Compounds and methods targeting interleukin-34
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- ELI LILLY & CO
- Filing Date
- 2026-02-04
- Publication Date
- 2026-06-09
AI Technical Summary
が上回る量である。そのような利益には、炎症又は免疫活性化のレベルの低下、免疫介在性疾患又は障害の安定化、又は免疫介在性障害の徴候若しくは症状の改善のうちのいずれか1つ以上が含まれる。代替的に、そのような利益には、以下:移植された臓器の免疫寛容の増加;安定化された自己免疫疾患又は障害;又は自己免疫障害の徴候若しくは症状の改善のうちのいずれか1つ以上が含まれる。
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Figure 2026094152000001_ABST
Abstract
Claims
1. An antibody that binds to human IL-34, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises heavy chain complementarity determining regions (HCDR) HCDR1, HCDR2, and HCDR3, and the VL comprises light chain complementarity determining regions (LCDR) LCDR1, LCDR2, and LCDR3. The HCDR1 includes sequence number 5, The HCDR2 includes sequence number 6, The HCDR3 includes sequence number 7, The aforementioned LCDR1 includes sequence number 8, The LCDR2 includes sequence number 9, The aforementioned LCDR3 is an antibody containing SEQ ID NO:
10.
2. The antibody according to claim 1, wherein VH comprises SEQ ID NO: 3 and VL comprises SEQ ID NO:
4.
3. The antibody according to claim 1 or 2, wherein the antibody comprises a heavy chain (HC) containing SEQ ID NO: 1 and a light chain (LC) containing SEQ ID NO:
2.
4. A nucleic acid comprising a sequence encoding an array sequence selected from one or more of the groups consisting of 11 and 12.
5. A vector comprising the nucleic acid described in claim 4.
6. The vector according to claim 5, wherein the vector comprises a first nucleic acid sequence encoding sequence number 11 and a second nucleic acid sequence encoding sequence number 12.
7. A composition comprising a first vector containing a nucleic acid sequence encoding sequence number 11, and a second vector containing a nucleic acid sequence encoding sequence number 12.
8. A cell comprising the vector according to claim 5 or 6.
9. A cell comprising a first vector containing a nucleic acid sequence encoding sequence number 11, and a second vector containing a nucleic acid sequence encoding sequence number 12.
10. The cell according to claim 8 or 9, wherein the cell is a mammalian cell.
11. A process for producing an antibody, comprising culturing the cells described in any one of claims 8 to 10 under conditions such that the antibody is expressed, and recovering the expressed antibody from the culture medium.
12. An antibody produced by the process described in claim 11.
13. A pharmaceutical composition comprising an antibody according to any one of claims 1 to 3 or 12, and a pharmaceutically acceptable excipient, diluent, or carrier.
14. A method for treating an immune-mediated disease in a subject requiring treatment, comprising administering to the subject a therapeutically effective amount of an antibody according to any one of claims 1 to 3 or 12, or a pharmaceutical composition according to claim 13.
15. The method according to claim 14, wherein the immune-mediated disease is selected from the group consisting of Alzheimer's disease; tauopathic diseases; Sjögren's syndrome (SS); rheumatoid arthritis (RA); inflammatory bowel disease (IBD), atopic dermatitis, renal disease, sepsis, and / or non-alcoholic fatty liver disease (NAFLD).
16. The method according to claim 15, wherein the immune-mediated disease is Alzheimer's disease.
17. An antibody according to any one of claims 1 to 3 or 12, for use in therapy.
18. An antibody according to any one of claims 1 to 3 or 12, or a pharmaceutical composition according to claim 13, for use in the treatment of immune-mediated diseases.
19. The antibody or pharmaceutical composition according to claim 18, wherein the immune-mediated disease is selected from the group consisting of Alzheimer's disease; tauopathic diseases; Sjögren's syndrome (SS); rheumatoid arthritis (RA); inflammatory bowel disease (IBD), atopic dermatitis, kidney disease, sepsis, amyotrophic lateral sclerosis (ALS), and / or non-alcoholic fatty liver disease (NAFLD).
