RU2014136332A - COMPOSITIONS AND METHODS OF APPLICATION OF CSF1R INHIBITORS - Google Patents

COMPOSITIONS AND METHODS OF APPLICATION OF CSF1R INHIBITORS Download PDF

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RU2014136332A
RU2014136332A RU2014136332A RU2014136332A RU2014136332A RU 2014136332 A RU2014136332 A RU 2014136332A RU 2014136332 A RU2014136332 A RU 2014136332A RU 2014136332 A RU2014136332 A RU 2014136332A RU 2014136332 A RU2014136332 A RU 2014136332A
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Сяолэй МА
Юнмэй Чэнь
Скотт Ставицки
Янь Ву
Флавиус Мартин
Вей Ю ЛИНЬ
Мелисса А. СТАРОВАСНИК
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Дженентек, Инк.
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Abstract

1. Выделенное антитело, которое связывается с IL-34 человека, причем антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков Glu103, Leu109, Gln106, Asn150, Leu127, Asn128, Ser184, Leu186, Asn187, Lys44, Glu121, Asp107, Glu111, Ser104, Gln120, Тrр116 и Asn61 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1 и где антитело ингибирует связывание между IL-34 человека и CSF-1R человека.2. Выделенное антитело, которое связывается с IL-34 человека, при этом антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков от Glu103 до Asn150 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1 и где антитело ингибирует связывание между IL-34 человека и CSF-1R человека.3. Антитело по п. 1 или 2, где антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков Glu103, Leu109, Gln106 и Asn150 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.4. Антитело по п. 3, где эпитоп дополнительно содержит по меньшей мере один из аминокислотных остатков Ser100, Glu123, Тrр116, Thr124, Leu127, Asn128, Gln131 и Thr134 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.5. Антитело по п. 1, где антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков Asn128, Ser184, Leu186, Asn187, Lys44 и Glu121 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.6. Антитело по п. 5, где эпитоп дополнительно содержит по меньшей мере один из аминокислотных остатков Phe40, Asp43, Leu125, Gln189, Thr36 и Val185 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.7. Антитело по п. 1, где антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков Asp107, Glu111, Ser104, Gln120, Glu103, Leu109, Тrр116 и Asn61 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.8. Антитело по п. 7, где эпитоп дополнительно содержит по м1. An isolated antibody that binds to human IL-34, wherein the antibody binds to an epitope containing at least one of the amino acid residues Glu103, Leu109, Gln106, Asn150, Leu127, Asn128, Ser184, Leu186, Asn187, Lys44, Glu121, Asp107 , Glu111, Ser104, Gln120, Trp116 and Asn61 of human IL-34, where the position of amino acid residues is based on the position in SEQ ID NO: 1 and where the antibody inhibits the binding between human IL-34 and human CSF-1R. 2. An isolated antibody that binds to human IL-34, wherein the antibody binds to an epitope containing at least one of the amino acid residues Glu103 to Asn150 of human IL-34, where the position of the amino acid residues is based on the position in SEQ ID NO: 1 and where the antibody inhibits the binding between human IL-34 and human CSF-1R. 3. The antibody according to claim 1 or 2, wherein the antibody binds to an epitope containing at least one of the amino acid residues Glu103, Leu109, Gln106 and Asn150 of IL-34, where the position of the amino acid residues is based on the position in SEQ ID NO: 1.4. The antibody of claim 3, wherein the epitope further comprises at least one of the amino acid residues Ser100, Glu123, Trp116, Thr124, Leu127, Asn128, Gln131 and Thr134 IL-34, where the position of the amino acid residues is based on the position in SEQ ID NO: 1.5 . The antibody of claim 1, wherein the antibody binds to an epitope containing at least one of the amino acid residues Asn128, Ser184, Leu186, Asn187, Lys44 and Glu121 of IL-34 