• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Humanized Anti-Factor D Antibodies and Uses Thereof The invention relates to anti-Factor D antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their production and their use in the preparation of compositions and medicaments for treatment of diseases and disorders associated with excessive or uncontrolled complement activation. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.
    公开号:AU2013200637A1
    申请号:U2013200637
    申请日:2013-02-06
    公开日:2013-02-28
    发明作者:Arthur J. Huang；Robert F. Kelley；Henry Lowman；Menno Van Lookeren Campagne；Charles M. Winter
    申请人:Genentech Inc；
    IPC主号:C07K16-18
    专利说明:
    We Claim: 1. An anti-Factor D antibody comprising light chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises light chain HVR-1 comprising ITSTDIDDDMN (SEQ ID NO: 30), light chain HVR-2 comprising GGNTLRP (SEQ ID NO: 35), and light chain HVR-3 comprising LQSDSLPYT (SEQ ID NO: 38), and wherein said substitution is one or more of the following: (a) amino acid at position 33 of the light chain is L or 1; (b) amino acid at position 34 of the light chain is A or Q; (c) amino acid at position 52 of the light chain is S or A; (d) amino acid at position 104 of the light chain is V; (e) amino acid at position 1 of the heavy chain is E; (f) amino acid at position 99 of the heavy chain is A or Q; or (g) amino acid at position 100 of the heavy chain is A or Q. 2. An anti-Factor D antibody comprising heavy chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises heavy chain HVR-1 comprising GYTFTNYGMN (SEQ ID NO: 39), heavy chain HVR-2 comprising WINTYTGETTYADDFKG (SEQ ID NO: 40), and heavy chain HVR-3 comprising EGGVNN (SEQ ID NO: 41), and wherein said substitution is one or more of the following: (a) amino acid at position 33 of the light chain is L or I; (b) amino acid at position 34 of the light chain is A or Q; (c) amino acid at position 52 of the light chain is S or A; (d) amino acid at position 104 of the light chain is V' (e) amino acid at position 1 of the heavy chain is E; (f) amino acid at position 99 of the heavy chain is A or Q; or (g) amino acid at position 100 of the heavy chain is A or Q. 3. An anti-Factor D antibody comprising light chain HVRs and heavy chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises light chain HVR-1 comprising ITSTDIDDDMN (SEQ ID NO: 30), light chain HVR-2 comprising GGNTLRP (SEQ ID NO: 35), and light chain HVR-3 comprising LQSDSLPYT (SEQ ID NO: 38), and heavy chain HVR-1 comprising GYTFTNYGMN (SEQ ID NO: 39), heavy chain HVR 2 comprising WINTYTGETTYADDFKG (SEQ ID NO: 40), and heavy chain HVR-3 comprising EGGVNN (SEQ ID NO: 41), and wherein said substitution is one or more of the following: (a) amino acid at position 33 of the light chain is L or I; (b) amino acid at position 34 of the light chain is A or Q; (c) amino acid at position 52 of the light chain is S or A; (d) amino acid at position 104 of the light chain is V; (e) amino acid at position I of the heavy chain is E; (f) amino acid at position 99 of the heavy chain is A or Q; or (g) amino acid at position 100 of the heavy chain is A or Q. 4. An anti-Factor D antibody comprising: (a) at least one, two, three, four, five or six HVRs selected from the group comprising: (i) an HVR-H1 comprising the amino acid sequence selected from SEQ ID NO: 39; (ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40; (iii) an HVR-H3 comprising the amino acid sequence selected from SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44 and SEQ ID NO: 45; (iv) an HVR-L1 comprising the amino acid sequence selected from SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33 and SEQ ID NO: 34; (v) an HVR-L2 comprising the amino acid sequence selected from SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 37; and (vi) an HVR-L3 comprising the amino acid sequence selected from SEQ ID NO: 38; or (b) at least one variant HVR, wherein the variant HVR comprises modification of at least one residue of the sequence depicted in SEQ ID NO: 39, 40, 41, 42, 43, 44, 45, 30, 31, 32, 33, 34, 35, 36, 37 or 38. 5. The antibody of Claim 4, comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39 6. The antibody of Claim 4, comprising an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40. 7. The antibody of Claim 4, comprising an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 41. 8. The antibody of Claim 4, comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 30. 9. The antibody of Claim 4, comprising an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35. 10. The antibody of Claim 4, comprising an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 38. 11. The antibody of Claim 4, comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 41.