20. The antibody or pharmaceutical composition according to claim 18, wherein the immune-mediated disease is Alzheimer's disease.
21. Use of the antibody according to any one of claims 1 to 3 or 12 in the manufacture of a pharmaceutical product for the treatment of an immune-mediated disease.
22. The use according to claim 21, wherein the immune-mediated disease is selected from the group consisting of Alzheimer's disease; tauopathic diseases; Sjögren's syndrome (SS); rheumatoid arthritis (RA); inflammatory bowel disease (IBD), atopic dermatitis, renal disease, sepsis, and / or non-alcoholic fatty liver disease (NAFLD).
23. The use according to claim 21, wherein the immune-mediated disease is Alzheimer's disease.
24. A method for determining human IL-34 levels in body fluids, (a) Contacting the body fluid with an anti-human IL-34 diagnostic monoclonal antibody or its antigen-binding fragment that specifically binds to human IL-34 consisting of the amino acid sequence of SEQ ID NO: 31, wherein the antibody or its antigen-binding fragment comprises, respectively, light chain complementarity-determining regions LCDR1, LCDR2, and LCDR3 containing the amino acid sequences (SEQ ID NO: 8), (SEQ ID NO: 9), and (SEQ ID NO: 10), and heavy chain complementarity-determining regions HCDR1, HCDR2, and HCDR3 containing the amino acid sequences (SEQ ID NO: 5), (SEQ ID NO: 6), and (SEQ ID NO: 7), (b) Optionally, remove any nonspecifically bound monoclonal antibody or its antigen-binding fragment, (c) A method comprising detecting and / or quantifying the amount of a monoclonal antibody or its antigen-binding fragment that is specifically bound to human IL-34.
25. The method according to claim 24, wherein the bodily fluid is blood, serum, plasma, or cerebrospinal fluid, and the contact occurs ex vivo.
26. A method for treating or preventing a disease characterized by amyloid-beta (Aβ) deposits in the brain of a human subject, comprising administering an effective amount of anti-N3pG Aβ antibody to the human subject in need of such treatment or prevention, simultaneously, separately, or sequentially in combination with an effective amount of the antibody described in any one of claims 1 to 3 or 12.
27. The method according to claim 26, wherein the anti-N3pGAβ antibody is donanemab, and the antibody described in any one of claims 1 to 3 or 12 is antibody 1.
28. The method according to claim 26, wherein the disease is Alzheimer's disease.
29. The method according to claim 26, wherein the anti-N3pG Aβ antibody is donanemab and the disease is Alzheimer's disease.
30. The method according to claim 29, wherein antibody 1 is administered sequentially after a series of treatments with donanemab.
31. A method for treating or preventing a disease characterized by amyloid-beta (Aβ) deposits in the brain of human subjects, i) Administering the aforementioned human subjects one or more doses of a first dose of anti-N3pGAβ antibody ranging from approximately 100 mg to approximately 700 mg, wherein each first dose is administered approximately once every four weeks. ii) Approximately four weeks after administering one or more first doses, administer one or more second doses of the anti-N3pGAβ antibody, ranging from more than 700 mg to approximately 1400 mg, to the human subject, wherein each second dose is administered approximately once every four weeks. The aforementioned anti-N3pGlu Aβ antibody is donanemab, and it is administered as follows: iii) A method comprising administering an effective amount of antibody 1 to the human subject simultaneously, separately, or sequentially.
32. The method according to claim 31, wherein the human subject is administered the first dose of donanemab once, twice, or three times before being administered the second dose.
33. The method according to claim 31 or 32, wherein the human subject is administered a first dose of donanemab of about 700 mg.
