Wisconsin Alumni Research Foundation patent applications published on November 30th, 2023

Summary of the patent applications from Wisconsin Alumni Research Foundation on November 30th, 2023

The Wisconsin Alumni Research Foundation (WARF) has recently filed several patents related to various fields of research. These patents cover methods, compositions, and kits for generating phenocopy signatures, directing the differentiation of human pluripotent stem cells, and deriving brain pericyte-like cells from stem cells. Additionally, WARF has filed patents for a microfluidic platform that controls and configures gradients, a method using short ultrasound pulses to target brain tissue, and a method of real-time sensing of cerebrospinal fluid clearance. They have also filed patents for using electrical stimulation to improve waste clearance from the brain and for recombinant microorganisms as delivery vehicles for biologics to the gastrointestinal tract.

Summary: - WARF has filed patents for methods of generating phenocopy signatures, directing stem cell differentiation, and deriving brain pericyte-like cells. - They have also filed patents for a microfluidic platform, targeting brain tissue with ultrasound pulses, and real-time sensing of cerebrospinal fluid clearance. - Additionally, WARF has filed patents for using electrical stimulation to improve waste clearance from the brain and for using recombinant microorganisms as delivery vehicles for biologics.

Notable applications:

• Generating phenocopy signatures to predict mutations in cells and identify subjects sensitive to drug treatment.
• Directing the differentiation of stem cells into biomimetic neural tissues resembling the developing human neural tube.
• Deriving brain pericyte-like cells from stem cells for studying brain development and diseases.
• Controlling and configuring gradients in a microfluidic platform for precise experimentation.
• Targeting brain tissue with short ultrasound pulses to manipulate tissue without causing damage.
• Real-time sensing of cerebrospinal fluid clearance for optimizing electrode targeting and programming in cranial nerve stimulation.
• Using electrical stimulation to improve waste clearance from the brain and enhance drug penetration.
• Using recombinant microorganisms as delivery vehicles for biologics to specific sites in the gastrointestinal tract.

Patent applications for Wisconsin Alumni Research Foundation on November 30th, 2023

MICROBES WITH REDUCED ADHESION CHARACTERISTICS (18323912)

Main Inventor

Jan Peter van Pijkeren

Brief explanation

- The patent application is about recombinant microorganisms and their use in delivering biologics to the gastrointestinal tract.

- The recombinant microorganisms have been modified to reduce the expression and/or activity of certain proteins that are involved in adhesion. - These modifications result in reduced adhesion characteristics compared to non-modified microbes. - The recombinant microorganisms also contain a recombinant gene that allows them to express a biologic. - The main purpose of the invention is to use these modified microorganisms as delivery vehicles for biologics to specific sites in the body, such as the gastrointestinal tract.

Abstract

Recombinant microorganisms and methods of using same. The recombinant microorganisms include one or more modifications that reduce the expression and/or activity of a sortase, a sortase-dependent protein, a fibronectin-binding protein, an autolysin, a surface-layer protein, an aggregation-promoting factor, and/or a collagen-binding protein. The modifications can reduce the adhesion characteristics with respect to the non-modified microbes. The recombinant microorganisms can further include a recombinant gene configured to express a biologic. The recombinant microorganisms can be used as delivery vehicles to deliver the biologics to sites such as the gastrointestinal tract.

Layered Stimulus Patterning to Synergistically Optimize Brain Clearance at Multiple Points in Clearance System and Real-Time Dial to Change Drug Delivery Profiles (18201881)

Main Inventor

Kip Ludwig

Brief explanation

- The patent application describes a method of using electrical stimulation to improve the clearance of waste biomolecules and drugs from the brain.

- Low frequency electrical stimulation is delivered to the cranial nerves during sleep to increase the presence and function of aquaporin-4 (AQP4) channels in the astrocytic endfeet surrounding blood vessels in the brain. - Higher frequency stimulation is used in bursts to pulse the underlying artery and drive cerebrospinal fluid (CSF) penetration into the brain tissue, increasing movement and the probability of waste biomolecules interacting with sites for active transport out of the brain. - During sleep, gamma frequency stimulation is used to promote a more phagocytic phenotype in glial cells, helping to break down waste biomolecules and misfolded proteins for clearance. - The electrical stimulation can be adjusted to selectively modify CSF clearance, such as quickly clearing drug concentrations in the brain during an overdose.

