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 AUTM's New Technology Profiles

Use of Cell-Penetrating Peptides and/or Antibody Drug Conjugates for Tumor Radiosensitization

Researchers at UC San Diego have demonstrated the therapeutic potential of utilizing cell penetrating peptides and antibody drug conjugates (ADC) to deliver radiosensitizers. Moreover, pretargeted ACPP technology allows for selective delivery of radiosensitizing agents to tumor as opposed to normal tissue and improvement in the therapeutic index of radiation therapy for non-resectable, locally aggressive tumors. Once cleaved, they release drug-conjugated polycation cell penetrating peptides that are taken up by tumor cells. Alternatively, ADC consist of a drug that is covalently attached to an antibody recognizing a specific cell surface receptor. The ADC binds to the specific receptor and undergoes receptor-mediated endocytosis whereby the drug is released from the antibody via endolysomal proteases.

Obstruction Prevention Airway Collar

Nearly 30% of surgeries require monitored anesthesia care (MAC), which includes local anesthesia along with sedation and analgesia. In such cases, patients are totally paralyzed, unconscious, and unable to feel pain. Though routine, patients under MAC are prone to airway obstruction either from the tongue falling back over the airway or the relaxation of laryngeal muscles. The most common methods of preventing such obstruction are naso-/oro-pharyngeal tubes, which extend from the nose/mouth to the pharynx, and medical devices that extend and support the neck. Medical devices are typically preferred as they do not carry the associated insertion risks that pharyngeal tubes do. Currently, however, most neck extending devices work only at one body position (e.g., a patient lying flat on his/her back) and are made from clunky and uncomfortable plastic.

To this end, researchers at UCI have developed a disposable medical collar to maintain patient airways for a variety of body positions. The collar is made of a dense foam which is wrapped around the patient’s neck, and is comfortable yet supportive enough to keep the airway clear. In addition to offering airway support at a variety of body positions, the collar is also entirely adjustable and can be fit to each individual patient. As each collar is disposable and used for only one patient, this shortens OR turnover time as the patient can be taken to the post-anesthesia recovery room while still wearing the device.

Preconditioned Human Mesenchymal Stem Cells (hMSCs) for Musculoskeletal Tissue Repair

Bone defects that extend beyond a critical size are associated with impaired native healing due to age or disease. Approximately 10% of patients with bone defects do not have sufficient bone repair processes, leading to fractures, infections, and other comorbidities. Human mesenchymal stem cell (hMSC)-based therapies have high therapeutic potential for such bone repair but have limited efficacy in vivo: calcification of surrounding tissue occurs due to limited oxygen supply and decreased nutrient exchange.

Researchers at the University of California, Davis have developed a novel treatment for bone repair that offers an optimized survival rate of human mesenchymal stem cells and engraftment once implanted into a bone defect. The method incorporates pre-treatment of the cells combined with an engineered cell carrier system, resulting in synergistically improved bone healing compared to existing monolayer cell therapies and spheroid formation methods. This method has successfully exhibited higher cell density, osteogenic potential and increased secretion of proangiogenic factors in vitro with significantly more bone healing in critical-sized femoral segment defects in rats in vivo. This method represents a simple approach for enhanced, long-term therapeutic bone healing.

3D Printable Bioactive Glass/Polymer Composite

Project ID:  D2018-16

 

Background

Popularity of 3D printing has grown exponentially in the last decade, leading to endless applications of rapid prototyping and production of parts in a variety of fields such as aerospace and medicine. In any application, it is critical that the appropriate printing material is selected to ensure proper function and durability of the printed parts. Filaments that are most commonly used in fused deposition modeling (FDM) 3D printing are made from polymers such as polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS). However, these materials are generally considered to have poor mechanical properties and may easily harbor harmful microbes. There is, therefore, the need for continuous improvement in 3D printing filaments. 

 

Invention Description

Researchers at the University of Toledo, led by Dr.  Aisling Coughlan, have developed a 3D printable filament from a composite material consisting of a polymer reinforced with a bioactive agent, which can generate 3D-printed objects with both functionality and increased mechanical integrity.

 

Applications

•       The composite filament material can be used in wide a variety of FDM 3D printing applications and possesses distinct advantages for hobby, educational, clinical  and other applications due to its bioactive nature and improved mechanical properties

 

Advantages

•       This filament allows for the 3D printing of antibacterial objects for use in a variety of applications

•       The filament generated is compatible with standard FDM 3D printers

•       Reinforcement with glass results in filament with superior mechanical properties

•       The filament can be made with a variety of polymer bases, pigments and additives

•       The filament can be made with current conventional extruder technology without the need for additional coating

•       The filament has potential for everyday hobby and clinical use

 

IP Status:       Patent Pending

 

A Novel IgG Protease with Therapeutic Potential for Immune-Mediated Diseases

Geolocation Estimation System Using Arbitrary Image as Input

A No Suture Chest Tube

In Emergency and Trauma Medicine, chest tubes are common medical devices used to treat patients. Typically, chest tubes are used to treat pneumothorax, air around the lung, and hemothorax, blood or fluid around the lung, in a trauma situation; however, they also can be used to treat other spontaneous conditions such as cancer, COPD, or body habitus. Curren practices for a patient requiring a chest tube would be to make a skin incision across the rib, insert the chest tube, and then use sutures to secure the tube within the chest and allow for the fluid to drain. Dressing for a typical chest tube would include Vaseline dressin that is airtight, cloth gauze, and tape strips. This current practice can be dangerous to the patient because sharp objects, such as sutures, expose the patient to the risk of infectious diseases.