    12. The antibody of Claim 4, comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 30, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 38. 13. The antibody of Claim 4, comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40, an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 41, an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 30, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 38. 14. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 18. 15. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 19. 16. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 6. 17. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 7. 18. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 18 and a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 6. 19. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 19 and a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 7. 20. An antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain selected from SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28 and SEQ ID NO: 29. 21. An antibody of Claim 4, wherein the antibody comprises a light chain variable domain selected from SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17. 22. A polypeptide comprising the following amino acid sequence: X1VQLVQSG PELKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWI NTYTGETT
    YADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCEREGGVX
    2 X3WGQGTLVTVSS (SEQ ID NO: 74), wherein X 1 is Q or E; X 2 is N, A or Q; and X 3 is N, A or Q. 23. A polypeptide comprising the following amino acid sequence:
    DIQVTQSPSSLSASVGDRVTITCITSTDIDDDX
    4
    X
    5
    WYQQKPGKVPKLLISGGX
    6 TLRPGVPSRF
    SGSGSGTDFTLTISSLQPEDVATYYCLQSDSLPYTFGQGTKX
    7 EIK (SEQ ID NO: 73), wherein
    X
    4 is M, L or !; X 5 is N, A or Q; X 6 is N, S or A; and X 7 is L or V. 24. A polypeptide comprising an amino acid sequence selected from the group comprising SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28 and SEQ ID NO: 29. 25. A polypeptide comprising an amino acid sequence selected from the group comprising SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17. 26. An anti-Factor D antibody comprising the polypeptide of Claim 22. 27. An anti-Factor D antibody comprising the polypeptide of Claim 23. 28. An anti-Factor D antibody comprising the polypeptide of Claim 22 and the polypeptide of Claim 23. 29. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 18. 30. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 19. 31. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO: 6. 32. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO: 7. 33. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 18 and a light chain variable domain sequence of SEQ ID NO: 6. 34. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 19 and a light chain variable domain sequence of SEQ ID NO: 7. 35. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 54.
    36. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 63. 37. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 47. 38. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 61. 39. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 54 and a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 47. 40. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 63 and a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 61. 41. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 54. 42. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 63. 43. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO: 47. 44. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO: 61. 45. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 54 and a light chain variable domain sequence of SEQ ID NO: 47. 46. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 63 and a light chain variable domain sequence of SEQ ID NO: 61. 47. The polypeptide the comprising the amino acid selected from the group comprising SEQ ID NO: 47 and 61. 48. The polypeptide the comprising the amino acid selected from the group comprising SEQ ID NO: 54 and 63. 49. The antibody of claim 4 or 14-19 or 26-28, wherein the antibody is humanized.