Abstract

Administration of low frequency electrical stimulation of the cranial nerves delivered during sleep increases the presence and function of aquaporin-4 (AQP4) channels in the astrocytic endfeet surrounding descending arterioles in the brain. This underlying low frequency stimulation pattern is overlaid with temporally patterned ‘bursts’ of higher frequency stimulation to pulse the underlying artery to drive cerebrospinal fluid (CSF) penetration into the parenchyma. This also serves to create more movement in general within the parenchymal extracellular space to increase the probability of waste biomolecules to interact with sites for active transport out of the brain. During the period of sleep, these two layered patterns will be periodically replaced with multiple continuous periods of stimulation at gamma frequency to promote a more phagocytic phenotype in glial cells to help break down waste biomolecules and misfolded proteins for subsequent clearance. Administration of electrical stimulation can be selectively modified to adjust CSF clearance, for example, to quickly clear drug concentrations in the brain during an overdose.

Use of Non-Invasive Sensory Systems to Titrate Cranial Nerve Stimulation to Enhance Brain Clearance Closed-Loop (18201887)

Main Inventor

Kip Ludwig

Brief explanation

- The patent application is about real-time sensing of cerebrospinal fluid (CSF) clearance.

- This sensing can help optimize electrode target engagement of peripheral cranial nerves and detect changes in the connected nerve truck and brain. - The CSF clearance data can be used in "open loop" systems to inform operator-controlled programming or sent directly to the stimulator for programming adjustments in a "closed loop" manner. - The innovation aims to improve the effectiveness and precision of electrode targeting and programming in cranial nerve stimulation.

Abstract

Real-time sensing of cerebrospinal fluid (CSF) clearance can be used to optimize electrode target engagement of the peripheral cranial nerves and detect associated changes within the connected nerve truck and brain. This CSF clearance data may be used in “open loop” systems to inform operator-controlled programming or sent directly to the stimulator itself to titrate programming “closed loop” on the device.

Non-Cavitational Mechanical Pulsed Ultrasound Therapy (18200869)

Main Inventor

John-Paul Yu

Brief explanation

The patent application describes a method of using short ultrasound pulses to apply mechanical forces to tissue without causing cavitation or cellular damage.

• Short ultrasound pulses are delivered at intermediate intensity to the target tissue.
• The pulses generate acoustic radiation forces in the tissue without causing cavitation or cellular fractionization.
• The invention optimizes the interaction between the pulses and radiation forces to apply mechanical forces to tissue.
• This method generates a broad spectrum of desired and varied bioeffects in the tissue.

Abstract

Short ultrasound pulses or bursts, delivered at intermediate intensity to the target tissue transmits acoustic radiation forces into the targeted tissue without generating acoustic cavitation and without cellular fractionization. Thus, the present invention exploits the mechanical effects of high-intensity pressure fields only, without cavitation, by optimizing the interaction between acoustic pulses and radiation forces to apply mechanical forces to tissue to generate a broad spectrum of desired and varied bioeffects.

Mechanical Pulsed Ultrasound Therapy for Modulating Neural Tissue Microenvironments (18200837)

Main Inventor

John-Paul Yu

Brief explanation

- The patent application describes a method using short ultrasound pulses to target brain tissue.

- The ultrasound pulses are delivered at intermediate intensity to avoid generating acoustic cavitation and damaging cells. - The invention focuses on utilizing the mechanical effects of high-intensity pressure fields without cavitation. - The goal is to apply a negative pressure to the brain tissue, degrade the perineuronal nets, and open the blood-brain barrier. - The innovation aims to improve the delivery of treatments or substances to the brain by safely manipulating brain tissue using ultrasound technology.

Abstract

Short ultrasound pulses or bursts, delivered at intermediate intensity to the target brain tissue transmits acoustic radiation forces into the targeted brain tissue without generating acoustic cavitation and without cellular fractionization. Thus, the present invention exploits the mechanical effects of high-intensity pressure fields only, without cavitation, by optimizing the interaction between acoustic pulses and radiation forces to apply a negative pressure to the brain tissue and degrading the perineuronal nets in the brain tissue and opening the blood-brain barrier.

Device And Method For Controlling And Configuring The Spacial And Temportal Evolution Of A Gradient In A MicroFluidic Environment (17752302)

Main Inventor

David J. Beebe

Brief explanation

The abstract describes a microfluidic platform that can control and configure the evolution of a gradient.

• The platform includes a plate with a chamber for holding cells or drug/reagent particles within a polymerized material.
• The platform also has multiple wells that can receive different types of media to create gradients in the polymerized material.
• The wells have two parts, one that connects to the outer surface of the plate and one that connects to the chamber.
• The cross-sectional areas of the wells are different, with the first part being larger than the second part.
• This design creates pinning valves in the second part of the wells, which help maintain the polymerized material in place.
• Overall, this microfluidic platform allows for precise control over the formation and configuration of gradients in the polymerized material.

