Treatment and prevention methods for Alzheimer's disease
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- EISAI R&D MANAGEMENT CO LTD
- Filing Date
- 2026-02-27
- Publication Date
- 2026-06-16
Smart Images
Figure 2026097906000030 
Figure 2026097906000031 
Figure 2026097906000032
Abstract
Claims
1. A method for reducing clinical functional decline in a subject with early-stage Alzheimer's disease, comprising administering a composition containing a therapeutically effective amount of at least one anti-Aβ protofibril antibody.
2. The method according to claim 1, wherein the at least one anti-Aβ protofibril antibody comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) comprising the amino acid sequences of SEQ ID NO: 5 (HCDR1), SEQ ID NO: 6 (HCDR2), and SEQ ID NO: 7 (HCDR3); and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) comprising the amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3).
3. The method according to claim 1, wherein the subject having early-stage Alzheimer's disease has been diagnosed with mild to moderate cognitive impairment due to Alzheimer's disease, and / or has been diagnosed with mild Alzheimer's disease-type dementia.
4. The method according to any one of claims 1 to 3, wherein the subject is ApoE4 positive.
5. The method according to any one of claims 1 to 4, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
6. The method according to claim 5, wherein the composition contains 5 mg / kg to 10 mg / kg of BAN2401 based on the body weight of the subject.
7. The method according to claim 5, wherein the composition comprises 10 mg / kg of BAN2401 based on the body weight of the subject.
8. The method according to any one of claims 1 to 7, wherein the composition is administered once every two weeks or once a month.
9. The method according to any one of claims 1 to 8, wherein the clinical functional impairment is reduced by at least 45% compared to placebo, as determined by ADCOMS after administration of the composition for six months.
10. The method according to any one of claims 1 to 9, wherein the clinical functional impairment is reduced by at least 35% compared to placebo, as determined by ADCOMS after administration of the composition for 12 months.
11. The method according to any one of claims 1 to 10, wherein the aforementioned clinical functional impairment is reduced by at least 30% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
12. The method according to any one of claims 1 to 11, wherein the clinical functional impairment is reduced by at least 47% compared to placebo, as determined by ADAS-Cog after administration of the composition for 18 months.
13. The method according to any one of claims 1 to 12, wherein the aforementioned clinical functional impairment is reduced by at least 26% compared to placebo, as determined by CDR-SB after administration of the composition for 18 months.
14. The method according to claim 11, wherein the subject having early-stage Alzheimer's disease is diagnosed with a possible mild to moderate cognitive impairment due to Alzheimer's disease, and the clinical functional decline is reduced by at least 33% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
15. The method according to claim 11, wherein the subject having early-stage Alzheimer's disease is diagnosed with mild Alzheimer's disease-type dementia, and the clinical functional decline is reduced by at least 35% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
16. The method according to any one of claims 9 to 15, wherein the composition comprises at least one anti-Aβ protofibril antibody in a concentration of 10 mg / kg, and is administered once every two weeks or once a month.
17. The method according to claim 16, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
18. The method according to any one of claims 9 to 17, wherein the subject is ApoE4 positive.
19. The method according to claim 18, wherein the clinical functional impairment is reduced by at least 63% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
20. The method according to claim 18, wherein the clinical functional impairment is reduced by at least 84% compared to placebo, as determined by ADAS-Cog after administration of the composition for 18 months.
21. The method according to claim 18, wherein the clinical functional impairment is reduced by at least 60% compared to placebo, as determined by CDR-SB after administration of the composition for 18 months.
22. The method according to any one of claims 1 to 17, wherein the subject is ApoE4 negative.
23. As a result of the above administration, cerebrospinal fluid Aβ １－４２ The method according to any one of claims 1 to 22, wherein a reduction in total tau, phosphotau, and / or neurogranin levels occurs.
24. The method according to any one of claims 1 to 23, wherein the administration slows the increase in cerebrospinal fluid neurofilament light chain levels.
25. The method according to any one of claims 1 to 24, wherein the subject is simultaneously administered at least one Alzheimer's disease drug other than BAN2401.
26. The method according to any one of claims 1 to 24, wherein the subject does not receive simultaneous administration of at least one Alzheimer's disease drug other than BAN2401.
27. A method for converting an amyloid-positive subject with early Alzheimer's disease to an amyloid-negative, comprising administering a composition containing a therapeutically effective amount of at least one anti-Aβ protofibril antibody.