34. The method according to any one of claims 31 to 33, wherein the human subject is administered one or more doses of donanemab in a second dose of approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, or approximately 1400 mg.
35. The method according to any one of claims 31 to 34, wherein the human subject is administered one or more doses of a second dose of approximately 1400 mg of donanemab.
36. The method according to any one of claims 31 to 35, wherein the anti-N3pGlu Aβ antibody is administered to the human subject over a series of treatment periods up to 72 weeks, or until a normal level of amyloid is achieved.
37. The method according to any one of claims 31 to 36, wherein the anti-N3pGlu Aβ antibody is administered to the human subject until the amyloid plaque level in the patient is about 25 centiloids or less.
38. The method according to any one of claims 31 to 36, wherein the anti-N3pGlu Aβ antibody is administered to the human subject for a series of treatments until the amyloid plaque level in the human subject is reduced to about 25 centiloids or less in two consecutive PET imaging scans, or to about 11 centiloids or less in one PET imaging scan, and optionally, the two consecutive PET imaging scans are spaced at least six months apart.
39. The method according to any one of claims 31 to 36, wherein the human subject is administered three doses of a first dose of 700 mg of donanemab once every four weeks, followed by a second dose of 1400 mg once every four weeks, over a series of treatment periods of up to 72 weeks.
40. The method according to any one of claims 31 to 36, wherein the human subject is administered a first dose of 700 mg once every four weeks, followed by a second dose of 1400 mg once every four weeks, until the amyloid plaque level in the subject is approximately 25 centiloids or less.
41. The method according to any one of claims 31 to 36, wherein the human subject is administered three doses of a first dose of 700 mg of donanemab once every four weeks, followed by a second dose of 1400 mg once every four weeks, until the amyloid plaque level in the subject is less than or equal to about 25 centiloids in two consecutive PET imaging scans, or less than or equal to about 11 centiloids in one PET imaging scan, and optionally, the two consecutive PET imaging scans are spaced at least six months apart.
42. The method according to any one of claims 31 to 41, wherein the human subject is administered the second dose of donanemab over a series of treatment periods sufficient to treat or prevent the disease.
43. The method according to any one of claims 31 to 42, wherein the treatment or prevention of the disease causes i) a reduction in Aβ deposits in the brain of the human subject, and / or ii) a delay in cognitive or functional decline in the human subject.
44. The method according to claim 43, wherein the reduction of Aβ deposits in the brain of the human subject is determined by amyloid PET brain imaging or a diagnostic method for detecting a biomarker of Aβ.
45. The method according to claim 43 or 44, wherein the second dose is administered to the human subject until the amount of Aβ deposits in the brain of the human subject is reduced by approximately 20 to 100%.
46. The method according to claim 45, wherein the Aβ deposits in the brain of the human subject are reduced by about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 75%, or about 100%.
47. The method according to any one of claims 31 to 44, wherein the second dose of donanemab is administered to the human subject until the Aβ deposits in the brain of the human subject are reduced by i) approximately 25 centroids to approximately 100 centroids on an approximate average, ii) approximately 50 centroids to approximately 100 centroids on an approximate average, iii) approximately 100 centroids, or iv) approximately 84 centroids.
48. The method according to any one of claims 31 to 47, wherein the disease characterized by the Aβ deposits in the brain of the human subject is selected from preclinical Alzheimer's disease (AD), clinical AD, prodromal AD, mild AD, moderate AD, severe AD, Down syndrome, clinical cerebral amyloid angiopathy, or preclinical cerebral amyloid angiopathy.
49. The method according to any one of claims 31 to 48, wherein the human subject is a patient with early symptomatic AD.
