SI2831113T1 - Protitelesa ligandom bradikininskega receptorja B1 - Google Patents

Protitelesa ligandom bradikininskega receptorja B1 Download PDF

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SI2831113T1
SI2831113T1 SI201331066T SI201331066T SI2831113T1 SI 2831113 T1 SI2831113 T1 SI 2831113T1 SI 201331066 T SI201331066 T SI 201331066T SI 201331066 T SI201331066 T SI 201331066T SI 2831113 T1 SI2831113 T1 SI 2831113T1
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seq
amino acid
des
bradykinin
binding fragment
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Dorothea KOMINOS
Jie Zhang
Alla Pritsker
Matthew Davison
Nicolas Baurin
Govindan Subramanian
Xin Chen
Han Li
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Sanofi
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Claims (13)

  1. Protitelesa ligandom bradikininskega receptorja BI Patentni zahtevki
    1. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Argg-Bradikinin, kjer protitelo ali njegov delec, ki veže antigen vsebuje: i) variabilno domeno težke verige, ki vsebuje zaporedje aminokislin komplementarnost določujoče regije težke verige 3 (HCDR3), zaporedje aminokislin komplementarnost določujoče regije težke verige 2 (HCDR2) in zaporedje aminokislin komplementarnost določujoče regije težke verige 1 (HCDR1), izbrano iz skupine, ki vsebuje: a) SEQ ID NO: 7 [XiY X2 X3D Χ4ΗΑΜ X5Y], kjer Xi je Y, F ali H, X2 je R, D, A, V, L, I, M, F, Y ali W, X3je Y, F, W ali H, Χ4 je D, E ali Y, in, Χ5 je D ali E; SEQ ID NO: 8 [YFXiPX2NGNTGYNQKFRG], kjer Xi je D, R, A, V, L, I, M, F, Y ali W, in X2 je Y, D, E, N ali Q; in SEQ ID NO: 9 [GYSFTDYX!lY], kjer X! je N, W ali Y; b) SEQ ID NO: 63 [XiEYDGX2YX3X4LDX5], kjer Xi je W ali F, X2 je N ali aminokisline ni; X3je Yali S, X4 je D ali P, in X5 je F ali Y; SEQ ID NO: 64 [WX,DPENGDX2X3YAPKFQG], kjer X, je I ali V, X2 je T ali S in X3 je G ali D; SEQ ID NO: 65 [GFNIKDYYXiH], kjer X! je L ali M; c) SEQ ID NO: 13; SEQ ID NO: 14; in SEQ ID NO: 15; d) SEQ ID NO: 32; SEQ ID NO: 33; in SEQ ID NO: 34; e) SEQ ID NO: 40; SEQ ID NO: 41; in SEQ ID NO: 42; f) SEQ ID NO: 47; SEQ ID NO: 48; in SEQ ID NO: 49; in g) SEQ ID NO: 55; SEQ ID NO: 56; in SEQ ID NO: 57; in ii) variabilno domeno lahke verige, ki vsebuje zaporedje aminokislin komplementarnost določujoče regije lahke verige 3 (LCDR3), zaporedje aminokislin komplementarnost določujoče regije lahke verige 2 (LCDR2) in zaporedje aminokislin komplementarnost določujoče regije lahke verige 1 (LCDR1), izbrano iz skupine, ki vsebuje: h) SEQ ID NO: 10 [QQ X, X2S X3P X4T], kjer X, je Y, F ali H, X2 je Y, F, H ali W, X3je Y, F, Tali H, in X4je W, Y, F, H ali L: SEQ ID NO: 11 [WASTRX,], kjer X, je E, D, Q ali N; in SEQ ID NO: 12 [KSSQSLL XiSSNQKN X2LA], kjer Xi je W, H, Y ali F, in X2 je H ali Y; i) SEQ ID NO: 66 [QXiX2X3SX4PX5T], kjer Xi je Q ali N, X2 je Y, F, D ali H, X3je Y, F, H ali W, X4je Y, F, Tali H in X5jeW, Y, F, H ali L; SEQ ID NO: 67 [X2ASTRX2], kjer Xije Wali G; in X2 je E, D, Q ali N; in SEQ ID NO: 68 [KSSQSLLX,X2SX3QX4NX5LA], kjer Xi je W, H, Y ali F, X2jeSali G, X3 je N ali D, Χ4 je K ali R, X5 je H ali Y, j) SEQ ID NO: 69 [XjQGTHFPYT], kjer X, je L ali M; SEQ ID NO: 36; in SEQ ID NO: 70 [KSSQSLLYSNGX1TYLN], kjer XI je K ali E; k) SEQ ID NO: 16; SEQ ID NO: 17; in SEQ ID NO: 18; l) SEQ ID NO: 35; SEQ ID NO: 36; in SEQ ID NO: 37; m) SEQ ID NO: 43; SEQ ID NO: 17; in SEQ ID NO: 44; n) SEQ ID NO: 50; SEQ ID NO: 51; in SEQ ID NO: 52; in o) SEQ ID NO: 58; SEQ ID NO: 59; in SEQ ID NO: 60
  2. 2. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Argg-Bradikinin, po zahtevku 1, kjer protitelo ali njegov delec, ki veže antigen vsebuje: a) variabilno domeno težke verige, ki vsebuje zaporedja aminokislin regij HCDR3, HCDR2 in HCDR1, določena v SEQ ID NO: 13, 14 oziroma 15 in eno ali več aminokislinskih substitucij na položajih, izbranih iz skupine, ki vsebuje HI, H5, H9, HI 1, H12, H16, H38, H40, H41, H43, H44, H66, H75, H79, H81, H82A, H83, H87 in H108, v skladu s Kabatom; in b) variabilno domeno lahke verige ki vsebuje zaporedja aminokislin regij LCDR3, LCDR2 in LCDR1, določena v SEQ ID NO: 16, 17 oziroma 18 in eno ali več aminokislinskih substitucij na položajih, izbranih iz skupine, ki vsebuje L5, L9, L15, L18, L19, L21, L22, L43, L63, L78, L79, L83, L85, L100 in L104, v skladu s Kabatom.
  3. 3. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Arg9-Bradikinin, po zahtevku 1, kjer protitelo ali njegov delec, ki veže antigen vsebuje zaporedja aminokislin variabilne domene težke verige in lahke verige določena v SEQ ID NO: 24 oziroma 30.
  4. 4. Farmacevtski sestavek, ki vsebuje protitelo ali njegov delec, ki veže antigen, po zahtevku 1 in enega ali več farmacevtsko sprejemljivih nosilcev.
  5. 5. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Argg-Bradikinin, po zahtevku 1, kjer protitelo ali njegov delec, ki veže antigen vsebuje: zaporedje aminokislin regije variabilne domene težke verige in zaporedje aminokislin variabilne domene lahke verige, kije vsaj 90% identično zaporedju aminokislin, izbranemu iz skupine, ki vsebuje: a) SEQ ID NO: 19 oziroma 26, b) SEQ ID NO: 20 oziroma 27, c) SEQ ID NO: 21 oziroma 28, d) SEQ ID NO: 22 oziroma 28, e) SEQ ID NO: 23 oziroma 29, f) SEQ ID NO: 24 oziroma 30, g) SEQ ID NO: 25 oziroma 31, h) SEQ ID NO: 38 oziroma 39, i) SEQ ID NO: 45 oziroma 46, j) SEQ ID NO: 53 oziroma 54, k) SEQ ID NO: 61 oziroma 62.
  6. 6. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Argg-Bradikinin, po zahtevku 1, kjer protitelo ali njegov delec, ki veže antigen vsebuje: a variabilno domeno težke verige, ki vsebuje zaporedje aminokislin in variabilno domeno lahke verige, ki vsebuje zaporedje aminokislin, izbrano iz skupine, ki vsebuje: a) SEQ ID NO: 19 oziroma 26, b) SEQ ID NO: 20 oziroma 27, c) SEQ ID NO: 21 oziroma 28, d) SEQ ID NO: 22 oziroma 28, e) SEQ ID NO: 23 oziroma 29, f) SEQ ID NO: 24 oziroma 30, g) SEQ ID NO: 25 oziroma 31, h) SEQ ID NO: 38 oziroma 39, i) SEQ ID NO: 45 oziroma 46, j) SEQ ID NO: 53 oziroma 54 k) SEQ ID NO: 61 oziroma 62.
