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

Patent metadata

Field	Value
Publication number	US-9464118-B2
Application number	US-201314388869-A
Country	US
Kind code	B2
Filing date	Apr 5, 2013
Priority date	Apr 5, 2012
Publication date	Oct 11, 2016
Grant date	Oct 11, 2016

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.

First claim

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:1, and homologs of this unit.

2. The polymer of claim 1 , wherein at least one other of the at least two units is selected from SEQ ID NO:1, 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 above-described units.

3. The polymer of claim 1 , wherein the at least two units are identical or nonidentical.

4. 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.

5. 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.

6. The polymer of claim 1 , wherein the at least two units are covalently or noncovalently linked to each other.

7. The polymer of claim 1 , wherein the at least two units are linked to each other directly.

8. The polymer of claim 1 , wherein the at least two units 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 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.

12. 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 4 μM.

13. The polymer of claim 1 , wherein the polymer binds amyloid-beta oligomers with a dissociation constant of not more than 1 μM.

14. The polymer of claim 13 , wherein the polymer binds amyloid-beta oligomers with a dissociation constant of not more than 20 pM.

15. A pharmaceutical composition which comprises the polymer of claim 1 .

16. A pharmaceutical composition which comprises the polymer of claim 13 .

17. A kit, probe or composition which comprises the polymer of claim 1 .

18. 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.

Assignees

• Forschungszentrum Juelich Gmbh

Inventors

• Willbold Dieter
• Funke Susanne Aileen
• Brener Oleksander
• Nagel-Steger Luitgard
• Bartnik Dirk

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• G01N2800/2821

  Alzheimer · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• G01N33/6896

  Neurological disorders, e.g. Alzheimer's disease · CPC title