ES2499040T3 - Moléculas de unión para las proteínas similares al factor VIII y factor VIII humano - Google Patents
Moléculas de unión para las proteínas similares al factor VIII y factor VIII humano Download PDFInfo
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- ES2499040T3 ES2499040T3 ES10182747.5T ES10182747T ES2499040T3 ES 2499040 T3 ES2499040 T3 ES 2499040T3 ES 10182747 T ES10182747 T ES 10182747T ES 2499040 T3 ES2499040 T3 ES 2499040T3
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- cys
- phe
- factor viii
- pro
- trp
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- 230000027455 binding Effects 0.000 title abstract description 6
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 title abstract description 4
- 102000057593 human F8 Human genes 0.000 title abstract description 4
- 229960000900 human factor viii Drugs 0.000 title abstract description 4
- 102000001690 Factor VIII Human genes 0.000 title description 4
- 108010054218 Factor VIII Proteins 0.000 title description 4
- 229960000301 factor viii Drugs 0.000 title description 4
- 102000004169 proteins and genes Human genes 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 title 1
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 22
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 20
- 229920001184 polypeptide Polymers 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 2
- 239000008280 blood Substances 0.000 abstract 1
- 210000004369 blood Anatomy 0.000 abstract 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 239000003636 conditioned culture medium Substances 0.000 abstract 1
- 239000003446 ligand Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 238000004007 reversed phase HPLC Methods 0.000 description 10
- 150000001413 amino acids Chemical group 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 2
- 238000008157 ELISA kit Methods 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- -1 formyl-substituted ethylene glycol methacrylate Chemical class 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-M hydrosulfide Chemical compound [SH-] RWSOTUBLDIXVET-UHFFFAOYSA-M 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Reciprocating Pumps (AREA)
Abstract
polipéptido que se une a un Factor VIII o un fragmento de este que retiene actividad procoagulante del factor VIII, en donde dicho polipéptido comprende una secuencia de aminoácido seleccionada del grupo que consiste de: Phe-Gly-Cys-Ser-Trp-Leu-Phe-Pro-Cys-Pro-Phe (sec. con núm. de ident.:5); Pro-His-Cys-Asn-Trp-Leu-Phe-Pro-Cys-Ser-Leu (sec. con núm. de ident.:6); Arg-Leu-Cys-Ser-Trp-Ile-Ser-Pro-Cys-Ser-Ala (sec. con núm. de ident.:7); Phe-His-Cys-Ile-Gly-Val-Trp-Phe-Cys-Leu-His (sec. con núm. de ident.:8); y Arg-Leu-Cys-Ser-Trp-Val-Ser-Pro-Cys-Ser-Ala (sec. con núm. de ident.:9).
Description
E10182747
04-09-2014
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- Tabla 2 :
- Secuencias de aminoácido de los polipéptidos de unión objetivo a partir de la genoteca TN8
- TN8 aislado
- Secuencia frecuencia (elución) Señal ELISA Sec. con núm. de ident.:
- C10
- His-Pro-Cys-Cly-Ser-Trp-Leu-Arg-Pro-Cys-Leu-His 10/192 (EG/pH2) 1.0 10
