-08 | The Research Foundation For The State University Of New York | Microenvironments for self-assembly of islet organoids from stem cells differentiation |
| WO2019067502A1 (en) | 2017-09-27 | 2019-04-04 | Alexion Pharmaceuticals, Inc. | METHODS FOR IMPROVING CARDIOVASCULAR FUNCTION AND TREATING CARDIOVASCULAR DISEASE USING RECOMBINANT ECTO-NUCLEOTIDE PYROPHOSPHATASE / PHOSPHODIESTERASE |
| CN110090295B (zh) * | 2018-01-29 | 2022-12-23 | 武汉康理通科技有限公司 | Ephrin-B1在制备治疗炎症性肠病的药物中的用途 |
| WO2019152827A1 (en) * | 2018-02-02 | 2019-08-08 | AskGene Pharma, Inc. | Novel antibody-drug conjugates (adc), methods of making, and methods of use thereof |
| US20210113606A1 (en) | 2018-02-12 | 2021-04-22 | Biontech Rna Pharmaceuticals Gmbh | Treatment using cytokine encoding rna |
| AU2019271148B2 (en) | 2018-05-14 | 2023-07-06 | Werewolf Therapeutics, Inc. | Activatable interleukin-2 polypeptides and methods of use thereof |
| SG11202011309SA (en) | 2018-05-14 | 2020-12-30 | Werewolf Therapeutics Inc | Activatable interleukin 12 polypeptides and methods of use thereof |
| WO2020020783A1 (en) | 2018-07-24 | 2020-01-30 | Biontech Rna Pharmaceuticals Gmbh | Il2 agonists |
| US20220002370A1 (en) | 2018-09-27 | 2022-01-06 | Xilio Development, Inc. | Masked cytokine polypeptides |
| SG11202100935TA (en) | 2018-09-28 | 2021-02-25 | Massachusetts Inst Technology | Collagen-localized immunomodulatory molecules and methods thereof |
| WO2020154032A1 (en) | 2019-01-23 | 2020-07-30 | Massachusetts Institute Of Technology | Combination immunotherapy dosing regimen for immune checkpoint blockade |
| WO2020152367A1 (en) | 2019-01-25 | 2020-07-30 | Ospedale San Raffaele S.R.L. | Inhibitor of dux4 and uses thereof |
| EP3920960B1 (en) | 2019-02-08 | 2024-04-17 | Biontech Cell & Gene Therapies Gmbh | Treatment involving car-engineered t cells and cytokines |
| US20220177544A1 (en) | 2019-03-18 | 2022-06-09 | Biontech Cell & Gene Therapies Gmbh | Interleukin-2 receptor (IL2R) and interleukin-2 (IL2) variants for specific activation of immune effector cells |
| WO2020200481A1 (en) | 2019-04-05 | 2020-10-08 | Biontech Rna Pharmaceuticals Gmbh | Treatment involving interleukin-2 (il2) and interferon (ifn) |
| AU2020258384A1 (en) | 2019-04-15 | 2021-11-04 | Qwixel Therapeutics Llc | Fusion protein composition(s) comprising targeted masked type I interferons (IFNA and IFNB) and an antibody against tumor antigen, for use in the treatment of cancer |
| CN114450022A (zh) | 2019-05-14 | 2022-05-06 | 狼人治疗公司 | 分离部分及其使用方法 |
| CN111944036A (zh) * | 2019-05-14 | 2020-11-17 | 上海盖浦生物科技有限公司 | 一种增殖免疫细胞的突变体蛋白 |
| TW202115105A (zh) | 2019-06-24 | 2021-04-16 | 德商拜恩迪克Ｒｎａ製藥有限公司 | Ｉｌ２激動劑 |
| US11642409B2 (en) | 2019-06-26 | 2023-05-09 | Massachusetts Insttute of Technology | Immunomodulatory fusion protein-metal hydroxide complexes and methods thereof |
| RU2714392C1 (ru) * | 2019-07-09 | 2020-02-14 | Екатерина Олеговна Кудасова | Способ модификации поверхности метилметакрилата стоматологического протеза низкотемпературной газоразрядной плазмой кислорода низкого давления за счет изменения контактного угла смачивания по воде и свободной поверхностной энергии |
| AU2020329290A1 (en) | 2019-08-13 | 2022-03-24 | Elpis Biopharmaceuticals | Engineered interleukin-2 receptor beta agonists |
| WO2021058091A1 (en) | 2019-09-24 | 2021-04-01 | Biontech Rna Pharmaceuticals Gmbh | Treatment involving therapeutic antibody and interleukin-2 (il2) |
