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Patent Digest: Summer 2020

Innovations in genome and tissue engineering, DNA synthesis and amplification, thrombosis research and more

To realize its overarching goal to invent and commercialize disruptive solutions for healthcare, energy, architecture, robotics, and manufacturing, the Wyss Institute is creating a patent portfolio in relevant areas that are or can become an essential basis for specific business development and commercialization efforts. To learn more about these innovations, contact our Business Development Team.

This Wyss Institute’s U.S. patents issued between July and September 2020 are as follows:

Patent Digest: Summer 2020
Multi-segment reinforced actuators and applications. Credit: Harvard University

Multi-segment reinforced actuators and applications

US Patent 10,788,058 (September 29, 2020)

Kevin Galloway, Conor Walsh, Donal Holland, Panagiotis Polygerinos, Tyler Clites, Paxton Maeder-York, Ryan Neff, Emily Marie Boggs, and Zivthan Dubrovsky

Abstract: A multi-segment reinforced actuator includes (a) a soft actuator body that defines a chamber and (b) a plurality of distinct reinforcement structures on or in respective segments of the soft actuator body. First and second reinforcement structures are respectively configured to produce a first and second actuation motions, respectively, in first and second segments of the soft actuator body when fluid flows into or out of the chamber. The actuation motions are selected bending, extending, expansion, contraction, twisting, and combinations thereof; and the first actuation motion differs from the second actuation motion. The actuator can be used, e.g., to facilitate bending of the thumb with corresponding bending, extending, expansion, contraction, and twisting actuation motions.

Large gene excision and insertion

US Patent 10,787,684 (September 29, 2020)

Susan M. Byrne and George M. Church

Abstract: Methods of simultaneously excising large nucleic acid sequences from a target nucleic acid and inserting large foreign nucleic sequences into the target nucleic acid sequence using DNA binding protein nucleases are described.

Method of making polynucleotides using closed-loop verification

US Patent 10,774,366 (September 15, 2020)

George M. Church, Kettner John Frederick Griswold, Jr.

Abstract: A method for making a polynucleotide is provided including (a) delivering one or more reaction reagents including an error prone or template independent DNA polymerase, cations and a selected nucleotide to a reaction site including an initiator sequence having a terminal nucleotide for a time period and under conditions capable of covalently adding one or more of the selected nucleotide to the terminal nucleotide at the 3′ end of the initiator such that the selected nucleotide becomes a terminal nucleotide, and (b) determining whether the selected nucleotide has been added to the terminal nucleotide, wherein if the selected nucleotide has not been added to the terminal nucleotide, then repeating step (a) until the selected nucleotide has been added, and (c) repeating steps (a) and (b) until the polynucleotide is formed.

RNA-guided transcriptional regulation

US Patent 10,767,194 (September 8, 2020)

George M. Church, Prashant G. Mali, and Kevin M. Esvelt

Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid. 

Patent Digest: Summer 2020
Compositions and methods for enrichment of cells. Credit: Harvard University

Compositions and methods for enrichment of cells

US Patent 10,758,573 (September 1, 2020)

Pascal Joly, Georg N. Duda, Thomas Schaus, Anke Dienelt, Andrea Sass, David J. Mooney

Abstract: The present invention is directed to a device for enriching cells with a cell surface marker, comprising an aptamer suitable for specifically binding the cell surface marker, and beads coupled thereto, wherein the aptamer is coupled to the beads in a manner that allows for release of cells expressing the cell surface marker, in the absence of a chemical agent, and production of a cell population enriched for cells expressing the cell surface marker, substantially free of beads and aptamer. Kits comprising the device or components thereof, and methods of cell enrichment, are also provided. In exemplary embodiments, the device contains an aptamer that specifically binds CD31.

Enhanced electrochemical detection using nanoparticles and precipitation

US Patent 10,753,940 (August 25, 2020)

Donald E. Ingber, Olivier Y. F. Henry, Michael Super

Abstract: The invention described herein relates generally to methods, sensors, devices and kits for electrochemical detection of a target analyte in a sample. In certain aspects, the methods, sensors, devices and kits described herein can be used to detect low concentrations of at least one target analyte using small sample volumes. In some embodiments, methods, sensors and kits for detecting a microbe, microbe fragment or released endotoxin in a test sample, including bodily fluids such as blood and tissues of a subject, food, water, and environmental surfaces, are also provided herein.

