August 2017 patents
Pneumatic insect robots, integrated organs on chips, HDAC inhibitors, gait analysis, delivery of Cas9, promotion of neuronal outgrowth, and more
Harvard faculty William Shih, George Whitesides, Kit Parker, Ronald Walsworth, George Church, Ralph Mazitschek, Theodore Betley, Junying Yuan, Don Ingber, Vahid Tarokh, David Mooney, Quan Lu, David Liu, Randy Buckner, and John Flanagan are among the inventors issued U.S. patents during August 2017.
The innovations recognized are as follows:
Lipid-coated nucleic acid nanostructures of defined shape
U.S. Patent 9,717,685 (August 1, 2017)
William M. Shih and Steven Perrault
Abstract: The invention provides nanoparticles containing a nucleic acid nanostructure, of defined shape and size, linked to a hydrophobic moiety and coated by lipids, compositions comprising the nanoparticles, and methods of producing and methods of using the nanoparticles.
Pneumatic insect robots
U.S. Patent 9,719,534 (August 1, 2017)
Yanina Shevchenko, George M. Whitesides, Adam Stokes, and Gabrielle Compton
Abstract: A modular pneumatic robotic actuator, including a first elongated hollow structure and a second elongated hollow structure connected to each other at a moveable joint; an inflatable bladder comprised of an elastomeric material disposed at the joint and immobilized between the first and second hollow structures, wherein the inflatable bladder inflates preferentially away from the joint; and a restraining membrane comprised of an elastomeric material disposed over the bladder and connecting the first and second hollow structures, wherein the restraining membrane is relaxed when the bladder is deflated.
Devices comprising muscle thin films and uses thereof in high throughput assays for determining contractile function
U.S. Patent 9,719,982 (August 1, 2017)
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.
Use of nuclear spin impurities to suppress electronic spin fluctuations and decoherence in composite solid-state spin systems
U.S. Patent 9,720,067 (August 1, 2017)
Ronald L. Walsworth, Nir Bar-Gill, Chinmay Belthangady, and Linh My Pham
Abstract: A solid state electronic spin system contains electronic spins disposed within a solid state lattice and coupled to an electronic spin bath and a nuclear spin bath, where the electronic spin bath composed of electronic spin impurities and the nuclear spin bath composed of nuclear spin impurities. The concentration of nuclear spin impurities in the nuclear spin bath is controlled to a value chosen so as to allow the nuclear spin impurities to effect a suppression of spin fluctuations and spin decoherence caused by the electronic spin bath. Sensing devices such as magnetic field detectors can exploit such a spin bath suppression effect, by applying optical radiation to the electronic spins for initialization and readout, and applying RF pulses to dynamically decouple the electronic spins from the electronic spin bath and the nuclear spin bath.
De novo design of allosteric proteins
U.S. Patent 9,721,061 (August 1, 2017)
Srivatsan Raman, Noah D. Taylor, and George M. Church
Abstract: Methods and compositions for making and isolating allosteric DNA binding proteins that bind to one or more allosteric effectors to induce a conformation change in the proteins are provided.
Histone deacetylase inhibitors
U.S. Patent 9,724,321 (August 8, 2017)
James Elliot Bradner and Ralph Mazitschek
Abstract: In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.
Synthesis of acyclic and cyclic amines using iron-catalyzed nitrene group transfer
U.S. Patent 9,724,682 (August 8, 2017)
Theodore Alexander Betley and Elisabeth Therese Hennessy
Abstract: The present invention provides novel synthetic methods for making acyclic secondary amines by reacting an azide with a compound bearing one or more C--H groups, catalyzed by a FeII-dipyrromethene complex. The acyclic secondary amines are thought to be formed through an intermolecular nitrene transfer. Also provided herein are methods of synthesizing protected (e.g., Boc- or Fmoc-protected) cyclic secondary amines (e.g., 5-, 6-, and 7-membered cyclic secondary amines) by reacting an azide that bears one or more C--H groups, catalyzed by a FeII-dipyrromethene complex. The protected cyclic secondary amines are thought to be formed through an intramolecular nitrene transfer and may be subsequently deprotected to yield cyclic secondary amines.
Substituted indoles and pyrroles as RIP kinase inhibitors
U.S. Patent 9,725,452 (August 8, 2017)
Junying Yuan, Alexei Degterev, and Gregory D. Cuny
Abstract: The present invention relates to heterocyclic compounds (e.g., compounds described by Formula (I)) and pharmaceutically acceptable salts thereof. The invention also features pharmaceutical compositions that include these compounds and their use in therapy for treating conditions in which necroptosis is likely to play a substantial role. The heterocyclic compounds described herein can also achieve improved activity and selectivity towards RIP1 and/or RIP3.
Integrated human organ-on-chip microphysiological systems
U.S. Patent 9,725,687 (August 8, 2017)
John P. Wikswo, Philip C. Samson, Frank Emmanuel Block III, Ronald S. Reiserer, Kevin Kit Parker, John A. McLean, Lisa Joy McCawley, Dmitry Markov, Daniel Levner, Donald E. Ingber, Geraldine A. Hamilton, Josue A. Goss, Robert Cunningham, David E. Cliffel, Jennifer Robin McKenzie, Anthony Bahinski, and Christopher David Hinojosa
Abstract: The invention provides integrated Organ-on-Chip microphysiological systems representations of living Organs and support structures for such microphysiological systems.