| WO2021129927A1 (en) | 2019-12-23 | 2021-07-01 | Biontech Cell & Gene Therapies Gmbh | Treatment with immune effector cells engineered to express an antigen receptor |
| WO2021129945A1 (en) | 2019-12-27 | 2021-07-01 | Biontech Cell & Gene Therapies Gmbh | In vitro and in vivo gene delivery to immune effector cells using nanoparticles functionalized with designed ankyrin repeat proteins (darpins) |
| JP2023515633A (ja) | 2020-02-28 | 2023-04-13 | ブリストル－マイヤーズ スクイブ カンパニー | 放射性標識されたフィブロネクチンに基づく足場および抗体ならびにそのセラノスティクス的使用 |
| WO2021185775A1 (en) | 2020-03-16 | 2021-09-23 | Biontech Cell & Gene Therapies Gmbh | Antigen-specific t cell receptors and t cell epitopes |
| WO2021197589A1 (en) | 2020-03-31 | 2021-10-07 | BioNTech SE | Treatment involving non-immunogenic rna for antigen vaccination |
| IL298431A (en) | 2020-05-26 | 2023-01-01 | Boehringer Ingelheim Int | Anti-pd-1 antibodies |
| JPWO2022030580A1 (da) * | 2020-08-06 | 2022-02-10 | ||
| KR102467827B1 (ko) * | 2020-08-31 | 2022-11-16 | 연세대학교 산학협력단 | 미생물 에어로졸화 과정 중 발생하는 손상 방지 방법 |
| TW202245808A (zh) | 2020-12-21 | 2022-12-01 | 德商拜恩迪克公司 | 用於治療癌症之治療性ｒｎａ |
| WO2022135666A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Treatment schedule for cytokine proteins |
| WO2022135667A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Therapeutic rna for treating cancer |
| CN112753846B (zh) * | 2021-01-27 | 2023-08-29 | 吉林农业大学 | 一种超持水大豆分离蛋白凝胶及其制备方法 |
| AU2022256732A1 (en) | 2021-04-12 | 2023-10-19 | Biontech Delivery Technologies Gmbh | Rna compositions comprising a buffer substance and methods for preparing, storing and using the same |
| CA3215771A1 (en) | 2021-04-20 | 2022-10-27 | BioNTech SE | Virus vaccine |
| WO2022241310A1 (en) * | 2021-05-14 | 2022-11-17 | Antlia Bioscience, Inc. | Modified b-type natriuretic peptide |
| KR20240027677A (ko) | 2021-06-04 | 2024-03-04 | 베링거 인겔하임 인터내셔날 게엠베하 | 항-sirp-알파 항체 |
| CN113391067B (zh) * | 2021-06-16 | 2023-07-25 | 军事科学院军事医学研究院军事兽医研究所 | 抗尼帕病毒g蛋白抗体的间接elisa检测方法 |
| WO2023051926A1 (en) | 2021-09-30 | 2023-04-06 | BioNTech SE | Treatment involving non-immunogenic rna for antigen vaccination and pd-1 axis binding antagonists |
| CA3235180A1 (en) | 2021-10-21 | 2023-04-27 | BioNTech SE | Coronavirus vaccine |
| EP4238577A3 (en) | 2021-10-22 | 2023-12-06 | BioNTech SE | Compositions for administration of different doses of rna |
| WO2023083434A1 (en) | 2021-11-09 | 2023-05-19 | BioNTech SE | Rna encoding peptidoglycan hydrolase and use thereof for treating bacterial infection |
| WO2023126053A1 (en) | 2021-12-28 | 2023-07-06 | BioNTech SE | Lipid-based formulations for administration of rna |
| WO2023141638A1 (en) * | 2022-01-21 | 2023-07-27 | The Methodist Hospital System | Methods for vascular regeneration and wound treatment |
| WO2023165681A1 (en) | 2022-03-01 | 2023-09-07 | BioNTech SE | Rna lipid nanoparticles (lnps) comprising a polyoxazoline and/or polyoxazine polymer |
| WO2023193892A1 (en) | 2022-04-05 | 2023-10-12 | BioNTech SE | Nucleic acid compositions comprising an inorganic polyphosphate and methods for preparing, storing and using the same |
| WO2023220597A1 (en) | 2022-05-10 | 2023-11-16 | Elpis Biopharmaceuticals | Engineered interleukin-2 receptor beta reduced-binding agonist |
| WO2024002985A1 (en) | 2022-06-26 | 2024-01-04 | BioNTech SE | Coronavirus vaccine |
| WO2024017479A1 (en) | 2022-07-21 | 2024-01-25 | BioNTech SE | Multifunctional cells transiently expressing an immune receptor and one or more cytokines, their use and methods for their production |