Patent Digest: Summer 2020
Enhanced electrochemical detection using nanoparticles and precipitation. Credit: Harvard University

Devices comprising muscle thin films and uses thereof in high throughput assays for determining contractile functionus

US Patent 10,753,925  (August 25, 2020)

Kevin Kit Parker, Adam W. Feinberg, Patrick W. Alford, Anna Grosberg, Mark Daniel Brigham, and Josue A. Goss

Abstract: The present invention provides high throughput assays for identifying compounds that modulate a contractile function, as well as devices suitable for use in these assays.

Precise microbiota engineering at the cellular level

US Patent 10,752,906 (August 25, 2020)

Kevin M. Esvelt, Stephanie Yaung

Abstract: Stably immunized cells and methods of making stably immunized cells are provided. Methods of altering the microbiota of an ecological environment are provided. Methods of modifying target chromosomes are provided. Methods of delivering genetic material to target cells are provided.

Specific nucleic acid amplification with compounded selectivityus

Patent 10,745,746 (August 18, 2020)

Xi Chen, David Yu Zhang, Peng Yin

Abstract: The present disclosure provides, in various aspects and embodiments, methods and compositions for selectively amplifying a rare target nucleic acid and/or suppressing amplification of non-target nucleic acids with sequences similar to the rare target nucleic acid. The methods and composition are useful, for example, for detecting rare alleles among a population of wild-type alleles.

Patent Digest: Summer 2020
Methods, systems, and compositions for determining blood clot formation, and uses thereof. Credit: Harvard University

Methods, systems, and compositions for determining blood clot formation, and uses thereof

US Patent 10,732,172 (August 4, 2020)

Donald E. Ingber, Abhishek Jain, Andries D. van der Meer, Alan David Michelson, Andrew L. Frelinger, III, Riccardo Barrile

Abstract: A method is directed to determining a thrombosis function and includes flowing a fluid sample over a surface having a fixed endothelial cell monolayer. The method further includes stimulating the fixed endothelial cell monolayer to induce formulation of a clot, the clot being formed via interaction between the fixed endothelial cell monolayer and the fluid sample. In response to the clot formation, the method further includes determining a thrombosis function associated with the fluid sample and the fixed endothelial cell monolayer.

Assays for antimicrobial activity and applications thereof

US Patent 10,718,766 (July 21, 2020)

Mark J. Cartwright, Nazita Gamini, Donald E. Ingber, Martin Rottman, Michael Super, Julie A. Tomolonis, Karen A. Sinclair

Abstract: The disclosure provides methods, compositions, and kits for enhanced detection of microbes in samples and monitoring of antimicrobial activity in a subject.

Manufacturing soft devices out of sheet materials

US Patent 10,718,358 (July 21, 2020)

Kevin C. Galloway

Abstract: A soft composite actuator is described, including a first elastomeric layer; a strain limiting layer; and a first radially constraining layer, wherein the first elastomeric layer is disposed between the first radially constraining layer and the strain limiting layer; and the elastomeric layer, the strain limiting layer, and the radially constraining layer are bonded together to form at least one bladder for holding pressurized fluid. Methods of using and making of the soft composite actuator are described.

RNA-guided human genome engineering

US Patent 10,717,990 (July 21, 2020)

Prashant G. Mali, George M. Church, and Luhan Yang

Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Patent Digest: Summer 2020
Tubular tissue construct and a method of printing. Credit: Harvard University

Tubular tissue construct and a method of printing

US Patent 10,702,630 (July 7, 2020)

Jennifer A. Lewis, Kimberly A. Homan, David B. Kolesky, Ryan L. Truby, and Mark A. Skylar-Scott

Abstract: A 3D printed tubular construct, such as a nephron, with or without embedded vasculature as well as methods of printing tubular tissue constructs are described.

Methods and compositions for protein identification

US Patent 10,697,974 (June 30, 2020)

Sungwook Woo and Peng Yin

Abstract: Provided herein, in some embodiments, are methods and compositions for protein identification.

Scaffolds for cell collection or elimination

US Patent 10,695,468 (June 30, 2020)

David J. Mooney and Omar Abdel-Rahman Ali

Abstract: A device that includes a scaffold composition and a bioactive composition with the bioactive composition being incorporated therein or thereon, or diffusing from the scaffold composition such that the scaffold composition and/or a bioactive composition captures and eliminates undesirable cells from the body a mammalian subject. The devices mediate active recruitment, sequestration, and removal or elimination of undesirable cells from their host.

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