The disclosed technology provides a new chest tube apparatus that can be used to improve the treatment of patients. The major difference is that this new chest tube requires no sutures after it is placed. Without the need for sutures, the invention becomes faster to secure than current methods, which can be critical in an emergency situation. Importantly, the invention works in the same circumstances as chest tubes used today. All of the dressings necessary to secure the tube come pre-attached to it, so no extra materials are required. This results in easy implementation in any emergency medical scenario.

 

Reference Number: D-1389

 

Market Applications:

  • Emergency Medicine
  • Trauma Medicine

 

Features, Benefits, & Advantages:

  • Lowers risk of infections
  • Faster to use
  • Easier to use than current methods
  • No sutures needed

 

Intellectual Property: A US. provisional patent, serial number 62559738, was filed on September 18, 2017.

 

Development Stage: The invention has been produced and tested.

 

Researchers:

  • Robert Stump, Department of Emergency Medicine, Texas Tech University Health Sciences Center, El Paso, Texas

 

Keywords: chest tubes, sutures, wound care, emergency medicine

Tunable nanocomplexes for delivery of plasmid DNA into human and vertebrate primary cells

Historically, poly(D,L-lactide-co-plycolide) (PLGA) complexes with polyethylenimine (PEI) coated surfaces have been used  as a DNA delivery mechanism in gene therapy. This allows for a complex that has relatively low cytotoxicity, binds DNA, and has a cationic surface to allow for easy entry into the target cell. However, these complexes still maintain an amount of cytotoxicity due to the nature of PEI. Smaller PEI molecules have low cytotoxic effects, but then have almost no transfection ability. The present invention uses lower molecular weight PEI along with an attached glycidyl hexadecyl ether to ultimately lower cytotoxic effects of the PEI-PLGA complex while increasing transfection ability. These PEI-PLGA complexes are successfully able to transfect genes into target cells, specifically macrophages, with decreased cytotoxicity and increased transfection ability.

 

Features, Benefits & Advantages:

- Decreased cytotoxicity in gene therapy complexes

- Increased transfection ability in nanocomplexes

 

Stage of Development:

- Efficacy testing has been completed with positive results.

 

Intellectual Property:

- A provisional patent application was filed 11/29/2017.

 

Primary Investigators:

Huanyu Dou, MD, Texas Tech University Health Sciences Center, El Paso, TX.

 

Keywords: Gene Therapy, Polyethylenimine, Transfection Ability

Portable Exhaled Breath Condensate (EBC) Analyzer for Asthma Diagnosis and Monitoring


Invention Summary:

Asthma, an increasingly important global health problem that affects ~ 300 million people worldwide, is characterized by variable airway inflammation and air flow obstruction. Currently available non-invasive methods for diagnosing and monitoring asthma involve measurements of exhaled nitric oxide (NO). Apart from the transient nature of NO, these methods are limited by low sensitivity and an inability to identify the nature and extent of airway inflammation. Measurement of alternative biomarkers in exhaled breath condensate (EBC) that can facilitate molecular phenotyping of asthma, thus enabling targeted treatment and more effective disease management, is an important clinical need.

Nitrite in EBC is a promising biomarker for the extent of inflammation and air-flow obstruction in the respiratory tract and is more stable than NO. Rutgers scientists have developed a novel portable device that employs reduced graphene oxide (rGO) as the sensing mechanism for detecting nitrite in very small volumes of EBC. The team has validated the performance of this device on clinical EBC samples. This enzyme-free and label-free method of detecting nitrite in EBC can pave the way for the development of portable breath analyzers for diagnosing and managing changes in respiratory tract inflammation and disease states.

Market Applications:

Point-of-Care analyzer for detecting and monitoring nitrite, an asthma-associated inflammation biomarker in EBC.

Advantages:

  • Portable
  • Highly sensitive in the clinically relevant µM range
  • Easy to use, no need to pretreat EBC
  • More reliable than measuring exhaled NO

 

Intellectual Property & Development Status:

Patent pending. Available for licensing and/or research collaboration.

Publication:

Gholizadeh A, Voiry D, Weisel C, Gow A, Laumbach R, Kipen H, Chhowalla M and Javanmard M. Toward point-of-care management of chronic respiratory conditions: Electrochemical sensing of nitrite content in exhaled breath condensate using reduced graphene oxide. (2017) Microsystems & Nanoengineering. 3:17022.