| WO2024028325A1 (en) | 2022-08-01 | 2024-02-08 | BioNTech SE | Nucleic acid compositions comprising amphiphilic oligo ethylene glycol (oeg)-conjugated compounds and methods of using such compounds and compositions |
| WO2024027910A1 (en) | 2022-08-03 | 2024-02-08 | BioNTech SE | Rna for preventing or treating tuberculosis |
| WO2024028445A1 (en) | 2022-08-03 | 2024-02-08 | BioNTech SE | Rna for preventing or treating tuberculosis |
| CN115960175A (zh) * | 2022-08-08 | 2023-04-14 | 江南大学 | 一种强化乳铁蛋白表达的毕赤酵母及其构建方法与应用 |
| WO2024080304A1 (ja) * | 2022-10-11 | 2024-04-18 | Ｊｃｒファーマ株式会社 | 血清アルブミンと生理活性を有する蛋白質との融合蛋白質 |
| JP2024056667A (ja) * | 2022-10-11 | 2024-04-23 | Ｊｃｒファーマ株式会社 | 血清アルブミンと生理活性を有する蛋白質との融合蛋白質 |
Family Cites Families (186)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4002531A (en) | 1976-01-22 | 1977-01-11 | Pierce Chemical Company | Modifying enzymes with polyethylene glycol and product produced thereby |
| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| US4714681A (en) | 1981-07-01 | 1987-12-22 | The Board Of Reagents, The University Of Texas System Cancer Center | Quadroma cells and trioma cells and methods for the production of same |
| US4474893A (en) | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
| US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
| US4741900A (en) | 1982-11-16 | 1988-05-03 | Cytogen Corporation | Antibody-metal ion complexes |
| NZ207394A (en) | 1983-03-08 | 1987-03-06 | Commw Serum Lab Commission | Detecting or determining sequence of amino acids |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| DE3668186D1 (de) | 1985-04-01 | 1990-02-15 | Celltech Ltd | Transformierte myeloma-zell-linie und dieselbe verwendendes verfahren zur expression eines gens, das ein eukaryontisches polypeptid kodiert. |
| US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
| US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
| GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| HU213344B (en) * | 1987-04-09 | 1997-05-28 | Delta Biotechnology Ltd | Process for producing of stable dezintegrating plasmid-vectors |
| US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
| US4994560A (en) | 1987-06-24 | 1991-02-19 | The Dow Chemical Company | Functionalized polyamine chelants and radioactive rhodium complexes thereof for conjugation to antibodies |
| US5489425A (en) | 1987-06-24 | 1996-02-06 | The Dow Chemical Company | Functionalized polyamine chelants |
| GB8717430D0 (en) | 1987-07-23 | 1987-08-26 | Celltech Ltd | Recombinant dna product |
| NZ226414A (en) | 1987-10-02 | 1992-07-28 | Genentech Inc | Cd4 peptide adhesion variants and their preparation and use |
| GB8725529D0 (en) | 1987-10-30 | 1987-12-02 | Delta Biotechnology Ltd | Polypeptides |
| JPH01215289A (ja) | 1988-02-22 | 1989-08-29 | Toa Nenryo Kogyo Kk | 遺伝子組換えによる正常ヒト血清アルブミンａの製造方法 |
| GB8809129D0 (en) | 1988-04-18 | 1988-05-18 | Celltech Ltd | Recombinant dna methods vectors and host cells |
| ZA894792B (en) | 1988-06-24 | 1991-04-24 | Dow Chemical Co | Macrocyclic bifunctional chelants,complexes thereof and their antibody conjugates |
| US5756065A (en) | 1988-06-24 | 1998-05-26 | The Dow Chemical Company | Macrocyclic tetraazacyclododecane conjugates and their use as diagnostic and therapeutic agents |
| HU219485B (hu) | 1988-06-24 | 2001-04-28 | Dow Chemical Co. | Eljárás 1,4,7,10-tetraaza-ciklododekán-származékok, ezek komplexei, valamint antitestekkel képzett konjugátumai, és ilyeneket tartalmazó gyógyszerkészítmények előállítására és a komplexeket, illetve konjugátumokat tartalmazó diagnosztikai készítmények |