    50. The antibody of claim 4 or 14-19 or 26-28, wherein the Factor D is mammalian Factor D. 51. The antibody of claim 50, wherein the Factor D is human Factor D. 52. A polynucleotide encoding an antibody of claim 4 or 14-19 or 26-28. 53. A polynucleotide encoding a polypeptide of claim 22-25 or 47-48. 54. A vector comprising the polynucleotide of Claim 52 or 53. 55. A host cell comprising the vector of claim 54. 56. A host cell of claim 55, wherein the host cell is eukaryotic. 57. A host cell of claim 55, wherein the host cell is a CHO cell. 58. A method of making an anti-Factor D antibody, wherein the method comprises (a) culturing the host cell of claim 56 or 57 under conditions suitable for expression of the polynucleotide encoding the antibody, and (b) isolating the antibody. 59. The antibody of claim 4 or 14-19 or 26-28, wherein the antibody is a monoclonal antibody. 60. The antibody of claim 59, wherein the antibody is an antibody fragment selected from a Fab, Fab'-SH, Fv, scFv, or (Fab') 2 fragment. 61. The antibody of claim 59, wherein the antibody is humanized. 62. The antibody of claim 59, which is produced in bacteria. 63. The antibody of claim 59, which is produced in CHO cells. 64. A pharmaceutical formulation comprising the anti-Factor D antibody of claim 59, and a pharmaceutically acceptable diluent, carrier or excipient. 65. An article of manufacture comprising: (a) the pharmaceutical formulation of claim 64; (b) a container; and (c) a package insert or label indicating that the compound can be used to treat a complemented-associated disorder. 66, A kit comprising an antibody of claim 4 or 14-19 or 26-28 and instructions for administering said antibody to treat a complement-associated disorder. 67. A kit of claim 66, wherein the complement-associated disorder is selected from the group comprising ocular diseases. 68. A kit of claim 67, wherein the ocular disease is selected from the group comprising age-related macular degeneration, diaetic retinopathy, choroidal neovascularization (CNV), uveitis, diabetic macular edema, pathological myopia, von Hippel-Lindau disease, histoplasmosis of the eye, Central Retinal Vein Occlusion (CRVO), corneal neovascularization, and retinal neovascularization. 69. A kit of claim 68, wherein the age-related macular degeneration is selected from the group comprising intermediate dry AMD, geographic atrophy and geographic atrophy.
    70. A method of treating a complement-associated disorder selected from the group comprising inflammatory disorders. 71. A method of claim 70, wherein the inflammatory disorder is an autoimmune disease. 72. A method of claim 71, wherein the autoimmune disease is selected from the group comprising systemic lupus erythematosus, myasthenia gravis, rheumatoid arthritis, Alzheimer's disease and multiple sclerosis. 73. A method of treating a complement-associated disorder selected from the group comprising ocular diseases. 74. A method of claim 73, wherein the ocular disease is selected from the group comprising age-related macular degeneration, diaetic retinopathy, choroidal neovascularization (CNV), uveitis, diabetic macular edema, pathological myopia, von Hippel Lindau disease, histoplasmosis of the eye, Central Retinal Vein Occlusion (CRVO), corneal neovascularization, and retinal neovascularization. 75. A method of claim 74, wherein the age-related macular degeneration is selected from the group comprising intermediate dry AMD, geographic atrophy and geographic atrophy. 76. The antibody made by the process of: (a) culturing a cell expressing an antibody comprising a heavy chain variable domain of any of claims 14-15, 29-30, 35-36 or 41-42 and a light chain variable domain of any of claims 16-17, 31-32, 37-38 or 43-44; and (b) isolating the antibody from said cultured cell.
    权利要求:
    Claims (53)
    [1] 1. An anti-Factor D antibody comprising light chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises light chain HVR-1 comprising ITSTDIDDDMN (SEQ ID NO: 30), light chain HVR-2 comprising GGNTLRP (SEQ ID NO: 35), and light chain HVR-3 comprising LQSDSLPYT (SEQ ID NO: 38), and wherein said substitution is one or more of the following: (a) amino acid at position 33 of the light chain is L or 1; (b) amino acid at position 34 of the light chain is A or Q; (c) amino acid at position 52 of the light chain is S or A; (d) amino acid at position 104 of the light chain is V; (e) amino acid at position 1 of the heavy chain is E; (f) amino acid at position 99 of the heavy chain is A or Q; or (g) amino acid at position 100 of the heavy chain is A or Q.