person, where the position of the amino acid residues is based on the position in SEQ ID NO: 1.6. The antibody of claim 5, wherein the epitope further comprises at least one of the amino acid residues Phe40, Asp43, Leu125, Gln189, Thr36 and Val185 of human IL-34, wherein the position of the amino acid residues is based on the position in SEQ ID NO: 1.7. The antibody of claim 1, wherein the antibody binds to an epitope containing at least one of the amino acid residues Asp107, Glu111, Ser104, Gln120, Glu103, Leu109, Trp116 and Asn61 of human IL-34, where the position of the amino acid residues is based on the position in SEQ ID NO: 1.8. The antibody of claim 7, wherein the epitope further comprises m

Claims (30)

1. Выделенное антитело, которое связывается с IL-34 человека, причем антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков Glu103, Leu109, Gln106, Asn150, Leu127, Asn128, Ser184, Leu186, Asn187, Lys44, Glu121, Asp107, Glu111, Ser104, Gln120, Тrр116 и Asn61 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1 и где антитело ингибирует связывание между IL-34 человека и CSF-1R человека.1. An isolated antibody that binds to human IL-34, wherein the antibody binds to an epitope containing at least one of the amino acid residues Glu103, Leu109, Gln106, Asn150, Leu127, Asn128, Ser184, Leu186, Asn187, Lys44, Glu121, Asp107 , Glu111, Ser104, Gln120, Trp116 and Asn61 of human IL-34, where the position of amino acid residues is based on the position in SEQ ID NO: 1 and where the antibody inhibits binding between human IL-34 and human CSF-1R. 2. Выделенное антитело, которое связывается с IL-34 человека, при этом антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков от Glu103 до Asn150 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1 и где антитело ингибирует связывание между IL-34 человека и CSF-1R человека.2. An isolated antibody that binds to human IL-34, wherein the antibody binds to an epitope containing at least one of the amino acid residues from Glu103 to Asn150 of human IL-34, where the position of the amino acid residues is based on the position in SEQ ID NO: 1 and where the antibody inhibits the binding between human IL-34 and human CSF-1R. 3. Антитело по п. 1 или 2, где антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков Glu103, Leu109, Gln106 и Asn150 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.3. The antibody according to claim 1 or 2, where the antibody binds to an epitope containing at least one of the amino acid residues Glu103, Leu109, Gln106 and Asn150 IL-34 person, where the position of the amino acid residues is based on the position in SEQ ID NO: 1. 4. Антитело по п. 3, где эпитоп дополнительно содержит по меньшей мере один из аминокислотных остатков Ser100, Glu123, Тrр116, Thr124, Leu127, Asn128, Gln131 и Thr134 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.4. The antibody of claim 3, wherein the epitope further comprises at least one of the amino acid residues Ser100, Glu123, Trp116, Thr124, Leu127, Asn128, Gln131 and Thr134 IL-34, where the position of the amino acid residues is based on the position in SEQ ID NO : one. 5. Антитело по п. 1, где антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков Asn128, Ser184, Leu186, Asn187, Lys44 и Glu121 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.5. The antibody according to claim 1, where the antibody binds to an epitope containing at least one of the amino acid residues Asn128, Ser184, Leu186, Asn187, Lys44 and Glu121 IL-34 person, where the position of the amino acid residues is based on the position in SEQ ID NO: one. 6. Антитело по п. 5, где эпитоп дополнительно содержит по меньшей мере один из аминокислотных остатков Phe40, Asp43, Leu125, Gln189, Thr36 и Val185 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.6. The antibody according to claim 5, where the epitope further comprises at least one of the amino acid residues Phe40, Asp43, Leu125, Gln189, Thr36 and Val185 of human IL-34, where the position of the amino acid residues is based on the position in SEQ ID NO: 1. 