| US5274119A (en) | 1988-07-01 | 1993-12-28 | The Dow Chemical Company | Vicinal diols |
| US4925648A (en) | 1988-07-29 | 1990-05-15 | Immunomedics, Inc. | Detection and treatment of infectious and inflammatory lesions |
| FR2649991B2 (fr) | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| US5601819A (en) | 1988-08-11 | 1997-02-11 | The General Hospital Corporation | Bispecific antibodies for selective immune regulation and for selective immune cell binding |
| EP0428615A4 (en) | 1988-08-11 | 1991-11-13 | California Biotechnology, Inc. | Method for stabilizing heterologous protein expression and vectors for use therein |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| EP0768377A1 (en) | 1988-09-02 | 1997-04-16 | Protein Engineering Corporation | Generation and selection of recombinant varied binding proteins |
| US5349052A (en) | 1988-10-20 | 1994-09-20 | Royal Free Hospital School Of Medicine | Process for fractionating polyethylene glycol (PEG)-protein adducts and an adduct for PEG and granulocyte-macrophage colony stimulating factor |
| US5342604A (en) | 1988-10-31 | 1994-08-30 | The Dow Chemical Company | Complexes possessing ortho ligating functionality |
| US5696239A (en) | 1988-10-31 | 1997-12-09 | The Dow Chemical Company | Conjugates possessing ortho ligating functionality and complexes thereof |
| JP2989002B2 (ja) | 1988-12-22 | 1999-12-13 | キリン―アムジエン・インコーポレーテツド | 化学修飾顆粒球コロニー刺激因子 |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5705363A (en) | 1989-03-02 | 1998-01-06 | The Women's Research Institute | Recombinant production of human interferon τ polypeptides and nucleic acids |
| US5231020A (en) | 1989-03-30 | 1993-07-27 | Dna Plant Technology Corporation | Genetic engineering of novel plant phenotypes |
| US5324844A (en) | 1989-04-19 | 1994-06-28 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| US5766883A (en) * | 1989-04-29 | 1998-06-16 | Delta Biotechnology Limited | Polypeptides |
| US5808003A (en) | 1989-05-26 | 1998-09-15 | Perimmune Holdings, Inc. | Polyaminocarboxylate chelators |
| DE69029036T2 (de) | 1989-06-29 | 1997-05-22 | Medarex Inc | Bispezifische reagenzien für die aids-therapie |
| US5413923A (en) | 1989-07-25 | 1995-05-09 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
| FR2650598B1 (fr) * | 1989-08-03 | 1994-06-03 | Rhone Poulenc Sante | Derives de l'albumine a fonction therapeutique |
| US5073627A (en) | 1989-08-22 | 1991-12-17 | Immunex Corporation | Fusion proteins comprising GM-CSF and IL-3 |
| WO1991005867A1 (en) | 1989-10-13 | 1991-05-02 | Amgen Inc. | Erythropoietin isoforms |
| US5667986A (en) * | 1989-10-18 | 1997-09-16 | Delta Biotechnology Limited | Yeast promoter for expressing heterologous polypeptides |
| GB8924021D0 (en) | 1989-10-25 | 1989-12-13 | Celltech Ltd | Recombinant dna method and vectors for the use therein |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| US5780225A (en) | 1990-01-12 | 1998-07-14 | Stratagene | Method for generating libaries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules |
| WO1991010737A1 (en) | 1990-01-11 | 1991-07-25 | Molecular Affinities Corporation | Production of antibodies using gene libraries |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| SG48759A1 (en) | 1990-01-12 | 2002-07-23 | Abgenix Inc | Generation of xenogenic antibodies |
| US5545618A (en) * | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
