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US 2023/0265178 A1Published application
Modified immunoglobulins for targeting amyloid deposits
AssigneesAttralus, Inc., University of Tennessee Research Foundation
InventorsJonathan S. WALL, James S. FOSTER, Spencer GUTHRIE
Life of this patent
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Abstract
Provided herein are modified immunoglobulins comprising an amyloid reactive peptide joined to an antibody, as well as humanized antibodies that bind to human amyloid fibrils and antibody-peptide fusion proteins. Also provided herein are methods of treating amyloid-based diseases by administering a modified immunoglobulin, humanized antibody, or antibody-peptide fusion protein.
Claims31
1-100. (canceled)
A modified immunoglobulin, comprising:
- (i) an amyloid reactive peptide;
- and
- (ii) an Ig antibody or functional fragment thereof that binds to human amyloid fibrils, wherein the Ig antibody or functional fragment thereof comprises a light chain comprising a light chain variable region (VL) and a heavy chain comprising a heavy chain variable region (VH), wherein:
- a) the VL comprises a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NOs:64-70, a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:21, and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:22, and the VH comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:17, a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:18, and a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:19;
- b) the VL comprises a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
- 20;
- a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:21, and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:22, and the VH comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:17, a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NOs:71-81;
- and a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:19;
- or
- c) the VL comprises a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NOs:64-70, a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:21, and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:22, and the VH comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:17, a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NOs:71-81;
- and a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:19.
8 more elements
A humanized antibody that binds to human amyloid fibrils, wherein the humanized antibody comprises a light chain variable region (VL) and a heavy chain variable region (VH), wherein
- a) the VL comprises a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NOs:64-70, a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:21, and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:22, and the VH comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:17, a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:18, and a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:19;
- b) the VL comprises a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:20;
- a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:21, and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:22, and the VH comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:17, a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NOs:71-81;
- and a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:19;
- or
- c) the VL comprises a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NOs:64-70, a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:21, and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:22, and the VH comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:17, a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NOs:71-81;
- and a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:19.
4 more elements
Dependencies are inferred from the claim text.