ES2537104T3 - Regiones de marco de inmunoglobulina que demuestran estabilidad potenciada en el entorno intracelular y métodos de identificación de las mismas - Google Patents
Regiones de marco de inmunoglobulina que demuestran estabilidad potenciada en el entorno intracelular y métodos de identificación de las mismas Download PDFInfo
- Publication number
- ES2537104T3 ES2537104T3 ES10009857.3T ES10009857T ES2537104T3 ES 2537104 T3 ES2537104 T3 ES 2537104T3 ES 10009857 T ES10009857 T ES 10009857T ES 2537104 T3 ES2537104 T3 ES 2537104T3
- Authority
- ES
- Spain
- Prior art keywords
- framework regions
- enhanced stability
- identification methods
- intracellular environment
- immunoglobulin framework
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
- G01N33/6857—Antibody fragments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/80—Immunoglobulins specific features remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/80—Immunoglobulins specific features remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies
- C07K2317/82—Immunoglobulins specific features remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies functional in the cytoplasm, the inner aspect of the cell membrane, the nucleus or the mitochondria
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Región de marco de fragmento variable de cadena sencilla (fragmento scFv) que tiene la estructura general: NH2-VL-enlazador-VH-COOH; o NH2-VH-enlazador-VL-COOH, caracterizada porque el dominio VL tiene la secuencia de región de marco de Seq. Id. No. 1 y el dominio VH tiene la secuencia de región de marco de Seq. Id. No. 11, en la que la región de marco de scFv es estable en condiciones reductoras.
Description
5
10
15
20
25
30
35
40
45
50
55
E10009857
18-05-2015
una fusión Gal4 (1-147)-VP16 para producir una proteína de fusión Gal4 (1-147)-VP16-scFv tras la expresión. Se cultivaron las células en DMEM complementado con FCS al 2,5% y l-glutamina 2 mM. Se llevaron a cabo transfecciones transitorias según el protocolo de Polyfect (Qiagen) en placas de cultivo tisular de 60 mm usando 0,01-0,1 µg del vector que contenía el constructo de scFv, 0,5 µg de un plásmido de expresión Gal4 (1-147)-VP16scFv dirigido por el promotor de CMV y 0,5 µg de un vector de expresión de lacZ como referencia para la eficacia de transfección. Se recogieron las células 24-48 horas tras la transfección, se resuspendieron en 1000 µl de tampón y se lisaron mediante tres ciclos de congelación-descongelación. Se centrifugó el lisado celular y se sometió a ensayo el sobrenadante para determinar la actividad luciferasa usando disolución de ensayo de luciferasa (Promega) y para determinar la actividad de LacZ según el protocolo convencional. Se corrigió la actividad luciferasa obtenida, con la actividad de LacZ para tener en cuenta la variación en la eficacia de transfección.
Ejemplo 3
Alineamiento múltiple y análisis de la comparación de secuencias
Para dilucidar el patrón general de secuencias de región de marco adecuadas para aplicaciones intracelulares, se aislaron todos los clones positivos (es decir, los que crecen en condiciones selectivas en el sistema de control de calidad) y se secuenció la parte que codifica para los scFv. Posteriormente, se dividieron las secuencias de scFv en sus componentes de cadena ligera y pesada para permitir el alineamiento de los dominios respectivos (tablas 1 y 2) según el esquema de numeración ajustado estructural de dominios de inmunoglobulina por Honegger (2001).
Para permitir la evaluación de los datos obtenidos, se generó un alineamiento que representaba la biblioteca no seleccionada (tabla 3). Con el fin de obtener secuencias no seleccionadas, se transformó la biblioteca en células de
E. coli que no expresan los genes de scFv y se recogieron los clones al azar para el aislamiento de plásmidos y la secuenciación de la secuencia de scFv. La biblioteca cubre el repertorio de anticuerpos humanos tal como se esperaba y por tanto no tiene sesgo hacia subgrupos específicos, distintos a los esperados por el patrón de expresión encontrado generalmente en seres humanos.
