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Targeting Proteins for Degradation

Andreas Matouschek

Patent #
US11008372B2
interested LPs
CP3
Identification Number
6634 MAT
Issue Date
2021-05-18
Organization
University of Texas at Austin
Date Added
2023-01-01
Tech Transfer Org
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CHatgpt summary & Analysis

Executive summary:
This investment memo discusses a new technology, namely the recombinant polypeptides called degradons, that selectively target and degrade disease-associated proteins. The technology has the potential to revolutionize the food, protein and agriculture industries, by developing new products and services that address the current and future needs of industrial partners, farmers, and consumers. Furthermore, the technology has the potential to catalyze economic and job growth in rural communities.

Core technology:
The degradon technology is a recombinant polypeptide comprising a target binding domain and a proteasome-binding domain. The technology is differentiated from current solutions on the market because it selectively targets and degrades disease-associated proteins, making it a potential game-changer in treating and preventing diseases.

Potential uses:
- Creating environmentally friendly animal feed through the selective degradation of plant proteins that are difficult to digest
- Developing novel crop protection technology by selectively targeting proteins that confer resistance to pests and diseases
- Enhancing the nutritive value of plant-based protein sources by selectively targeting specific proteins that diminish the digestibility of otherwise nutritious plant proteins
- Further applications in human and animal health, such as drug development and disease treatment.

Recommendation:
Further due diligence is warranted to explore the commercial potential of this technology. The potential applications in food, protein, and agriculture industries align with the firm’s mission to revolutionize these industries, and the potential to catalyze economic growth in rural communities aligns with the firm’s mission of generating significant returns for investors while doing good.

Sources:
- US Patent US11008372B2
- Google Patents: US11008372B2
- "Targeted Protein Degradation: A Rising Tide for Drug Discovery" - ACS Publications.

Abstract

Embodiments provided here include recombinant polypeptides, termed degradons, comprising a target binding domain and a proteasome-binding domain. Degradons of the embodiments are able to selectively target and degrade proteins bound by the target-binding domain, such as proteins associated with disease. Vectors encoding degradons and methods of treating disease with degradons and degradon expression vectors are likewise provided.

Claims

  1. A recombinant polypeptide that binds to a target polypeptide, the recombinant polypeptide comprising a target-binding domain and a proteasome-binding domain that comprises a ubiquitin-like domain, wherein said target binding domain comprises an antibody or a fragment thereof that binds to the target polypeptide.
  2. The polypeptide of claim 1, wherein the target polypeptide is a polypeptide associated with a disease.
  3. The polypeptide of claim 1, wherein the target polypeptide is not a reporter protein; wherein the target-binding domain does not bind to the Huntingtin protein (HTT); or wherein the target-binding domain does not bind to protein having a poly-Q sequence.
  4. The polypeptide of claim 1, wherein the target-binding domain is position N-terminally relative to the proteasome binding domain.
  5. The polypeptide of claim 1, wherein the target-binding domain is position C-terminally relative to the proteasome binding domain.
  6. The polypeptide of claim 1, wherein the proteasome-binding domain comprises a domain from human Rad23b.
  7. The polypeptide of claim 6, wherein the proteasome-binding domain comprises amino acids 1-83 of human Rad23b.
  8. The polypeptide of claim 1, wherein the target-binding domain and the proteasome-binding domain are separated by a linker.
  9. The polypeptide of claim 1, further comprising a cell-penetrating peptide (CPP) sequence or a cellular receptor-binding sequence.
  10. The polypeptide of claim 1, wherein the antibody or antibody fragment comprises a monobody or scFv.
  11. The polypeptide of claim 10, wherein the antibody or antibody fragment comprises the HA4 monobody, Nsa1 monobody, and/or the Cs1 monobody.
  12. The polypeptide of claim 1, wherein the target-binding domain binds to a prion, a viral polypeptide, a disease-associated protein, a cellular polypeptide having a disease-associated mutation or the product of an oncogene.
  13. The polypeptide of claim 12, wherein the target-binding domain binds to the product of an oncogene.
  14. The polypeptide of claim 12, wherein the oncogene is Abl and/or Shp2.
  15. The polypeptide of claim 12, wherein the target binding domain binds to the SH2 domain of Abl, the N-terminal SH2 domain of Shp2, and/or C-terminal SH2 domain of Shp2.
  16. The polypeptide of claim 12, wherein the target-binding domain binds to misfolded beta-amyloid.
  17. A nucleic acid molecule encoding a polypeptide according to claim 1.
  18. A pharmaceutical composition comprising: a polypeptide according to claim 1.
  19. The polypeptide of claim 1, wherein the target binding domain comprises a monobody that binds to the target polypeptide.
  20. The polypeptide of claim 1, wherein the target binding domain comprises an scFv that binds to the target polypeptide.
  21. The polypeptide of claim 1, wherein the target binding domain comprises an antibody that binds to the target polypeptide.
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CAGR:
19.9
%
# LPs Interested:
1
Competition:
Medium
Tech Transfer
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Market Category & Size
Biologics
$18.2B by 2027
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Technology Readiness Level
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