28. The method according to claim 27, wherein the at least one anti-Aβ protofibril antibody comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) comprising the amino acid sequences of SEQ ID NO: 5 (HCDR1), SEQ ID NO: 6 (HCDR2), and SEQ ID NO: 7 (HCDR3); and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) comprising the amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3).
29. The method according to claim 27, wherein the subject having early-stage Alzheimer's disease has been diagnosed with mild to moderate cognitive impairment due to Alzheimer's disease, and / or has been diagnosed with mild Alzheimer's disease-type dementia.
30. The method according to any one of claims 27 to 29, wherein the subject is ApoE4 positive.
31. The method according to any one of claims 27 to 30, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
32. The method according to any one of claims 27 to 31, wherein the composition comprises 5 mg / kg to 10 mg / kg of BAN2401 based on the body weight of the subject.
33. The method according to claim 32, wherein the composition comprises 10 mg / kg of BAN2401 based on the body weight of the subject.
34. The method according to any one of claims 27 to 33, wherein the composition is administered once every two weeks or once a month.
35. The method according to any one of claims 27 to 31, wherein, upon administration of the composition, 50% to 100% of subjects become amyloid-negative as determined by visual interpretation of amyloid PET images after administration of the composition for six months.
36. The method according to any one of claims 27 to 31, wherein, upon administration of the composition, at least 55% of the subjects become amyloid-negative as determined by visual interpretation of amyloid PET images after administration of the composition for 12 months.
37. The method according to any one of claims 27 to 31, wherein, upon administration of the composition, at least 70% of the subjects become amyloid-negative as determined by visual interpretation of amyloid PET images after administration of the composition for 18 months.
38. The method according to any one of claims 35 to 37, wherein the composition comprises at least one anti-Aβ protofibril antibody in a concentration of 10 mg / kg, and is administered once every two weeks or once a month.
39. The method according to any one of claims 35 to 38, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
40. The method according to any one of claims 35 to 39, wherein the subject is ApoE4 positive.
41. The method according to any one of claims 35 to 39, wherein the subject is ApoE4 negative.
42. As a result of the above administration, cerebrospinal fluid Aβ １－４２ The method according to any one of claims 35 to 41, wherein a reduction in total tau, phosphotau, and / or neurogranin levels occurs.
43. The method according to any one of claims 35 to 42, wherein the administration results in a slowing of the increase in cerebrospinal fluid neurofilament light chain levels.
44. A method for reducing brain amyloid levels in a subject requiring such reduction, comprising administering a composition comprising a therapeutically effective amount of at least one anti-Aβ protofibril antibody.
45. The method according to claim 44, wherein the antibody comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) containing the amino acid sequences of SEQ ID NO: 5 (HCDR1), SEQ ID NO: 6 (HCDR2), and SEQ ID NO: 7 (HCDR3); and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) containing the amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3).
46. The method according to claim 44 or 45, wherein the subject has Alzheimer's disease, Down syndrome, chronic traumatic encephalopathy, cerebral amyloid angiopathy, Lewy body dementia, or another brain disease or condition involving soluble and / or insoluble Aβ aggregates containing Aβ peptide.
47. The method according to claim 46, wherein the Alzheimer's disease is early-stage Alzheimer's disease.
48. The method according to claim 47, wherein the subject having early-stage Alzheimer's disease has been diagnosed with mild to moderate cognitive impairment due to Alzheimer's disease, and / or has been diagnosed with mild Alzheimer's disease-type dementia.
49. The method according to any one of claims 44 to 48, wherein the subject is ApoE4 positive.
50. The method according to any one of claims 44 to 49, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
51. The method according to claim 50, wherein the composition contains BAN2401 at a concentration of 2.5 mg / kg to 10 mg / kg based on the body weight of the subject.
52. The method according to claim 51, wherein the composition comprises 10 mg / kg of BAN2401 based on the body weight of the subject.
53. The method according to any one of claims 44 to 52, wherein the composition is administered once every two weeks or once a month.
54. The method according to any one of claims 44 to 53, wherein the mean change from the adjusted baseline of the target PET SUVr value is reduced by at least -0.20 after administration of the composition for 12 months.
55. The method according to any one of claims 44 to 53, wherein the adjusted mean of the target PET SUVr value from baseline is reduced by at least -0.25 after administration of the composition for 18 months.