Se agruparon las secuencias de VH y VL según su subgrupo. Se destacaron los cambios en la secuencia consenso específica de subgrupo. Un experto en la técnica puede distinguir entre cambios positivos, neutros y negativos basándose en el entorno estructural del residuo intercambiado particular (por ejemplo Honegger, 2001). Un intercambio de un residuo perteneciente a un grupo particular de aminoácidos por un residuo del mismo grupo se valida en general como un intercambio neutro. Un intercambio de un residuo perteneciente al grupo de aminoácidos hidrófobos que apuntan al núcleo hidrófobo de la proteína por un aminoácido del grupo de aminoácidos polares pero no cargados o cargados positiva o negativamente sería enormemente desfavorable debido a que sitios donadores/aceptores de hidrógeno no satisfechos alteran el empaquetamiento compacto del núcleo hidrófobo. Por tanto, un cambio de este tipo se considera negativo. Un intercambio de un residuo perteneciente al grupo de aminoácidos polares pero no cargados en la superficie del dominio de inmunoglobulina por un aminoácido del grupo de aminoácidos cargados positiva o negativamente es sumamente favorable ya que aumenta la solubilidad de la proteína. Por tanto, un cambio de este tipo se valida positivamente, mientras que el intercambio de un residuo polar a uno hidrófobo es sumamente desfavorable ya que disminuye la solubilidad de la proteína y por tanto se valida negativamente. En las posiciones con un ángulo phi positivo conservado, un intercambio de cualquier aminoácido por glicina se valida positivamente mientras que un intercambio de glicina por cualquier aminoácido se valida negativamente porque la glicina es el único aminoácido que puede formar un ángulo phi positivo. La pérdida de un puente salino conservado entre las posiciones 45-53, 45-100, 77-100 y 108-137 debido a un intercambio de un aminoácido del grupo de residuos cargados positiva o negativamente por un aminoácido no cargado da como resultado una estabilidad termodinámica disminuida y, por tanto, se considera negativa.
Finalmente, se eligieron 7 dominios VL y 4 dominios VH que se seleccionaron preferentemente durante el control de calidad (es decir, mostrando los intercambios menos negativos y más positivos de la secuencia consenso y que cubren los subgrupos) y que muestran cada uno un alto funcionamiento in vivo en levadura. Las secuencias se resumen en la tabla 5 e incluyen dos Vκ1 (k I 27 (1. x) y k III 25 (2. x)), dos Vκ3 (k IV 103 (3. x) y k IV135 (5. x)), una Vλ1 (k IV 107 (4. x)), dos Vλ3 (a33 (7. x) y a43 (6. x)), una VH1b (a33 (x. 3)) y tres VH3 (una fwl0 (x. 2), a43 (x. 4) y a44 (x. 1)). Estos dominios VL y VH se intercambiaron proporcionando 22 combinaciones novedosas en el formato de scFv (1.1, 2.1, 3.1, 4.1, 5.1, 1.2, 2.2, 3.2, 4.2, 5.2, 1.3, 2.3, 3.3, 4.3, 5.3, 7.3, 1.4, 2.4, 3.4, 4.4, 5.4, 6.4).
Ejemplo 4
Evaluación del funcionamiento in vivo de dominios intercambiados
a) Funcionamiento en un ensayo intracelular en levadura y células de mamífero
Se sometieron a prueba las 22 combinaciones para determinar su funcionamiento in vivo en levadura y células de mamífero tal como se describe en el ejemplo 2 (figuras 3 y 4).