| US5747334A (en) | 1990-02-15 | 1998-05-05 | The University Of North Carolina At Chapel Hill | Random peptide library |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9013017D0 (en) * | 1990-06-11 | 1990-08-01 | Mars Uk Ltd | Compounds |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| US5225341A (en) | 1990-07-19 | 1993-07-06 | The Regents Of The University Of California | Biologically safe plant transformation system using a ds transposon |
| US5202239A (en) * | 1990-08-07 | 1993-04-13 | Scios Nova Inc. | Expression of recombinant polypeptides with improved purification |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5698426A (en) | 1990-09-28 | 1997-12-16 | Ixsys, Incorporated | Surface expression libraries of heteromeric receptors |
| ATE175118T1 (de) | 1990-10-05 | 1999-01-15 | Medarex Inc | Gezielte immunostimulierung mit bispezifischen stoffen |
| JPH07108232B2 (ja) * | 1990-10-09 | 1995-11-22 | エム・ディ・リサーチ株式会社 | ペプチド又は蛋白質の製造方法 |
| EP0557300B1 (en) | 1990-10-29 | 1997-11-19 | Chiron Corporation | Bispecific antibodies, method of production, and uses thereof |
| ATE164395T1 (de) | 1990-12-03 | 1998-04-15 | Genentech Inc | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
| CA2108147C (en) | 1991-04-10 | 2009-01-06 | Angray Kang | Heterodimeric receptor libraries using phagemids |
| AU665758B2 (en) | 1991-04-26 | 1996-01-18 | Surface Active Limited | Novel antibodies, and methods for their use |
| US5646012A (en) * | 1991-04-30 | 1997-07-08 | Rhone-Poulenc Rorer S.A. | Yeast promoter and use thereof |
| DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
| CA2110799A1 (en) | 1991-06-14 | 1992-12-23 | Arnold H. Horwitz | Microbially-produced antibody fragments and their conjugates |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| US5885793A (en) | 1991-12-02 | 1999-03-23 | Medical Research Council | Production of anti-self antibodies from antibody segment repertoires and displayed on phage |
| US5428139A (en) | 1991-12-10 | 1995-06-27 | The Dow Chemical Company | Bicyclopolyazamacrocyclophosphonic acid complexes for use as radiopharmaceuticals |
| FR2686620B1 (fr) * | 1992-01-27 | 1995-06-23 | Rhone Poulenc Rorer Sa | Serum-albumine humaine, preparation et utilisation. |
| FR2686900B1 (fr) * | 1992-01-31 | 1995-07-21 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides ayant une activite de stimulation des colonies de granulocytes, leur preparation et compositions pharmaceutiques les contenant. |
| FR2686899B1 (fr) * | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| WO1993017715A1 (en) | 1992-03-05 | 1993-09-16 | Board Of Regents, The University Of Texas System | Diagnostic and/or therapeutic agents, targeted to neovascular endothelial cells |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
| US5775745A (en) | 1992-06-09 | 1998-07-07 | Hoppe Holding Ag | Latch and lockset system |
| US5505931A (en) | 1993-03-04 | 1996-04-09 | The Dow Chemical Company | Acid cleavable compounds, their preparation and use as bifunctional acid-labile crosslinking agents |
| EP0955062B1 (en) | 1992-07-31 | 2007-04-18 | Genentech, Inc. | Human growth hormone aqueous formulation |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| US5441050A (en) | 1992-12-18 | 1995-08-15 | Neoprobe Corporation | Radiation responsive surgical instrument |
| DK82893D0 (da) * | 1993-07-08 | 1993-07-08 | Novo Nordisk As | Peptid |
| US5512459A (en) | 1993-07-20 | 1996-04-30 | Bionebraska, Inc. | Enzymatic method for modification or recombinant polypeptides |
