Therapeutic use of bispecific anti-A beta / TfR antibodies

Abstract

The present invention provides a pharmaceutical composition that overcomes the problems associated with long-term chronic administration of anti-A beta antibodies to prevent or significantly delay the onset of dementia. [Solution] A pharmaceutical composition is provided for use in treating subjects who test positive for amyloid plaque deposition in the brain, comprising a bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody, wherein the antibody is administered intravenously to the subject at a dose of approximately 3.6 mg / kg of body weight, in the following manner: (i) during the induction phase, once every four weeks (Q4W) for a total of seven times, and thereafter, (ii) during the maintenance phase, (a) once every three months (Q3M) or once every twelve weeks (Q12W), or (b) once every six months (Q6M) or once every twenty-six weeks (Q26W).

Claims

[Claim 1] A bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use in treating subjects who test positive for amyloid plaque deposition in the brain, wherein the treatment comprises administering the antibody at a dose of approximately 3.6 mg / kg intravenously to the subject (i) once every four weeks (Q4W) for a total of seven times during the induction phase, and then (ii) during the maintenance phase (a) once every three months (Q3M) or once every 12 weeks (Q12W), or (b) once every six months (Q6M) or once every 26 weeks (Q26W). [Claim 2] A bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use according to claim 1, wherein, when the administration of the composition is determined by visual reading of amyloid PET images after seven administrations in the induction phase, at least 70% of the subjects become amyloid-negative. [Claim 3] A bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use according to claim 1, wherein, when the administration of the composition is determined by visual reading of amyloid PET images after four administrations in the induction phase, at least 70% of the subjects become amyloid-negative. [Claim 4] A bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use according to claim 1, wherein, when the administration of the composition is determined by visual reading of amyloid PET images after seven administrations in the induction phase, at least 75% of the subjects become amyloid-negative. [Claim 5] A bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use according to claim 1, wherein, when the administration of the composition is determined by visual reading of amyloid PET images after four administrations in the induction phase, at least 75% of the subjects become amyloid-negative. [Claim 6] A bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use according to claim 1, which reduces the amyloid plaque deposition in the brain of the subject by at least 70% compared to before treatment or baseline, as determined by visual reading of amyloid PET images. [Claim 7] A bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use according to claim 1, which reduces the amyloid plaque deposition in the brain of the subject by at least 75% compared to before treatment or baseline, as determined by visual reading of amyloid PET images. [Claim 8] The bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use according to any one of claims 1 to 7, wherein the bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody comprises a binding site that specifically binds to human A beta, and the binding site comprises a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 4 and a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO:

8. [Claim 9] The bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use according to any one of claims 1 to 8, wherein the bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody is trontinemab. [Claim 10] A bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use according to any one of claims 1 to 9, wherein the administered dose results in a smaller number of ARIA events compared to aducanumab and / or lecanemab. [Claim 11] A bispecific anti-human amyloid-beta peptide / human transferrin receptor 1 antibody for use according to any one of claims 1 to 10, wherein the subject is diagnosed with prodromal Alzheimer's disease, mild Alzheimer's disease, or mild cognitive impairment.

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