b) Expresión de proteína soluble en condiciones reductoras en levadura
Para comparar los rendimientos de proteína soluble tras la expresión en condiciones reductoras, se expresaron las
15
Claims (1)
-
imagen1
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38264902P | 2002-05-22 | 2002-05-22 | |
| US382649P | 2002-05-22 | ||
| US43825603P | 2003-01-03 | 2003-01-03 | |
| US438256P | 2003-01-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2537104T3 true ES2537104T3 (es) | 2015-06-02 |
Family
ID=29553590
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10010455.3T Expired - Lifetime ES2656427T3 (es) | 2002-05-22 | 2003-05-21 | Marcos de inmunoglobulina que demuestran estabilidad mejorada en el ambiente intracelular y métodos para su identificación |
| ES10009857.3T Expired - Lifetime ES2537104T3 (es) | 2002-05-22 | 2003-05-21 | Regiones de marco de inmunoglobulina que demuestran estabilidad potenciada en el entorno intracelular y métodos de identificación de las mismas |
| ES03732434T Expired - Lifetime ES2399617T3 (es) | 2002-05-22 | 2003-05-21 | Regiones de marco de inmunoglobulina que demuestran estabilidad potenciada en el entorno intracelulcar y métodos de identificación de las mismas |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10010455.3T Expired - Lifetime ES2656427T3 (es) | 2002-05-22 | 2003-05-21 | Marcos de inmunoglobulina que demuestran estabilidad mejorada en el ambiente intracelular y métodos para su identificación |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03732434T Expired - Lifetime ES2399617T3 (es) | 2002-05-22 | 2003-05-21 | Regiones de marco de inmunoglobulina que demuestran estabilidad potenciada en el entorno intracelulcar y métodos de identificación de las mismas |
Country Status (15)
| Country | Link |
|---|---|
| US (5) | US8853362B2 (es) |
| EP (5) | EP2332989B1 (es) |
| JP (10) | JP2006508638A (es) |
| CN (4) | CN103739706B (es) |
| AU (2) | AU2003238370B2 (es) |
| CA (2) | CA2483285C (es) |
| CY (1) | CY1114225T1 (es) |
| DK (2) | DK2332989T3 (es) |
| ES (3) | ES2656427T3 (es) |
| HK (3) | HK1071378A1 (es) |
| HU (1) | HUE048922T2 (es) |
| NZ (1) | NZ536412A (es) |
| PT (2) | PT2332989E (es) |
| SI (2) | SI2332989T1 (es) |
| WO (1) | WO2003097697A2 (es) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0226727D0 (en) * | 2002-11-15 | 2002-12-24 | Medical Res Council | Intrabodies |
| EP2371960A3 (en) * | 2005-03-25 | 2012-01-11 | National Research Council of Canada | Method for isolation of soluble polypeptides |
| AU2016204739C1 (en) * | 2005-06-07 | 2017-10-19 | Esbatech, An Alcon Biomedical Research Unit Llc | Stable and soluble antibodies inhibiting TNFalpha |
| DK2390267T3 (da) | 2005-06-07 | 2013-08-26 | Esbatech A Novartis Co Llc | Stabile og opløselige antistoffer, der hæmmer TNF(alfa) |
| AU2011265593B2 (en) * | 2005-06-07 | 2013-08-15 | Esbatech, An Alcon Biomedical Research Unit Llc | Stable and soluble antibodies inhibiting TNFalpha |
| AU2013207650B2 (en) * | 2005-06-07 | 2016-04-21 | Esbatech, An Alcon Biomedical Research Unit Llc | Stable and soluble antibodies inhibiting TNFalpha |
| RU2460540C2 (ru) | 2006-04-28 | 2012-09-10 | Деленекс Терапьютикс Аг | Антитела, связывающиеся с внеклеточным доменом тирозинкиназного рецептора (alk) |
| CN101505794B (zh) | 2006-07-10 | 2013-09-04 | 艾斯巴技术,爱尔康生物医药研究装置有限责任公司 | 穿过上皮和/或内皮层的scFV抗体 |
| EP2118138A1 (en) | 2007-03-12 | 2009-11-18 | Esbatech AG | Sequence based engineering and optimization of single chain antibodies |