- B05
- Arg-Gly-Cys-Gly-Ser-Trp-Leu-Arg-Pro-Cys-Leu-Asp 2/192 (EG/pH2) 0.2 11
- E04
- His-Pro-Cys-Gly-Ser-Trp-Leu-His-Pro-Cys-Ala-Ala 3/192 (EG/pH2) 0.3 12
- F02
- His-Pro-Cys-Gly-Ser-Trp-Phe-Asn-Pro-CyS-Ala-His 5/192 (EG/pH2) 0.3 13
- A02
- His-Pro-Cys-Gly-Ser-Trp-Phe-Arg-Pro-Cys-Phe-His 3/96 (EG) 0.7 14
- H07
- His-Ala-Cys-Gly-Ser-Th-Phe-Arg-Pro-Cys-His-Ala 3/192 0.4 15
- E02
- His-Leu-Cys-Gly-Ala-Trp-Phe-Arg-Pre-Cys-Asp-Ala 6/192 (EG/pH2) 0.4 16
- C12
- His-Leu-Cys-Phe-Ala-Trp-Phe-Arg-Pro-Cys-Asp-Ala 1/96 (EG) 0.4 17
- A01
- His-Gly-Cys-Gly-Ala-Trp-Phe-Arg-Pro-Cys-His-Ala 4/192 (EG/pH2) 0.2 18
- E01
- His-Pro-Cys-Gly-Ala-Trp-Phe-Asn-Pro-Cys-Pro-Arg 1/96 (pH2) 0.2 19
- H08
- His-Pro-Cys-Gly-Ala-Trp-Leu-Arg-Pro-Cys-Tyr-Asn 1/96 (EG) 1.0 20
- A11/G 10
- His-Arg-Cys-Gly-Ser-Trp-Leu-His-Pro-Cys-Leu-Ala 1/96 (EG) 0.3 21
- Tabla 3 :
- Secuencias de aminoácido de los polipéptidos de unión objetivo a partir de la genoteca TN9
- TN9 aislado
- Secuencia frecuencia (elución) Señal ELISA Sec. con núm. de ident.:
- B04
- Phe-Cys-Trp-Val-Phe-Ala-Phe-Asp-His-Cys-His 6/192 (EG/pH2) 0.8 22
- G02
- Phe-Cys-Trp-Val-His-Pro-Phe-Ala-His-Cys-Leu 2/96 (EG) 0.2 23
- B01
- Phe-Cys-His-Val-Phe-Ris-Phe-Ser-His-Cys-Asp 5/192 (EG/pH2) 0.2 24
- A01
- Phe-Cys-Trp-Val-Phe-Ala-Phe-Asp-His-Cys-His 12/192 (EG/pH2) 1.2 25
- E03
- Phe-Cys-Trp-Val-Pbe-Asn-Phe-Ser-His-Cys-Ser 4/192 (EG/pH2) 1.1 26
- C02
- Phe-Cys-Trp-Val-Phe-Pro-Phe-Asn-His-Cys-Asp 5/96 (pH2) 0.4 27
- E12
- Pho-Cys-Trp-Val-Phe-Pro-Phe-Asn-His-Cys-Ser 6/96 (EG) 1.0 28
- E09
- Phe-Cys-Trp-Val-Phe-Pro-Phe-Gln-Cys-Ala 4/192 (EG/pH2) 1.1 29
- D06
- Phe-Cys-Trp-Val-Phe-Pro-Phe-His-His-Cys-Phe 2/192 (EG/pH2) 0.3 30
- C01
- Phe-Cys-His-Val-Phe-Asn-Phe-Val-His-Cys-Ser 2/192 (EG/pH2) 0.5 31
- H11
- Phe-Cys-His-Val-Phe-Pro-Phe-Leu-His-Cys-Asp 2/192 (EG/pH2) 0.2 32
Ejemplo II: Preparación de Ligandos de Afinidad para un Factor VIII Diana
55 Basándose en los datos presentados anteriormente, se seleccionaron y sintetizaron nueve péptidos para la inmovilización sobre un material de matriz de afinidad. Los péptidos sintetizados se indican en la Tabla 4.
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E10182747
04-09-2014
Tabla 4
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- Secuencia de Aminoácidos de los Ligandos de Afinidad y sus Densidades sobre un Soporte Sólido
- Ligando de afinidad
- Fago aislado Secuencia (Bucle bisulfuro subrayado) Densidad del Ligando mg/ml (µmol/ml)
- CS-453
- C10-TN8 AEGTGDHPCGSWLRPCLHDPGPEGGGS-NHMH2 2.64 (0.98)
- CS-454
- E02-TN8 AEGTGDHLCGAWFRPCDADPGPEGGGS-NHNH2 1.79 (0.67)
- CS-455
- A09-TN7 AEGTGDFHCIGVWFCLHDPGPEGGGS-NHNH2 2.21 (0.83)
- CS-456
- A08-TN7 AEGTGDFGCSWLFPCPFDPGPEGGGS-NHNH2 3.69 (1.43)
- CS-458
- B04-TN9 AEGTGDFCWVFAFDHCHDPGPEGGGS-NHNH2 3.15 (1.17)
- CS-459
- E09-TN9 AEGTGDFCWVFPEQHCADPGPEGGGS-NHNH2 2.72 (1.02)
- CS-460
- D06-TN9 AEGTGDFCWVFPFHHCFDPGPEGGGS-NHNH2 4.24 (1.54)
- GI-1
- C05/G10-TN7 Acetil-AEGTGDRLCSWVSPCSADPEGGGSK 0.83 (0.32)
- GI-2
- A11/G10-TN8 Acetil-AEGTGDHRCGSWLHPCLADPEGGGSK 0.43 (0.16)
30
Los péptidos de afinidad de la Tabla 4 se identifican, en el orden anterior, con las sec. con núms. de ident.: 36-44.