| GB9317618D0 (en) | 1993-08-24 | 1993-10-06 | Royal Free Hosp School Med | Polymer modifications |
| US5643575A (en) | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| AU696293B2 (en) | 1993-12-08 | 1998-09-03 | Genzyme Corporation | Process for generating specific antibodies |
| US5705483A (en) | 1993-12-09 | 1998-01-06 | Eli Lilly And Company | Glucagon-like insulinotropic peptides, compositions and methods |
| DK144093D0 (da) * | 1993-12-23 | 1993-12-23 | Novo Nordisk As | |
| AU1736495A (en) | 1994-01-31 | 1995-08-15 | Trustees Of Boston University | Polyclonal antibody libraries |
| US5516637A (en) | 1994-06-10 | 1996-05-14 | Dade International Inc. | Method involving display of protein binding pairs on the surface of bacterial pili and bacteriophage |
| US5985660A (en) | 1994-06-15 | 1999-11-16 | Systemix, Inc. | Method of identifying biological response modifiers involved in dendritic and/or lymphoid progenitor cell proliferation and/or differentiation |
| US5639642A (en) * | 1994-06-16 | 1997-06-17 | Novo Nordisk A/S | Synthetic leader peptide sequences |
| US5623054A (en) | 1994-06-23 | 1997-04-22 | The General Hospital Corporation | Crucifer AFT proteins and uses thereof |
| US5574008A (en) | 1994-08-30 | 1996-11-12 | Eli Lilly And Company | Biologically active fragments of glucagon-like insulinotropic peptide |
| US5512549A (en) | 1994-10-18 | 1996-04-30 | Eli Lilly And Company | Glucagon-like insulinotropic peptide analogs, compositions, and methods of use |
| EP1978033A3 (en) | 1995-04-27 | 2008-12-24 | Amgen Fremont Inc. | Human antibodies derived from immunized xenomice |
| AU2466895A (en) | 1995-04-28 | 1996-11-18 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5804162A (en) | 1995-06-07 | 1998-09-08 | Alliance Pharmaceutical Corp. | Gas emulsions stabilized with fluorinated ethers having low Ostwald coefficients |
| US5811097A (en) | 1995-07-25 | 1998-09-22 | The Regents Of The University Of California | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
| GB9526733D0 (en) * | 1995-12-30 | 1996-02-28 | Delta Biotechnology Ltd | Fusion proteins |
| AU718254B2 (en) | 1996-01-19 | 2000-04-13 | Betagene, Inc. | Recombinant expression of proteins from secretory cell lines |
| US6087129A (en) * | 1996-01-19 | 2000-07-11 | Betagene, Inc. | Recombinant expression of proteins from secretory cell lines |
| US6110707A (en) * | 1996-01-19 | 2000-08-29 | Board Of Regents, The University Of Texas System | Recombinant expression of proteins from secretory cell lines |
| JP2978435B2 (ja) | 1996-01-24 | 1999-11-15 | チッソ株式会社 | アクリロキシプロピルシランの製造方法 |
| ATE395359T1 (de) | 1996-03-01 | 2008-05-15 | Novo Nordisk As | Peptid zur appetitzügelung, dessen zusammensetzungen und verwendung |
| US5912229A (en) * | 1996-03-01 | 1999-06-15 | Novo Nordisk Als | Use of a pharmaceutical composition comprising an appetite-suppressing peptide |
| WO1997033899A1 (en) | 1996-03-14 | 1997-09-18 | Human Genome Sciences, Inc. | Apoptosis inducing molecule i |
| CA2248868A1 (en) | 1996-03-22 | 1997-09-25 | Human Genome Sciences, Inc. | Apoptosis inducing molecule ii |
| US6300065B1 (en) * | 1996-05-31 | 2001-10-09 | Board Of Trustees Of The University Of Illinois | Yeast cell surface display of proteins and uses thereof |
| US6110703A (en) * | 1996-07-05 | 2000-08-29 | Novo Nordisk A/S | Method for the production of polypeptides |
| WO1998005782A1 (en) * | 1996-08-02 | 1998-02-12 | Zymogenetics, Inc. | Testis-specific insulin homolog polypeptides |