50. The method according to claim 49, wherein the human subject has prodromal AD and mild dementia due to AD.
51. The method according to any one of claims 26 to 50, wherein the human subject is i) determined to have a very low to moderate tau load, or is determined to have a very low to moderate tau load, ii) determined to have a low to moderate tau load, or is determined to have a low to moderate tau load, iii) determined to have a very low to moderate tau load, or has a very low to moderate tau load and one or two alleles of APOE e4, iv) determined to have a low to moderate tau load, or has a low to moderate tau load and one or two alleles of APOE e4, or v) has one or two alleles of APOE e4.
52. The method according to claim 51, wherein the human subject has a very low to moderate tau load if the tau load measured by PET brain imaging is 1.46 SUVr or less, or ii) has a low to moderate tau load if the tau load measured by PET brain imaging is between 1.10 SUVr and 1.46 SUVr.
53. The method according to any one of claims 26 to 50, wherein the human subject i) does not have a high tau load or is determined not to have a high tau load, or ii) possesses one or two alleles of APOE e4 and does not have a high tau load or is determined not to have a high tau load.
54. The method according to claim 53, wherein the human subject has a high tau load if the tau load measured by PET brain imaging exceeds 1.46 SUVr.
55. The method according to claim 51 or 53, wherein the tau load in the human subject is determined using PET brain imaging or a diagnostic method for detecting a tau biomarker.
56. In the manufacture of a pharmaceutical product for the treatment or prevention of a disease characterized by Aβ deposition in the brain of human subjects, the use of an anti-N3pGlu Aβ antibody simultaneously, separately, or sequentially combined with antibody 1, wherein one or more first doses of the anti-N3pGlu Aβ antibody of approximately 100 mg to approximately 700 mg are administered, each first dose administered approximately every four weeks, followed by one or more second doses of more than 700 mg to approximately 1400 mg administered four weeks after the administration of the first doses, each second dose of the anti-N3pGlu Aβ antibody administered approximately every four weeks. The aforementioned anti-N3pGlu Aβ antibody is donanemab.
57. The use according to claim 56, wherein the human subject is administered the first dose of donanemab once, twice, or three times before being administered the second dose of donanemab.
58. The use according to claim 56 or 57, wherein the human subject is administered three times a first dose of donanemab, approximately 700 mg.
59. The use according to any one of claims 56 to 58, wherein the human subject is administered one or more doses of a second dose of donanemab, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, or approximately 1400 mg.
60. The use according to any one of claims 56 to 59, wherein the human subject is administered one or more doses of a second dose of approximately 1400 mg of donanemab.
61. The use according to any one of claims 56 to 60, wherein the anti-N3pGlu Aβ antibody is administered to the human subject over a series of treatment periods up to 72 weeks, or until a normal level of amyloid is achieved.
62. The use according to any one of claims 56 to 61, wherein the anti-N3pGlu Aβ antibody is administered to the human subject until the amyloid plaque level in the patient is about 25 centiloids or less.
63. The use according to any one of claims 56 to 61, wherein the anti-N3pGlu Aβ antibody is administered to the human subject until the amyloid plaque level in the patient is less than or equal to about 25 centroids in two consecutive PET imaging scans, or less than or equal to about 11 centroids in one PET imaging scan, and optionally, the two consecutive PET imaging scans are spaced at least six months apart.
64. The use according to any one of claims 56 to 61, wherein the human subject is administered three doses of a first dose of 700 mg of donanemab once every four weeks, followed by a second dose of 1400 mg of donanemab once every four weeks, over a period of up to 72 weeks.
65. The use according to any one of claims 56 to 61, wherein the human subject is administered three doses of a first dose of 700 mg of donanemab once every four weeks until the amyloid plaque level in the patient is less than or equal to about 25 centiloids, and then a second dose of 1400 mg of donanemab is administered once every four weeks.
66. The use according to any one of claims 56 to 61, wherein the human subject is administered three doses of a first dose of 700 mg of donanemab once every four weeks, followed by a second dose of 1400 mg of donanemab once every four weeks, until the amyloid plaque level in the patient is less than or equal to about 25 centiloids in two consecutive PET imaging scans, or less than or equal to about 11 centiloids in one PET imaging scan, and optionally, the two consecutive PET imaging scans are spaced at least six months apart.