| WO2008131575A2 (en) * | 2007-04-27 | 2008-11-06 | Esbatech Ag | Anti-alk antibodies suitable for treating metastatic cancers or tumors |
| WO2009000098A2 (en) * | 2007-06-25 | 2008-12-31 | Esbatech Ag | Sequence based engineering and optimization of single chain antibodies |
| CN102838673B (zh) * | 2007-06-25 | 2016-05-11 | 艾斯巴技术-诺华有限责任公司 | 修饰抗体的方法和具有改善的功能性质的修饰抗体 |
| US8323647B2 (en) | 2007-09-13 | 2012-12-04 | Delenex Therapeutics Ag | Humanized antibodies against the β-amyloid peptide |
| AU2016273957C1 (en) * | 2008-06-25 | 2019-04-18 | Novartis Ag | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFa |
| AU2015201794B2 (en) * | 2008-06-25 | 2017-01-19 | Novartis Ag | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFa |
| AU2013202997B2 (en) * | 2008-06-25 | 2015-01-22 | Novartis Ag | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFalpha |
| WO2009155723A2 (en) | 2008-06-25 | 2009-12-30 | Esbatech, An Alcon Biomedical Research Unit Llc | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFα |
| AU2009264567B2 (en) * | 2008-06-25 | 2014-06-12 | Novartis Ag | Humanization of rabbit antibodies using a universal antibody framework |
| ES2890405T3 (es) | 2008-06-25 | 2022-01-19 | Novartis Ag | Humanización de anticuerpos de conejo usando un armazón de anticuerpo universal |
| CN102143976B (zh) | 2008-06-25 | 2015-11-25 | 艾斯巴技术-诺华有限责任公司 | 抑制vegf的稳定和可溶的抗体 |
| PT2307458T (pt) * | 2008-06-25 | 2018-07-18 | Esbatech Alcon Biomed Res Unit | Humanização de anticorpos de coelho utilizando uma estrutura de anticorpos universal |
| KR101650165B1 (ko) | 2008-06-25 | 2016-08-22 | 에스바테크 - 어 노바티스 컴파니 엘엘씨 | 면역결합제의 용해도 최적화 |
| CN102089431A (zh) | 2008-06-30 | 2011-06-08 | 艾斯巴技术,爱尔康生物医药研究装置有限责任公司 | 官能化的多肽 |
| EP2769711A1 (en) | 2008-07-10 | 2014-08-27 | ESBATech, an Alcon Biomedical Research Unit LLC | Methods and Compositions for Enhanced Delivery of Macromolecules |
| SG10201708233VA (en) * | 2009-02-24 | 2017-11-29 | Esbatech Alcon Biomed Res Unit | Methods for identifying immunobinders of cell-surface antigens |
| JP5764071B2 (ja) | 2009-02-24 | 2015-08-12 | エスバテック − ア ノバルティスカンパニー エルエルシー | 細胞表面抗原のイムノバインダーを同定するための方法 |
| US8399625B1 (en) | 2009-06-25 | 2013-03-19 | ESBATech, an Alcon Biomedical Research Unit, LLC | Acceptor framework for CDR grafting |
| US9597379B1 (en) | 2010-02-09 | 2017-03-21 | David Gordon Bermudes | Protease inhibitor combination with therapeutic proteins including antibodies |
| US8771669B1 (en) | 2010-02-09 | 2014-07-08 | David Gordon Bermudes | Immunization and/or treatment of parasites and infectious agents by live bacteria |
| US8524220B1 (en) | 2010-02-09 | 2013-09-03 | David Gordon Bermudes | Protease inhibitor: protease sensitivity expression system composition and methods improving the therapeutic activity and specificity of proteins delivered by bacteria |
| UY33679A (es) | 2010-10-22 | 2012-03-30 | Esbatech | Anticuerpos estables y solubles |
| EP2476754A1 (en) * | 2011-01-14 | 2012-07-18 | Bundesrepublik Deutschland, Letztvertreten Durch Den Präsidenten Des Paul-Ehrlich-Instituts | Methods for the identification and repair of amino acid residues destabilizing single-chain variable fragments (scFv) |
| DK2744931T3 (en) | 2011-08-18 | 2018-08-06 | Affinity Biosciences Pty Ltd | SOLUBLE POLYPEPTIDES |
| CA2850572A1 (en) | 2011-10-20 | 2013-04-25 | Esbatech, A Novartis Company Llc | Stable multiple antigen-binding antibody |