| US6458924B2 (en) * | 1996-08-30 | 2002-10-01 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| US6277819B1 (en) | 1996-08-30 | 2001-08-21 | Eli Lilly And Company | Use of GLP-1 or analogs in treatment of myocardial infarction |
| US6006753A (en) | 1996-08-30 | 1999-12-28 | Eli Lilly And Company | Use of GLP-1 or analogs to abolish catabolic changes after surgery |
| WO1998011136A1 (en) | 1996-09-09 | 1998-03-19 | Novo Nordisk A/S | A cDNA AND PEPTIDE WITH RELATION TO CANCER AND WEIGHT LOSS |
| AU7364696A (en) | 1996-09-18 | 1998-04-14 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor-like genes |
| US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
| UA65549C2 (uk) * | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція |
| EP1306092A3 (en) | 1996-11-05 | 2003-05-07 | Eli Lilly & Company | Use of GLP-1 and analogs administered peripherally, in regulation of obesity |
| JP2001504105A (ja) | 1996-11-12 | 2001-03-27 | ノボ ノルディスク アクティーゼルスカブ | Ｇｌｐ―１ペプチドの利用 |
| KR100942002B1 (ko) | 1996-12-03 | 2010-02-12 | 암젠 프레몬트 인코포레이티드 | 복수의 ｖｈ 및 ｖｋ 부위를 함유하는 사람 면역글로불린 유전자좌를 갖는 형질전환된 포유류 및 이로부터 생성된 항체 |
| EP0954589A1 (en) * | 1997-01-24 | 1999-11-10 | Novo Nordisk A/S | Synthetic leader peptide sequences |
| ATE200030T1 (de) | 1997-01-29 | 2001-04-15 | Polymasc Pharmaceuticals Plc | Pegylationsverfahren |
| US20030049618A1 (en) * | 1997-03-07 | 2003-03-13 | Ruben Steven M. | 186 human secreted proteins |
| US20030065139A1 (en) * | 1998-03-19 | 2003-04-03 | Craig A. Rosen | Secreted protein hmmbd35 |
| US20030175858A1 (en) * | 1997-03-07 | 2003-09-18 | Ruben Steven M. | 186 human secreted proteins |
| US6420526B1 (en) * | 1997-03-07 | 2002-07-16 | Human Genome Sciences, Inc. | 186 human secreted proteins |
| US20060084082A1 (en) * | 1997-03-07 | 2006-04-20 | Human Genome Sciences, Inc. | 186 human secreted proteins |
| US5981488A (en) | 1997-03-31 | 1999-11-09 | Eli Lillly And Company | Glucagon-like peptide-1 analogs |
| US7227002B1 (en) | 1997-04-14 | 2007-06-05 | Micromet Ag | Human antibodies that bind human 17-A1/EpCAM tumor antigen |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| GB9713412D0 (en) | 1997-06-26 | 1997-08-27 | Delta Biotechnology Ltd | Improved protein expression strains |
| ATE447583T1 (de) | 1997-09-17 | 2009-11-15 | Genentech Inc | Polypeptide und dafür kodierende nukleinsäure |
| CA2309541C (en) | 1997-11-03 | 2011-01-11 | Human Genome Sciences, Inc. | Vegi, an inhibitor of angiogenesis and tumor growth |
| DE69942306D1 (de) | 1998-02-27 | 2010-06-10 | Novo Nordisk As | Abkömmlinge von glp-1 analogen |
| US7205280B2 (en) * | 1998-03-11 | 2007-04-17 | Cognosci, Inc. | Methods of suppressing microglial activation |
| US6548653B1 (en) * | 1998-06-15 | 2003-04-15 | Genzyme Transgenics Corporation | Erythropoietin analog-human serum albumin fusion |
| MY155270A (en) | 1998-09-24 | 2015-09-30 | Lilly Co Eli | Use of glp-1 or analogs in treatment of stroke |
| US7259136B2 (en) | 1999-04-30 | 2007-08-21 | Amylin Pharmaceuticals, Inc. | Compositions and methods for treating peripheral vascular disease |
| BR0010750A (pt) | 1999-05-17 | 2002-02-26 | Conjuchem Inc | Peptìdeos insulinotrópicos de longa duração |
| US6514500B1 (en) * | 1999-10-15 | 2003-02-04 | Conjuchem, Inc. | Long lasting synthetic glucagon like peptide {GLP-!} |
| US20020048571A1 (en) | 1999-07-19 | 2002-04-25 | Jeno Gyuris | Chimeric polypeptides of serum albumin and uses related thereto |
