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Molecular guide system peptides and uses thereof

A guiding system and molecular technology, applied in the direction of medical preparations containing non-active ingredients, medical preparations containing active ingredients, polypeptides containing positioning/targeting motifs, etc.

Pending Publication Date: 2020-06-12
SRI INTERNATIONAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The ability of MAbs to modulate protein-protein interactions is inherently exceptionally strong such that they cannot penetrate cells and modulate intracellular protein-protein interactions constituting life-threatening diseases (such as infectious diseases, cancer, and other challenging and intractable diseases) Major unmet need in treatment of

Method used

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  • Molecular guide system peptides and uses thereof
  • Molecular guide system peptides and uses thereof
  • Molecular guide system peptides and uses thereof

Examples

Experimental program
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Embodiment 1

[0116] Until recently, no systemic approach to targeting intracellular / subcellular components has been reported. Appropriate FOX-Three technology is a platform for the systematic discovery of MGS capable of delivering MAbs to cellular and subcellular targets. The FOX-Three platform identifies MGS with three key attributes: the ability to home in on desired cell types, the ability to trigger cellular uptake, and the ability to deliver payloads to discrete locations within target cells. exist figure 1 An overview of MGS is shown in .

[0117] The FOX-Three platform is based on an established phage display library containing 10 9 -10 12 A candidate peptide-based MGS member that can be rapidly screened against target cells and subcellular systems to identify specifically targeted MGS ( figure 2 ). Peptides are a well-known class of biomolecules that are readily synthesized both by biological methods and by man-made chemical methods. Thus, the capabilities of the FOX-Three p...

Embodiment 2

[0134] MGS can impact the treatment of a variety of diseases and open up new treatment options. Targeting protein interactions leads to a new class of intracellularly acting drugs with the potential to treat "undruggable" targets. Treatment indications include cancer, emerging infectious diseases and bioterrorism, cardiac disease, diabetes, fibrosis, neurological and neurodegenerative diseases. MGS has broad applicability and can be used to deliver small molecule drugs, imaging agents, nucleic acid and protein delivery, nanoparticles and cell therapy.

[0135] Small peptide-MGS delivers large mAbs into cells in vitro and in vivo. Small peptides will not be able to carry MAbs that are almost 60 times larger than their molecular weight. Cells were treated with MAb only, no cellular uptake occurred. However, a 20-4000-fold increase in cellular uptake was observed when the MAb was conjugated to one of the identified MGS peptides. Not only does the peptide deliver a cell-imperm...

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Abstract

Disclosed are compositions comprising an antibody conjugated to one or more molecular guidance system (MGS) peptides. Disclosed are methods of treating a subject in need thereof comprising administering to the subject in need thereof an effective amount of an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target involved in the disease process. Disclosed are methods of targeting an intracellular target comprising administering an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target.

Description

Background technique [0001] There is an urgent need for systemic cell-targeting systems that deliver therapeutic antibodies to specific cell types and specific locations within said cells. [0002] The therapeutic monoclonal antibody (MAb) market has grown dramatically to over $70B in the past decade and is expected to grow to $125B by 2020. There are currently 47 therapeutic MAbs on the market that have been approved by the FDA for a range of diseases. However, MAbs are not cell permeable, thus they are restricted to extracellular and cell surface therapeutic targets. This leaves a large number of therapeutic targets, especially protein-protein interactions, unavailable for MAb therapy within the cell. The ability of MAbs to modulate protein-protein interactions is inherently exceptionally strong such that they cannot penetrate cells and modulate intracellular protein-protein interactions constituting life-threatening diseases (such as infectious diseases, cancer, and other...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K47/60
CPCA61K47/64C07K14/00C07K2317/77C07K2319/05C07K2319/30A61P35/00C07K7/08G01N33/5076G01N2500/10A61K38/00C07K14/4702C07K16/2803
Inventor 凯瑟琳·C·布朗N·柯林斯李顺子柯蒂斯·奥尔雷德基恩·钟迈克尔·麦圭尔
Owner SRI INTERNATIONAL