| US10078085B2 (en) * | 2012-08-22 | 2018-09-18 | Mogam Biothechnology Institute | Screening and engineering method of super-stable immunoglobulin variable domains and their uses |
| KR102345999B1 (ko) | 2012-11-05 | 2021-12-30 | 델레넥스 쎄라퓨틱스 아게 | Il-1 베타 결합성분 |
| EP4001307A1 (en) | 2012-12-17 | 2022-05-25 | Cell Medica Inc. | Antibodies against il-1 beta |
| WO2014124677A1 (en) | 2013-02-15 | 2014-08-21 | Esbatech - A Novartis Company Llc | Acceptor framework for cdr grafting |
| EP2958939A1 (en) * | 2013-02-20 | 2015-12-30 | ESBATech - a Novartis Company LLC | Acceptor framework for cdr grafting |
| LT2981822T (lt) | 2013-05-06 | 2020-12-28 | Scholar Rock, Inc. | Kompozicijos ir būdai, skirti augimo faktoriaus moduliacijai |
| US9737592B1 (en) | 2014-02-14 | 2017-08-22 | David Gordon Bermudes | Topical and orally administered protease inhibitors and bacterial vectors for the treatment of disorders and methods of treatment |
| ES2941897T3 (es) | 2014-11-12 | 2023-05-26 | Seagen Inc | Compuestos que interaccionan con glicanos y procedimientos de uso |
| US9879087B2 (en) | 2014-11-12 | 2018-01-30 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
| CN107531793B (zh) | 2015-10-13 | 2022-01-11 | 优瑞科生物技术公司 | 对人类cd19具有专一性的抗体药剂和其用途 |
| CN115927191A (zh) | 2015-10-23 | 2023-04-07 | 优瑞科生物技术公司 | 抗体/t细胞受体嵌合构建体及其用途 |
| IL258768B2 (en) | 2015-11-12 | 2023-11-01 | Siamab Therapeutics Inc | Compounds interacting with glycans and methods of use |
| US11434294B2 (en) | 2016-02-25 | 2022-09-06 | Cell Medica, Inc. | Binding members to PD-L1 |
| MX2019003225A (es) * | 2016-09-21 | 2019-06-10 | Aptevo Res & Development Llc | Proteínas de unión a cd123 y composiciones y métodos relacionados. |
| EP3541847A4 (en) | 2016-11-17 | 2020-07-08 | Seattle Genetics, Inc. | COMPOUNDS INTERACTING WITH GLYCANE AND METHODS OF USE |
| 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 |
| KR20240044544A (ko) | 2017-03-03 | 2024-04-04 | 씨젠 인크. | 글리칸-상호작용 화합물 및 사용 방법 |
| CN112218621A (zh) * | 2018-04-10 | 2021-01-12 | 西北大学 | 包含基于靶向亲和域的膜蛋白的胞外囊泡 |
| US20200102373A1 (en) * | 2018-09-27 | 2020-04-02 | Colorado State University Research Foundation | Scfv's for live cell imaging and other uses |
| WO2022013787A1 (en) | 2020-07-16 | 2022-01-20 | Novartis Ag | Anti-betacellulin antibodies, fragments thereof, and multi-specific binding molecules |
| US20240150449A1 (en) | 2021-03-10 | 2024-05-09 | Mabylon Ag | Antibodies against tdp-43 and methods of using the same |
| WO2023139292A1 (en) | 2022-01-24 | 2023-07-27 | Cambridge Enterprise Limited | Tau therapy |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2919890B2 (ja) | 1988-11-11 | 1999-07-19 | メディカル リサーチ カウンスル | 単一ドメインリガンド、そのリガンドからなる受容体、その製造方法、ならびにそのリガンドおよび受容体の使用 |
| US5817311A (en) * | 1993-03-05 | 1998-10-06 | Universite Catholique De Louvain | Methods of inhibiting T-cell medicated immune responses with LO-CD2a-specific antibodies |
| DE4425115A1 (de) | 1994-07-15 | 1996-01-18 | Boehringer Mannheim Gmbh | Verfahren zur Modifizierung der Stabilität von Antikörpern |
| US6706484B1 (en) * | 1995-08-18 | 2004-03-16 | Morphosys Ag | Protein/(poly)peptide libraries |
| JP4436457B2 (ja) | 1995-08-18 | 2010-03-24 | モルフォシス アイピー ゲーエムベーハー | 蛋白質／（ポリ）ペプチドライブラリー |
| US6262238B1 (en) | 1997-01-14 | 2001-07-17 | Roche Diagnostic, Gmbh | Process for modifying the stability of antibodies |
| AU3587599A (en) | 1997-11-28 | 1999-06-16 | Invitrogen Corporation | Single chain monoclonal antibody fusion reagents that regulate transcript ion in vivo |
