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Composition

A composition and the technology of the next group, applied in the direction of drug combination, fusion polypeptide, fusion with toxin, etc., can solve problems such as neuron death

Inactive Publication Date: 2015-03-11
AFFIRIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Although the exact mechanism by which α-syn accumulates functional damage and ultimately leads to the death of neurons is not yet fully understood, recent studies have shown that the accumulation of abnormally folded α-syn is involved in the degenerative process and is the above-mentioned protein. underlying cause of illness

Method used

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Experimental program
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Effect test

Embodiment approach

[0052] According to a preferred embodiment of the present invention, the epitope comprises or consists of the amino acid sequence KNEEGAP or DMPVDPDN.

[0053] Mimotopes of the aforementioned epitopes are well known to those skilled in the art (see eg WO2009 / 103105, WO 2011 / 020133).

[0054] Preferably, the composition of the invention comprises at least one mimotope comprising or consisting of the amino acid sequence

[0055] (X 1 ) n x 2 x 3 x 4 x 5 GX 6 P(X 7 ) m (Formula I),

[0056] in

[0057] x 1 is any amino acid residue,

[0058] x 2 is an amino acid residue selected from the group consisting of lysine (K), arginine (R), alanine (A) and histidine (H),

[0059] x 3 is an amino acid residue selected from the group consisting of asparagine (N), glutamine (Q), serine (S), glycine (G) and alanine (A), preferably asparagine (N), serine (S), glycine (G) and alanine (A),

[0060] x 4 is an amino acid residue selected from the group consisting of glut...

Embodiment 1

[0198] Example 1: Effect of mimotope-CRM197 conjugates using different adjuvant systems: Immunization Originality (Fig.1)

[0199] In multiple parallel experiments, female BALB / c mice were repeatedly immunized with the same amount of AFFITOPE peptide (the mimotope disclosed in this application) coupled to CRM-197, preferably containing C- or N- terminal cysteine ​​residues (use 10 μg of peptide per immunization). Different formulations using the same AFFITOPE conjugate are compared to a suitable control group (eg: PBS alone or adjuvant alone or CRM-197+adjuvant).

[0200] The following peptide-conjugates or combinations of conjugates were used:

[0201] · DQPVLPD conjugated to CRM197

[0202] · YDRPVQPDR coupled to CRM197

[0203] · DHPVHPDS coupled to CRM197

[0204] Conjugation of KNDEGAP to CRM197

[0205] Adjuvants used in this example are:

[0206] Aluminum hydroxide, aluminum hydroxide and the TLR agonist MPLA, squalene-based adjuvants, oil-in-water emulsions (...

Embodiment 2

[0210] Example 2: Effect of Mimotope-KLH Conjugates Using Different Adjuvant Systems: Immunogens sex (Fig.2)

[0211] In multiple parallel experiments, female BALB / c mice were repeatedly immunized with the same dose of mimotope peptide conjugated to KLH (eg, 10 μg peptide per immunization). Different formulations using the same mimotope conjugate are compared to a suitable control group (eg: PBS alone or adjuvant alone or KLH + adjuvant).

[0212] The following peptide-conjugates or combinations of conjugates are used:

[0213] · DQPVLPD coupled to KLH

[0214] · YDRPVQPDR coupled to KLH

[0215] · DHPVHPDS conjugated to KLH

[0216] Conjugation of KNDEGAP to KLH

[0217] The adjuvant (with embodiment 1) that present embodiment uses:

[0218] Aluminum Hydroxide, Aluminum Hydroxide and MPLA, Addavax and QuilA.

[0219] After immunization, an in vitro ELISA assay was performed using plasma from individual mice to determine antibody titers (see Example 1 for methods des...

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Abstract

The present invention relates to a composition comprising at least one mimotope of an epitope of alpha-synuclein for use in a method for preventing and / or treating ß-amyloidoses including Alzheimer's disease, wherein said at least one mimotope is coupled or fused to a pharmaceutically acceptable carrier protein selected from the group consisting of a non-toxic diphtheria toxin mutant, keyhole limpet hemocyanin (KLH), diphtheria toxin (DT), tetanus toxid (TT) and Haemophilus influenzae protein D (protein D).

Description

technical field [0001] The present invention relates to the prevention and treatment of diseases associated with the formation and / or aggregation of beta-amyloid proteins (beta-amyloidosis). Background technique [0002] Various degenerative diseases are characterized by the accumulation and aggregation of misfolded specific proteins. These so-called proteopathies include diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD) or inclusion body myositis (IBM) as well as systemic Systemic entities encompass various amyloidoses. [0003] The present invention relates to the prevention, treatment and diagnosis of AD associated with the accumulation and aggregation of misfolded alpha-synuclein (α-syn). Other diseases targeted by the present invention include, but are not limited to, frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and dementia and IBM of Down syndrome (DS). [0004] α-syn (originally identified as ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00
CPCA61K2039/6037A61K2039/6081A61K2039/55555A61K2039/55577A61K39/0007A61K2039/55505A61K2039/55566A61P25/28A61P31/00A61P35/00A61K39/0003A61K39/05A61K39/39A61K2039/55511A61K2039/55516A61K2039/55561A61K2039/55572A61K2039/6075C07K7/06C07K14/34C07K14/43504C07K2319/00C07K2319/55
Inventor M.曼德勒W.佐纳F.马特纳W.施密特
Owner AFFIRIS AG