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Compositions and methods for treating alzheimer's disease

A technology for Alzheimer's disease and biological samples, applied in chemical instruments and methods, drug combinations, nervous system diseases, etc., can solve problems such as poor transformation of mice

Inactive Publication Date: 2014-10-08
CANGENE U S +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, these aggressive immunotherapies resulted in mice that did not translate well in humans because of treatment-related adverse events during clinical trials, including autoimmune meningoencephalitis (Gilman et al., Clinical effects of Abeta immunization (AN1792 )in patients with AD in an interrupted trial, Neurology ,2005,10;64(9):1553-62)

Method used

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  • Compositions and methods for treating alzheimer's disease
  • Compositions and methods for treating alzheimer's disease
  • Compositions and methods for treating alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0137] Embodiment 1: cyclic peptide and Coupling of Microspheres

[0138] Various peptides derived from Αβ and microsphere coupling, Superparamagnetic carboxylated Microspheres. Αβ(1-42) and Microsphere 26 area coupling, Αβ(1-40) is coupled to microsphere 28 area, cyclic peptide cSNK (sequence: CGSNKGC) coupled with BSA is coupled to microsphere 18 area, and BSA is coupled to microsphere 30 area couplet. Αβ(1-42) and Αβ(1-40) were purchased from Bachem (Torrance, CA). Cyclic peptides were provided by the laboratory of Dr. Neil Cashman, Brain Research Center (Vancouver, BC).

[0139] The cyclic peptide comprises an amino acid sequence with at least SNK, a conformational epitope corresponding to the solvent-exposed, antibody-accessible knuckle region of oligomeric Aβ described in PCT application PCT / CA2011 / 000238.

[0140] Microspheres (regions 018, 026, 028 and 030) were obtained from Luminex Corporation (Austin, TX). 1.25×10 as required 6 The 1× scale coupling...

Embodiment 2

[0141] Example 2: Collection of plasma samples

[0142] 295 plasma samples from 295 donors were tested in the study. All donors were adults residing in Canada ranging in age from 18 to 75 years. Donors consisted of 159 men and 136 women. Plasma samples were collected between April 15, 2010, and February 15, 2011.

Embodiment 3

[0145] Example 3: multiplex immunoassay

[0146] The conjugated microspheres described in Example 1 were immunoassayed on collected plasma samples.

[0147] Each assay was performed by diluting the peptide-coated microspheres in PBS-T so that when 100 [mu]L was added to each well of a 96-well microplate, 3000 microspheres of each microsphere type were present per well. After adding the microspheres to the microplate, 50 μL each of the diluted plasma samples were added to the microspheres. The IVIG product was used as a control for each assay and 50 μL of the IVIG product (1 in 100 dilution in PBS-T) was diluted and added to the remaining wells. The mixture of plasma samples and peptide-coated microspheres was incubated at room temperature on a plate shaker in the dark for 60 minutes. Remove unbound antibody and remaining matrix by placing the microplate on a magnetic separator plate for 1 min, then pouring the supernatant into a sink by inverting the microplate attached to...

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Abstract

The present disclosure provides for a hyperimmune preparation comprising human polyclonal antibodies or fragments thereof specific to a cyclic peptide having an amino acid sequence comprising SNK. The cyclic peptide may comprise an amino acid sequence GSNK (SEQ ID NO: 1 ), SNKG(SEQ ID NO: 2), GSNKG (SEQ ID N0:3), CSNKG (SEQ ID NO: 4), CGSNKGC (SEQ ID NO: 5), CGSNKGG (SEQ ID NO: 6), or CCGSNKGC (SEQ ID NO: 7). The antibodies in the hyperimmune preparation may have a titer ranging from about 200 to about 400 mean fluorescence intensity (MFI). In one embodiment, greater than about 80% of the antibodies in the hyperimmune preparation are IgG. The fragments of the antibodies are Fab, F(ab')2, scFv, disulfide linked Fv, or mixtures thereof.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Application Nos. 61 / 558,430 (filed November 10, 2011) and 61 / 589,809 (filed January 23, 2012) and U.S. Application No. 13 / 582,308 (filed August 31, 2012) Submission), each of which is incorporated herein by reference in its entirety. technical field [0003] The present invention relates to compositions and methods for treating and preventing Alzheimer's disease in a subject. The invention also discloses the composition and method for screening and diagnosing Alzheimer's disease. Background of the invention [0004] Alzheimer's disease (AD) is a common dementia (memory and cognitive confusion) neurodegenerative disease. Accumulation in the brain of extracellular plaques primarily composed of amyloid beta peptides (also known as amyloid beta, Abeta, or Aβ), including Aβ(1-40), Aβ(1-42), and Aβ(1-43) block related. These Αβ peptides are proteolytic products of the amyloid prec...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P25/28
CPCC07K2317/34G01N33/6896C07K2317/21C07K16/18C07K16/06A61P25/28C07K14/4711
Inventor N·R·卡什曼G·马克拉蒂
Owner CANGENE U S
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