Drug-Free Targeted Tumor Killing with Multimeric Antibody Conjugate
Patent Number: US20180303935A1
 
Executive Summary:
  • Invention Type: Therapeutic and Diagnostic
  • Patent Status: Pending
  • Patent Link: https://patents.google.com/patent/US20180303935A1
  • Related Patent Link: https://patents.google.com/patent/WO2017066583A1
  • Research Institute: University of Utah
  • Disease Focus: Glioblastoma
  • Basis of Invention: Monoclonal antibodies show limited clinical efficacy as a single agent therapy for solid and blood cancers. The required high doses result in undesired adverse immunogenicity and toxicity. Conjugating antibodies to cytotoxic drug have shown durable clinical response. However, antibody drug conjugate designing is complex, with knowledge of linkers, drug and antibody combinations in the context of a specific cancer. The novel therapy describes a new approach for modifying and improving antibody avidity by using graphene oxide (GO) as a targeted delivery scaffold. The GO-based aqueous composition allows non-covalent association of multiple antibody molecules on individual GO molecules, resulting in high efficacy antibodies
  • How it works: The invention features compositions and methods comprising conjugating or more therapeutic agents, such as chemotherapy drugs, antibodies non-covalently conjugated to a nanomaterial (e.g. graphene oxide). GO is a pharmaceutical suitable targeted delivery scaffold. The non-covalent drug conjugate to GO scaffold when administered in vivo can diffuse out of the blood circulation, penetrate through the tissue to reach target cells and rapidly eliminate established disease such as lymphomas in the absence of activating the host effector mechanisms.
  • Lead Challenge Inventor: Xinjian Chen and Peter Jensen
  • Inventors: Xinjian Chen, Chengke Luo, Peter Jensen, Li Lan, Alana Welm
  • Development Stage: Preclinical
  • Novelty:
    • Invention allows non-covalent binding of therapeutics (drugs/antibody) to graphene oxide-based nanomaterial, thereby increasing the direct targeting cancer cells with 1000x more potency
    • Composition improves avidity for antigen by 10-fold
  • Clinical Applications:
    • Cancer
    • Autoimmune disorders
    • Prevention of graft rejection
 
General Description:
The invention describes the compositions comprising one or more therapeutic agents non-covalently conjugated to a nanomaterial (e.g. graphene oxide). Also, described herein, are methods of preparing stable compositions, the methods comprising a plurality of antibodies non-covalently bound to graphene oxide that are physiologically acceptable compositions.
 
Scientific Progress:
In vivo data available to establish proof of concept of preparing and administering pharmaceutical composition of drug/nanomaterial complex. Currently, in collaboration with Huntsman Cancer Institute, extended validation and biological characterization is underway.
 
Future Directions:
  • Clinical validation in humans
 
Strengths:
  • Composition involves easy, reproducible, non-covalent and stable ratiometric formulation
  • GO-based aqueous composition Increases efficacy for anti-CD20 and anti-HER2 antibodies in osteosarcoma, lymphoma and pancreatic xenograft tumor models
  • Formulation decreases required dose for effective tumor killing with minimal to no adverse effects
 
Weaknesses:
  • Not yet tested in humans
 
Patent Status:
Legal status: Pending
  • Priority date: 2015-10-16
  • Filing date: 2016-10-14
  • Publication date: 2018-10-25
 
Publication PMID: 26859679
 
Publication:
Luo, C., Deng, Z. Li, L., Clayton, F., Chen, A.L., Wei, R., Miles, R., Stephens, D.M., Glenn, M., Wang, X., Jensen, P.E., and Chen, X. (2016). Association of rituximab with graphene oxide confers direct cytotoxicity for CD20-positive lymphoma cells. Oncotarget. 7(11):12806-22.
 
Inventor Bios: Xinjian Chen and Peter Jensen
https://medicine.utah.edu/faculty/mddetail.php?facultyID=u0484340
 
https://healthcare.utah.edu/fad/mddetail.php?physicianID=u0465568