56. The method according to any one of claims 44 to 55, wherein the composition comprises at least one anti-Aβ protofibril antibody in a concentration of 10 mg / kg and is administered once every two weeks or once a month.
57. The method according to any one of claims 44 to 55, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
58. The method according to any one of claims 44 to 57, wherein the subject is ApoE4 positive.
59. The method according to any one of claims 44 to 53, wherein the subject is ApoE4 negative.
60. As a result of the above administration, cerebrospinal fluid Aβ １－４２ The method according to any one of claims 44 to 59, wherein a reduction in total tau, phosphotau, and / or neurogranin levels occurs.
61. The method according to any one of claims 44 to 60, wherein the administration results in a slowing of the increase in cerebrospinal fluid neurofilament light chain levels.
62. A method for preventing the target Alzheimer's disease, To measure the brain amyloid level of the subject; If the brain amyloid level of the subject exceeds a first predetermined level, administer a composition containing a therapeutically effective amount of at least one anti-Aβ protofibril antibody. To measure the brain amyloid level after administration of the subject mentioned above. If the post-administration brain amyloid level exceeds a second predetermined level, administer the composition. After administration, monitor the brain amyloid level of the subject until it falls below a first predetermined level. Optionally, administer at least one additional therapeutic agent selected from a BACE inhibitor, a γ-secretase inhibitor, a γ-secretase modulator, an Aβ peptide production inhibitor other than the at least one anti-Aβ protofibril antibody, an agent that reduces Aβ peptide levels other than the at least one anti-Aβ protofibril antibody, and combinations thereof, which are suitable for maintaining the predetermined brain amyloid level. A method that includes this.
63. The determination of pre- and / or post-administration brain amyloid levels is based on pre-administration cerebrospinal fluid Aβ １－４２ The method according to claim 62, further comprising determining total tau, phosphotau, neurogranin, and / or neurofilament light chain levels.
64. Post-administration cerebrospinal fluid Aβ １－４２ If the total tau, phosphotau, neurogranin, and / or neurofilament light chain levels exceed a predetermined level, administer the composition. The method according to claim 62 or 63, further comprising:
65. The method according to any one of claims 62 to 64, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
66. The method according to claim 65, wherein the composition comprises 2.5 mg / kg to 10 mg / kg of BAN2401 based on the body weight of the subject.
67. The method according to claim 66, wherein the composition comprises 10 mg / kg of BAN2401 based on the body weight of the subject.
68. The method according to any one of claims 62 to 67, wherein the composition is administered once every two weeks or once a month.
69. The method according to any one of claims 62 to 68, wherein the brain amyloid level is reduced after administration compared to the brain amyloid level before administration.
70. The method according to any one of claims 62 to 69, wherein if the brain amyloid level is reduced by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% compared to the brain amyloid level before administration, the administration is discontinued.
71. The method according to any one of claims 62 to 70, wherein the brain amyloid level is determined by visual interpretation of amyloid PET images.
72. The cerebrospinal fluid Aβ １－４２ The level of cerebrospinal fluid Aβ after the administration is the same as before the administration. １－４２ The method according to any one of claims 62 to 71, wherein the level is reduced compared to the level.
73. The method according to any one of claims 62 to 72, wherein the total cerebrospinal fluid tau level is reduced after administration compared to the total cerebrospinal fluid tau level before administration.
74. The method according to any one of claims 62 to 73, wherein the cerebrospinal fluid phosphotau level is reduced after administration compared to the cerebrospinal fluid phosphotau level before administration.
75. The method according to any one of claims 62 to 74, wherein the cerebrospinal fluid neurolanin level is reduced after administration compared to the cerebrospinal fluid neurolanin level before administration.
76. The method according to any one of claims 62 to 75, wherein the rate of increase in cerebrospinal fluid level of neurofilament light chains after administration is lower than the rate of increase in cerebrospinal fluid level before administration.
77. The method according to any one of claims 62 to 76, wherein the at least one optional additional therapeutic agent suitable for maintaining the predetermined brain amyloid level is a BACE inhibitor.