Trackable Quorum-Sensing Molecules for Diagnostic Applications

Princeton Docket # 17-3325-1

 

High quality medical imaging technology has been one of most important developments in clinical care and personalized medicine. Pinpointing the source and cause of disease in a patient allows targeted and optimal treatment, saving time and money. Applying this type of imaging accuracy to the identification of bacterial pathogens and infection sites is a critical unmet need. Overuse of broad-spectrum antibiotics is rapidly selecting for resistance, but the time required to biopsy and culture for species determination limits the use of targeted techniques. To allow in vivo imaging of bacterial infections, researchers at Princeton University have created a method to conjugate trackable probes to quorum-sensing (QS) molecules.

 

Quorum sensing is a cell-cell communication process that bacterial collectives use to regulate group behaviors such as biofilm formation and the synchronous production of virulence factors. This process involves the production, release, and population-wide detection of extracellular signal molecules called autoinducers. As these molecules are highly species specific, a trackable QS probe can be used as a diagnostic to determine both the location and the identity of a specific pathogen in many systems. These probes can be fluorescent for surface detection, or radionuclides such as PET probes for in vivo medical imaging.

 

This method represents a significant improvement over other infection-detection strategies. Metabolic and white blood cell labeling methods struggle to differentiate between infection and inflammation. Radiolabeled antibiotics detect infection, but cannot determine the species responsible. In addition, using labeled antibiotics can contribute to the resistance that this method seeks to avoid. Targeted and limited use of antibiotic compounds is a key part of the war against resistance, and this technology is a novel method to quickly narrow in on the most effective

 

Applications:        

•       Pinpoint the location and identity of a bacterial pathogen in many systems including:

o       In vivo medical imaging with radionuclide or PET probes

o       In vitro medical or industrial monitoring with fluorescent probes

•       Multiplex probes from different species to identify mixed populations

 

Advantages:

•       Can determine species identity

•       Does not use resistance-cause antibiotics

•       Can also disperse biofilms, increasing the effectiveness of treatment

 

Publication:

Kim, M. K., Zhao, A., Wang, A., Brown, Z. Z., Muir, T. W., Stone, H. A., & Bassler, B. L. (2017). Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development. Nature Microbiology, 2, 17080. https://doi.org/10.1038/nmicrobiol.2017.80

 

Inventors:

 

Bonnie L. Bassler, Princeton's Squibb Professor and Chair of the Department of Molecular Biology and a Howard Hughes Medical Institute investigator, is a world leader in the science of quorum sensing and the study of how bacteria communicate. Bassler is a member of the American Academy of Arts and Sciences, National Academy of Sciences, National Academy of Medicine, and the Royal Society. She has won many awards including the 2015 Shaw Prize in Life Sciences and Medicine, the 2011 Richard Lounsbery Award, and the 2002 MacArthur Foundation genius award.

 

Howard A. Stone is the Donald R. Dixon '69 and Elizabeth W. Dixon Professor and Chair of the Mechanical and Aerospace Engineering Department. In addition to being a member of the American Academy of Arts and Sciences, the National Academy of Engineering, and the National Academy of Sciences, Professor Stone was the winner of the inaugural Batchelor Prize sponsored by the Journal of Fluid Mechanics for the breadth and depth of his research over a 10-year period (1998-2007) and for his widely acknowledged leadership in fluid mechanics generally, as well as the APS Fluid Dynamics Prize in 2016.

 

Tom W. Muir, Van Zandt Williams, Jr. Class of ’65 Professor of Chemistry and Department Chair. The Muir lab combines tools of synthetic chemistry, protein biochemistry, and cell biology. Prof. Muir received the Irving Sigal Award from the Protein Society, the 2008 Blavatnik Award from the New York Academy of Sciences, and the 2013 Arthur C. Cope Scholar Award from the American Chemical Society. 

 

Min Young Kim was a Ph.D. graduate student in the Department of Chemistry, working with Bonnie L. Bassler (Molecular Biology) and Howard A. Stone (Mechanical Engineering) at Princeton University. He earned his Ph.D. degree at Princeton University in 2017.  He investigated the fundamental mechanisms underlying how bacteria colonize surfaces. He also developed physical and chemical strategies to manipulate bacterial colonization by modulating quorum sensing. Dr. Kim received the STX graduate fellowship in 2012.

 

Aishan Zhao is a graduate student in the Chemistry Department, working with Prof. Tom Muir.  Her research specialty is using chemical biology tools to study the quorum sensing of S. aureus, including biosynthesis of autoinducing peptides, and analysis of signal detection, transduction, and response. She also developed chemical applications for applying quorum sensing signaling molecules to health-care and industrial devices. She received the McKinney Fellowship in 2013.

 

Intellectual Property Status

Patent protection is pending.

 

Princeton is seeking to identify appropriate partners for the further development and commercialization of this technology.

 

Contacts:

 

Linda Jan

Princeton University Office of Technology Licensing • (609) 2583653• ljan@princeton.edu

 

Laurie Tzodikov

Princeton University Office of Technology Licensing • (609) 258-7256• tzodikov@princeton.edu

 

 


    
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