US2015158937A1PendingUtilityA1

Treatment and prophylaxis of amyloidosis

Assignee: ONCLAVE THERAPEUTICS LTDPriority: Dec 28, 2007Filed: Jun 25, 2014Published: Jun 11, 2015
Est. expiryDec 28, 2027(~1.4 yrs left)· nominal 20-yr term from priority
A61P 9/00A61P 43/00A61P 7/00A61P 31/04A61P 31/06A61P 25/00A61P 29/00A61P 25/28A61P 35/02A61P 25/02A61P 31/08A61P 35/00A61P 13/12A61P 11/00A61P 19/02A61P 19/04A61P 19/00A61P 1/04A61P 17/06A61P 17/00A61P 17/02A61K 2039/505C07K 2317/24C07K 2317/52C07K 2317/32C07K 16/18C07K 2317/34A61K 49/16A61K 51/1018C07K 2317/567C07K 2317/92Y10S530/809A61K 39/0008C07K 2317/565A61K 49/00C07K 2317/56A61K 39/395
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Claims

Abstract

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.

Claims

exact text as granted — not AI-modified
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.

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