78. The method according to claim 77, wherein the BACE inhibitor is elenbecestat.
79. The method according to any one of claims 62 to 78, wherein the subject is ApoE4 positive.
80. A method for preventing the target Alzheimer's disease, To measure the brain amyloid level of the subject; If the brain amyloid level of the subject exceeds a first predetermined level, administer a composition comprising a therapeutically effective amount of at least one anti-Aβ protofibril antibody and a composition comprising a therapeutically effective amount of at least one therapeutic agent selected from a BACE inhibitor, a γ-secretase inhibitor, a γ-secretase modulator, an Aβ peptide production inhibitor other than the at least one anti-Aβ protofibril antibody, and an agent that reduces the Aβ peptide level other than the at least one anti-Aβ protofibril antibody. To measure the brain amyloid level after administration of the subject mentioned above. If the post-administration brain amyloid level exceeds a second predetermined level, administer a composition comprising a therapeutically effective amount of at least one anti-Aβ protofibril antibody and a composition comprising a therapeutically effective amount of at least one therapeutic agent selected from a BACE inhibitor, a γ-secretase inhibitor, a γ-secretase modulator, an Aβ peptide production inhibitor other than the at least one anti-Aβ protofibril antibody, and an agent that reduces the Aβ peptide level other than the at least one anti-Aβ protofibril antibody. After administration, monitor the brain amyloid level of the subject until it falls below a first predetermined level. Administering at least one additional therapeutic agent selected from a BACE inhibitor, a γ-secretase inhibitor, a γ-secretase modulator, an Aβ peptide production inhibitor other than the at least one anti-Aβ protofibril antibody, and an agent that reduces the Aβ peptide level other than the at least one anti-Aβ protofibril antibody, which is suitable for maintaining the predetermined brain amyloid level. A method that includes this.
81. The determination of pre- and / or post-administration brain amyloid levels is based on pre-administration cerebrospinal fluid Aβ １－４２ The method according to claim 80, further comprising determining total tau, phosphotau, neurogranin, and / or neurofilament light chain levels.
82. Cerebrospinal fluid Aβ after administration １－４２ administering the composition when the levels of total tau, phospho-tau, neurogranin, and / or neurofilament light chain exceed a predetermined level The method according to claim 80 or 81, further comprising:
83. The method according to any one of claims 80 to 82, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
84. The method according to any one of claims 80 to 83, wherein the at least one therapeutic agent is a BACE inhibitor.
85. The method according to claim 84, wherein the BACE inhibitor is elenbecestat.
86. The method according to claim 80, wherein the composition comprises 2.5 mg / kg to 10 mg / kg of BAN2401 based on the body weight of the subject.
87. The method according to claim 86, wherein the composition comprises 10 mg / kg of BAN2401 based on the body weight of the subject.
88. The method according to any one of claims 80 to 87, wherein the composition is administered once every two weeks or once a month.
89. The method according to any one of claims 80 to 88, wherein the brain amyloid level is reduced after administration compared to the brain amyloid level before administration.
90. The method according to any one of claims 80 to 89, wherein if the brain amyloid level is reduced by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% compared to the brain amyloid level before administration, the administration is discontinued.
91. The method according to any one of claims 80 to 90, wherein the brain amyloid level is determined by visual interpretation of amyloid PET images.
92. The cerebrospinal fluid Aβ １－４２ The level of cerebrospinal fluid Aβ after the administration is the same as before the administration. １－４２ The method according to any one of claims 80 to 91, wherein the level is reduced compared to the level.
93. The method according to any one of claims 80 to 92, wherein the total cerebrospinal fluid tau level is reduced after administration compared to the total cerebrospinal fluid tau level before administration.
94. The method according to any one of claims 80 to 93, wherein the cerebrospinal fluid phosphotau level is reduced after administration compared to the cerebrospinal fluid phosphotau level before administration.
95. The method according to any one of claims 80 to 94, wherein the cerebrospinal fluid neurolanin level is reduced after administration compared to the cerebrospinal fluid neurolanin level before administration.
96. The method according to any one of claims 80 to 95, wherein the rate of increase in cerebrospinal fluid level of neurofilament light chains after administration is lower than the rate of increase in cerebrospinal fluid level before administration.
97. The method according to any one of claims 80 to 96, wherein the at least one optional additional therapeutic agent suitable for maintaining the predetermined brain amyloid level is a BACE inhibitor.
