Binding agonist for treatment of neurological and other disorders

a neurodegenerative and other disorder technology, applied in the field of binding agonists for neurological and other disorders, can solve the problems of less likely to provide disease modification with significant clinical benefit, unclear whether, and phenotypical heterogeneity of neurodegenerative disorders, and achieve the effect of restoring or enhancing the bdnf-trkb pathway

Pending Publication Date: 2021-11-11
GLAXOSMITHKLINE INTPROP DEV LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The TrkB binding agonist effectively activates TrkB, potentiates BDNF-induced signaling, and maintains cell surface receptor levels, potentially offering a therapeutic benefit by enhancing neuronal survival and plasticity in neurological disorders.

Problems solved by technology

However, neurological disorders are phenotypically heterogeneous, both in familial and sporadic forms, and often have an unknown etiology.
Thus targeting a single pathological mechanism, is less likely to provide disease modification with a significant clinical benefit, unless the nature of the pathological mechanism is the key “driver” of the disease.
However, it remains unclear whether they are the cause of the disease or the consequence of the primary and / or secondary damage.
Consequently, therapies based on some of these individual mechanisms have not been clinically successful.
However, clinical success by lowering toxic proteins has been limited, such as AB in Alzheimer's Disease, although recent trials in patients with mild disease show encouraging results.

Method used

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  • Binding agonist for treatment of neurological and other disorders
  • Binding agonist for treatment of neurological and other disorders
  • Binding agonist for treatment of neurological and other disorders

Examples

Experimental program
Comparison scheme
Effect test

embodiment 1

ng agonist, wherein the agonist potentiates BDNF-induced agonism of TrkB.

embodiment 2

ding agonist of embodiment 1, wherein the agonist does not compete with BDNF for binding to TrkB.

embodiment 3

ding agonist of embodiment 1 or 2, wherein the potentiating effect of BDNF-induced agonism of TrkB is measured by increased activation of TrkB in the presence of a saturating concentration of BDNF in the presence of the TrkB binding agonist, compared with the absence of the TrkB binding agonist.

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Abstract

The present invention relates to TrkB binding agonists, and to the use of such agonists in the treatment of neurological disorders and other disorders. The present invention also relates to specific TrkB binding agonists comprising CDRs, variable regions, heavy and light chains, and variant sequences thereof.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional application of U.S. application Ser. No. 15 / 776,493 filed May 16, 2018, which is a 371 National Stage Entry of International Application No. PCT / EP2016 / 077644 filed Nov. 15, 2016, which claims priority to and the benefit of International Application No. PCT / CN2015 / 094779 filed Nov. 17, 2015, International Application No. PCT / CN2016 / 095545 filed Aug. 16, 2016 and Great Britain Application No. GB1618814.6 filed Nov. 8, 2016, all of which are incorporated herein by reference in their entirety.FIELD OF THE INVENTION[0002]The present invention relates to TrkB binding agonists, and to the use of such agonists in the treatment of neurological disorders and other disorders. The present invention also relates to specific TrkB binding agonists comprising CDRs, variable regions, heavy and light chains, and variant sequences thereof.BACKGROUND OF THE INVENTION[0003]Neurological disorders are increasing in incidence an...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): C07K16/28A61P25/00A61P27/16
CPCC07K16/2863A61K2039/505A61P27/16A61P25/00A61K39/39541C07K16/286C07K2317/75A61P21/00A61P21/02A61P25/02A61P25/06A61P25/14A61P25/16A61P25/20A61P25/22A61P25/24A61P25/28A61P27/00A61P27/02A61P27/06A61P3/04A61P43/00A61P9/00C07K2317/24C07K2317/33C07K2317/565C07K16/2878
InventorBHINDER, TEJINDER KAURDING, CHONGFENG, XUJIANG, WENQINGLEWIS, ALAN PETERMA, YINGLINAGAPPAN, GUHANPARMAR, RADHA SHAHQIU, YANGSHENGYANG, LIUQINGZHANG, QINGZHOU, YANJIAO
OwnerGLAXOSMITHKLINE INTPROP DEV LTD