| GB2344886B (en) | 1999-03-10 | 2000-11-01 | Medical Res Council | Selection of intracellular immunoglobulins |
| EP2392596A3 (en) | 1999-12-28 | 2013-11-27 | ESBATech, an Alcon Biomedical Research Unit LLC | Intrabodies with defined framework that is stable in a reducing environment and applications thereof |
| GB0008419D0 (en) | 2000-04-05 | 2000-05-24 | Bioinvent Int Ab | A method for invitro molecular evolution of antibody function |
| EP1156062A1 (en) | 2000-05-12 | 2001-11-21 | GPC Biotech AG | Immunomodulatory human MHC class II antigen-binding peptides/proteins |
| US6410271B1 (en) | 2000-06-23 | 2002-06-25 | Genetastix Corporation | Generation of highly diverse library of expression vectors via homologous recombination in yeast |
| DE10039191C1 (de) | 2000-08-10 | 2002-01-17 | Infineon Technologies Ag | Hochfrequenz-Eingangsstufe |
-
2003
- 2003-05-21 WO PCT/EP2003/005324 patent/WO2003097697A2/en active Application Filing
- 2003-05-21 CN CN201410031953.4A patent/CN103739706B/zh not_active Expired - Lifetime
- 2003-05-21 SI SI200332427T patent/SI2332989T1/sl unknown
- 2003-05-21 ES ES10010455.3T patent/ES2656427T3/es not_active Expired - Lifetime
- 2003-05-21 EP EP10009857.3A patent/EP2332989B1/en not_active Expired - Lifetime
- 2003-05-21 JP JP2004506369A patent/JP2006508638A/ja not_active Withdrawn
- 2003-05-21 CN CN201510685456.0A patent/CN105175535A/zh active Pending
- 2003-05-21 CN CN038146266A patent/CN1662556B/zh not_active Expired - Lifetime
- 2003-05-21 PT PT100098573T patent/PT2332989E/pt unknown
- 2003-05-21 ES ES10009857.3T patent/ES2537104T3/es not_active Expired - Lifetime
- 2003-05-21 PT PT37324340T patent/PT1506236E/pt unknown
- 2003-05-21 US US10/515,241 patent/US8853362B2/en active Active
- 2003-05-21 HU HUE15160739A patent/HUE048922T2/hu unknown
- 2003-05-21 EP EP19200477.8A patent/EP3656787A1/en not_active Withdrawn
- 2003-05-21 ES ES03732434T patent/ES2399617T3/es not_active Expired - Lifetime
- 2003-05-21 SI SI200332610T patent/SI2947095T1/sl unknown
- 2003-05-21 CN CN201010575786.1A patent/CN102093477B/zh not_active Expired - Lifetime
- 2003-05-21 AU AU2003238370A patent/AU2003238370B2/en not_active Expired
- 2003-05-21 EP EP10010455.3A patent/EP2314622B1/en not_active Expired - Lifetime
- 2003-05-21 CA CA2483285A patent/CA2483285C/en not_active Expired - Lifetime
- 2003-05-21 DK DK10009857.3T patent/DK2332989T3/en active
- 2003-05-21 NZ NZ536412A patent/NZ536412A/en not_active IP Right Cessation
- 2003-05-21 DK DK03732434.0T patent/DK1506236T3/da active
- 2003-05-21 EP EP15160739.7A patent/EP2947095B1/en not_active Expired - Lifetime
- 2003-05-21 EP EP03732434A patent/EP1506236B1/en not_active Expired - Lifetime
- 2003-05-21 CA CA2867542A patent/CA2867542C/en not_active Expired - Lifetime
-
2005
- 2005-05-13 HK HK05104060.2A patent/HK1071378A1/xx not_active IP Right Cessation
-
2010
- 2010-03-17 JP JP2010060713A patent/JP2010187678A/ja not_active Withdrawn
- 2010-06-24 AU AU2010202634A patent/AU2010202634B2/en not_active Expired
-
2011
- 2011-06-23 HK HK11106519.6A patent/HK1152320A1/xx not_active IP Right Cessation
-
2012
- 2012-08-28 JP JP2012187518A patent/JP6075836B2/ja not_active Expired - Lifetime
-
2013
- 2013-02-04 JP JP2013019425A patent/JP6100544B2/ja not_active Expired - Lifetime
- 2013-04-08 CY CY20131100292T patent/CY1114225T1/el unknown
- 2013-09-19 JP JP2013193935A patent/JP2013256533A/ja active Pending