Los nueve primeros péptidos de afinidad fueron producidos por métodos de síntesis clásicos en fase sólida como se describe anteriormente. Para facilitar la inmovilización sobre un soporte sólido, una región enlazadora corta de siete
35 aminoácidos hidrazida-funcional (-PGPEGGGS-NHNH2; SEC. CON NÚM. DE IDENT.: 45) fue incorporada en el extremo carboxi-terminal de siete de los péptidos (véase la Tabla 4). Un enlazador de inmovilización alternativo se utilizó con dos de los péptidos (GI-1 y GI-2 en la Tabla 4), es decir, -PEGGGSK; (SEC. CON NÚM. DE IDENT.: 46), exhibiendo una lisina Cterminal para la inmovilización y un amino-terminal acetilado.
40 Los ligandos candidatos se inmovilizaron sobre una resina cromatográfica de etilenglicol metacrilato formil-sustituido (Toyopearl Formyl 650-M, tamaño de poro de ~1000Å; TosoHaas, Montgomeryville, PA). Los péptidos que contienen hidrazida se inmovilizaron para facilitar la formación del enlace hidrazona, los péptidos GI-1 y -2 se inmovilizaron mediante aminación reductora usando NaCNBH3. La cantidad de polipéptido inmovilizado sobre el soporte sólido se determinó mediante la cuantificación de la cantidad de polipéptido libre restante en solución. La cantidad de ligando inmovilizado por ml
45 de resina estaba en el intervalo de 0.7-1.5µmol para los péptidos de hidrazina inmovilizados.
Los nueve péptidos fueron evaluados por cromatografía de afinidad por su capacidad para capturar el REFACTO® descrito en el Ejemplo I, bajo condiciones específicas de unión y liberación. Los tampones usados en estas evaluaciones se exponen en la Tabla 5.
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E10182747
04-09-2014
Tabla 6
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- Resumen de los Datos Obtenidos con Nueve Ligandos de Afinidad
- Condición de elución (% Recuperación)
- Péptido
- Prueba Flujo a B pH2 Total
- Resina sin tratar
- Actividad RP-HPLC 64.4 2.8 0 0 67.2
- 64.4
- 0.6 65.0
- CS-453
- Actividad RP-HPLC 0 43.2 0 0 43.2
- 0
- 26.4 26.4
- CS-454
- Actividad RP-HPLC 2.5 45.1 0 0 47.6
- 2.2
- 42.4 44.6
- CS-455
- Actividad RP-HPLC 65.8 1.4 0 0 67.2
- 61.6
- 1.3 62.9
- CS-456
- Actividad RP-HPLC 3.4 44.8 0 0 48.2
- 4.8
- 43.0 47.8
- CS-458
- Actividad RP-HPLC 1.8 54.3 0 0 56.1
- 1.4
- 55,6 57.0
- CS-459
- Actividad RP-HPLC 1.5 42.1 0 0 43.7
- 6.4
- 31.2 37.6
- CS-460
- Actividad RP-HPLC 24.6 28.8 0 0 53.4
- 28.4
- 0
- 28.4
- GI-1
- Actividad RP-HPLC 65.7 0 0 0 65.7
- 64.0
- 0
- 64.0
- GI-2
- Actividad RP-HPLC 31.3 28.1 0 2.0 61.4
- 33.7
- 20.3 53.9
En general, la cantidad total de factor VIII diana recuperada después de la cromatografía sobre los nueve ligandos estaba en el rango de 40-67%. Los ligandos de polipéptido CS-453, CS-454, CS-456 y CS-459 capturaron prácticamente todo el factor
45 VIII diana aplicado, con material unido eluido en presencia de etilenglicol. No se encontró actividad en el eluato de pH 2, por lo tanto, se supuso que ninguna diana permaneció unida al ligando, La incapacidad de las resinas CS-455 y GI-1 para capturar la diana puede ser debido a la degradación o inestabilidad del péptido, o a la baja densidad del ligando en el soporte.
