ES2506665T3 - Polipéptidos homólogos IL-17 e IL-17R y usos terapéuticos de los mismos - Google Patents
Polipéptidos homólogos IL-17 e IL-17R y usos terapéuticos de los mismos Download PDFInfo
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- ES2506665T3 ES2506665T3 ES09009972.2T ES09009972T ES2506665T3 ES 2506665 T3 ES2506665 T3 ES 2506665T3 ES 09009972 T ES09009972 T ES 09009972T ES 2506665 T3 ES2506665 T3 ES 2506665T3
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Abstract
Anticuerpo antagonista aislado que se une a un polipéptido IL-17E (PRO10272) (a) que consiste en los aminoácidos 1 a 177 o los aminoácidos 33 a 177 de la secuencia de aminoácidos mostrada en la figura 6, o (b) está codificado por la secuencia codificante de longitud completa del ADNc (DNA 147531-2821) depositado bajo el número de acceso ATCC PTA-1185, y que: (i) bloquea la unión de dicho polipéptido IL-17E al polipéptido IL-17RH1 (PRO5801) de la figura 12; y/o (ii) inhibe la actividad de IL-17E para estimular la producción de IL-8 en células TK-10; y/o (iii) inhibe la actividad de IL-17E para activar NF-kB en células 293 y/o células TK-10.
Description
E09009972
03-10-2014
- Residuos originales
- Sustituciones Ejemplares Sustituciones preferentes
- Ala (A)
- val, leu, ile val
- Arg (R)
- lys; gln; asn lys
- Asn (N)
- gln, su; lys; arg gln
- Asp (D)
- glu glu
- Cys (C)
- ser ser
- Gln (Q)
- asn asn
- Glu (E)
- asp asp
- Gly (G)
- pro; ala ala
- Su (H)
- asn, gln, lys; arg arg
- Ile (I)
-
leu; val; met; ala; phe;
imagen35
- imagen36
- norleucina leu
- Leu (L)
- norleucina; ile; val; met; ala; phe ile
- Lys (K)
- arg; gln; asn arg
- Met (M)
- leu; phe; ile leu
- Phe (F)
- leu, val, ile; ala; tyr leu
- Pro (P)
- ala ala
- Ser (S)
- thr thr
- Thr (T)
- ser ser
- Trp (W)
- tyr; phe tyr
- Tyr (Y)
- prt; phe; thr; ser phe
- Val (V)
- ile; leu; met; phe; ala; norleucina leu
Las modificaciones sustanciales en la función inmunológica o la identidad del polipéptido PRO se llevan a cabo mediante la selección de sustituciones que difieren considerablemente en su efecto sobre el mantenimiento de (a) la estructura del esqueleto del polipéptido en el ámbito de la sustitución, por ejemplo, como una conformación en hoja o
5 helicoidal, (b) la carga o hidrofobicidad de la molécula en el sitio de destino, o (c) la mayor parte de la cadena lateral. Los residuos que se producen naturalmente se dividen en grupos basados en la propiedades comunes de la cadena lateral:
(1) hidrofóbico: norleucina, met, ala, val, leu, ile;
(2) hidrofílico neutral: cys, ser, thr; 10 (3) ácido: ASP, glu;
- (4)
- de base: asn, gln, su, lys, arg;
- (5)
- residuos que influyen en la orientación de la cadena: gly, pro, y
- (6)
- aromáticos: trp, tyr, phe.
15 Las sustituciones no conservadores implicarán el intercambio de un elemento de una de estas clases por otra clase. Estos residuos sustituidos también pueden introducirse en los sitios de sustitución conservadora o, más preferiblemente, en los restantes sitios (no conservados).
Las variaciones se pueden realizar utilizando los procedimientos conocidos en el arte como mutagénesis mediada por
20 oligonucleótidos (sitio-dirigida), escaneo de alanina, y mutagénesis de PCR. Mutagénesis dirigida [Carter et al., Nucl. Acids Res., 13:4331 (1986); Zoller et al., Nucl. Acids Res., 10:6487 (1987)], mutagénesis cassette (Wells et al., Gene,
34:315 [1985]), mutagénesis de selección de restricción (Wells et al., Philos. Trans. R. Soc. London SerA, 317:415 [1986]) u otras técnicas conocidas pueden realizarse en el ADN clonado para producir el ADN variante PRO.
