October 2016 patents
Innovations in treating cancer and infection by inhibiting the PD-1 pathway; nanoelectronic tissue scaffolds; soft robotic actuators; generating direct triplet entangled photons, and more
Harvard faculty Arlene Sharpe, Charles Lieber, Daniel Kohane, Gregory Verdine, George Whitesides, Eric Mazur, Ulrich von Andrian, David Weitz, Jonathan Seidman, and Christine Seidman are among the inventors issued U.S. patents during October 2016.
The innovations recognized are as follows:
Methods and compositions for the treatment of persistent infections and cancer by inhibiting the programmed cell death 1 (PD-1) pathway
U.S. Patent 9,457,080 (October 4, 2016)
Gordon Freeman, Arlene Sharpe, David M. Dorfman, Rafi Ahmed, Daniel Barber, and E. John Wherry
Abstract: The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.
Scaffolds comprising nanoelectronic components for cells, tissues, and other applications
U.S. Patent 9,457,128 (October 4, 2016)
Charles M. Lieber, Jia Liu, Bozhi Tian, Tal Dvir, Robert S. Langer, and Daniel S. Kohane
Abstract: The present invention generally relates to nanoscale wires and tissue engineering. In various embodiments, cell scaffolds for growing cells or tissues can be formed that include nanoscale wires that can be connected to electronic circuits extending externally of the cell scaffold. The nanoscale wires may form an integral part of cells or tissues grown from the cell scaffold, and can even be determined or controlled, e.g., using various electronic circuits. This approach 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. Accordingly, 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.
Ligation of stapled polypeptides
U.S. Patent 9,458,189 (October 4, 2016)
Gregory L. Verdine and Eileen Jeanne Kennedy
Abstract: The present invention provides technology for making large (e.g., greater than 50 amino acids), semi-synthetic, stapled or stitched proteins. The method essentially involves ligating a synthetically produced stapled or stitched peptide to a larger protein. Modified version of IL-13 and MYC are provided as illustrative examples.
Multiple input biologic classifier circuits for cells
U.S. Patent 9,458,509 (October 4, 2016)
Yaakov Benenson, Ron Weiss, Liliana Wroblewska, and Zhen Xie
Abstract: Provided herein are high-input detector modules and multi-input biological classifier circuits and systems that integrate sophisticated sensing, information processing, and actuation in living cells and permit new directions in basic biology, biotechnology and medicine. The multi-input biological classifier circuits described herein comprise synthetic, scaleable transcriptional/post-transcriptional regulatory circuits that are designed to interrogate the status of a cell by simultaneously sensing expression levels of multiple endogenous inputs, such as microRNAs. The classifier circuits then compute whether to trigger a desired output or response if the expression levels match a pre-determined profile of interest.
Screening assays and methods
U.S. Patent 9,463,431 (October 11, 2016)
J. Christopher Love, Hidde L. Ploegh, and Jehnna Ronan
Abstract: Screening assays and methods of performing such assays are provided. In certain examples, the assays and methods may be designed to determine whether or not two or more species can associate with each other. In some examples, the assays and methods may be used to determine if a known antigen binds to an unknown monoclonal antibody.
Stabilized alpha helical peptides and uses thereof
U.S. Patent 9,464,115 (October 11, 2016)
Loren D. Walensky, Stanley J. Korsmeyer, and Gregory Verdine
Abstract: Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking ("hydrocarbon stapling") moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death.
Soft robotic actuators
U.S. Patent 9,464,642 (October 11, 2016)
Filip Ilievski, Xin Chen, Aaron D. Mazzeo, George M. Whitesides, Robert F. Shepherd, Ramses V. Martinez, Won Jae Choi, Sen W. Kwok, Stephen Morin, Adam Stokes, and Zhihong Nie
Abstract: A soft robotic device includes a flexible body having a width, a length and a thickness, wherein the thickness is at least 1 mm, the flexible body having at least one channel disposed within the flexible body, the channel defined by upper, lower and side walls, wherein at least one wall is strain limiting; and a pressurizing inlet in fluid communication with the at least one channel, the at least one channel positioned and arranged such that the wall opposite the strain limiting wall preferentially expands when the soft robotic device is pressurized through the inlet.
Direct entangled triplet-photon sources and methods for their design and fabrication
U.S. Patent 9,470,956 (October 18, 2016)
Eric Mazur, Christopher Courtney Evans, Michael Gerhard Moebius, Orad Reshef, and Sarah E. Griesse-Nascimento
Abstract: The present teachings are generally directed to devices and methods for triplet photons generations, and in particular to on-chip integrated sources for generating direct triplet entangled photons.
U.S. Patent 9,474,717 (October 25, 2016)
Ulrich H. von Andrian, Omic C. Farokhzad, Robert S. Langer, Tobias Junt, Elliott Ashley Moseman, Liangfang Zhang, Pamela Basto, Matteo Iannacone, and Frank Alexis
Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at last one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.
Droplet formation using fluid breakup
U.S. Patent 9,475,013 (October 25, 2016)
Adam R. Abate and David A. Weitz
Abstract: The present invention generally relates to systems and methods for creating droplets. In one aspect, a plurality of droplets (27) is introduced into a continuous fluid stream (21) to cause the continuous fluid stream to form discrete droplets. In some cases, the droplets that are formed from the continuous fluid stream may be substantially monodisperse. The continuous fluid stream may, in some cases, be a jetting fluid stream flowing at a relatively high linear flow rate, and in certain embodiments, high rates of droplet formation from the jetting fluid may thereby be achieved. Additionally, certain aspects of the invention are generally directed to devices, such as microfluidic devices, able to form such droplets. For example, in one set of embodiments, a device may include a junction (14) where a plurality of droplets (27) can be introduced into a continuous fluid stream (21), and optionally, the device may include additional junctions (12) able to cause the formation of the plurality of droplets and/or the formation of the continuous fluid stream. Still other disclosed aspects are generally directed to methods of making such devices, methods of using such devices, kits involving such devices, and the like.
Methods of making oligonucleotide probes
U.S. Patent 9,476,089 (October 25, 2016)
Chao-ting Wu and Brian Beliveau
Abstract: The present invention relates to methods of making linear nucleic acid probes using rolling circle amplification methods. In one aspect, an oligonucleotide template sequence is contacrted with one or more first primers, a first polymerase and first nucleotides under conditions that extend one or more hybridize primers to make a strand complementary to the oligonucleotide template sequence thereby forming a double stranded oligonucleotide. The double stranded oligonucleotide is circularized. A rolling circle template is obtained from the circularized double stranded oligonucleotide. The rolling circle template is contacted with one or more second primers, a second polymerase and second nucleotides under conditions that form a single stranded nucleic acid, and the single stranded nucleic acid is cleaved to form the plurality of nucleic acid probes.
Structural mutations in titin cause dilated cardiomyopathy
U.S. Patent 9,476,097 (October 25, 2016)
Jonathan G. Seidman, Christine E. Seidman, and Daniel E. Herman
Abstract: Provided herein are diagnostic markers and methods for identifying a subject having an increased susceptibility for developing or having dilated cardiomyopathy. The method comprises determining if the subject has a mutation in the TTN nucleic as acid or titin polypeptide. Further provided herein are methods of treating subjects having or at risk of having dilated cardiomyopathy.