67. The use according to any one of claims 56 to 66, wherein the human subject is administered the second dose of donanemab over a series of treatment periods sufficient to treat or prevent the disease.
68. The use according to any one of claims 56 to 67, wherein the treatment or prevention of the disease causes i) a reduction in Aβ deposits in the brain of the human subject, and / or ii) a delay in cognitive or functional decline in the human subject.
69. The use according to claim 68, wherein the reduction of Aβ deposits in the brain of the human subject is determined by amyloid PET brain imaging or a diagnostic method for detecting a biomarker of Aβ.
70. The use according to claim 68 or 69, wherein the second dose of donanemab is administered to the human subject until the amount of Aβ deposits in the brain of the human subject is reduced by approximately 20 to 100%.
71. The use according to claim 70, wherein the Aβ deposits in the brain of the human subject are reduced by about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 75%, or about 100%.
72. The use according to claim 70 or 71, wherein the Aβ deposits in the brain of the patient are reduced by 100%.
73. The use according to any one of claims 56 to 72, wherein the second dose of donanemab is administered to the human subject until the Aβ deposits in the brain of the human subject are reduced by i) approximately 25 centroids to approximately 100 centroids on an approximate average, ii) approximately 50 centroids to approximately 100 centroids on an approximate average, iii) approximately 100 centroids, or iv) approximately 84 centroids.
74. The use according to any one of claims 56 to 73, wherein the disease characterized by the Aβ deposits in the brain of the human subject is selected from preclinical Alzheimer's disease, clinical AD, prodromal AD, mild AD, moderate AD, severe AD, Down syndrome, clinical cerebral amyloid angiopathy, or preclinical cerebral amyloid angiopathy.
75. The use according to any one of claims 56 to 74, wherein the human subject is a patient with early symptomatic AD, or the human subject has prodromal AD or mild dementia due to AD.
76. The use according to any one of claims 56 to 75, wherein the human subject is i) determined to have a very low to moderate tau load, or is determined to have a very low to moderate tau load, ii) determined to have a low to moderate tau load, or is determined to have a low to moderate tau load, iii) determined to have a very low to moderate tau load, or has a very low to moderate tau load and one or two alleles of APOE e4, iv) determined to have a low to moderate tau load, or has a low to moderate tau load and one or two alleles of APOE e4, or v) has one or two alleles of APOE e4.
77. The use according to claim 76, wherein the human subject has a very low to moderate tau load if the tau load measured by PET brain imaging is 1.46 SUVr or less, or ii) has a low to moderate tau load if the tau load measured by PET brain imaging is between 1.10 SUVr and 1.46 SUVr.
78. The use according to any one of claims 56 to 75, wherein the human subject i) does not have a high tau load or is determined not to have a high tau load, or ii) possesses one or two alleles of APOE e4 and does not have a high tau load or is determined not to have a high tau load.
79. The use according to claim 78, wherein the human subject has a high tau load if the tau load measured by PET brain imaging exceeds 1.46 SUVr.
80. The use according to claim 76 or 78, wherein the tau load in the human subject is determined using tau PET brain imaging or a diagnostic method for detecting tau biomarkers.
81. i) A method for treating or preventing a disease characterized by amyloid-beta (Aβ) deposits in the brain of a human subject who is determined to have a very low to moderate tau load, or a low to moderate tau load, or who is determined to have a very low to moderate tau load, or a low to moderate tau load and one or two alleles of APOE e4, i) Administering a first dose of donanemab, approximately 100 mg to approximately 700 mg, to the human subject, wherein each first dose of donanemab is administered approximately once every four weeks. ii) Administering to the human subject one or more times a second dose of donanemab, ranging from more than 700 mg to approximately 1400 mg, four weeks after administering the first dose, wherein each second dose is administered approximately once every four weeks. A method comprising simultaneously, separately, or sequentially combining an effective amount of antibody 1.
