December 2017 patents
Innovations in filtration, drug delivery into cells, nucleic acid editing, compartmentalized chemistry, artificial skin, treatment of flavivirus infections, monolithic fabrication of structures, and more
Harvard faculty John Mekalanos, Rob Wood, George Church, David Weitz, David Liu, Conor Walsh, Radhika Nagpal, Chad Vecitis, Arlene Sharpe, David Sinclair, Daniel Finley, John Collier, David Clarke, George Whitesides, Joanna Aizenberg, and Marko Lončar are among the inventors issued U.S. patents in December 2017.
The innovations recognized are as follows:
Methods for displaying polypeptides and uses thereof
U.S Patent 9,833,503 (December 5, 2017)
John Mekalanos and Marek Basler
Abstract: Provided herein are methods and compositions for displaying a polypeptide on a tubular structure and uses of such displayed polypeptides in the production of antibodies or vaccines.
Monolithic fabrication of three-dimensional structures
U.S. Patent 9,833,978 (December 5, 2017)
Pratheev Sabaratnam Sreetharan, John Peter Whitney, and Robert J. Wood
Abstract: A multi-layer, super-planar structure can be formed from distinctly patterned layers. The layers in the structure can include at least one rigid layer and at least one flexible layer; the rigid layer includes a plurality of rigid segments, and the flexible layer can extend between the rigid segments to serve as a joint. The layers are then stacked and bonded at selected locations to form a laminate structure with inter-layer bonds, and the laminate structure is flexed at the flexible layer between rigid segments to produce an expanded three-dimensional structure, wherein the layers are joined at the selected bonding locations and separated at other locations.
Recombinant cells and organisms having persistent nonstandard amino acid dependence and methods of making them
U.S. Patent 9,834,775 (December 5, 2017)
George M. Church, Daniel J. Mandell, and Marc J. Lajoie
Abstract: Recombinant cells and recombinant organisms persistently expressing nonstandard amino acids (NSAAs) are provided. Methods of making recombinant cells and recombinant organisms dependent on persistently expressing NSAAs for survival are also provided. These methods may be used to make safe recombinant cells and recombinant organisms and/or to provide a selective pressure to maintain one or more reassigned codon functions in recombinant cells and recombinant organisms.
Compartmentalised combinatorial chemistry by microfluidic control
U.S. Patent 9,839,890 (December 12, 2017)
Andrew Griffiths, David Weitz, Darren Link, Keunho Ahn, and Jerome Bibette
Abstract: The invention describes a method for the synthesis of compounds comprising the steps of: (a) compartmentalising two or more sets of primary compounds into microcapsules; such that a proportion of the microcapsules contains two or more compounds; and (b) forming secondary compounds in the microcapsules by chemical reactions between primary compounds from different sets; wherein one or both of steps (a) and (b) is performed under microfluidic control; preferably electronic microfluidic control, The invention further allows for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, and which is co-compartmentalised into the microcapsules.
Droplet creation techniques
U.S. Patent 9,839,911 (December 12, 2017)
David A. Weitz and Adam R. Abate
Abstract: The present invention is generally related to systems and methods for producing droplets. The droplets may contain varying species, e.g., for use as a library. In some cases, at least one droplet is used to create a plurality of droplets, using techniques such as flow-focusing techniques. In one set of embodiments, a plurality of droplets, containing varying species, can be divided to form a collection of droplets containing the various species therein. A collection of droplets, according to certain embodiments, may contain various subpopulations of droplets that all contain the same species therein. Such a collection of droplets may be used as a library in some cases, or may be used for other purposes.
Methods for nucleic acid editing
U.S. Patent 9,840,699 (December 12, 2017)
David R. Liu and Alexis Christine Komor
Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing enzymes or enzyme domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing enzymes or domains, are provided.
Artificial skin and elastic strain sensor
U.S. Patent 9,841,331 (December 12, 2017)
Robert J. Wood, Yong-Lae Park, Carmel S. Majidi, Bor-rong Chen, Leia Stirling, Conor James Walsh, Radhika Nagpal, Diana Young, and Yigit Menguc
Abstract: An elastic strain sensor can be incorporated into an artificial skin that can sense flexing by the underlying support structure of the skin to detect and track motion of the support structure. The uni-directional elastic strain sensor can be formed by filling two or more channels in an elastic substrate material with a conductive liquid. At the ends of the channels, a loop port connects the channels to form a serpentine channel. The channels extend along the direction of strain and the loop portions have sufficiently large cross-sectional area in the direction transverse to the direction of strain that the sensor is unidirectional. The resistance is measured at the ends of the serpentine channel and can be used to determine the strain on the sensor. Additional channels can be added to increase the sensitivity of the sensor. The sensors can be stacked on top of each other to increase the sensitivity of the sensor. In other embodiments, two sensors oriented in different directions can be stacked on top of each other and bonded together to form a bidirectional sensor. A third sensor formed by in the shape of a spiral or concentric rings can be stacked on top and used to sense contact or pressure, forming a three dimensional sensor. The three dimensional sensor can be incorporated into an artificial skin to provide advanced sensing.