50 Ejemplo III: Comparativo Unión de nhfVIII y REFACTO®
Se realizaron experimentos para demostrar que los ligandos de polipéptido inmovilizado del Ejemplo II unen y liberan el factor VIII humano nativo (nhfVIII) en condiciones similares y con rendimientos similares a los observados con REFACTO® el polipéptido similar a factor VIII.
55 Para estos experimentos, el nhfVIII se obtuvo de American Diagnostica, Inc. (Greenwich, CT; producto # 408 nat) en forma de un polvo liofilizado que contiene agentes estabilizantes. El nhfVIII se reconstituyó según las instrucciones del fabricante en un tampón de reconstitución (72 mM NH4OAc, pH 6.3, 360 mM NaCl, 0.04% Tween 80 (Tampón 1). Un kit comercial ELISA (kit IMUBIND fVIII ELISA, Producto # 884, American, Inc., Greenwich, CT) desarrollado para detectar
60 el factor VIII se utilizó de acuerdo con las especificaciones del fabricante, a fin de detectar tanto la REFACTO® como las
15
Claims (1)
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imagen1 imagen2
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US224785 | 1999-01-04 | ||
| US09/224,785 US6197526B1 (en) | 1999-01-04 | 1999-01-04 | Polypeptides for binding human factor VIII and fragments of human factor VIII |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2499040T3 true ES2499040T3 (es) | 2014-09-26 |
Family
ID=22842198
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06009040T Expired - Lifetime ES2328722T3 (es) | 1999-01-04 | 2000-01-03 | Moleculas de union para proteinas de factor humano viii y de tipo factor viii. |
| ES10182747.5T Expired - Lifetime ES2499040T3 (es) | 1999-01-04 | 2000-01-03 | Moléculas de unión para las proteínas similares al factor VIII y factor VIII humano |
| ES10182741.8T Expired - Lifetime ES2524965T3 (es) | 1999-01-04 | 2000-01-03 | Moléculas de unión para las proteínas similares al factor VIII y factor VIII humano |
| ES09155033T Expired - Lifetime ES2390360T3 (es) | 1999-01-04 | 2000-01-03 | Moléculas de unión para el factor VIII humano y proteínas similares al factor VIII humano |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06009040T Expired - Lifetime ES2328722T3 (es) | 1999-01-04 | 2000-01-03 | Moleculas de union para proteinas de factor humano viii y de tipo factor viii. |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10182741.8T Expired - Lifetime ES2524965T3 (es) | 1999-01-04 | 2000-01-03 | Moléculas de unión para las proteínas similares al factor VIII y factor VIII humano |
| ES09155033T Expired - Lifetime ES2390360T3 (es) | 1999-01-04 | 2000-01-03 | Moléculas de unión para el factor VIII humano y proteínas similares al factor VIII humano |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US6197526B1 (es) |
| EP (5) | EP2298791B8 (es) |
| JP (3) | JP4733272B2 (es) |
| AT (1) | ATE433992T1 (es) |
| AU (3) | AU769745B2 (es) |
| CA (1) | CA2354599C (es) |
| DE (1) | DE60042430D1 (es) |
| DK (4) | DK2090582T3 (es) |
| ES (4) | ES2328722T3 (es) |
| HK (1) | HK1038756A1 (es) |
| PT (3) | PT1705183E (es) |
| WO (1) | WO2000040602A1 (es) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7820796B2 (en) * | 1998-03-12 | 2010-10-26 | Genetics Institute, Llc. | Methods for producing Factor VIII proteins |
