US2016376335A1PendingUtilityA1

Polymers containing multivalent amyloid-beta-binding d-peptides and their use

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Assignee: FORSCHUNGSZENTRUM JUELICH GMBHPriority: Apr 5, 2012Filed: Sep 13, 2016Published: Dec 29, 2016
Est. expiryApr 5, 2032(~5.7 yrs left)· nominal 20-yr term from priority
Inventors:Dieter WillboldSusanne Aileen FunkeOleksander BrenerLuitgard Nagel-StegerDirk Bartnik
A61P 43/00A61P 25/28A61K 38/00C07K 7/06G01N 33/6896C07K 14/001C07K 14/4711G01N 2800/2821C07K 7/08G01N 2333/4709
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Claims

Abstract

The invention relates to novel multivalent polymeric amyloid-beta-binding substances composed of several interconnected substances which per se already have amyloid-beta-binding properties, and to the use of these substances, referred to hereinbelow as “polymers”, in particular in medicine.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A polymer which comprises at least two units which bind to amyloid-beta oligomers, wherein at least one of the at least two units is selected from:
 SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64. SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, and homologs of the these units.   
     
     
         2 . The polymer of  claim 1 , wherein the at least two units are peptides essentially composed of D-amino acids or antibodies or antibody fragments which bind to amyloid-beta. 
     
     
         3 . The polymer of  claim 1 , wherein each of the at least two units binds to a monomer and/or oligomer and/or fibrils of the amyloid-beta peptide with a dissociation constant (K D  value) of not more than 500 μM. 
     
     
         4 . The polymer of  claim 1 , wherein each of the at least two units binds to a monomer and/or oligomer and/or fibrils of the amyloid-beta peptide with a dissociation constant (K D  value) of not more than 10 μM. 
     
     
         5 . The polymer of  claim 1 , wherein the polymer comprises 2, 3, 4, 5, 6, 7, 8, 9, 10 or more units which bind to amyloid-beta oligomers. 
     
     
         6 . The polymer of  claim 1 , wherein at least one other of the at least two units is different from a first unit and is a unit selected from:
 SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64. SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79 and homologs of these units.   
     
     
         7 . The polymer of  claim 1 , wherein the at least two units are covalently or noncovalently linked to each other. 
     
     
         8 . The polymer of  claim 1 , wherein the at least two units are linked to each other directly or are linked to each other via a linker group. 
     
     
         9 . The polymer of  claim 1 , wherein the at least two units are linked to each other in a linear or branched fashion. 
     
     
         10 . The polymer of  claim 1 , wherein the polymer is a dendrimer and/or wherein the at least two units are linked to a platform molecule. 
     
     
         11 . The polymer of  claim 1 , wherein the at least two units are identical or nonidentical. 
     
     
         12 . A polymer which binds amyloid-beta oligomers with a dissociation constant of not more than 1 μM. 
     
     
         13 . The polymer of  claim 12 , wherein the polymer binds amyloid-beta oligomers with a dissociation constant of not more than 10 nM. 
     
     
         14 . A pharmaceutical composition, wherein the composition comprises the polymer of  claim 1 . 
     
     
         15 . A pharmaceutical composition, wherein the composition comprises the polymer of  claim 12 . 
     
     
         16 . A method of treating Alzheimer's disease in a subject in need thereof, wherein the method comprises administering to the subject the polymer of  claim 1  in an amount which is effective for treating Alzheimer's disease. 
     
     
         17 . A method of treating Alzheimer's disease in a subject in need thereof, wherein the method comprises administering to the subject the polymer of  claim 12  in an amount which is effective for treating Alzheimer's disease. 
     
     
         18 . A kit or composition which comprises the polymer of  claim 1 . 
     
     
         19 . A probe which comprises the polymer of  claim 1 . 
     
     
         20 . A process for preparing the polymer of  claim 1 , wherein the process comprises a peptide synthesis method or an organic synthesis method for low-molecular-weight compounds or wherein the polymer is prepared via a recombinant production of proteins. 
     
     
         21 . A method of identifying and/or qualitatively and/or quantitatively determining amyloid-beta oligomers, wherein the method comprises using as a probe the polymer of  claim 1 . 
     
     
         22 . A method of preventing the formation of amyloid-beta oligomers, wherein the method comprises employing the polymer of  claim 1  to prevent the formation of amyloid-beta oligomers. 
     
     
         23 . A method of forming nontoxic polymer-amyloid-beta oligomer complexes, wherein the method comprises employing as the polymer the polymer of  claim 1 .

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