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November 2nd, 2017

October 2017 patents

Innovations in artificial skin, soft actuators, CRISPR enzymes, nanoelectronic scaffolds, antimicrobial assays, machine learning and more

Harvard faculty Andy Myers, George Church, Lee Rubin, Amy Wagers, Jeff Lichtman, Charlie Lieber, David Weitz, Matthew Shair, Roy Gordon, Timothy Mitchison, George Whitesides, Don Ingber, Adam Cohen, David Cox, Ken Nakayama, Eric Mazur, Peng Yin, Rob Wood, Daniel Branton, and John Rinn are among the inventors issued U.S. patents in October 2017.

The innovations recognized are as follows:

Trioxacarcins, trioxacarcin-antibody conjugates, and uses thereof
U.S. Patent 9,775,915 (October 3, 2017)

Andrew G. Myers, Daniel J. Smaltz, and Andreas Schumacher

Abstract: Provided herein are trioxacarcin-antibody drug conjugates of Formula (A): and pharmaceutically acceptable salts thereof, comprising at least one instance of the group -L1-(A-L2)a-B attached thereto, wherein a is an integer between 1 and 10, inclusive, L1 is absent or is a linking group, A is a moiety formed from the reaction of two complimentary groups (X and Y), L2 is absent or is another linking group, and B is an antibody or antibody fragment. Also provided are methods of preparing these antibody-drug conjugates, pharmaceutically acceptable compositions thereof, and methods of their use and treatment. Further provided are precursors to the trioxacarcin-antibody drug conjugates, novel trioxacarcins without an antibody conjugated thereto, pharmaceutical compositions thereof, and methods of their use and treatment.

Structure A

Mutants of Cre recombinase
U.S. Patent 9,777,262 (October 3, 2017)

Nikolai A. Eroshenko and George M. Church

Abstract: The present invention relates to mutants of Cre recombinase.

Methods of increasing satellite cell proliferation with kinase inhibitors
U.S. Patent 9,782,417 (October 10, 2017)

Lee L. Rubin, Amanda Gee, and Amy J. Wagers

Abstract: The invention provides methods for inducing, enhancing or increasing satellite cell proliferation, and an assay for screening for a candidate compound for inducing, enhancing or increasing satellite cell proliferation. Also provided are methods for repairing or regenerating a damaged muscle tissue of a subject.

High density membrane protein membranes
U.S. Patent 9,783,678 (October 10, 2017)

Manish Kumar and Thomas Walz

Abstract: Embodiments of the invention provide methods for preparing high density membrane protein membranes by slow, controlled removal of detergent from mixtures of detergent, block copolymers and membrane protein mixtures. Membranes created by this method are also provided. The structure of these membranes may be varied by varying the amount of membrane protein.

Methods, apparatuses and systems for collection of tissue sections
U.S. Patent 9,784,648 (October 10, 2017)

Kenneth Jeffrey Hayworth, Richard Schalek, Juan Carlos Tapia, Narayanan Kasthuri, and Jeff Lichtman

Abstract: Methods, apparatuses and systems for facilitating automated or semi-automated collection of tissue samples cut by a microtome. In one example, a collection apparatus may be moved back and forth between respective positions at which the collection apparatus is operatively coupled to a microtome so as to collect cut tissue samples, or routine access to the microtome is provided. Relatively easy movement and positioning of the collection apparatus is facilitated, while at the same time ensuring structural stability and appropriate alignment and/or isolation between the collection apparatus and the microtome. A fluid reservoir receives samples cut by the microtome, and the collection apparatus may collect samples via a conveyor-like substrate disposed near/in the reservoir. A linear movement of the substrate may be controlled based on a cutting rate of the microtome, and the fluid level in the reservoir may be automatically maintained to facilitate effective sample collection.

Dynamic decoupling in solid state spin ensembles
U.S. Patent 9,784,804 (October 10, 2017)

Ronald Walsworth and Linh My Pham

Abstract: Long spin coherence lifetimes are realized for ensembles of electronic spin impurities in solid state spin systems, for example NV color centers in diamond, by using spin-control RF pulse sequences to provide dynamic decoupling of the ensembles of spin impurities from environmental sources of decoherence such as dipolar and hyperfine interactions with proximal spin and other paramagnetic impurities in diamond. In this way, the measurement sensitivity of the coherent evolution of ensembles of solid state spin impurities are increased. Using the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence, the spin coherence lifetimes of NV ensembles can be extended to more than 2 ms in room temperature diamond, and sensitivity of magnetometry that uses NV ensembles can be increased.