    [2] 2. An anti-Factor D antibody comprising heavy chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises heavy chain HVR-1 comprising GYTFTNYGMN (SEQ ID NO: 39), heavy chain HVR-2 comprising WINTYTGETTYADDFKG (SEQ ID NO: 40), and heavy chain HVR-3 comprising EGGVNN (SEQ ID NO: 41), and wherein said substitution is one or more of the following: (a) amino acid at position 33 of the light chain is L or I; (b) amino acid at position 34 of the light chain is A or Q; (c) amino acid at position 52 of the light chain is S or A; (d) amino acid at position 104 of the light chain is V' (e) amino acid at position 1 of the heavy chain is E; (f) amino acid at position 99 of the heavy chain is A or Q; or (g) amino acid at position 100 of the heavy chain is A or Q.
    [3] 3. An anti-Factor D antibody comprising light chain HVRs and heavy chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises light chain HVR-1 comprising ITSTDIDDDMN (SEQ ID NO: 30), light chain HVR-2 comprising GGNTLRP (SEQ ID NO: 35), and light chain HVR-3 comprising LQSDSLPYT (SEQ ID NO: 38), and heavy chain HVR-1 comprising GYTFTNYGMN (SEQ ID NO: 39), heavy chain HVR 2 comprising WINTYTGETTYADDFKG (SEQ ID NO: 40), and heavy chain HVR-3 comprising EGGVNN (SEQ ID NO: 41), and wherein said substitution is one or more of the following: (a) amino acid at position 33 of the light chain is L or I; (b) amino acid at position 34 of the light chain is A or Q; (c) amino acid at position 52 of the light chain is S or A; (d) amino acid at position 104 of the light chain is V; (e) amino acid at position I of the heavy chain is E; (f) amino acid at position 99 of the heavy chain is A or Q; or (g) amino acid at position 100 of the heavy chain is A or Q.
    [4] 4. An anti-Factor D antibody comprising: (a) at least one, two, three, four, five or six HVRs selected from the group comprising: (i) an HVR-H1 comprising the amino acid sequence selected from SEQ ID NO: 39; (ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40; (iii) an HVR-H3 comprising the amino acid sequence selected from SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44 and SEQ ID NO: 45; (iv) an HVR-L1 comprising the amino acid sequence selected from SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33 and SEQ ID NO: 34; (v) an HVR-L2 comprising the amino acid sequence selected from SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 37; and (vi) an HVR-L3 comprising the amino acid sequence selected from SEQ ID NO: 38; or (b) at least one variant HVR, wherein the variant HVR comprises modification of at least one residue of the sequence depicted in SEQ ID NO: 39, 40, 41, 42, 43, 44, 45, 30, 31, 32, 33, 34, 35, 36, 37 or 38.
    [5] 5. The antibody of Claim 4, comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39
    [6] 6. The antibody of Claim 4, comprising an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40.
    [7] 7. The antibody of Claim 4, comprising an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 41.
    [8] 8. The antibody of Claim 4, comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 30.
    [9] 9. The antibody of Claim 4, comprising an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35.
    [10] 10. The antibody of Claim 4, comprising an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 38.
    [11] 11. The antibody of Claim 4, comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 41.
    [12] 12. The antibody of Claim 4, comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 30, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 38.
    [13] 13. The antibody of Claim 4, comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40, an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 41, an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 30, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 38.
    [14] 14. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 18.
    [15] 15. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 19.
    [16] 16. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 6.
    [17] 17. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 7.
    [18] 18. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 18 and a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 6.
    [19] 19. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 19 and a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 7.
    [20] 20. An antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain selected from SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28 and SEQ ID NO: 29.
    [21] 21. An antibody of Claim 4, wherein the antibody comprises a light chain variable domain selected from SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17.
    [22] 22. A polypeptide comprising the following amino acid sequence: X1VQLVQSG PELKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWI NTYTGETT YADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCEREGGVX 2 X3WGQGTLVTVSS (SEQ ID NO: 74), wherein X 1 is Q or E; X 2 is N, A or Q; and X 3 is N, A or Q.