98. The method according to claim 97, wherein the BACE inhibitor is elenbecestat.
99. A method for treating a subject with early-stage Alzheimer's disease, comprising administering a composition containing a therapeutically effective amount of at least one anti-Aβ protofibril antibody, A method wherein the clinical functional impairment of the subject is reduced by at least 35% compared to placebo when determined by ADCOMS after administration of the composition for 6 months, reduced by at least 30% compared to placebo when determined by ADCOMS after administration of the composition for 12 months, and / or reduced by at least 25% compared to placebo when determined by ADCOMS after administration of the composition for 18 months.
100. The method according to claim 99, wherein the at least one anti-Aβ protofibril antibody comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) comprising the amino acid sequences of SEQ ID NO: 5 (HCDR1), SEQ ID NO: 6 (HCDR2), and SEQ ID NO: 7 (HCDR3); and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) comprising the amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3).
101. The method according to claim 99 or 100, wherein the subject having early-stage Alzheimer's disease has been diagnosed with mild to moderate cognitive impairment due to Alzheimer's disease, and / or has been diagnosed with mild Alzheimer's disease-type dementia.
102. The method according to any one of claims 99 to 101, wherein the subject is ApoE4 positive.
103. The method according to any one of claims 99 to 102, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
104. The method according to claim 103, wherein the composition contains 5 mg / kg to 10 mg / kg of BAN2401 based on the body weight of the subject.
105. The method according to claim 103, wherein the composition comprises 10 mg / kg of BAN2401 based on the body weight of the subject.
106. The method according to any one of claims 99 to 105, wherein the composition is administered once every two weeks or once a month.
107. The method according to any one of claims 99 to 106, wherein the clinical functional impairment is reduced by at least 45% compared to placebo, as determined by ADCOMS after administration of the composition for six months.
108. The method according to any one of claims 99 to 106, wherein the clinical functional impairment is reduced by at least 35% compared to placebo, as determined by ADCOMS after administration of the composition for 12 months.
109. The method according to any one of claims 99 to 106, wherein the clinical functional impairment is reduced by at least 30% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
110. The method according to any one of claims 99 to 106, wherein the clinical functional impairment is reduced by at least 47% compared to placebo, as determined by ADAS-Cog after administration of the composition for 18 months.
111. The method according to any one of claims 99 to 106, wherein the clinical functional impairment is reduced by at least 26% compared to placebo, as determined by CDR-SB after administration of the composition for 18 months.
112. The method according to claim 109, wherein the subject having early-stage Alzheimer's disease is diagnosed with a possible mild to moderate cognitive impairment due to Alzheimer's disease, and the clinical functional decline is reduced by at least 33% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
113. The method according to claim 109, wherein the subject having early-stage Alzheimer's disease is diagnosed with mild Alzheimer's disease-type dementia, and the clinical functional decline is reduced by at least 35% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
114. The method according to any one of claims 107 to 109, wherein the composition comprises at least one anti-Aβ protofibril antibody in a concentration of 10 mg / kg, and is administered once every two weeks or once a month.
115. The method according to claim 114, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
116. The method according to any one of claims 99 to 115, wherein the subject is ApoE4 positive.
117. The method according to claim 116, wherein the clinical functional impairment is reduced by at least 63% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
118. The method according to claim 116, wherein the clinical functional impairment is reduced by at least 84% compared to placebo, as determined by ADAS-Cog after administration of the composition for 18 months.
119. The method according to claim 116, wherein the aforementioned clinical functional impairment is reduced by at least 60% compared to placebo, as determined by CDR-SB after administration of the composition for 18 months.
120. The method according to any one of claims 99 to 114, wherein the subject is ApoE4 negative.
121. As a result of the above administration, cerebrospinal fluid Aβ １－４２ The method according to any one of claims 99 to 120, wherein a reduction in total tau, phosphotau, and / or neurogranin levels occurs.
122. The method according to any one of claims 99 to 121, wherein the administration results in a slowing of the increase in cerebrospinal fluid neurofilament light chain levels.
123. The method according to any one of claims 99 to 122, wherein the subject is simultaneously administered at least one Alzheimer's disease drug other than BAN2401.
124. The method according to any one of claims 99 to 122, wherein the subject does not receive simultaneous administration of at least one Alzheimer's disease drug other than BAN2401.
125. A method for treating a subject with early-stage Alzheimer's disease, comprising administering a composition containing a therapeutically effective amount of at least one anti-Aβ protofibril antibody, A method by which the severity of at least one symptom associated with Alzheimer's disease is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% compared to the severity of the same symptom in the same subject before treatment.
