Monoclonal antibody
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Abstract
The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer'"'"'s disease. The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies having the ability to specifically recognize and bind to specific epitopes from a range of β-amyloid proteins. The antibodies enabled by the teaching of the present invention are particularly useful for the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer'"'"'s Disease (AD).
110 Citations
134 Claims
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1-118. -118. (canceled)
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119. A method for preventing, treating or alleviating the effects of an amyloidosis in a mammal comprising administering to the mammal a monoclonal antibody or antigen-binding fragment thereof, wherein the monoclonal antibody or antigen-binding fragment thereof is capable of specifically binding beta-amyloid and wherein
(a) CDR1 of the light chain variable region has the amino acid sequence of SEQ ID NO: - 23;
(b) CDR2 of the light chain variable region has the amino acid sequence of SEQ ID NO;
24; and(c) CDR3 of the light chain variable region has the amino acid sequence of SEQ ID NO;
25. - View Dependent Claims (122, 129, 130, 131)
- 23;
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120. A method for preventing, treating or alleviating the effects of an amyloidosis in a mammal comprising administering to the mammal a monoclonal antibody or antigen-binding fragment thereof, wherein the monoclonal antibody or antigen-binding fragment thereof is capable of specifically binding beta-amyloid and wherein
(a) CDR1 of the heavy chain variable region has the amino acid sequence of SEQ ID NO: - 26;
(b) CDR2 of the heavy chain variable region has the amino acid sequence of SEQ ID NO;
27; and(c) CDR3 of the heavy chain variable region has the amino acid sequence of SEQ ID NO;
28. - View Dependent Claims (121)
- 26;
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123. A method for retaining or increasing cognitive memory capacity in a mammal comprising administering to the mammal a monoclonal antibody or antigen-binding fragment thereof, wherein the monoclonal antibody or antigen-binding fragment thereof is capable of specifically binding beta-amyloid and wherein
(a) CDR1 of the light chain variable region has the amino acid sequence of SEQ ID NO: - 23;
(b) CDR2 of the light chain variable region has the amino acid sequence of SEQ ID NO;
24; and(c) CDR3 of the light chain variable region has the amino acid sequence of SEQ ID NO;
25. - View Dependent Claims (126)
- 23;
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124. A method for retaining or increasing cognitive memory capacity in a mammal comprising administering to the mammal a monoclonal antibody or antigen-binding fragment thereof, wherein the monoclonal antibody or antigen-binding fragment thereof is capable of specifically binding beta-amyloid and wherein
(a) CDR1 of the heavy chain variable region has the amino acid sequence of SEQ ID NO: - 26;
(b) CDR2 of the heavy chain variable region has the amino acid sequence of SEQ ID NO;
27; and(c) CDR3 of the heavy chain variable region has the amino acid sequence of SEQ ID NO;
28. - View Dependent Claims (125)
- 26;
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127. A method for preventing, treating or alleviating the effects of an amyloidosis in a mammal comprising administering to the mammal a monoclonal antibody or antigen binding fragment thereof wherein the monoclonal antibody is produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750.
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128. A method for retaining or increasing cognitive memory capacity in a mammal comprising administering to the mammal a monoclonal antibody or antigen binding fragment thereof wherein the monoclonal antibody is produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750.