| US6197526B1 (en) * | 1999-01-04 | 2001-03-06 | Dyax Corp. | Polypeptides for binding human factor VIII and fragments of human factor VIII |
| US7112438B2 (en) | 1999-01-04 | 2006-09-26 | Dyax Corp. | Binding molecules for human factor VIII and factor VIII-like proteins |
| FR2830865B1 (fr) * | 2001-10-17 | 2004-10-22 | Centre Nat Rech Scient | Leurres peptidiques pour la preparation de medicaments destines a la prevention ou au traitement des pathologies auto-immunes, ou des troubles lies a l'apparition d'anticorps diriges contre des proteines exogenes |
| US20030149246A1 (en) * | 2002-02-01 | 2003-08-07 | Russell John C. | Macromolecular conjugates and processes for preparing the same |
| EP1504265B1 (en) * | 2002-04-29 | 2011-11-30 | Affibody AB | Sandwich assay |
| US20090215025A1 (en) * | 2005-12-07 | 2009-08-27 | Technische Universitat Munchen | Small peptidic and peptido-mimetic affinity ligands for factor viii and factor viii-like proteins |
| TW200745163A (en) | 2006-02-17 | 2007-12-16 | Syntonix Pharmaceuticals Inc | Peptides that block the binding of IgG to FcRn |
| EP2156179B1 (en) | 2007-04-04 | 2021-08-18 | The Regents of The University of California | Methods for using a nanopore |
| TW200911289A (en) | 2007-08-09 | 2009-03-16 | Syntonix Pharmaceuticals Inc | Immunomodulatory peptides |
| TWI573806B (zh) | 2008-04-17 | 2017-03-11 | 巴克斯歐塔公司 | 生物活性胜肽 |
| WO2010014909A1 (en) * | 2008-08-01 | 2010-02-04 | Syntonix Pharmaceuticals, Inc. | Immunomodulatory peptides |
| US8324914B2 (en) | 2010-02-08 | 2012-12-04 | Genia Technologies, Inc. | Systems and methods for characterizing a molecule |
| SG191186A1 (en) | 2010-12-15 | 2013-07-31 | Baxter Int | Eluate collection using conductivity gradient |
| US9486507B2 (en) * | 2011-06-10 | 2016-11-08 | Biogen Ma Inc. | Pro-coagulant compounds and methods of use thereof |
| CA2930665A1 (en) | 2013-11-18 | 2015-05-21 | Rubius Therapeutics, Inc. | Synthetic membrane-receiver complexes |
| CN109689682B (zh) | 2016-09-19 | 2022-11-29 | 豪夫迈·罗氏有限公司 | 基于补体因子的亲和层析 |
| SG11202000979SA (en) | 2017-08-04 | 2020-02-27 | Shire Human Genetic Therapies | Antibody-resin coupling apparatus and methods |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4757006A (en) | 1983-10-28 | 1988-07-12 | Genetics Institute, Inc. | Human factor VIII:C gene and recombinant methods for production |
| SE8501050D0 (sv) | 1985-03-05 | 1985-03-05 | Kabivitrum Ab | Biologically active fragments of human antihemophilic factor and method for preparation thereof |
| ES8801674A1 (es) | 1985-04-12 | 1988-02-16 | Genetics Inst | Un procedimiento para la preparacion de una proteina que presenta actividad procoagulante. |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| EP0436597B1 (en) * | 1988-09-02 | 1997-04-02 | Protein Engineering Corporation | Generation and selection of recombinant varied binding proteins |
| US5661008A (en) | 1991-03-15 | 1997-08-26 | Kabi Pharmacia Ab | Recombinant human factor VIII derivatives |
| SE468050C (sv) * | 1991-03-15 | 1998-04-27 | Pharmacia & Upjohn Ab | Rekombinant derivat av human faktor VIII |
| AU1757592A (en) * | 1991-03-27 | 1992-11-02 | Scripps Research Institute, The | Therapeutic fragments of von willebrand factor |
