January 2020 patents
Innovations in targeting and binding microbes, sequencing nucleic acids, creating sensitive artificial skin, modifying the optical properties of thin films, and more
Harvard faculty Daniel Kahne, Don Ingber, Rob Wood, Conor Walsh, Radhika Nagpal, Greg Verdine, Joanna Aizenberg, Eric Mazur, and Mike Aziz are among the inventors issued U.S. patents in January 2020.
The innovations recognized are as follows:
Modified lipopolysaccharide glycoform and method of use
U.S. Patent 10,525,126 (January 7, 2020)
Thomas J. Silhavy, Marcin Grabowicz, Daniel Kahne, Matthew Lebar, and Dorothee Andres
Abstract: The present disclosure generally relates to genetic engineering of bacteria. More particularly, the present disclosure describes genetic engineering of E. coli to create mutant O-antigen ligase, as well as novel lipopolysaccharide molecules resulting from that genetic engineering. Methods for using those novel molecules are also described.
Engineered microbe-targeting molecules and uses thereof
U.S. Patent 10,526,399 (January 7, 2020)
Donald E. Ingber, Michael Super, Jeffrey Charles Way, Mark J. Cartwright, Julia B. Berthet, Dinah R. Super, Martin Rottman, and Alexander L. Watters
Abstract: Described herein are engineered microbe-targeting or microbe-binding molecules, kits comprising the same and uses thereof. Some particular embodiments of the microbe-targeting or microbe-binding molecules comprise a carbohydrate recognition domain of mannose-binding lectin, or a fragment thereof, linked to a portion of a Fc region. In some embodiments, the microbe-targeting molecules or microbe-binding molecules can be conjugated to a substrate, e.g., a magnetic microbead, forming a microbe-targeting substrate (e.g., a microbe-targeting magnetic microbead). Such microbe-targeting molecules and/or substrates and the kits comprising the same can bind and/or capture of a microbe and/or microbial matter thereof, and can thus be used in various applications, e.g., diagnosis and/or treatment of an infection caused by microbes such as sepsis in a subject or any environmental surface. Microbe-targeting molecules and/or substrates can be regenerated after use by washing with a low pH buffer or buffer in which calcium is insoluble.
RNA-guided gene drives
U.S. Patent 10,526,618 (January 7, 2020)
Kevin M. Esvelt and Andrea L. Smidler
Abstract: RNA guided Cas9 gene drives and method for their use are disclosed.
Augmenting in situ nucleic acid sequencing of expanded biological samples with in vitro sequence information
U.S. Patent 10,526,649 (January 7, 2020)
Fei Chen, Shahar Alon, Andrew Payne, Asmamaw Wassie, Daniel Goodwin, Edward Stuart Boyden, Evan Daugharthy, and Jonathan Scheiman
Abstract: The invention provides in situ nucleic acid sequencing to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ sequencing of nucleic acids in a process referred to herein as "expansion sequencing" (ExSEQ).
Artificial skin and elastic strain sensor
U.S. Patent 10,527,507 (January 7, 2020)
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 unidirectional 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.
Ras inhibitory peptides and uses thereof
U.S. Patent 10,533,039 (January 14, 2020)
Gregory L. Verdine and John Hanney McGee
Abstract: The present invention provides peptides comprising a sequence of X−6X−5X−4X−3X−2X−1X1PX3X4PX6X7PGX10X11AX13X14X15X16LX18X19X20X21X22X23LX25X26 YLX29X30X31X32 (SEQ ID NO: 13) wherein the amino acids X−6, X−5, X−4, X−3, X−2, X−1, X1, X3, X4, X6, X7, X10, X11, X13, X14, X15, X16, X18, X19, X20, X21, X22, X25, X26, X29, X30, X31, and X32 are as defined herein. The present invention further provides pharmaceutical compositions comprising the peptides and methods of using the peptides for treating proliferative diseases such as cancer which are associated with Ras. Also provided are methods of screening a library of peptide dimers using a peptide dimer display technology.
Engineered opsonin for pathogen detection and treatment
U.S. Patent 10,538,562 (January 21, 2020)
Michael Super, Jeffrey Charles Way, and Donald E. Ingber
Abstract: The present invention provides for engineered molecular opsonins that may be used to bind biological pathogens or identify subclasses or specific pathogen species for use in devices and systems for treatment and diagnosis of patients with infectious diseases, blood-borne infections or sepsis. An aspect of the invention provides for mannose-binding lectin (MBL), which is an abundant natural serum protein that is part of the innate immune system. The ability of this protein lectin to bind to surface molecules on virtually all classes of biopathogens (viruses, bacteria, fungi, protozoans) make engineered forms of MBL extremely useful in diagnosing and treating infectious diseases and sepsis.
Fusion proteins for treating cancer and related methods
U.S. Patent 10,538,566 (January 21, 2020)
Jeffrey Charles Way and Avram Lev Robinson-Mosher
Abstract: Aspects of the disclosure provide fusion proteins that bind cells expressing one or more target molecules including, for example, one or more cell surface multisubunit signaling receptors (e.g., EGFRvIII-expressing cells that also express interferon receptors) and that induce anti-proliferative effects, and related compositions and methods for the treatment of cancer.
Modifying optical properties of thin film structures using an absorbing element
U.S. Patent 10,539,727 (January 21, 2020)
Grant England, Calvin Russell, Theresa Kay, Elijah Shirman, Ian Burgess, Nicolas Vogel, and Joanna Aizenberg
Abstract: A method of making a multi-layered film includes depositing thin film layers onto a first side of a double-sided transparent substrate. The thin film layers are transparent, and two adjacent layers of said plurality of thin film layers have different refractive indices. One or more absorbers are deposited at an interface formed between two of the thin film layers that are adjacent to one another, or formed by the first side of the substrate and one of the thin film layers. The absorbers absorb selected wavelengths of incident light and reflect part of the incident light after inducing a phase shift. The location of the interface is selected to provide desired wavelengths of absorbed and reflected light. The multi-layered film has a first appearance when viewed from the first side of the substrate and a second appearance when viewed from the second side of the substrate.
N-type doping of strained epitaxial germanium films through co-implantation and nanosecond pulsed laser melting
U.S. Patent 10,541,136 (January 21, 2020)
Eric Mazur, Michael J. Aziz, Hemant Gandhi, and David Pastor
Abstract: In one aspect a method of fabricating an n-doped strained germanium (Ge) film is disclosed, which includes depositing a strained Ge film on an underlying substrate, implanting at least one electron-donating dopant in the Ge film, and exposing the implanted Ge film to one or more laser pulses having a pulsewidth in a range of about 1 ns to about 100 ms so as to generate a substantially crystalline strained Ge film. In some embodiments, the pulses can cause melting followed by substantial recrystallization of at least a portion of the implanted Ge film. In some embodiments, the resultant Ge film can have a thickness in a range of about 10 nm to about 1 microns.
Simultaneous vector magnetometry with nitrogen vacancy centers in diamond or other solid-state spin sensors
U.S. Patent 10,545,200 (January 28, 2020)
John Francis Barry, Jennifer May Schloss, Matthew James Turner, Mikael Paul Backlund, and Ronald Walsworth
Abstract: A system and method for performing vector magnetometry are described. A method can include illuminating diamond with a modulated optical signal and a modulated microwave (MW) signal. A first, bias magnetic field is also applied to the diamond. Light emitted from the diamond in response to the optical signal, the MW signal, and the first magnetic field is detected via a single detector at a fixed position relative to the diamond. A modulation of the detected light encodes information corresponding to a plurality of nitrogen vacancy (NV) axes of the diamond.