126. The method according to claim 125, wherein the at least one anti-Aβ protofibril antibody comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) comprising the amino acid sequences of SEQ ID NO: 5 (HCDR1), SEQ ID NO: 6 (HCDR2), and SEQ ID NO: 7 (HCDR3); and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) comprising the amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3).
127. The method according to claim 125 or 126, wherein the subject having early-stage Alzheimer's disease has been diagnosed with mild to moderate cognitive impairment due to Alzheimer's disease, and / or has been diagnosed with mild Alzheimer's disease-type dementia.
128. The method according to any one of claims 125 to 127, wherein the subject is ApoE4 positive.
129. The method according to any one of claims 125 to 128, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
130. The method according to claim 129, wherein the composition comprises 5 mg / kg to 10 mg / kg of BAN2401 based on the body weight of the subject.
131. The method according to claim 129, wherein the composition comprises 10 mg / kg of BAN2401 based on the body weight of the subject.
132. The method according to any one of claims 125 to 131, wherein the composition is administered once every two weeks or once a month.
133. The method according to any one of claims 125 to 132, wherein the at least one symptom associated with Alzheimer's disease is clinical impairment, and the clinical impairment is reduced by at least 45% compared to placebo, as determined by ADCOMS after administration of the composition for six months.
134. The method according to any one of claims 125 to 132, wherein the at least one symptom associated with Alzheimer's disease is clinical impairment, and the clinical impairment is reduced by at least 35% compared to placebo, as determined by ADCOMS after administration of the composition for 12 months.
135. The method according to any one of claims 125 to 132, wherein the at least one symptom associated with Alzheimer's disease is clinical impairment, and the clinical impairment is reduced by at least 30% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
136. The method according to any one of claims 125 to 132, wherein the clinical functional impairment is reduced by at least 47% compared to placebo, as determined by ADAS-Cog after administration of the composition for 18 months.
137. The method according to any one of claims 125 to 132, wherein the clinical functional impairment is reduced by at least 26% compared to placebo, as determined by CDR-SB after administration of the composition for 18 months.
138. The method according to claim 135, wherein the subject having early-stage Alzheimer's disease is diagnosed with a possible mild to moderate cognitive impairment due to Alzheimer's disease, and the clinical functional decline is reduced by at least 33% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
139. The method according to claim 135, wherein the subject having early-stage Alzheimer's disease is diagnosed with mild Alzheimer's disease-type dementia, and the clinical functional decline is reduced by at least 35% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
140. The method according to any one of claims 125 to 139, wherein the composition comprises at least one anti-Aβ protofibril antibody in a concentration of 10 mg / kg, and is administered once every two weeks or once a month.
141. The method according to claim 140, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
142. The method according to any one of claims 125 to 141, wherein the subject is ApoE4 positive.
143. The method according to claim 142, wherein the clinical functional impairment is reduced by at least 63% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
144. The method according to claim 142, wherein the clinical functional impairment is reduced by at least 84% compared to placebo, as determined by ADAS-Cog after administration of the composition for 18 months.
145. The method according to claim 142, wherein the aforementioned clinical functional impairment is reduced by at least 60% compared to placebo, as determined by CDR-SB after administration of the composition for 18 months.
146. The method according to any one of claims 125 to 145, wherein the at least one symptom associated with Alzheimer's disease is selected from clinical functional decline and brain amyloid levels.
147. As a result of the above administration, cerebrospinal fluid Aβ １－４２ The method according to any one of claims 125 to 146, wherein a reduction in total tau, phosphotau, and / or neurogranin levels occurs.
148. The method according to any one of claims 125 to 147, wherein the administration results in a slowing of the increase in cerebrospinal fluid neurofilament light chain levels.
149. The method according to any one of claims 125 to 148, wherein the subject is simultaneously administered at least one Alzheimer's disease drug other than BAN2401.
150. The method according to any one of claims 125 to 148, wherein the subject does not receive simultaneous administration of at least one Alzheimer's disease drug other than BAN2401.
151. A method for treating a subject with early-stage Alzheimer's disease, comprising administering a composition containing a therapeutically effective amount of at least one anti-Aβ protofibril antibody, A method in which the severity of at least one symptom associated with Alzheimer's disease is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% compared to the severity of the same symptom in subjects who received a placebo.
152. The method according to claim 151, wherein the severity of at least one symptom associated with Alzheimer's disease is determined by ADCOMS, PET, MMSE, CDR-SB, and / or ADAS-Cog.