    [23] 23. A polypeptide comprising the following amino acid sequence: DIQVTQSPSSLSASVGDRVTITCITSTDIDDDX 4 X 5 WYQQKPGKVPKLLISGGX 6 TLRPGVPSRF SGSGSGTDFTLTISSLQPEDVATYYCLQSDSLPYTFGQGTKX 7 EIK (SEQ ID NO: 73), wherein X 4 is M, L or !; X 5 is N, A or Q; X 6 is N, S or A; and X 7 is L or V.
    [24] 24. A polypeptide comprising an amino acid sequence selected from the group comprising SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28 and SEQ ID NO: 29.
    [25] 25. A polypeptide comprising an amino acid sequence selected from the group comprising SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17.
    [26] 26. An anti-Factor D antibody comprising the polypeptide of Claim 22.
    [27] 27. An anti-Factor D antibody comprising the polypeptide of Claim 23.
    [28] 28. An anti-Factor D antibody comprising the polypeptide of Claim 22 and the polypeptide of Claim 23.
    [29] 29. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 18.
    [30] 30. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 19.
    [31] 31. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO: 6.
    [32] 32. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO: 7.
    [33] 33. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 18 and a light chain variable domain sequence of SEQ ID NO: 6.
    [34] 34. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 19 and a light chain variable domain sequence of SEQ ID NO: 7.
    [35] 35. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 54.
    [36] 36. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 63.
    [37] 37. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO:
    [38] 47. 38. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO:
    [39] 61. 39. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 54 and a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 47. 40. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 63 and a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO: 61. 41. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 54. 42. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 63. 43. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO: 47. 44. The antibody of Claim 4, wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO: 61. 45. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 54 and a light chain variable domain sequence of SEQ ID NO: 47. 46. The antibody of Claim 4, wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 63 and a light chain variable domain sequence of SEQ ID NO: 61. 47. The polypeptide the comprising the amino acid selected from the group comprising SEQ ID NO: 47 and 61. 48. The polypeptide the comprising the amino acid selected from the group comprising SEQ ID NO: 54 and 63. 49. The antibody of claim 4 or 14-19 or 26-28, wherein the antibody is humanized. 50. The antibody of claim 4 or 14-19 or 26-28, wherein the Factor D is mammalian Factor D. 51. The antibody of claim 50, wherein the Factor D is human Factor D. 52. A polynucleotide encoding an antibody of claim 4 or 14-19 or 26-28. 53. A polynucleotide encoding a polypeptide of claim 22-25 or 47-48. 54. A vector comprising the polynucleotide of Claim 52 or 53. 55. A host cell comprising the vector of claim 54. 56. A host cell of claim 55, wherein the host cell is eukaryotic. 57. A host cell of claim 55, wherein the host cell is a CHO cell. 58. A method of making an anti-Factor D antibody, wherein the method comprises (a) culturing the host cell of claim 56 or 57 under conditions suitable for expression of the polynucleotide encoding the antibody, and (b) isolating the antibody. 59. The antibody of claim 4 or 14-19 or 26-28, wherein the antibody is a monoclonal antibody. 60. The antibody of claim 59, wherein the antibody is an antibody fragment selected from a Fab, Fab'-SH, Fv, scFv, or (Fab') 2 fragment. 61. The antibody of claim 59, wherein the antibody is humanized.
    [40] 62. The antibody of claim 59, which is produced in bacteria.
    [41] 63. The antibody of claim 59, which is produced in CHO cells.
    [42] 64. A pharmaceutical formulation comprising the anti-Factor D antibody of claim 59, and a pharmaceutically acceptable diluent, carrier or excipient.
    [43] 65. An article of manufacture comprising: (a) the pharmaceutical formulation of claim 64; (b) a container; and (c) a package insert or label indicating that the compound can be used to treat a complemented-associated disorder. 66, A kit comprising an antibody of claim 4 or 14-19 or 26-28 and instructions for administering said antibody to treat a complement-associated disorder.
