AR116526A1 - Anticuerpos anti-hla-g, composiciones que comprenden anticuerpos anti-hla-g y métodos de uso de anticuerpos anti-hla-g - Google Patents

Anticuerpos anti-hla-g, composiciones que comprenden anticuerpos anti-hla-g y métodos de uso de anticuerpos anti-hla-g

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AR116526A1
AR116526A1 ARP190102737A ARP190102737A AR116526A1 AR 116526 A1 AR116526 A1 AR 116526A1 AR P190102737 A ARP190102737 A AR P190102737A AR P190102737 A ARP190102737 A AR P190102737A AR 116526 A1 AR116526 A1 AR 116526A1
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hla
mediated
suppression
seq
inhibits
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Tizona Therapeutics
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Abstract

En el presente documento se proporcionan anticuerpos que se unen selectivamente a HLA-G y composiciones que comprenden los anticuerpos. También se proporcionan métodos para usar los anticuerpos, tales como métodos terapéuticos y de diagnóstico. Reivindicación 1: Un anticuerpo que se une específicamente a un HLA-G humano (hHLA-G) y es capaz de 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ó 16 de los siguientes: a) inhibir una función inmunosupresora de HLA-G; b) bloquear la interacción y/o unión de HLA-G a ILT2; c) bloquear la interacción y/o unión de HLA-G a ILT4; d) bloquear la interacción y/o unión de HLA-G a KIR2DL4; e) inhibir la supresión de células NK mediada por HLA-G; f) inhibir la supresión de linfocitos T citotóxicos mediada por HLA-G; g) inhibir la supresión de células B mediada por HLA-G; h) inhibir la supresión de neutrófilos mediada por HLA-G; i) inhibir la supresión de monocitos mediada por HLA-G; j) inhibir la supresión de macrófagos mediada por HLA-G; k) inhibir la supresión de células dendríticas mediada por HLA-G; l) inhibir la supresión de la citólisis y/o proliferación de células NK y/o T mediada por HLA-G; m) inhibir la supresión por HLA-G de células mieloides; n) inhibir la supresión de fagocitosis mediada por HLA-G; o) inhibir la generación, expansión o función mediada por HLA-G de células reguladoras T; o p) inhibir metástasis. Reivindicación 3: Una composición farmacéutica que comprende una cantidad efectiva de un anticuerpo que se une a hHLA-G y tiene 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, ó 16 de las siguientes características: a) inhibe una función inmunosupresora de HLA-G; b) bloquea la interacción y/o unión de HLA-G a ILT2; c) bloquea la interacción y/o unión de HLA-G a ILT4; d) bloquea la interacción y/o unión de HLA-G a KIR2DL4; e) inhibe la supresión de células NK mediada por HLA-G; f) inhibe la supresión de linfocitos T citotóxicos mediada por HLA-G; g) inhibe la supresión de células B mediada por HLA-G; h) inhibe la supresión de neutrófilos mediada por HLA-G; i) inhibe la supresión de monocitos mediada por HLA-G; j) inhibe la supresión de macrófagos mediada por HLA-G; k) inhibe la supresión de células dendríticas mediada par HLA-G; l) inhibe la supresión de la citólisis y/o proliferación de células NK y/o T mediada por HLA-G; m) inhibe la supresión por HLA-G de células mieloides; n) inhibe la supresión de fagocitosis mediada por HLA-G; o) inhibe la generación o expansión mediada HLA-G de células reguladoras T; o p) inhibe metástasis. Reivindicación 10: El anticuerpo de conformidad con la reivindicación 1, que comprende una región constante de la cadena pesada humana o fragmento o una variante de la misma y/o una región constante de la cadena ligera o fragmento o variante de la misma, en donde la región constante o fragmento de la variante del mismo comprende hasta 20 sustituciones de aminoácidos conservadoramente modificadas de cualquier secuencia expuesta en SEQ ID Nº 170 - 200 y/o SEQ ID Nº 204 - 228. Reivindicación 11: Una molécula de anticuerpo aislada capaz de unirse a HLA-G humano (hHLA-G), que comprende una región variable de la cadena pesada (VH) y una región variable de la cadena ligera (VL), en donde la VH y/o VL comprende 1, 2, 3, 4, 5 ó 6 de: a) una VHCDR1 que tiene la secuencia establecida en SEQ ID Nº 1 - 14 o SEQ ID Nº 18 - 34, b) una VHCDR2 que tiene la secuencia establecida en SEQ ID Nº 38 - 50 o SEQ ID Nº 54 - 71, c) una VHCDR3 que tiene la secuencia establecida en SEQ ID Nº 76 - 101, d) una VLCDR1 que tiene la secuencia establecida en SEQ ID Nº 105 - 124, e) una VLCDR2 que tiene la secuencia establecida en SEQ ID Nº 128 - 145, y f) una VLCDR3 que tiene la secuencia establecida en SEQ ID Nº 149 - 166. Reivindicación 13: Una molécula de anticuerpo aislada capaz de unirse a HLA-G humano (hHLA-G), que comprende una región variable de la cadena pesada (VH) y/o una región variable de la cadena ligera (VL), en donde la VH comprende al menos una secuencia establecida en cualquiera de SEQ ID Nº 170 - 200 y la VL comprende al menos una secuencia establecida en cualquiera de SEQ ID Nº 204 - 228. Reivindicación 14: Un ácido nucleico aislado que codifica para el anticuerpo de conformidad con la reivindicación 1, la reivindicación 12 o la reivindicación 13. Reivindicación 15: Un vector de expresión que comprende el ácido nucleico de conformidad con la reivindicación 14. Reivindicación 16: Una célula hospedera procariota o eucariota que comprende el vector de conformidad con la reivindicación 15. Reivindicación 17: Un virus oncolítico que codifica para el ácido nucleico de conformidad con cualquiera de las reivindicaciones 14 - 16. Reivindicación 18: Un método para la producción de una proteína recombinante que comprende las etapas de expresar el ácido nucleico de conformidad con la reivindicación 14 o la reivindicación 15 en una célula hospedera procariota o eucariota y recuperar la proteína de la célula o del sobrenadante del cultivo celular. Reivindicación 19: Un método para el tratamiento de un sujeto que padezca cáncer, una infección crónica o una enfermedad inflamatoria, que comprende la etapa de administrar al sujeto una composición farmacéutica que comprenda una cantidad eficaz del anticuerpo de conformidad con la reivindicación 1 o la composición farmacéutica de conformidad con la reivindicación 3. Reivindicación 21: El método de conformidad con la reivindicación 19, en donde el cáncer es un cáncer hematológico.
ARP190102737A 2018-09-27 2019-09-26 Anticuerpos anti-hla-g, composiciones que comprenden anticuerpos anti-hla-g y métodos de uso de anticuerpos anti-hla-g AR116526A1 (es)

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IL298867A (en) * 2020-06-11 2023-02-01 Tizona Therapeutics Combines bispecific immune cells with binding specificity for HLA-G and another antigen
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US11795227B2 (en) * 2021-03-24 2023-10-24 Shine-On Biomedical Co., Ltd. Immunomodulation and anti-tumor-related nanobody and nucleic acid encoding sequence thereof, and uses of the same
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WO2023182866A1 (ko) * 2022-03-25 2023-09-28 에이치케이이노엔 주식회사 Hla-g 특이적 항체 및 이의 용도
CN115819583A (zh) * 2022-03-31 2023-03-21 台州恩泽医疗中心(集团) 一种抗hla-g分子的单克隆抗体及其用途
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