153. The method according to claim 151, wherein the at least one anti-Aβ protofibril antibody comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) comprising the amino acid sequences of SEQ ID NO: 5 (HCDR1), SEQ ID NO: 6 (HCDR2), and SEQ ID NO: 7 (HCDR3); and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) comprising the amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3).
154. The method according to claim 151, wherein the subject having early-stage Alzheimer's disease has been diagnosed with a mild to moderate possibility of cognitive impairment due to Alzheimer's disease, and / or has been diagnosed with mild Alzheimer's disease-type dementia.
155. The method according to any one of claims 151 to 154, wherein the subject is ApoE4 positive.
156. The method according to any one of claims 151 to 155, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
157. The method according to claim 156, wherein the composition comprises 5 mg / kg to 10 mg / kg of BAN2401 based on the body weight of the subject.
158. The method according to claim 156, wherein the composition comprises 10 mg / kg of BAN2401 based on the body weight of the subject.
159. The method according to any one of claims 151 to 158, wherein the composition is administered once every two weeks or once a month.
160. The method according to any one of claims 151 to 159, wherein the clinical functional impairment is reduced by at least 45% compared to placebo, as determined by ADCOMS after administration of the composition for six months.
161. The method according to any one of claims 151 to 159, wherein the at least one symptom associated with Alzheimer's disease is clinical impairment, and the clinical impairment is reduced by at least 35% compared to placebo, as determined by ADCOMS after administration of the composition for 12 months.
162. The method according to any one of claims 151 to 159, wherein the at least one symptom associated with Alzheimer's disease is clinical impairment, and the clinical impairment is reduced by at least 30% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
163. The method according to any one of claims 151 to 159, wherein the clinical functional impairment is reduced by at least 47% compared to placebo, as determined by ADAS-Cog after administration of the composition for 18 months.
164. The method according to any one of claims 151 to 159, wherein the aforementioned clinical functional impairment is reduced by at least 26% compared to placebo, as determined by CDR-SB after administration of the composition for 18 months.
165. The method according to claim 162, wherein the subject having early-stage Alzheimer's disease is diagnosed with a possible mild to moderate cognitive impairment due to Alzheimer's disease, and the clinical functional decline is reduced by at least 33% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
166. The method according to claim 162, wherein the subject having early-stage Alzheimer's disease is diagnosed with mild Alzheimer's disease-type dementia, and the clinical functional decline is reduced by at least 35% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
167. The method according to any one of claims 160 to 166, wherein the composition comprises at least one anti-Aβ protofibril antibody in a concentration of 10 mg / kg and is administered once every two weeks or once a month.
168. The method according to claim 167, wherein the at least one anti-Aβ protofibril antibody is BAN2401.
169. The method according to any one of claims 160 to 167, wherein the subject is ApoE4 positive.
170. The method according to claim 169, wherein the clinical functional impairment is reduced by at least 63% compared to placebo, as determined by ADCOMS after administration of the composition for 18 months.
171. The method according to claim 169, wherein the clinical functional impairment is reduced by at least 84% compared to placebo, as determined by ADAS-Cog after administration of the composition for 18 months.
172. The method according to claim 169, wherein the aforementioned clinical functional impairment is reduced by at least 60% compared to placebo, as determined by CDR-SB after administration of the composition for 18 months.
173. The method according to any one of claims 151 to 169, wherein the at least one symptom associated with Alzheimer's disease is selected from clinical functional decline and brain amyloid levels.
174. As a result of the above administration, cerebrospinal fluid Aβ １－４２ The method according to any one of claims 151 to 173, wherein a reduction in total tau, phosphotau, and / or neurogranin levels occurs.
175. The method according to any one of claims 151 to 173, wherein the administration results in a slowing of the increase in cerebrospinal fluid neurofilament light chain levels.
176. The method according to any one of claims 151 to 173, wherein the subject is simultaneously administered at least one Alzheimer's disease drug other than BAN2401.
177. The method according to any one of claims 151 to 173, wherein the subject does not receive simultaneous administration of at least one Alzheimer's disease drug other than BAN2401.
178. The method according to any one of claims 80 to 99, wherein the subject is ApoE4 positive.
179. The method according to any one of claims 27, 62-78, 80-98, 125, or 151, wherein the subject is ApoE4 negative.