Polyethersulfone filtration membrane
U.S. Patent 9,844,756 (December 19, 2017)
Chad D. Vecitis and Jose Carlos Mierzwa
Abstract: Provided herein are filtration membranes, method of manufacturing said membranes and use of such membranes for the removal of substances from fluids or substances.
Single agent anti-PD-L1 and PD-L2 dual binding antibodies and methods of use
U.S. Patent 9,845,356 (December 19, 2017)
Gordon J. Freeman and Arlene H. Sharpe
Abstract: The present invention is based, in part, on the identification of novel antibodies that have binding affinity for both PD-L1 and PD-L2 and methods of using same. In one aspect, an isolated monoclonal antibody, or antigen-binding fragment thereof, which specifically binds both PD-L1 and PD-L2, is provided. In one embodiment, both PD-L1 and PD-L2 are human PD-L1 and human PD-L2.
Compositions and methods for enhancing bioenergetic status in female germ cells
U.S. Patent 9,845,482 (December 19, 2017)
Jonathan L. Tilly and David A. Sinclair
Abstract: Compositions and methods comprising bioenergetic agents for restoring the quality of aged oocytes, enhancing oogonial stem cells or improving derivatives thereof (e.g., cytoplasm or isolated mitochondria) for use in fertility-enhancing procedures, are described.
USP14 inhibitors for treating or preventing viral infections
U.S. Patent 9,849,135 (December 26, 2017)
Daniel J. Finley, Dilip Nag, and Laura D. Kramer
Abstract: Disclosed herein are methods of treating or preventing a viral infection resulting from infection by a flavivirus, comprising administering to a subject a small molecule inhibitor of USP14, represented by Formula (I) or a pharmaceutically acceptable salt, solvate, hydrate, prodrug, chemically-protected form, enantiomer or stereoisomer thereof, and pharmaceutical compositions comprising an effective amount of a compound of Formula (I) for use in the method.
Method for delivering agents into cells using bacterial toxins
U.S. Patent 9,850,475 (December 26, 2017)
R. John Collier and Bradley L. Pentelute
Abstract: The invention provides compositions and methods for delivering a bioactive moiety comprising at least one non-natural component into a cell cytosol of a eukaryotic cell. The bioactive moiety is linked to an A component of a bacterial toxin, a functional wild-type or modified fragment thereof, or an A component surrogate or mimetic. For delivery, the cell is contacted with the linked bioactive moiety and a corresponding B component of the bacterial toxin or a functional fragment thereof.
Assays and other reactions involving droplets
U.S. Patent 9,850,526 (December 26, 2017)
Jeremy Agresti, Liang-Yin Chu, David A. Weitz, Jin-Woong Kim, Amy Rowat, Morten Sommer, Gautam Dantas, and George Church
Abstract: The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer. After the PCR reaction, unbound DNA may be removed from the gel, e.g., via diffusion or washing. Thus, a gel particle having bound DNA may be formed in one embodiment of the invention.
Systems and methods for separating and recovering rare earths
U.S. Patent 9,850,555 (December 26, 2017)
William Daley Bonificio and David Clarke
Abstract: The present application is generally directed to separation and recovery of rare earths using biomass, liposomes, and/or other materials. In some embodiments, a composition comprising rare earths is exposed to biomass, where some of the rare earths are transferred to the biomass, e.g., via absorption. The composition may then be separated from the biomass. A solution may be exposed to the biomass thereby enriching the solution in one or more rare earths, relative to other rare earths in the biomass. The solution and the biomass may then be separated, and the rare earths recovered from the solution. In some cases, this process may be repeated with different solutions, which may result in different solutions enriched in various rare earths. Similar processes may be used to separate the rare earths from thorium and uranium. Liposomes may be used instead of and/or in addition to biomass.
Soft buckling actuators
U.S. Patent 9,850,922 (December 26, 2017)
Dian Yang and George M. Whitesides
Abstract: A soft actuator is described, including: a rotation center having a center of mass; a plurality of bucklable, elastic structural components each comprising a wall defining an axis along its longest dimension, the wall connected to the rotation center in a way that the axis is offset from the center of mass in a predetermined direction; and a plurality of cells each disposed between two adjacent bucklable, elastic structural components and configured for connection with a fluid inflation or deflation source; wherein upon the deflation of the cell, the bucklable, elastic structural components are configured to buckle in the predetermined direction. A soft actuating device including a plurality of the soft actuators and methods of actuation using the soft actuator or soft actuating device disclosed herein are also described.
Manipulation of fluids in three-dimensional porous photonic structures with patterned surface properties
U.S. Patent 9,851,310 (December 26, 2017)
Joanna Aizenberg, Ian Burgess, Lidiya Mishchenko, Benjamin Hatton, and Marko Lončar
Abstract: A three-dimensional porous photonic structure, whose internal pore surfaces can be provided with desired surface properties in a spatially selective manner with arbitrary patterns, and methods for making the same are described. When exposed to a fluid (e.g., via immersion or wicking), the fluid can selectively penetrate the regions of the structure with compatible surface properties. Broad applications, for example in security, encryption and document authentication, as well as in areas such as simple microfluidics and diagnostics, are anticipated.