Methods and systems for scaffolds comprising nanoelectronic components
U.S. Patent 9,786,850 (October 10, 2017)

Charles M. Lieber, Bozhi Tian, and Jia Liu

Abstract: The present invention generally relates to nanoscale wires and tissue engineering. Systems and methods are provided in various embodiments for preparing cell scaffolds that can be used for growing cells or tissues, where the cell scaffolds comprise nanoscale wires. In some cases, the nanoscale wires can be connected to electronic circuits extending externally of the cell scaffold. Such cell scaffolds can be used to grow cells or tissues which can be determined and/or controlled at very high resolutions, due to the presence of the nanoscale wires, and such cell scaffolds will find use in a wide variety of novel applications, including applications in tissue engineering, prosthetics, pacemakers, implants, or the like. This approach thus allows for the creation of fundamentally new types of functionalized cells and tissues, due to the high degree of electronic control offered by the nanoscale wires and electronic circuits.

Methods of introducing a fluid into droplets
U.S. Patent 9,789,482 (October 17, 2017)

Darren Roy Link, David A. Weitz, Galder Cristobal-Azkarate, Zhengdong Cheng, and Keunho Ahn

Abstract: Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one aspect, the invention relates to systems and methods for making droplets of fluid surrounded by a liquid, using, for example, electric fields, mechanical alterations, the addition of an intervening fluid, etc. In another aspect, the invention relates to systems and methods for dividing a fluidic droplet into two droplets, for example, through charge and/or dipole interactions with an electric field. The invention also relates to systems and methods for fusing droplets, according to another aspect of the invention, for example, through charge and/or dipole interactions. Another aspect of the invention provides the ability to determine droplets, or a component thereof, for example, using fluorescence and/or other optical techniques (e.g., microscopy), or electric sensing techniques such as dielectric sensing.

OSW-1 analogs and conjugates, and uses thereof
U.S. Patent 9,790,253 (October 17, 2017)

Matthew D. Shair and Anthony William George Burgett

Abstract: Provided are a number of compounds structurally related to OSW-1, a natural compound that binds OSBPs. Also provided are pharmaceutical compositions comprising the OSW-1 analogs, as well as methods for use of these OSW-1 analogs, or pharmaceutically acceptable salts, enantiomers, or stereoisomers thereof in the treatment of atherosclerosis. Alzheimer's disease, and cancer, including p21-deficient cancer. Conjugates of OSW-1 analogs with monoclonal antibodies, including monoclonal antibodies targeted to cancer cells, are also provided. Also provided are pharmaceutical compositions comprising the conjugates, as well as methods for use of these conjugates, in the treatment of cancer, including p21-deficient cancer.

Vapor source using solutions of precursors in terpenes
U.S. Patent 9,790,378 (October 17, 2017)

Roy Gerald Gordon

Abstract: This disclosure relates to terpene solutions of metal precursors used for chemical vapor deposition, atomic layer deposition, spray pyrolysis or misted deposition. The terpenes do not supply impurities such as oxygen or halogens to the material being produced, nor do they etch or corrode them. In spray pyrolysis or misted deposition, small droplets provide uniform coating. Terpenes have high flash points and low flammability, reducing the risk of fires. Terpenes have low toxicity and are biodegradable. They are available in large amounts from renewable, natural plant sources, and are low in cost.