Traveling wave MRI in high BO field strengths
U.S. Patent 9,726,736 (August 8, 2017)
Abstract: In an MRI scanner, the transmission and reception of RF excitation and detected signal waves is accomplished using far field excitation instead of conventional near field excitation. By superimposing two counter-propagating waves from the same source in the MRI sample interference fringes are recorded in the sample in such a way that the relative phase between the two propagation wave vectors determines the periodicity of the maxima and minima in the interference fringe pattern. The complete fringe pattern, known as a spatial hologram, contains both the phase and amplitude information of the information-bearing wave. When exposed to a replica of the original reference wave, the fringe pattern acts as a diffraction grating, reproducing the information-bearing field propagating at the same relative phase.
Method and apparatus for using gait analysis to determine a health quality measure
U.S. Patent 9,727,698 (August 8, 2017)
Saeed S. Ghassemzadeh, Lusheng Ji, Robert Raymond Miller II, Manish Gupta, and Vahid Tarokh
Abstract: A method, computer-readable storage device and apparatus for calculating a health quality measure are disclosed. For example, a method receives characteristics of motion information, wherein the characteristics of motion information is based upon gait information, monitors the characteristics of motion information over a time period to determine a plurality of different modes of motion within the time period, and calculates the health quality measure based upon the plurality of different modes of motion.
Laser-actuated therapeutic nanoparticles
U.S. Patent 9,731,012 (August 15, 2017)
Praveen Arany and David J. Mooney
Abstract: The invention provides compositions and methods for laser actuated drug delivery. Compositions comprise serum albumin based particles conjugated with therapeutic agents which cab become bioavailable upon actuation of the particles by light, e.g. low power laser.
ARRDC1-mediated microvesicles (ARMMs) and uses thereof
U.S. Patent 9,737,480 (August 22, 2017)
Quan Lu, Joseph F. Nabhan, and Stanley N. Cohen
Abstract: The invention provide isolated arrestin domain-containing protein 1 (ARRDC1)-mediated micro vesicles (ARMMs). Methods for generating and for isolating ARMMs are also provided herein. ARMMs can be used to deliver agents, for example, nucleic acids (e.g., siRNAs, microRNAs, lincRNAs), proteins (e.g., transcription factors, chromatin modulators, kinases, phosphorylases, or recombinases), or small molecules to target cells in vitro and in vivo, and methods for such ARMM-mediated delivery are provided herein. Diagnostic and therapeutic methods using ARMMs are also described herein.
Use of cationic lipids to deliver CAS9
U.S. Patent 9,737,604 (August 22, 2017)
David R. Liu, John Anthony Zuris, and David B. Thompson
Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases. Compositions, methods, strategies, and systems for the delivery of functional effector proteins into cells is useful for therapeutic and research purposes, including, but not limited to, the targeted manipulation of a gene associated with disease, the modulation of the expression level of a gene associated with disease, and the programming of cell fate.
Methods for the fabrication of polymeric fibers
U.S. Patent 9,738,046 (August 22, 2017)
Kevin Kit Parker, Mohammad Reza Badrossamay, and Josue Adrian Goss
Abstract: In accordance with an exemplary embodiment, a method is provided for forming a micron, submicron and/or nanometer dimension polymeric fiber. The method includes providing a stationary deposit of a polymer. The method also includes contacting a surface of the polymer to impart sufficient force in order to decouple a portion of the polymer from the contact and to fling the portion of the polymer away from the contact and from the deposit of the polymer, thereby forming a micron, submicron and/or nanometer dimension polymeric fiber.
Alpha/beta-polypeptide analogs of glucagon-like peptide-1
U.S. Patent 9,738,697 (August 22, 2017)
Samuel H. Gellman, Lisa M. Johnson, Alan Attie, Mark P. Keller, and Alan Saghatelian
Abstract: Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one α-amino acid found in the native GLP-1 is replaced with a β-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.
Magnetic resonance imaging method and apparatus with interleaved resting state functional magnetic resonance imaging sequences and morphological magnetic resonance imaging sequences
U.S. Patent 9,739,856 (August 22, 2017)
Randy Buckner, Bjoern Heismann, and Arne Hengerer
Abstract: In a method and apparatus for acquiring magnetic resonance data, a resting state functional magnetic resonance imaging sequence is executed in alternation with a morphological data acquisition sequence. The alternating sequences are executed with no time interruptions therebetween, with at least one repetition of the alternating sequences. The resting state functional magnetic resonance imaging sequence can be a BOLD-EPI sequence, and the morphological imaging sequence can be an MPRAGE sequence.
Methods of promoting neuronal outgrowth by gypican 2 that binds to receptor protein tyrosine phosphatase sigma
U.S. Patent 9,744,188 (August 29, 2017)
John G. Flanagan, Yingjie Shen, Edith Yvonne Jones, Alexadru Radu Aricescu, and Charlotte Hannah Coles
Abstract: Disclosed herein are methods of inducing neuronal outgrowth of a neuron. The methods comprise contacting the neuron with an agent that binds receptor protein tyrosine phosphatase σ (RPTPσ), to thereby induce neuronal outgrowth of the neuron. The agent may induces clustering of RPTPσ and/or inhibit binding of chondroitin sulfate proteoglycan (CSPG) to RPTPσ. Examples of suitable agents are heparan sulfate proteoglycan, heparan sulfate, heparan sulfate oligosaccharides, or heparin oligosaccharides. Additional agents are also disclosed. The neuron can be a CNS neuron or peripheral neuron. Also disclosed herein are methods of treating neuronal injury in a subject comprising, administering to the subject an agent that binds RPTPσ. Administration may be to a site of neuronal injury, to thereby induce neuronal outgrowth at the site of neuronal injury.