HUMANIZED ANTIBODY IGG1
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Accused Products
Abstract
The present invention is related to chimeric and humanized antibody and to methods and compositions for the therapeutic and diagnostic use in the treatment of amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer'"'"'s disease.
113 Citations
207 Claims
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1-155. -155. (canceled)
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156. A chimeric antibody or a fragment thereof, or a humanized antibody or a fragment thereof, which specifically binds to at least one epitope on the β
- -amyloid protein wherein the epitope comprises at least two consecutive amino acid residues predominantly involved in binding to the antibody, wherein the at least two consecutive amino acid residues are selected from the group consisting of;
a) -Lys-Leu- embedded within the following core sequence (SEQ ID NO;
10);Xaa1-Xaa2-Lys-Leu-Xaa3 wherein Xaa1 is an amino acid selected from the group consisting of His, Asn, Gln Lys, and Arg, Xaa2 is an amino acid selected from the group consisting of Asn and Gln; and Xaa3 is an amino acid selected from the group consisting of Ala, Val, Leu, norleucine, Met, Phe, and Ile and b) Phe-Phe- embedded within the following core sequence (SEQ ID NO;
9);Xaa3-Phe-Phe-Xaa4-Xaa5-Xaa6, wherein Xaa3 is an amino acid residue selected from the group consisting of Ala, Val, Leu, norleucine, Met, Phe, and Ile; Xaa4 is an amino acid residue selected from the group consisting of Ala, Val, Leu, Ser and Ile; Xaa5 is an amino acid residue selected from the group consisting of Glu and Asp, and Xaa6 is an amino acid residue selected from the group consisting of Glu and Asp, wherein said chimeric antibody or a fragment thereof, or a humanized antibody or a fragment thereof comprises a variant Fc region, and wherein said variant Fc region comprises at least one amino acid modification relative to a wild type Fc region, such that said molecule has modified effector function than the wild type Fc region. - View Dependent Claims (157, 159, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 205, 206, 207)
- -amyloid protein wherein the epitope comprises at least two consecutive amino acid residues predominantly involved in binding to the antibody, wherein the at least two consecutive amino acid residues are selected from the group consisting of;
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158. A humanized antibody or a fragment thereof which comprises in the variable region at least one CDR of non-human origin and one or more human- or primate-derived framework regions and, optionally, a constant region derived from a human or primate source antibody, which humanized antibody or fragment thereof is capable of specifically binding β
- -amyloid protein, β
-amyloid monomeric peptide, polymeric soluble amyloid pepides comprising a plurality of β
-amyloid monomeric units, β
-amyloid fibers, fibrils or filaments, and a β
-amyloid polymeric peptide in isolation or as part of a β
-amyloid plaque, at an epitope comprising the following amino acid sequence (SEQ ID NO;
11);Xaa1-Xaa2-Lys-Leu-Xaa3-Phe-Phe-Xaa4-Xaa5-Xaa6, wherein Xaa1 is an amino acid residue selected from the group consisting of His, Asn, Gln, but particularly His; Xaa2 is an amino acid residue selected from the group consisting of Asn and Gln, but particularly Gln; and Xaa3 is an amino acid residue selected from the group consisting of Val, Leu, and Ile, but particularly Val; Xaa4 is an amino acid residue selected from the group consisting of Ala and Val, but particularly Ala; Xaa5 is an amino acid residue selected from the group consisting of Glu and Asp, but particularly Glu; and Xaa6 is an amino acid residue selected from the group consisting of Glu and Asp, but particularly Asp.
- -amyloid protein, β
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160. A chimeric antibody or a fragment thereof, or a humanized antibody or a fragment thereof, wherein at least one of the amino acids of a light chain and a heavy chain CDR region as given in SEQ ID NOs:
- 1-6 is changed through a conservative substitution such that the antibody maintains its full functionality.
- View Dependent Claims (161)
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182. An isolated light chain variable region (LCVR) comprising human- or primate-derived framework regions and at least one CDR having an amino acid sequence selected from SEQ ID NO:
- 4, SEQ ID NO;
5, and SEQ ID NO;
6.
- 4, SEQ ID NO;
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183. An isolated heavy chain variable region (HCVR) comprising human- or primate-derived framework regions and at least one CDR having an amino acid sequence selected from the group of sequences consisting of SEQ ID NO:
- 2 and SEQ ID NO;
3.
- 2 and SEQ ID NO;
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184. A light chain variable region (LCVR) of SEQ ID NO:
- 12.
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202. An antibody comprising at least one variable region as in SEQ ID NO:
- 27 or SEQ ID NO;
29, or a variant thereof. - View Dependent Claims (203)
- 27 or SEQ ID NO;
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204. A method for disaggregating preformed beta-amyloid fibers, comprising interacting an hC2 antibody with preformed beta-amyloid fibers.
Specification