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132. A method for preventing, treating or alleviating the effects of a disease or disorder caused by or associated with amyloid, amyloid-like proteins, or amyloid plaque formation in a mammal in need thereof comprising administering to the subject a composition comprising a monoclonal antibody or functional fragment thereof, which monoclonal antibody or functional fragment thereof recognizes and binds to at least two binding sites on β
- -amyloid proteins, amyloid β
fibers, amyloid β
monomers or amyloid β
oligomers, wherein said at least two binding sites are selected from the group consisting of a binding site comprisingi) one His amino acid residue embedded within a sequence selected from the group consisting of SEQ ID NO;
13, SEQ ID NO;
14, SEQ ID NO;
16, SEQ ID NO;
18, andor SEQ ID NO;
20;ii) at least two consecutive amino acid residues predominantly involved in the binding of the antibody, and wherein the two consecutive amino acid residues are -Phe-Phe-amino acid residues embedded within a the sequence selected from the group consisting of SEQ ID NO;
14, SEQ ID NO;
15, SEQ ID NO;
16, SEQ ID NO;
17, SEQ ID NO;
18, SEQ ID NO;
19 and or SEQ ID NO;
20, wherein said monoclonal antibody or a functional fragment thereof predominantly binds to said two consecutive -Phe-Phe-amino acid residues is predominantly involved in binding to the antibody; andiii) at least two consecutive amino acid residues predominantly involved in the binding of the antibody, and wherein the two consecutive amino acid residues are -Lys-Leu-amino acid residues embedded within a the sequence selected from the group consisting of SEQ ID NO;
13, SEQ ID NO;
15, SEQ ID NO;
16, SEQ ID NO;
17, SEQ ID NO;
18, and or SEQ ID NO;
20.
- -amyloid proteins, amyloid β
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133. A method for reducing the plaque load in the brain of a mammal suffering from a disease or condition leading to an increased plaque load in the brain comprising administering to said mammal a monoclonal antibody or functional fragment thereof which recognizes and binds to at least two binding sites on β
- -amyloid proteins, amyloid β
fibers, amyloid β
monomers or amyloid β
oligomers, wherein said at least two binding sites are selected from the group consisting of a binding site comprisingi) one His amino acid residue embedded within a sequence selected from the group consisting of SEQ ID NO;
13, SEQ ID NO;
14, SEQ ID NO;
16, SEQ ID NO;
18, and SEQ ID NO;
20;ii) at least two consecutive amino acid residues predominantly involved in the binding of the antibody, and wherein the two consecutive amino acid residues are -Phe-Phe-amino acid residues embedded within a the sequence selected from the group consisting of SEQ ID NO;
14, SEQ ID NO;
15, SEQ ID NO;
16, SEQ ID NO;
17, SEQ ID NO;
18, SEQ ID NO;
19 and SEQ ID NO;
20, wherein said monoclonal antibody or a functional fragment thereof predominantly binds to said two consecutive -Phe-Phe-amino acid residues is predominantly involved in binding to the antibody; andiii) at least two consecutive amino acid residues predominantly involved in the binding of the antibody, and wherein the two consecutive amino acid residues are -Lys-Leu-amino acid residues embedded within a the sequence selected from the group consisting of SEQ ID NO;
13, SEQ ID NO;
15, SEQ ID NO;
16, SEQ ID NO;
17, SEQ ID NO;
18, and SEQ ID NO;
20.
- -amyloid proteins, amyloid β
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134. A method for preventing, treating or alleviating the effects of a disease or disorder caused by or associated with amyloid, amyloid-like proteins, or amyloid plaque formation comprising administering to a subject in need thereof a monoclonal antibody or functional fragment thereof, which antibody or functional fragment thereof is capable of:
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i) inhibiting the aggregation of the Aβ
monomers to high molecular polymeric fibrils upon co-incubation with an amyloid monomeric peptides such as β
-amyloid monomeric peptides, Aβ
monomeric peptides, Aβ
1-39, Aβ
1-40, Aβ
1-41, Aβ
1-42, or Aβ
1-43 monomeric peptides; andii) disaggregating the preformed polymeric fibrils or filaments by at least 35%, at least 40%, at least 50%, at least 60%, or at least 70% upon co-incubation at a molar concentration ratio of between 1;
30 and 1;
100 with preformed high molecular polymeric amyloid fibrils or filaments formed by the aggregation of amyloid monomeric peptides, such as β
-amyloid monomeric peptides, Aβ
monomeric peptides, Aβ
1-39, Aβ
1-40, Aβ
1-41, Aβ
1-42, or Aβ
1-43 monomeric peptides.
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Specification