82. A method for treating or preventing a disease characterized by amyloid-beta (Aβ) deposits in the brain of human subjects, The process includes determining whether the human subject has tau loading in the temporal lobe, occipital lobe, parietal lobe, or frontal lobe of the brain, and if the human subject has tau loading in the temporal lobe, occipital lobe, parietal lobe, or frontal lobe of the brain, i) Administering the aforementioned human subjects one or more doses of a first dose of anti-N3pGlu Aβ antibody ranging from approximately 100 mg to approximately 700 mg, wherein each first dose is administered approximately once every four weeks. ii) Approximately four weeks after administering the first dose, administer to the human subject one or more times a second dose of anti-N3pGlu Aβ antibody ranging from more than 700 mg to approximately 1400 mg, wherein each second dose is administered approximately once every four weeks. A method comprising simultaneously, separately, or sequentially combining an effective amount of antibody 1.
83. The method according to claim 82, wherein the human subject has a tau load in the posterolateral temporal lobe or temporal lobe of the brain.
84. The method according to any one of claims 82, wherein the human subject has a tau load in the occipital lobe of the brain.
85. The method according to claim 82, wherein the human subject has a tau load in the parietal lobe of the brain.
86. The method according to claim 82, wherein the human subject has a tau load in the frontal lobe of the brain.
87. The method according to claim 82, wherein the human subject has tau loading in the posterolateral temporal lobe (PLT) and / or occipital lobe of the brain.
88. The method according to any one of claims 82 to 87, wherein the human subject has tau loading in i) the parietal or precuneus region, or ii) the frontal region, along with tau loading in the PLT or occipital region of the brain.
89. The method according to any one of claims 82 to 86, wherein the human subject has a tau load isolated in the frontal lobe of the brain, or a tau load in a region of the temporal lobe that does not include the posterolateral temporal region (PLT).
90. The method according to any one of claims 82 to 88, wherein the human subject has tau loading in the posterolateral temporal lobe, occipital lobe, and parietal lobe of the brain.
91. The method according to any one of claims 82 to 88, wherein the human subject has tau loading in the posterolateral temporal lobe, occipital lobe, parietal lobe, and frontal lobe of the brain.
92. The method according to any one of claims 82 to 88, wherein the human subject has tau loading in the posterolateral temporal lobe, occipital lobe, parietal lobe, and / or frontal lobe of the brain.
93. The method according to any one of claims 82 to 92, wherein the human subject is administered the first dose once, twice, or three times before being administered the second dose.
94. The method according to any one of claims 82 to 93, wherein the human subject is administered a first dose of approximately 700 mg.
95. The method according to any one of claims 82 to 94, wherein the human subject is administered a second dose of approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, or approximately 1400 mg once or more.
96. The method according to any one of claims 82 to 95, wherein the human subject is administered a second dose of approximately 1400 mg once or more.
97. The method according to any one of claims 82 to 96, wherein the anti-N3pGlu Aβ antibody is administered to the human subject for a period of up to 72 weeks, or until a normal level of amyloid is achieved.
98. The method according to any one of claims 82 to 97, wherein the anti-N3pGlu Aβ antibody is administered to the human subject until the amyloid plaque level in the patient is about 25 centiloids or less.
99. The method according to any one of claims 82 to 98, wherein the anti-N3pGlu Aβ antibody is administered to the human subject until the amyloid plaque level in the human subject is less than or equal to about 25 centiloids in two consecutive PET imaging scans, or less than or equal to about 11 centiloids in one PET imaging scan, wherein optionally, the two consecutive PET imaging scans are spaced at least six months apart.
100. The method according to any one of claims 82 to 99, wherein the human subject is administered a first dose of 700 mg three times, once every four weeks, and then a second dose of 1400 mg once every four weeks for a maximum of 72 weeks.