Abstract

A microfluidic platform is provided for controlling and configuring the evolution of a gradient. The microfluidic platform includes a plate having an outer surface and defining a chamber therein for receiving cells and/or drug/reagent particles of interest captured within a polymerized material. A plurality of wells are adapted for receiving a one or more types of desired media to form gradients in the polymerized material. The plurality of wells have first portions communicating with the outer surface of the plate and second portions communicating with the chamber. The first and second portions of the plurality of wells having corresponding widths and cross-sectional areas, and each of the plurality of wells is spaced from an adjacent well of the plurality of wells by a distance. The cross-sectional areas of the first portions of the plurality of wells are greater than the cross-sectional areas of the second portions of the plurality of wells such that the second portions of the plurality of wells form pinning valves to maintain the material to be polymer.

METHOD OF CREATING HUMAN PLURIPOTENT STEM CELL DERIVED BRAIN PERICYTE-LIKE CELLS (18302630)

Main Inventor

Eric V. Shusta

Brief explanation

- The patent application describes a population of brain pericyte-like cells that are derived from human pluripotent stem cells (hPSCs).

- These cells express markers typically found in pericytes, which are cells that play a role in maintaining the blood-brain barrier and regulating blood flow in the brain. - However, these pericyte-like cells do not express a specific marker called ACTA2. - The invention provides a method for generating these pericyte-like cells from hPSCs, which could have potential applications in studying brain development and diseases, as well as in drug discovery and regenerative medicine.

Abstract

A population of brain pericyte-like cells, wherein the cells express pericyte markers but do not express ACTA2 and wherein the cells are generated from hPSCs, is disclosed herein.

Methods and Culture Substrates for Controlled Induction of Biomimetic Neural Tissues Comprising Singular Rosette Structures (18448674)

Main Inventor

Randolph Scott Ashton

Brief explanation

- The patent application describes methods, compositions, and kits for directing the differentiation of human pluripotent stem cells, neuromesodermal progenitors, and neural stem cells into biomimetic neural tissues.

- The goal is to create neural tissues that resemble the developing human neural tube, specifically focusing on the formation of rosette structures. - The patent application also mentions the creation of engineered neural tissue preparations that contain biomimetic neural tissues with regional neural progenitor phenotypes.

Abstract

Described herein are methods, compositions, and kits for directed differentiation of human pluripotent stem cells, neuromesodermal progenitors, and neural stem cells into biomimetic neural tissues comprising one or more rosette structures. Preferably, the methods provided herein direct differentiation of human pluripotent stem cells, neuromesodermal progenitors, and neural stem cells into biomimetic neural tissues comprising a singular neural rosette structure that is comparable to at least a portion of the developing human neural tube. Also described are engineered neural tissue preparations comprising biomimetic neural tissues comprising a singular rosette structure having regional neural progenitor phenotypes.

METHODS OF GENERATING PHENOCOPY SIGNATURES AND USES THEREOF (18326364)

Main Inventor

Shuang Zhao

Brief explanation

The patent application describes methods of generating phenocopy signatures and their various uses. Phenocopy signatures are gene expression patterns that can predict the presence of mutations in cells.

• Methods of generating phenocopy signatures:

 - Determine gene expression signatures that can predict mutations in training cells.

• Uses of phenocopy signatures:

 - Identify cells that exhibit phenocopy signatures.
 - Identify subjects with cells that exhibit phenocopy signatures.
 - Predict cells sensitive to treatment with drugs using phenocopy signatures.
 - Treat cells with phenocopy signatures predicted to be sensitive to drugs.
 - Predict subjects sensitive to treatment with drugs using phenocopy signatures.
 - Treat subjects with phenocopy signatures predicted to be sensitive to drugs.

Abstract

Methods of generating phenocopy signatures and uses thereof. The methods of generating phenocopy signatures can include determining gene expression signatures that predict the presence of mutations in training cells. Uses of the phenocopy signatures include identifying cells exhibiting the phenocopy signatures, identifying subjects comprising cells that exhibit the phenocopy signatures, methods of using the phenocopy signatures to predict cells sensitive to treatment with drugs, methods of treating cells with phenocopy signatures predicted to be sensitive to treatment with drugs, methods of using phenocopy signatures to predict subjects sensitive to treatment with drugs, and methods of treating subjects with phenocopy signatures predicted to be sensitive to treatment with drugs.