25 El análisis de escaneo de aminoácidos también puede ser empleado para identificar uno o más aminoácidos a lo largo de una secuencia contigua. Entre los aminoácidos de exploración preferidos están aminoácidos relativamente pequeños, neutrales. Estos aminoácidos son la alanina, glicina, serina y cisteína. La alanina es típicamente un aminoácido de exploración preferido en este grupo, ya que elimina la cadena lateral más allá del beta-carbono y tiene menos posibilidades de alterar la conformación de la cadena principal de la variante (Cunningham y Wells, Science,
36
E09009972
03-10-2014
- Molécula de ADN
- Tejidos con expresión significativa Tejidos sin expresión significativa
- DNA1738942974
- altamente expresada en el músculo, la columna vertebral y el cerebro no se expresa en la glándula del intestino, mama, la médula, el útero, la tráquea, de colon, las glándulas salivales, pulmón, páncreas, hígado, próstata, las glándulas suprarrenales, los riñones, el timo, la placenta, el corazón, el estómago y el bazo
- DNA1475312821
- expresada en bajos niveles en el cerebro, riñón, pulmón, próstata, testículos, la médula espinal, la glándula suprarrenal y en la tráquea sin expresión en el corazón, hígado, colon, la médula, el músculo del intestino, bazo, estómago, útero, la placenta, timo, el músculo, el útero, la placenta, el páncreas, las glándulas salivales y la glándula mamaria
- Molécula de ADN
- Tejidos con expresión significativa Tejidos sin expresión significativa
- DNA166819
- altamente expresada en los testículos, el timo del riñón y estómago no se expresa en la glándula del intestino, mama, la médula, el útero, la tráquea, de colon, las glándulas salivales, pulmón, músculo, páncreas, hígado, próstata, glándulas suprarrenales, la placenta del corazón, la columna vertebral, el cerebro y el bazo
- Molécula de ADN
- Tejidos con expresión significativa Tejidos sin expresión significativa
- DNA1152912681
- altamente expresada en el riñón; expresión significativa en el hígado y los órganos periféricos como el colon, el intestino delgado, próstata, testículos, páncreas y útero no se expresa en el corazón, la médula ósea, el bazo y la placenta
- Molécula de ADN
- Tejidos con expresión significativa Tejidos sin expresión significativa
- DNA1646252890
- altamente expresado en la próstata; expresado en los riñones, la espina dorsal, la placenta, hígado, pulmón, colon, bazo, útero, dendrocite y el hipocampo, el intestino, glándula mamaria, la médula ósea, testículos, músculos, el estómago y el timo débilmente expresado en el corazón, el cartílago, tumores de colon, la sustancia negra y los macrófagos, no se expresa en linfoblastos
- Molécula de ADN
- Tejidos con expresión significativa Tejidos sin expresión significativa
- DNA1195022789
- fuertemente expresado en la glándula mamaria, la placenta y de próstata; expresado en el intestino, colon, pulmón, riñón, timo, el estómago, el bazo y la columna vertebral no se expresa en el músculo, hígado y corazón; débilmente expresado en la médula, el útero, testículos y el cerebro
- DNA1540952998
- expresa con fuerza en el cerebro fetal; expresión significativa en el útero y los testículos, expresado en la próstata, esófago y los tumores esofagiales, estómago normal y el tumor de estómago, riñón, pero se expresó más alto en el tumor de riñón, el tumor de pulmón y tumor rectal la expresión insignificante en la glándula mamaria, no de la médula ósea, la tráquea, colon, pulmón, músculo, páncreas, hígado, glándula suprarrenal, timo, la placenta, el corazón, el cerebro y el bazo, recto, expresado en el tumor de hígado
5 Ejemplo 20
Identificación de las interacciones receptor/ligando – Descripción del ensayo de cribado de polipéptidos PRO para la identificación de las interacciones receptor/ligando
10 En este ensayo, se prueban varios polipéptidos PRO para su capacidad para unirse a un grupo de receptores potenciales o moléculas de ligando con el fin de identificar las interacciones receptor/ligando. La identificación de un ligando para un receptor conocido, un receptor para un ligando conocido o un nuevo par receptor/ligando es útil para una variedad de indicaciones que incluyen, por ejemplo, las moléculas bioactivas diana (vinculadas al ligando o al
15 receptor) a una célula conocida que expresa el receptor o ligando, el uso del receptor o ligando como reactivo para detectar la presencia del ligando o receptor en una composición sospechosa de contener las mismas, en la que la composición puede incluir células sospechosas que expresan el ligando o receptor, la modulación del crecimiento de otra actividad biológica o inmunológica de una célula conocida que expresar el receptor o ligando, la modulación de la respuesta inmunitaria de las células o hacia las células que expresan el receptor o ligando, permitiendo la preparación
20 de los agonistas, antagonistas y/o anticuerpos dirigidos contra el receptor o ligando que modulan el crecimiento de una actividad biológica o inmunológica de una célula que exprese el receptor o ligando, y varias otras indicaciones que serán evidente para el experto en la materia.