    [44] 67. A kit of claim 66, wherein the complement-associated disorder is selected from the group comprising ocular diseases.
    [45] 68. A kit of claim 67, wherein the ocular disease is selected from the group comprising age-related macular degeneration, diaetic retinopathy, choroidal neovascularization (CNV), uveitis, diabetic macular edema, pathological myopia, von Hippel-Lindau disease, histoplasmosis of the eye, Central Retinal Vein Occlusion (CRVO), corneal neovascularization, and retinal neovascularization.
    [46] 69. A kit of claim 68, wherein the age-related macular degeneration is selected from the group comprising intermediate dry AMD, geographic atrophy and geographic atrophy.
    [47] 70. A method of treating a complement-associated disorder selected from the group comprising inflammatory disorders.
    [48] 71. A method of claim 70, wherein the inflammatory disorder is an autoimmune disease.
    [49] 72. A method of claim 71, wherein the autoimmune disease is selected from the group comprising systemic lupus erythematosus, myasthenia gravis, rheumatoid arthritis, Alzheimer's disease and multiple sclerosis.
    [50] 73. A method of treating a complement-associated disorder selected from the group comprising ocular diseases.
    [51] 74. A method of claim 73, wherein the ocular disease is selected from the group comprising age-related macular degeneration, diaetic retinopathy, choroidal neovascularization (CNV), uveitis, diabetic macular edema, pathological myopia, von Hippel Lindau disease, histoplasmosis of the eye, Central Retinal Vein Occlusion (CRVO), corneal neovascularization, and retinal neovascularization.
    [52] 75. A method of claim 74, wherein the age-related macular degeneration is selected from the group comprising intermediate dry AMD, geographic atrophy and geographic atrophy.
    [53] 76. The antibody made by the process of: (a) culturing a cell expressing an antibody comprising a heavy chain variable domain of any of claims 14-15, 29-30, 35-36 or 41-42 and a light chain variable domain of any of claims 16-17, 31-32, 37-38 or 43-44; and (b) isolating the antibody from said cultured cell.
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    同族专利:
    公开号 | 公开日
    AU2013200637B2|2015-07-16|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US6956107B2|1998-02-20|2005-10-18|Tanox, Inc.|Inhibitors of complement activation|
    UA99591C2|2005-11-04|2012-09-10|Дженентек, Инк.|Use of complement pathway inhibitors to treat ocular diseases|
    CA2657013A1|2006-07-06|2008-01-10|Organogenesis Inc.|Temperature-responsive microcarrier|
    法律状态:
    2015-07-30| DA3| Amendments made section 104|Free format text: THE NATURE OF THE AMENDMENT IS: AMEND THE NAME OF THE INVENTOR TO READ HUANG, ARTHUR J.; KELLEY, ROBERT F.; LOWMAN, HENRY; VAN LOOKEREN CAMPAGNE, MENNO AND WINTER, CHARLES M. |
    2015-11-12| FGA| Letters patent sealed or granted (standard patent)|
    2020-11-26| MK14| Patent ceased section 143(a) (annual fees not paid) or expired|
    优先权:
    申请号 | 申请日 | 专利标题
    US61/048,431||2008-04-28||
    US61/048,689||2008-04-29||
    AU2009241348A|AU2009241348C1|2008-04-28|2009-04-27|Humanized anti-Factor D antibodies and uses thereof|
    AU2013200637A|AU2013200637B2|2008-04-28|2013-02-06|Humanized anti-Factor D antibodies and uses thereof|AU2013200637A| AU2013200637B2|2008-04-28|2013-02-06|Humanized anti-Factor D antibodies and uses thereof|
    AU2015238842A| AU2015238842A1|2008-04-28|2015-10-08|Humanized anti-Factor D antibodies and uses thereof|
    AU2017225033A| AU2017225033A1|2008-04-28|2017-09-06|Humanized anti-Factor D antibodies and uses thereof|
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