-
2014
- 2014-08-26 US US14/469,276 patent/US9518108B2/en not_active Expired - Lifetime
-
2015
- 2015-08-19 JP JP2015161600A patent/JP6261136B2/ja not_active Expired - Lifetime
- 2015-08-19 JP JP2015161601A patent/JP2015214583A/ja active Pending
-
2016
- 2016-05-16 HK HK16105597.8A patent/HK1217712A1/zh not_active IP Right Cessation
- 2016-11-01 US US15/340,195 patent/US10125186B2/en not_active Expired - Lifetime
-
2017
- 2017-08-24 JP JP2017161036A patent/JP2017201990A/ja active Pending
-
2018
- 2018-10-30 US US16/175,002 patent/US10570190B2/en not_active Expired - Fee Related
-
2019
- 2019-01-23 JP JP2019009288A patent/JP6918033B2/ja not_active Expired - Lifetime
- 2019-12-16 US US16/716,137 patent/US20200165322A1/en not_active Abandoned
-
2020
- 2020-05-14 JP JP2020085288A patent/JP2020171286A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2537104T3 (es) | Regiones de marco de inmunoglobulina que demuestran estabilidad potenciada en el entorno intracelular y métodos de identificación de las mismas | |
| WO2021254341A1 (zh) | 一种冠状病毒假病毒包装系统及其包装方法、冠状病毒假病毒在评估消杀效力中的应用 | |
| Hawes et al. | The endoplasmic reticulum: a dynamic and well‐connected organelle | |
| Yuwen et al. | Nuclear localization of a double-stranded RNA-binding protein encoded by the vaccinia virus E3L gene | |
| Guo et al. | The NS16 protein of aquareovirus-C is a fusion-associated small transmembrane (FAST) protein, and its activity can be enhanced by the nonstructural protein NS26 | |
| Seiradake et al. | Production of cell surface and secreted glycoproteins in mammalian cells | |
| Boncompain et al. | Synchronizing protein transport in the secretory pathway | |
| EP2674497A1 (en) | A light regulated transgene expression system | |
| ES2547700T3 (es) | Nueva línea de células humanas permanente | |
| AR020331A1 (es) | Construccion, y metodo para producir una proteina en una celula de planta | |
| Giarola et al. | What can we learn from the transcriptome of the resurrection plant Craterostigma plantagineum? | |
| Fonstein et al. | Chromosomal structure of Rhodobacter capsulatus strain SB1003: cosmid encyclopedia and high-resolution physical and genetic map. | |
| Lee et al. | Kinesin motors in plants: from subcellular dynamics to motility regulation | |
| HRP20192243T1 (hr) | Polipeptidni ekspresijski sustavi | |
| Cheley et al. | Cellular synthesis and modification of murine hepatitis virus polypeptides | |
| UY24667A1 (es) | Metodo para inmortalizar celulas de pollo | |
| Kubíková et al. | Structural basis for binding of Drosophila Smaug to the GPCR Smoothened and to the germline inducer Oskar | |
| Bétermier et al. | Functional domains of bacteriophage Mu transposase: properties of C‐terminal deletions | |
| ES2507665T3 (es) | Recombinación de ADN específica de secuencia en células eucariotas | |
| Morgan et al. | An essential and highly selective protein import pathway encoded by nucleus-forming phage | |
| Luo et al. | Cotreatment with RepSox and LBH589 improves the in vitro developmental competence of porcine somatic cell nuclear transfer embryos | |
| Juillot et al. | Signalling to the nucleus under the control of light and small molecules | |
| Makuch | Yeast two-hybrid screen | |
| Huang et al. | Involvement of G9A-like protein (GLP) in the development of mouse preimplantation embryos in vitro | |
| Xu et al. | A mammalian expression system for high throughput antibody screening |