7. Антитело по п. 1, где антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков Asp107, Glu111, Ser104, Gln120, Glu103, Leu109, Тrр116 и Asn61 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.7. The antibody according to claim 1, wherein the antibody binds to an epitope containing at least one of the amino acid residues Asp107, Glu111, Ser104, Gln120, Glu103, Leu109, Trp116 and Asn61 IL-34, where the position of the amino acid residues is based on the position in SEQ ID NO: 1. 8. Антитело по п. 7, где эпитоп дополнительно содержит по меньшей мере один из аминокислотных остатков Pro152, Val108, Leu110, Gln106, Glu123, Leu127, Lys117, Ilе60 и Lys55 IL-34 человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 1.8. The antibody according to claim 7, where the epitope further comprises at least one of the amino acid residues Pro152, Val108, Leu110, Gln106, Glu123, Leu127, Lys117, Il60 and Lys55 IL-34, where the position of the amino acid residues is based on the position in SEQ ID NO: 1. 9. Антитело по любому из пп. 7 или 8, где антитело содержит последовательность вариабельной области тяжелой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 3 и/или последовательность вариабельной области легкой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 4.9. The antibody according to any one of paragraphs. 7 or 8, wherein the antibody comprises a heavy chain variable region sequence with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 3 and / or a light chain variable region sequence with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 3 : four. 10. Антитело по любому из пп. 7 или 8, где антитело содержит (a) HVR-H1, включающую аминокислотную последовательность STWIH (SEQ ID NO: 59); (b) HVR-H2, включающую аминокислотную последовательность RISPYYYYSDYADSVKG (SEQ ID NO: 52); и (с) HVR-Н3, включающую аминокислотную последовательность GLGKGSKRGAMDY (SEQ ID NO: 33), и где антитело дополнительно содержит (d) HVR-L1, включающую аминокислотную последовательность RASQDVSTAVA (SEQ ID NO: 50); (е) HVR-L2, включающую аминокислотную последовательность SASFLYS (SEQ ID NO: 53); и (f) HVR-L3, включающую аминокислотную последовательность QQSFYFPNT (SEQ ID NO: 39).10. The antibody according to any one of paragraphs. 7 or 8, where the antibody contains (a) HVR-H1 comprising the amino acid sequence STWIH (SEQ ID NO: 59); (b) HVR-H2, comprising the amino acid sequence RISPYYYYSDYADSVKG (SEQ ID NO: 52); and (c) HVR-H3 comprising the amino acid sequence GLGKGSKRGAMDY (SEQ ID NO: 33), and wherein the antibody further comprises (d) HVR-L1 comprising the amino acid sequence RASQDVSTAVA (SEQ ID NO: 50); (e) HVR-L2 comprising the amino acid sequence of SASFLYS (SEQ ID NO: 53); and (f) HVR-L3 comprising the amino acid sequence QQSFYFPNT (SEQ ID NO: 39). 11. Выделенное антитело, которое связывается с IL-34 человека, где антитело ингибирует связывание между IL-34 человека и CSF-1R человека и где антитело связывается с димером IL-34.11. An isolated antibody that binds to human IL-34, where the antibody inhibits binding between human IL-34 and human CSF-1R, and where the antibody binds to an IL-34 dimer. 12. Антитело по п. 11, где антитело содержит (a) HVR-H1, включающую аминокислотную последовательность STWIH (SEQ ID NO: 59); (b) HVR-H2, включающую аминокислотную последовательность RISPYYYYSDYADSVKG (SEQ ID NO: 52) или RIS PYSGYTNYADSVKG (SEQ ID NO: 51); и (с) HVR-H3, включающую аминокислотную последовательность GLGKGSKRGAMDY (SEQ ID NO: 33) или GINQGSKRGAMDY (SEQ ID NO: 32), и где антитело содержит (d) HVR-L1, включающую аминокислотную последовательность RASQDVSTAVA (SEQ ID NO: 50); (e) HVR-L2, включающую аминокислотную последовательность SASFLYS (SEQ ID NO: 53); и (f) HVR-L3, включающую аминокислотную последовательность QQSFYFPNT (SEQ ID NO: 39) или QQSYTTPPT (SEQ ID NO: 43), или QQYTALPYT (SEQ ID NO: 49), или QQYSDLPYT (SEQ ID NO: 45), или QQYSDVPYT (SEQ ID NO: 47), или QQSRTARPT (SEQ ID NO: 41), или QQSFYFPN (SEQ ID NO: 38), или QQSYTTPP (SEQ ID NO: 42), или QQYTALPY (SEQ ID NO: 48), или QQYSDLPY (SEQ ID NO: 44), или QQYSDVPY (SEQ ID NO: 46), или QQSRTARP (SEQ ID NO: 40).12. The antibody of claim 11, wherein the antibody contains (a) HVR-H1 comprising the amino acid sequence STWIH (SEQ ID NO: 59); (b) HVR-H2 comprising the amino acid sequence RISPYYYYSDYADSVKG (SEQ ID NO: 52) or RIS PYSGYTNYADSVKG (SEQ ID NO: 51); and (c) HVR-H3 comprising the amino acid sequence GLGKGSKRGAMDY (SEQ ID NO: 33) or GINQGSKRGAMDY (SEQ ID NO: 32), and where the antibody contains (d) HVR-L1 comprising the amino acid sequence RASQDVSTAVA (SEQ ID NO: 50 ); (e) HVR-L2 comprising the amino acid sequence of SASFLYS (SEQ ID NO: 53); and (f) HVR-L3 comprising the amino acid sequence QQSFYFPNT (SEQ ID NO: 39) or QQSYTTPPT (SEQ ID NO: 43), or QQYTALPYT (SEQ ID NO: 49), or QQYSDLPYT (SEQ ID NO: 45), or QQYSDVPYT (SEQ ID NO: 47), or QQSRTARPT (SEQ ID NO: 41), or QQSFYFPN (SEQ ID NO: 38), or QQSYTTPP (SEQ ID NO: 42), or QQYTALPY (SEQ ID NO: 48), or QQYSDLPY (SEQ ID NO: 44), or QQYSDVPY (SEQ ID NO: 46), or QQSRTARP (SEQ ID NO: 40). 13. Антитело по п. 11, где антитело содержит (a) HVR-H1, включающую аминокислотную последовательность STWIH (SEQ ID NO: 59); (b) HVR-H2, включающую аминокислотную последовательность RISPYSGYTNYADSVKG (SEQ ID NO: 51); и (с) HVR-H3, включающую аминокислотную последовательность GLGKGSKRGAMDY (SEQ ID NO: 33), и где антитело содержит (d) HVR-L1, включающую аминокислотную последовательность RASQDVSTAVA (SEQ ID NO: 50); (е) HVR-L2, включающую аминокислотную последовательность SASFLYS (SEQ ID NO: 53); и (f) HVR-L3, включающую аминокислотную последовательность QQYSDLPYT (SEQ ID NO: 45).13. The antibody of claim 11, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence STWIH (SEQ ID NO: 59); (b) HVR-H2 comprising the amino acid sequence RISPYSGYTNYADSVKG (SEQ ID NO: 51); and (c) HVR-H3 comprising the amino acid sequence GLGKGSKRGAMDY (SEQ ID NO: 33), and wherein the antibody comprises (d) HVR-L1 comprising the amino acid sequence RASQDVSTAVA (SEQ ID NO: 50); (e) HVR-L2 comprising the amino acid sequence of SASFLYS (SEQ ID NO: 53); and (f) HVR-L3 comprising the amino acid sequence QQYSDLPYT (SEQ ID NO: 45). 14. Антитело по п. 11 или 12, где антитело содержит последовательность вариабельной области тяжелой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 5 и/или последовательность вариабельной области легкой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 6,14. The antibody according to claim 11 or 12, where the antibody contains a sequence of the variable region of the heavy chain with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 5 and / or a sequence of the variable region of the light chain with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 6, или где антитело содержит последовательность вариабельной области тяжелой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 7 и/или последовательность вариабельной области легкой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 8,or where the antibody contains a heavy chain variable region sequence with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 7 and / or a light chain variable region sequence with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 8, или где антитело содержит последовательность вариабельной области тяжелой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 9 и/или последовательность вариабельной области легкой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 10,or where the antibody contains a heavy chain variable region sequence with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 9 and / or a light chain variable region sequence with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 10, или где антитело содержит последовательность вариабельной области тяжелой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 11 и/или последовательность вариабельной области