CRISPR enzymes and systems
U.S. Patent 9,790,490 (October 17, 2017)

Feng Zhang, Bernd Zetsche, Ian Slaymaker, Jonathan Gootenberg, and Omar O. Abudayyeh

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Methods and compositions for labeling nucleic acids
U.S. Patent 9,790,541 (October 17, 2017)

Adrian Salic and Timothy J. Mitchison

Abstract: The present invention relates to methods for the labeling of nucleic acid polymers in vitro and in vivo. In particular, the methods include a [3+2] cycloaddition between a nucleotide analogue incorporated into a nucleic acid polymer and a reagent attached to a label. Such methods do not require fixation and denaturation and therefore can be applied to the labeling of nucleic acid polymers in living cells and in organisms. Also provided are methods for measuring cellular proliferation. In these methods, the amount of label incorporated into the DNA is measured as an indication of cellular proliferation. The methods of the invention can be used in a wide variety of applications including clinical diagnosis of diseases and disorders in which cellular proliferation is involved, toxicity assays, and as a tool for the study of chromosomes' ultrastructures.

Soft actuators and soft actuating devices
U.S. Patent 9,790,968 (October 17, 2017)

Dian Yang and George M. Whitesides

Abstract: A soft buckling linear actuator is described, including: a plurality of substantially parallel bucklable, elastic structural components each having its longest dimension along a first axis; and a plurality of secondary structural components each disposed between and bridging two adjacent bucklable, elastic structural components; wherein every two adjacent bucklable, elastic structural components and the secondary structural components in-between define a layer comprising a plurality of cells each capable of being connected with a fluid inflation or deflation source; the secondary structural components from two adjacent layers are not aligned along a second axis perpendicular to the first axis; and the secondary structural components are configured not to buckle, the bucklable, elastic structural components are configured to buckle along the second axis to generate a linear force, upon the inflation or deflation of the cells. Methods of actuation using the same are also described.

Assays for antimicrobial activity and applications thereof
U.S. Patent 9,791,440 (October 17, 2017)

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

Optogenetic probes for measuring membrane potential
U.S. Patent 9,791,455 (October 17, 2017)

Adam E. Cohen, Joel Kralj, and Adam D. Douglass

Abstract: The invention provides methods, cells and constructs for optical measurement of membrane potential. These methods can be used in cells that are not accessible to presently available methods using electrodes. The methods can be directed to, for example, high-throughput drug screening assays to determine agents that can affect membrane potential of a target cell.

Systems and methods for machine learning enhanced by human measurements
U.S. Patent 9,792,532 (October 17, 2017)

David Cox, Walter Scheirer, Samuel Anthony, and Ken Nakayama

Abstract: In various embodiments, training objects are classified by human annotators, psychometric data characterizing the annotation of the training objects is acquired, a human-weighted loss function based at least in part on the classification data and the psychometric data is computationally derived, and one or more features of a query object are computationally classified based at least in part on the human-weighted loss function.

Silicon-based visible and near-infrared optoelectric devices
U.S. Patent 9,793,425 (October 17, 2017)

Eric Mazur and James Edward Carey

Abstract: In one aspect, the present invention provides a silicon photodetector having a surface layer that is doped with sulfur inclusions with an average concentration in a range of about 0.5 atom percent to about 1.5 atom percent. The surface layer forms a diode junction with an underlying portion of the substrate. A plurality of electrical contacts allow application of a reverse bias voltage to the junction in order to facilitate generation of an electrical signal, e.g., a photocurrent, in response to irradiation of the surface layer. The photodetector exhibits a responsivity greater than about 1 A/W for incident wavelengths in a range of about 250 nm to about 1050 nm, and a responsivity greater than about 0.1 A/W for longer wavelengths, e.g., up to about 3.5 microns.

Spatial sequestration of dynamic nucleic acid circuits
U.S. Patent 9,796,748 (October 24, 2017)

Thomas E. Schaus, David Yu Zhang, Wei Sun, and Peng Yin

Abstract: The invention provides systems and methods for spatial sequestration of elements in nucleic acid circuits.

Compositions and methods relating to nucleic acid nano- and micro-technology
U.S. Patent 9,796,749 (October 24, 2017)

Peng Yin and Diming Wei

Abstract: The invention provides nucleic acid structures of controlled size and shape, comprised of a plurality of oligonucleotides, and methods for their synthesis. The structures are formed, at least in part, by the self-assembly of single stranded oligonucleotides. The location of each oligonucleotide in the resultant structure is known. Accordingly, the structures may be modified with specificity.