  7. 7. Farmacevtski sestavek, ki vsebuje protitelo ali njegov delec, ki veže antigen, po zahtevku 2 in enega ali več farmacevtsko sprejemljivih nosilcev.
  8. 8. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Argg-Bradikinin, po zahtevku 1, kjer protitelo ali njegov delec, ki veže antigen vsebuje: a) variabilno domeno težke verige, ki vsebuje konsenzus zaporedij aminokislin regij HCDR3, HCDR2 in HCDR1, določenih v SEQ ID NO: 7, 8 oziroma 9; in b) variabilno domeno lahke verige, ki vsebuje zaporedja aminokislin regij LCDR3, LCDR2 in LCDR1, določenih v SEQ ID NO: 10, 11 oziroma 12.
  9. 9. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Argg-Bradikinin, po zahtevku 8, kjer protitelo ali njegov delec, ki veže antigen vsebuje: a) variabilno domeno težke verige, ki vsebuje zaporedja aminokislin regij HCDR3, HCDR2 in HCDR1, določenih v SEQ ID NO: 13, 14 oziroma 15; in b) variabilno domeno lahke verige, ki vsebuje zaporedja aminokislin regij LCDR3, LCDR2 in LCDR1, določenih v SEQ ID NO: 16, 17 oziroma 18.
  10. 10. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Argg-Bradikinin, po zahtevku 1, kjer protitelo ali njegov delec, ki veže antigen vsebuje: a) variabilno domeno težke verige, ki vsebuje zaporedja aminokislin regij HCDR3, HCDR2 in HCDR1 določenih v SEQ ID NO: 32, 33 oziroma 34; in b) variabilno domeno lahke verige, ki vsebuje zaporedja aminokislin regij LCDR3, LCDR2 in LCDR1, določenih v SEQ ID NO: 35, 36 oziroma 37.
  11. 11. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Arg9-Bradikinin, po zahtevku 1, kjer protitelo ali njegov delec, ki veže antigen vsebuje: a) variabilno domeno težke verige, ki vsebuje zaporedja aminokislin regij HCDR3, HCDR2 in HCDR1, določenih v SEQ ID NO: 40, 41 oziroma 42; in b) variabilno domeno lahke verige, ki vsebuje zaporedja aminokislin regij LCDR3, LCDR2 in LCDR1, določenih v SEQ ID NO: 43, 17 oziroma 44.
  12. 12. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Argg-Bradikinin, po zahtevku 1, kjer protitelo ali njegov delec, ki veže antigen vsebuje: a) variabilno domeno težke verige, ki vsebuje zaporedja aminokislin regij HCDR3, HCDR2 in HCDR1, določenih v SEQ ID NO: 47, 48 oziroma 49; in b) variabilno domeno lahke verige, ki vsebuje zaporedja aminokislin regij LCDR3, LCDR2 in LCDR1, določenih v SEQ ID NO: 50, 51 oziroma 52.
  13. 13. Izolirano monoklonsko protitelo ali njegov delec, ki veže antigen, ki se specifično veže na Kalidin ali des-Argio-Kalidin, vendar ne na Bradikinin ali des-Argg-Bradikinin, po zahtevku 1, kjer protitelo ali njegov delec, ki veže antigen vsebuje: a) variabilno domeno težke verige, ki vsebuje zaporedja aminokislin regij HCDR3, HCDR2 in HCDR1, določenih v SEQ ID NO: 55, 56 oziroma 57; in b) variabilno domeno lahke verige, ki vsebuje zaporedja aminokislin regij LCDR3, LCDR2 in LCDR1, določenih v SEQ ID NO: 58, 59 oziroma 60.
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