легкой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 12,or where the antibody contains a sequence of the variable region of the heavy chain with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 11 and / or a sequence of the variable region of the heavy chain with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 12, или где антитело содержит последовательность вариабельной области тяжелой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 13 и/или последовательность вариабельной области легкой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 14.or wherein the antibody comprises a heavy chain variable region sequence with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 13 and / or a light chain variable region sequence with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 14. 15. Выделенное антитело, которое связывается с IL-34 человека, по п. 1, где антитело ингибирует связывание между IL-34 человека и CSF-1R человека и где антитело нейтрализует активность IL-34.15. An isolated antibody that binds to human IL-34, according to claim 1, wherein the antibody inhibits binding between human IL-34 and human CSF-1R, and where the antibody neutralizes the activity of IL-34. 16. Антитело по п. 15, где антитело содержит (a) HVR-H1, включающую аминокислотную последовательность SNYIH (SEQ ID NO: 55); (b) HVR-H2, включающую аминокислотную последовательность SITPASGDTDYADSVKG (SEQ ID NO: 54); и (с) HVR-H3, включающую аминокислотную последовательность SRGAYRFAY (SEQ ID NO: 56), и где антитело содержит (a) HVR-L1, включающую аминокислотную последовательность RASQDVSTAVA (SEQ ID NO: 50); (b) HVR-L2, включающую аминокислотную последовательность SASFLYS (SEQ ID NO: 53); и (с) HVR-L3, включающую аминокислотную последовательность QQSYTTPPT (SEQ ID NO: 43).16. The antibody of claim 15, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence SNYIH (SEQ ID NO: 55); (b) HVR-H2 comprising the amino acid sequence SITPASGDTDYADSVKG (SEQ ID NO: 54); and (c) an HVR-H3 comprising the amino acid sequence SRGAYRFAY (SEQ ID NO: 56), and wherein the antibody comprises (a) an HVR-L1 comprising the amino acid sequence RASQDVSTAVA (SEQ ID NO: 50); (b) HVR-L2 comprising the amino acid sequence of SASFLYS (SEQ ID NO: 53); and (c) HVR-L3 comprising the amino acid sequence QQSYTTPPT (SEQ ID NO: 43). 17. Антитело по пп. 15 или 16, где антитело содержит последовательность вариабельной области тяжелой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 15 и последовательность вариабельной области легкой цепи с по меньшей мере 90% идентичностью последовательности с аминокислотной последовательностью SEQ ID NO: 16.17. The antibody according to paragraphs. 15 or 16, wherein the antibody comprises a heavy chain variable region sequence with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 15 and a light chain variable region sequence with at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 16 . 18. Антитело по п. 1, где антитело представляет собой биспецифическое антитело.18. The antibody of claim 1, wherein the antibody is a bispecific antibody. 19. Антитело по п. 18, где биспецифическое антитело содержит первичную специфичность связывания для IL-34 человека (SEQ ID NO: 1) и вторичную специфичность связывания для CSF-1 человека.19. The antibody of claim 18, wherein the bispecific antibody comprises primary binding specificity for human IL-34 (SEQ ID NO: 1) and secondary binding specificity for human CSF-1. 