TREATMENT AND PROPHYLAXIS OF AMYLOIDOSIS
Methods useful for effecting prophylaxis or treatment of amyloidosis, including AA Amyloidosis and AL amyloidosis, by administering peptides comprising neoepitopes, such as AA fragments from a C-terminal region of AA, and antibodies specific for neoepitopes of aggregated amyloid proteins, for example, antibodies specific for the C-terminal region of AA fibrils. Antibodies for inhibition of formation and/or increasing clearance of amyloid deposits in a patient thus effecting prophylaxis or treating amyloid disease.
1 .- 90 . (canceled)
91 . A nucleic acid encoding a humanized light chain variable region or a humanized heavy chain variable region, wherein the nucleic acid specifically hybridizes under stringent hybridization conditions to a nucleic acid having a nucleotide sequence that is the complement of a nucleic acid that encodes the humanized light chain variable region or humanized heavy chain variable region set forth as any one of SEQ ID NOs: 155, 156, 157, 161, 162 and 163.
92 . The nucleic acid of claim 91 , which encodes a humanized light chain variable region comprising the amino acid sequence of any one of SEQ ID NOs: 155, 156 and 157.
93 . The nucleic acid of claim 92 , which encodes the amino acid sequence of SEQ ID NO. 157.
94 . A nucleic acid encoding a humanized heavy chain variable region comprising the amino acid sequence of any one of SEQ ID NOs: 161, 162 and 163.
95 . The nucleic acid of claim 94 , which encodes the amino acid sequence of SEQ ID NO. 163.
96 . The nucleic acid of claim 92 , which further comprises a nucleic acid encoding a light chain constant region.
97 . The nucleic acid of claim 96 , wherein the light chain constant region is a human kappa constant region.
98 . The nucleic acid of claim 94 , which further comprises a nucleic acid encoding a heavy chain constant region.
99 . The nucleic acid of claim 98 , wherein the heavy chain constant region is a human IgG1 constant region.
100 . A vector comprising at least one of (a) a nucleic acid encoding a humanized light chain variable region comprising the amino acid sequence set forth as any one of SEQ ID NOs: 155, 156 and 157, and (b) a nucleic acid encoding a heavy chain variable region comprising the amino acid sequence set forth as any one of SEQ ID NOs: 161, 162 and 163.
101 . The vector of claim 100 , which comprises the nucleic acid of (a) and a promoter that controls expression of the nucleic acid of (a).
102 . The vector of claim 101 , wherein the nucleic acid of (a) encodes the amino acid sequence of SEQ ID NO: 157.
103 . The vector of claim 102 , wherein the nucleic acid further encodes a human kappa constant region.
104 . The vector of claim 100 , which comprises the nucleic acid of (b) and a promoter that controls expression of the nucleic acid of (b).
105 . The vector of claim 104 , wherein the nucleic acid of (b) encodes the amino acid sequence of SEQ ID NO: 163.
106 . The vector of claim 105 , wherein the nucleic acid further encodes a human IgG1 constant region.
107 . The vector of claim 100 , further comprising a promoter that controls expression of the nucleic acid of (a) or the nucleic acid of (b).
108 . The vector of claim 100 comprising the nucleic acid of (a) and the nucleic acid of (b).
109 . The vector of claim 108 , further comprising a promoter that controls expression of the nucleic acid of (a) and the nucleic acid of (b).
110 . The vector of claim 108 , further comprising a first promoter that controls expression of the nucleic acid of (a) and a second promoter that controls expression of the nucleic acid of (b).
111 . A host cell comprising at least one of (a) a nucleic acid encoding a light chain variable region comprising the amino acid sequence set forth as any one of SEQ ID NOs: NOs: 155, 156 and 157, and (b) a nucleic acid encoding a heavy chain variable region comprising the amino acid sequence set forth as any one of SEQ ID NOs: 161, 162 and 163.
112 . The host cell of claim 111 , which is a mammalian host cell.
113 . The host cell of claim 112 , which is a CHO cell.
114 . The host cell of claim 111 comprising the nucleic acid of (a) and the nucleic acid of (b).
115 . The host cell of claim 111 comprising a vector comprising the nucleic acid of (a) or the nucleic acid of (b).
116 . The host cell of claim 114 , wherein the vector comprises a promoter that controls expression of the nucleic acid of (a) or the nucleic acid of (b).
117 . The host cell of claim 1101 comprising a vector comprising the nucleic acid of (a) and the nucleic acid of (b).
118 . The host cell of claim 111 comprising a first vector comprising the nucleic acid of (a) and a second vector comprising the nucleic acid of (b).
119 . The host cell of claim 117 , wherein the vector comprises a promoter that controls expression of the nucleic acid of (a) and the nucleic acid of (b).
120 . The host cell of claim 117 , wherein the vector comprises a first promoter that controls expression of the nucleic acid of (a) and a second promoter that controls expression of the nucleic acid of (b).
121 . The host cell of claim 111 , wherein the host cell expresses the light chain variable region set forth as any one of SEQ ID NOs: 155-157.
122 . The host cell of claim 111 , wherein the host cell expresses the heavy chain variable region set forth as any one of SEQ ID NOs: 161-163.
123 . The host cell of claim 111 , wherein the host cell expresses the light chain variable region set forth as any one of SEQ ID NOs: 155-157 and the heavy chain variable region set forth as any one of SEQ ID NOs: 161-163.
124 . The host cell of claim 111 , wherein the host cell expresses an antibody comprising a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157.
125 . The host cell of claim 111 , wherein the host cell expresses an antibody comprising a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163.
126 . The host cell of claim 111 , wherein the host cell expresses an antibody comprising a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157 and a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163.
127 . The host cell of claim 111 , comprising the nucleic acid of (a) linked to a nucleic acid encoding a human kappa constant region, and the nucleic acid of (b) linked to a nucleic acid encoding a human IgG1 constant region.
128 . The host cell of claim 127 , wherein the host cell expresses an antibody comprising a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157 and a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163.