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Claims (1)
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imagen1
Applications Claiming Priority (30)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US664848 | 1976-03-08 | ||
| US17209699P | 1999-12-23 | 1999-12-23 | |
| US172096P | 1999-12-23 | ||
| WOPCT/US99/31274 | 1999-12-30 | ||
| PCT/US1999/031274 WO2000053752A2 (en) | 1999-03-08 | 1999-12-30 | Promotion or inhibition of angiogenesis and cardiovascularization |
| US17548100P | 2000-01-11 | 2000-01-11 | |
| US175481P | 2000-01-11 | ||
| PCT/US2000/004341 WO2000053756A2 (en) | 1999-03-08 | 2000-02-18 | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| WOPCT/US00/04341 | 2000-02-18 | ||
| WOPCT/US00/05841 | 2000-03-02 | ||
| PCT/US2000/005841 WO2000053758A2 (en) | 1999-03-08 | 2000-03-02 | Compositions and methods for the treatment of immune related diseases |
| US19100700P | 2000-03-21 | 2000-03-21 | |
| WOPCT/US00/07532 | 2000-03-21 | ||
| PCT/US2000/007532 WO2000070050A1 (en) | 1999-05-14 | 2000-03-21 | Compositions and methods for the treatment of immune related diseases |
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| PT (4) | PT1897947E (es) |
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| US7718397B2 (en) | 2000-03-21 | 2010-05-18 | Genentech, Inc. | Nucleic acids encoding receptor for IL-17 homologous polypeptides and uses thereof |
| CA2406245A1 (en) * | 2000-04-18 | 2001-10-25 | Schering Corporation | Il-174 uses, compositions and methods |
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| US20030096969A1 (en) | 2000-06-02 | 2003-05-22 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
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| AU2002225714A1 (en) * | 2000-11-10 | 2002-05-21 | The Regents Of The University Of California | Il-17 receptor-like protein, uses thereof, and modulation of catabolic activity of il-17 cytokines on bone and cartilage |
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| US20050089957A1 (en) * | 2001-10-19 | 2005-04-28 | Audrey Goddard | Compositions and methods for the diagnosis and treatment of inflammatory bowel disorders |
| CA2497661A1 (en) * | 2002-09-11 | 2004-03-25 | Genentech, Inc. | Compositions and methods for the diagnosis of immune related diseases using pro71061 |
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| EP1599498A2 (en) * | 2003-03-03 | 2005-11-30 | Genentech, Inc. | Compositions and methods for the treatment of systemic lupus erythematosis |
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| WO2000073452A2 (en) * | 1999-06-02 | 2000-12-07 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
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| WO2000053752A2 (en) * | 1999-03-08 | 2000-09-14 | Genentech, Inc. | Promotion or inhibition of angiogenesis and cardiovascularization |
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| JP2001510035A (ja) * | 1997-07-16 | 2001-07-31 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | インターロイキン−２０ |
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| WO2000042188A2 (en) * | 1999-01-11 | 2000-07-20 | Schering Corporation | Interleukin-17 related mammalian cytokines. polynucleotides encoding them. uses |
| AU3632600A (en) * | 1999-05-14 | 2000-12-05 | Genentech Inc. | Compositions and methods for the treatment of immune related diseases |
| DE60045931D1 (de) * | 1999-07-07 | 2011-06-16 | Zymogenetics Inc | Menschliches Rezeptor für Zytokine |
| JP2003527104A (ja) * | 1999-12-23 | 2003-09-16 | ジェネンテック・インコーポレーテッド | Ｉｌ−１７相同的ポリペプチドとその治療上の用途 |
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2000
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- 2000-12-20 PT PT07016903T patent/PT1897947E/pt unknown
- 2000-12-20 WO PCT/US2000/034956 patent/WO2001046420A2/en active Application Filing
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