| AU774555B2 (en) | 1999-07-19 | 2004-07-01 | Gpc Biotech Inc. | Chimeric polypeptides of serum albumin and uses related thereto |
| ES2484966T3 (es) * | 2000-04-12 | 2014-08-12 | Novozymes Biopharma Dk A/S | Proteínas de fusión de albúmina |
| EP1282436B1 (en) | 2000-05-19 | 2008-06-11 | Amylin Pharmaceuticals, Inc. | Treatment of acute coronary syndrome with glp-1 |
| MXPA02006118A (es) | 2000-10-20 | 2004-08-23 | Amylin Pharmaceuticals Inc | Tratamiento de la invernacion del miocardio y cardiopatia diabetica con un peptido glp-1. |
| US7101561B2 (en) | 2000-12-01 | 2006-09-05 | Innogenetics N.V. | Purified hepatitis C virus envelope proteins for diagnostic and therapeutic use |
| EA005584B1 (ru) * | 2000-12-07 | 2005-04-28 | Эли Лилли Энд Компани | Слитые белки glp-1 |
| US20030143191A1 (en) | 2001-05-25 | 2003-07-31 | Adam Bell | Chemokine beta-1 fusion proteins |
| WO2003018516A2 (en) | 2001-08-23 | 2003-03-06 | Eli Lilly And Company | Glucagon-like peptide-1 analogs |
| AU2002339862A1 (en) * | 2001-09-04 | 2003-05-26 | Aventis Pharmaceuticals Inc. | Abrogen polypeptides, nucleic acids encoding them and methods for using them to inhibit angiogenesis |
| AU2002332041A1 (en) * | 2001-10-05 | 2003-04-22 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| JP5232352B2 (ja) | 2001-10-10 | 2013-07-10 | ノボ ノルデイスク エイ エス | ペプチドの改造および複合糖質化 |
| EP1463752A4 (en) * | 2001-12-21 | 2005-07-13 | Human Genome Sciences Inc | ALBUMIN FUSION PROTEINS |
| WO2003054182A2 (en) | 2001-12-21 | 2003-07-03 | Nexia Biotechnologies, Inc. | Production of butyrylcholinesterases in transgenic mammals |
| US20080167238A1 (en) | 2001-12-21 | 2008-07-10 | Human Genome Sciences, Inc. | Albumin Fusion Proteins |
| WO2003060071A2 (en) * | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| WO2005003296A2 (en) * | 2003-01-22 | 2005-01-13 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| KR101271635B1 (ko) * | 2001-12-21 | 2013-06-12 | 휴먼 게놈 사이언시즈, 인코포레이티드 | 알부민 융합 단백질 |
| EP1494704A1 (en) | 2002-04-04 | 2005-01-12 | Novo Nordisk A/S | Glp-1 agonist and cardiovascular complications |
| CN1241946C (zh) * | 2002-07-01 | 2006-02-15 | 美国福源集团 | 对多种细胞具刺激增生作用的人血清白蛋白重组融合蛋白 |
| EA008831B1 (ru) | 2003-06-12 | 2007-08-31 | Эли Лилли Энд Компани | Слитые белки аналогов glp-1 |
| PL1729795T3 (pl) * | 2004-02-09 | 2016-08-31 | Human Genome Sciences Inc | Białka fuzyjne albuminy |
| US20070270339A1 (en) * | 2004-04-23 | 2007-11-22 | Serono, Inc. | Use of GPCR54 Ligands for the Treatment of Infertility |
| AU2005323063B2 (en) | 2004-12-24 | 2011-01-27 | Amylin Pharmaceuticals, Llc | Use of GLP-1 and agonists thereof to prevent cardiac myocyte apoptosis |
| ATE550032T1 (de) | 2005-04-11 | 2012-04-15 | Amylin Pharmaceuticals Inc | Verwendung von glp-1, exendin und agonisten davon zur verzögerung oder verhinderung von kardialer remodellierung |
| BRPI0614761A2 (pt) | 2005-08-12 | 2009-05-19 | Human Genome Sciences Inc | proteìnas de fusão de albumina |
| CA2652907A1 (en) | 2006-05-26 | 2007-12-06 | Amylin Pharmaceuticals, Inc. | Compositions and methods for treatment of diabetes |
| AU2007258609B2 (en) | 2006-06-07 | 2013-01-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| WO2008019143A2 (en) | 2006-08-04 | 2008-02-14 | Amylin Pharmaceuticals, Inc | Use of exendins and glp-i receptor agonists for altering lipoprotein particle size and subclass composition |
| JP5005450B2 (ja) * | 2007-07-13 | 2012-08-22 | 本田技研工業株式会社 | 燃料給油管の口元内部構造 |
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