101. The method according to any one of claims 82 to 100, wherein the human subject is administered a first dose of 700 mg once every four weeks, followed by a second dose of 1400 mg once every four weeks, until the amyloid plaque level in the subject is approximately 25 centiloids or less.
102. The method according to any one of claims 82 to 101, wherein the human subject is administered a first dose of 700 mg three times at 4 weeks, followed by a second dose of 1400 mg at 4 weeks, until the amyloid plaque level in the subject is less than or equal to about 25 centiloids after two consecutive PET imaging scans, or less than or equal to about 11 centiloids after one PET imaging scan, and optionally, the two consecutive PET imaging scans are spaced at least 6 months apart.
103. The method according to any one of claims 82 to 102, wherein the human subject is administered the second dose for a period of time sufficient to treat or prevent the disease.
104. The method according to any one of claims 82 to 103, wherein the treatment or prevention of the disease causes i) a reduction in Aβ deposits in the brain of the human subject, and / or ii) a delay in cognitive or functional decline in the human subject.
105. The method according to claim 97, wherein the reduction of Aβ deposits in the brain of the human subject is determined by amyloid PET brain imaging or a diagnostic method for detecting a biomarker of Aβ.
106. The method according to claim 97 or 98, wherein the second dose is administered to the human subject until the amount of Aβ deposits in the brain of the human subject is reduced by approximately 20 to 100%.
107. The method according to claim 106, wherein the Aβ deposits in the brain of the human subject are reduced by about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 75%, or about 100%.
108. The method according to any one of claims 82 to 107, wherein the second dose is administered to the human subject until the Aβ deposits in the brain of the human subject are reduced by i) approximately 25 centroids to approximately 100 centroids on an approximate average, ii) approximately 50 centroids to approximately 100 centroids on an approximate average, iii) approximately 100 centroids, or iv) approximately 84 centroids.
109. The method according to any one of claims 82 to 108, wherein the disease characterized by the Aβ deposits in the brain of the human subject is selected from preclinical Alzheimer's disease (AD), clinical AD, prodromal AD, mild AD, moderate AD, severe AD, Down syndrome, clinical cerebral amyloid angiopathy, or preclinical cerebral amyloid angiopathy.
110. The method according to any one of claims 82 to 109, wherein the human subject is a patient with early symptomatic AD.
111. The method according to claim 109, wherein the human subject has prodromal AD and mild dementia due to AD.
112. The method according to any one of claims 82 to 111, wherein the human subject is i) determined to have a very low to moderate tau load, or is determined to have a very low to moderate tau load, or ii) has a low to moderate tau load, or is determined to have a low to moderate tau load.
113. The method according to claim 112, wherein the human subject has a very low to moderate tau load when the tau load measured by PET brain imaging is 1.46 SUVr or less, or ii) has a low to moderate tau load when the tau load measured by PET brain imaging is between 1.10 SUVr and 1.46 SUVr.
114. The method according to any one of claims 82 to 113, wherein the human subject does not have a high tau load, or is determined not to have a high tau load.
115. The method according to claim 114, wherein the human subject has a high tau load if the tau load measured by PET brain imaging exceeds 1.46 SUVr.
116. The method according to claim 114 or 115, wherein the tau load in the human subject is determined using PET brain imaging or a diagnostic method for detecting a tau biomarker.
117. The method according to any one of claims 82 to 116, wherein the anti-N3pGlu Aβ antibody comprises donanemab.
118. The method according to any one of claims 82 to 117, wherein the patient has one or two alleles of APOE e4.
119. A method for reducing / preventing a further increase in tau load, or for slowing the rate of tau accumulation in the temporal, occipital, parietal, or frontal lobes of a human brain, comprising administering an effective amount of anti-N3pGlu Aβ antibody to a human subject simultaneously, separately, or sequentially in combination with antibody 1.