| WO1997035196A1 (en) * | 1996-03-20 | 1997-09-25 | Dyax Corp. | Engineering affinity ligands for macromolecules |
| US5817752A (en) | 1996-06-06 | 1998-10-06 | La Jolla Pharmaceutical Company | Cyclic polypeptides comprising a thioether linkage and methods for their preparation |
| KR20000016414A (ko) | 1996-06-06 | 2000-03-25 | 와이즈먼 앤드루 | Apl 면역반응성 펩티드, 그것의 콘주게이트 및 apl항체-매개병변의 치료방법 |
| PT1095143E (pt) * | 1998-05-08 | 2008-11-28 | Sanquin Bloedvoorziening | Inibidor para o diagnóstico e tratamento de doentes com hemofilia a |
| US5994310A (en) | 1998-09-03 | 1999-11-30 | Bayer Corporation | Peptide ligands for affinity purification of human Factor VIII |
| US6197526B1 (en) * | 1999-01-04 | 2001-03-06 | Dyax Corp. | Polypeptides for binding human factor VIII and fragments of human factor VIII |
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1999
- 1999-01-04 US US09/224,785 patent/US6197526B1/en not_active Expired - Lifetime
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2000
- 2000-01-03 JP JP2000592310A patent/JP4733272B2/ja not_active Expired - Lifetime
- 2000-01-03 DK DK09155033.5T patent/DK2090582T3/da active
- 2000-01-03 EP EP10182741.8A patent/EP2298791B8/en not_active Expired - Lifetime
- 2000-01-03 ES ES06009040T patent/ES2328722T3/es not_active Expired - Lifetime
- 2000-01-03 CA CA2354599A patent/CA2354599C/en not_active Expired - Lifetime
- 2000-01-03 EP EP06009040A patent/EP1705183B1/en not_active Expired - Lifetime
- 2000-01-03 DK DK10182747.5T patent/DK2301953T3/da active
- 2000-01-03 PT PT06009040T patent/PT1705183E/pt unknown
- 2000-01-03 PT PT101827475T patent/PT2301953E/pt unknown
- 2000-01-03 AT AT06009040T patent/ATE433992T1/de active
- 2000-01-03 EP EP10182747.5A patent/EP2301953B1/en not_active Expired - Lifetime
- 2000-01-03 ES ES10182747.5T patent/ES2499040T3/es not_active Expired - Lifetime
- 2000-01-03 HK HK02100182.6A patent/HK1038756A1/zh unknown
- 2000-01-03 EP EP00904186A patent/EP1147128A4/en not_active Withdrawn
- 2000-01-03 EP EP09155033A patent/EP2090582B1/en not_active Expired - Lifetime
- 2000-01-03 WO PCT/US2000/000043 patent/WO2000040602A1/en not_active Ceased
- 2000-01-03 DK DK06009040T patent/DK1705183T3/da active
- 2000-01-03 ES ES10182741.8T patent/ES2524965T3/es not_active Expired - Lifetime
- 2000-01-03 PT PT101827418T patent/PT2298791E/pt unknown
- 2000-01-03 DK DK10182741.8T patent/DK2298791T3/en active
- 2000-01-03 AU AU25982/00A patent/AU769745B2/en not_active Expired
- 2000-01-03 ES ES09155033T patent/ES2390360T3/es not_active Expired - Lifetime
- 2000-01-03 DE DE60042430T patent/DE60042430D1/de not_active Expired - Lifetime
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2001
- 2001-01-08 US US09/756,594 patent/US6492105B2/en not_active Expired - Lifetime
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2004
- 2004-04-30 AU AU2004201810A patent/AU2004201810A1/en not_active Abandoned
- 2004-04-30 AU AU2004201830A patent/AU2004201830B2/en not_active Expired
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2010
- 2010-05-10 JP JP2010108017A patent/JP5368371B2/ja not_active Expired - Lifetime
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2012
- 2012-12-27 JP JP2012284538A patent/JP5572207B2/ja not_active Expired - Lifetime
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