20. Биспецифическое антитело по п. 19, где антитело ингибирует связывание IL-34 человека с CSF-1R человека и ингибирует связывание CSF-1 человека с CSF-1R человека.20. The bispecific antibody of claim 19, wherein the antibody inhibits the binding of human IL-34 to human CSF-1R and inhibits the binding of human CSF-1 to human CSF-1R. 21. Выделенное антитело, которое связывается с CSF-1R человека, при этом антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков Arg144, Gln248, Gln249, Ser250, Phe252 и Asn254 CSF-1R человека, где положение аминокислотных остатков основано на положении в SEQ ID NO: 2, и где антитело ингибирует связывание между IL-34 человека и CSF-1R человека.21. An isolated antibody that binds to human CSF-1R, wherein the antibody binds to an epitope containing at least one of the amino acid residues Arg144, Gln248, Gln249, Ser250, Phe252 and Asn254 of human CSF-1R, where the position of the amino acid residues is based on position in SEQ ID NO: 2, and where the antibody inhibits the binding between human IL-34 and human CSF-1R. 22. Антитело по п. 21, где антитело связывается с эпитопом, включающим аминокислотный остаток Arg144 CSF-1R, где положение аминокислотного остатка основано на положении в SEQ ID NO: 2.22. The antibody of claim 21, wherein the antibody binds to an epitope comprising the amino acid residue Arg144 CSF-1R, where the position of the amino acid residue is based on the position in SEQ ID NO: 2. 23. Антитело по п. 22, где эпитоп дополнительно содержит по меньшей мере один из аминокислотных остатков Arg142, Arg146 и Arg150 CSF-1R человека и где положение аминокислотных остатков основано на положении в SEQ ID NO: 2.23. The antibody of claim 22, wherein the epitope further comprises at least one of human amino acid residues Arg142, Arg146, and Arg150 CSF-1R, and wherein the position of the amino acid residues is based on the position in SEQ ID NO: 2. 24. Антитело по п. 21, где антитело связывается с эпитопом, содержащим по меньшей мере один из аминокислотных остатков Gln248, Gln249, Ser250, Phe252 и Asn254 CSF-1R человека и где положение аминокислотных остатков основано на положении в SEQ ID NO: 2.24. The antibody according to claim 21, where the antibody binds to an epitope containing at least one of the amino acid residues Gln248, Gln249, Ser250, Phe252 and Asn254 CSF-1R of a person and where the position of the amino acid residues is based on the position in SEQ ID NO: 2. 25. Выделенная нуклеиновая кислота, кодирующая антитело по любому из пп. 1-24.25. The selected nucleic acid encoding an antibody according to any one of paragraphs. 1-24. 26. Фармацевтическая композиция, содержащая антитело по любому из пп. 1-24 и фармацевтически приемлемый носитель.26. A pharmaceutical composition comprising an antibody according to any one of paragraphs. 1-24 and a pharmaceutically acceptable carrier. 27. Антитело по любому из пп. 1-24 для применения в качестве лекарственного средства.27. The antibody according to any one of paragraphs. 1-24 for use as a medicine. 28. Антитело по любому из пп. 1-24 для применения в лечении миелоидного патогенного иммунологического заболевания.28. The antibody according to any one of paragraphs. 1-24 for use in the treatment of myeloid pathogenic immunological disease. 29. Антитело по любому из пп. 1-24 для применения по п. 28, где миелоидное патогенное иммунологическое заболевание представляет собой ревматоидный артрит, воспалительное заболевание кишечника, рассеянный склероз, синдром активации макрофагов (MAS), дискоидную волчанку, саркоидоз, васкулит и реакцию «трансплантат против хозяина».29. The antibody according to any one of paragraphs. 1-24 for use according to claim 28, wherein the myeloid pathogenic immunological disease is rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, macrophage activation syndrome (MAS), lupus erythematosus, sarcoidosis, vasculitis, and graft versus host disease. 30. Промышленное изделие, содержащее антитело по любому из пп. 1-24 и дополнительно содержащее инструкции для введения индивидууму эффективного количества антитела для лечения миелоидного патогенного иммунологического заболевания у индивидуума. 30. An industrial product containing the antibody according to any one of paragraphs. 1-24 and further containing instructions for administering to the individual an effective amount of an antibody for treating a myeloid pathogenic immunological disease in an individual.
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Effective date: 20180109