Anti-transthyretin antibodies
OwnerYue Liu, Tarlochan S. Nijjar +2inventors
InventorsYue Liu, Tarlochan S. Nijjar, Avijit Chakrabartty, Jeffrey N. Higaki
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Abstract
The invention provides antibodies that specifically bind transthyretin (TTR). The antibodies can be used for treating or effecting prophylaxis of diseases or disorders associated with TTR accumulation or accumulation of TTR deposits (e.g., TTR amyloidosis). The antibodies can also be used for diagnosing TTR amyloidosis and inhibiting or reducing aggregation of TTR, among other applications.
Claims52
An antibody that binds to transthyretin and comprises three heavy chain CDRs and three light chain CDRs substantially from antibody 14G8.
An antibody that binds to transthyretin and comprises three heavy chain CDRs and three light chain CDRs substantially from antibody 9D5.
6-8. (canceled)
14-34. (canceled)
40-42. (canceled)
(canceled)
A method of humanizing an antibody, the method comprising:
- (a) selecting one or more acceptor antibodies;
- (b) identifying the amino acid residues of the mouse antibody to be retained;
- (c) synthesizing a nucleic acid encoding a humanized heavy chain comprising CDRs of the mouse antibody heavy chain and a nucleic acid encoding a humanized light chain comprising CDRs of the mouse antibody light chain;
- and
- (d) expressing the nucleic acids in a host cell to produce a humanized antibody;
- wherein the mouse antibody is 14G8, wherein 14G8 is characterized by a mature heavy chain variable region of SEQ ID NO:
- 61 and a mature light chain variable region of SEQ ID NO:
- 70.
A method of producing a humanized, chimeric, or veneered antibody, the method comprising:
- (a) culturing cells transformed with nucleic acids encoding the heavy and light chains of the antibody, so that the cells secrete the antibody;
- and
- (b) purifying the antibody from cell culture media;
- wherein the antibody is a humanized, chimeric, or veneered form of 14G8.
A method of producing a cell line producing a humanized, chimeric, or veneered antibody, the method comprising:
- (a) introducing a vector encoding heavy and light chains of an antibody and a selectable marker into cells;
- (b) propagating the cells under conditions to select for cells having increased copy number of the vector;
- (c) isolating single cells from the selected cells;
- and
- (d) banking cells cloned from a single cell selected based on yield of antibody;
- wherein the antibody is a humanized, chimeric, or veneered form of 14G8.
72-80. (canceled)
82-88. (canceled)
Dependencies are inferred from the claim text.