Systems and methods for nucleic acid sequencing
U.S. Patent 9,797,010 (October 24, 2017)

David A. Weitz, Jeremy Agresti, Michael P. Weiner, Adam R. Abate, and Tony Hung

Abstract: The present invention relates to systems and methods for sequencing nucleic acids, including sequencing nucleic acids in fluidic droplets. In one set of embodiments, the method employs sequencing by hybridization using droplets such as microfluidic droplets. In some embodiments, droplets are formed which include a target nucleic acid, a nucleic acid probe, and at least one identification element, such as a fluorescent particle. The nucleic acid probes that hybridize to the target nucleic acid are determined, in some instances, by determining the at least one identification element. The nucleic acid probes that hybridize to the target nucleic acid may be used to determine the sequence of the target nucleic acid. In certain instances, the microfluidic droplets are provided with reagents that modify the nucleic acid probe. In some cases, a droplet, such as those described above, is deformed such that the components of the droplets individually pass a target area.

Apparatus, system, and method for providing fabric-elastomer composites as pneumatic actuators
U.S. Patent 9,797,415 (October 24, 2017)

Ramses V. Martinez and George M. Whitesides

Abstract: Soft pneumatic actuators based on composites consisting of elastomers with embedded sheet or fiber structures (e.g., paper or fabric) that are flexible but not extensible are described. On pneumatic inflation, these actuators move anisotropically, based on the motions accessible by their composite structures. They are inexpensive, simple to fabricate, light in weight, and easy to actuate. This class of structure is versatile: the same principles of design lead to actuators that respond to pressurization with a wide range of motions (bending, extension, contraction, twisting, and others). Paper, when used to introduce anisotropy into elastomers, can be readily folded into three-dimensional structures following the principles of origami; these folded structures increase the stiffness and anisotropy of the elastomeric actuators, while keeping them light in weight.

Multi-axis force sensing soft artificial skin
U.S. Patent 9,797,791 (October 24, 2017)

Daniel Vogt, Yong-Lae Park, and Robert J. Wood

Abstract: A sensor including a layer having viscoelastic properties, the layer comprising a void, the void filled with a fluid; and optionally, a more rigid sensing element embedded within the layer. When a force is applied to a surface of the sensor, the shape of the void changes, causing the electrical resistance of the fluid in the void to change. When included, the more rigid sensing element can bear upon the void to cause the electrical resistance of the fluid in the void to change. A direction and intensity of the force can be determined by measuring the change of the electrical resistance of different voids positioned about the sensing element. The layer can be an elastomer, preferably silicone rubber. The fluid can be a conductive liquid, preferably Eutectic Gallium Indium. The sensing element can be plastic and can have a "Joystick" shape. The voids can take the form of channels or microchannels having a predefined pattern and/or shape.

Graphene supported artificial membranes and uses thereof
U.S. Patent 9,797,863 (October 24, 2017)

Slaven Garaj and Daniel Branton

Abstract: The invention features the use of graphene, a one atom thick planar sheet of bonded carbon atoms, in the formation of artificial lipid membranes. The invention also features the use of these membranes to detect the properties of polymers (e.g., the sequence of a nucleic acid) and identify transmembrane protein-interacting compounds.

High-throughput methodology for identifying RNA-protein interactions transcriptome-wide
U.S. Patent 9,797,887 (October 24, 2017)

Brian D. Gregory, John Rinn, Fan Li, Cole Trapnell, and Loyal A. Goff

Abstract: Methods of identifying RNA-protein interaction sites are provided. Systems for identifying RNA-protein interaction sites are provided. Systems for identifying secondary structures are provided. Methods of identifying secondary structures are provided. Methods of identifying RNA-binding proteins are provided.

Nuclear singlet states as a contrast mechanism for NMR spectroscopy
U.S. Patent 9,804,239 (October 31, 2017)

Ronald L. Walsworth, Stephen J. Devience, and Matthew S. Rosen

Abstract: Methods and systems for Nuclear Magnetic Resonance (NMR) spectra of complex chemical mixtures are described. The methods and systems allow undesired NMR spectral background to be removed or suppressed and target spectral peaks to be uncovered, for example, when strong background signals overlap weaker peaks. In some embodiments, the methods and systems employ a quantum filter utilizing nuclear spin singlet states.

Tags: issued patents

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