December 2015 patents
Protein matrix vaccines, HDAC inhibitors, photocatalysis, supercharged proteins, and more
Professors Ralph Mazitschek, David Liu, Daniel Finley, Randall King, Adam Cohen, Adrian Salic, John Mekalanos, Gary King, Eric Mazur, Don Ingber, and Robert Westervelt are among the faculty members issued U.S. patents this December.
The patents include:
Histone deacetylase inhibitors
U.S. Patent 9,199,923 (December 1, 2015)
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 compound 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.
Small molecule-dependent inteins and uses thereof
U.S. Patent 9,200,045 (December 1, 2015)
David R. Liu and Sun H. Peck
Abstract: Elucidating the function of proteins in mammalian cells is particularly challenging due to the inherent complexity of these systems. Methods to study protein function in living cells ideally perturb the activity of only the protein of interest but otherwise maintain the natural state of the host cell or organism. Ligand-dependent inteins offer single-protein specificity and other desirable features as an approach to control protein function in cells post-translationally. Some aspects of this invention provide second-generation ligand-dependent inteins that splice to substantially higher yields and with faster kinetics in the presence of the cell-permeable small molecule 4-HT, especially at 37° C., while exhibiting comparable or improved low levels of background splicing in the absence of 4-HT, as compared to the parental inteins. These improvements were observed in four protein contexts tested in mammalian cells at 37° C., as well as in yeast cells assayed at 30° C. or 37° C. The newly evolved inteins described herein are therefore promising tools as conditional modulators of protein structure and function in yeast and mammalian cells.
Methods and compositions for enhancing proteasome activity
U.S. Patent 9,201,073 (December 1, 2015)
Daniel J. Finley, John W. Hanna, Nathaniel A. Hathaway, Randall W. King, and Byung-Hoon Lee
Abstract: This invention relates to methods and compositions for enhancing proteasome activity in a cell. The methods and compositions for enhancing the activity of the proteasome in cells modulate the activity of Ubp6 (yeast) or Usp14 (human), an endogenous inhibitor of the proteasome. The methods and compositions partially or completely reduce the inhibitory activity of Usp14 on a proteasome, thereby specifically enhancing the protein-degradation activity of the proteasome. The invention also provides methods of screening to identify inhibitors of Ubp6, Usp14, and/or both Ubp6 and Usp14.
Inhibitors of anaphase promoting complex activity
U.S. Patent 9,205,069 (December 8, 2015)
Randall King, Xing Zeng, and Shantanu Gaur
Abstract: The invention provides an anti-proliferative composition comprising a non-peptide analog of the C-terminal isoleucine-arginine (IR) tail motif of an activator of an anaphase promoting complex (APC). The invention further provides methods of inhibiting the ubiquitination activity of the APC by administering compositions of the invention.
Nanostructures, systems, and methods for photocatalysis
U.S. Patent 9,205,420 (December 8, 2015)
Steven Y. Reece and Thomas D. Jarvi
Abstract: The present invention generally relates to nanostructures and compositions comprising nanostructures, methods of making and using the nanostructures, and related systems. In some embodiments, a nanostructure comprises a first region and a second region, wherein a first photocatalytic reaction (e.g., an oxidation reaction) can be carried out at the first region and a second photocatalytic reaction (e.g., a reduction reaction) can be carried out at the second region. In some cases, the first photocatalytic reaction is the formation of oxygen gas from water and the second photocatalytic reaction is the formation of hydrogen gas from water. In some embodiments, a nanostructure comprises at least one semiconductor material, and, in some cases, at least one catalytic material and/or at least one photosensitizing agent.
Systems, methods, and workflows for optogenetics analysis
U.S. Patent 9,207,237 (December 8, 2015)
Adam E. Cohen, Joel Kralj, Adam D. Douglass, and Daniel Hochbaum
Abstract: The invention provides methods for characterizing cellular physiology by incorporating into an electrically excitable cell an optical reporter of, and an optical actuator of, electrical activity. A signal is obtained from the optical reporter in response to a stimulation of the cell. Either or both of the optical reporter and actuator may be based on genetically-encoded rhodopsins incorporated into the cell. The invention provides all optical methods that may be used instead of, or as a complement to, traditional patch clamp technologies and that can provide rapid, accurate, and flexible assays of cellular physiology.
Methods and compositions for labeling polypeptides
U.S. Patent 9,212,381 (December 15, 2015)
Adrian Salic and Jing Liu
Abstract: Synthesis of many proteins is tightly controlled at the level of translation and plays an essential role in fundamental processes such as cell growth and proliferation, signaling, differentiation or death. Methods that allow imaging and identification of nascent proteins allow for dissecting regulation of translation, both spatially and temporally, including in whole organisms. Described herein are robust chemical methods for imaging and affinity-purifying nascent polypeptides in cells and in animals, based on puromycin analogs. Puromycin analogs of the present invention form covalent conjugates with nascent polypeptide chains, which are rapidly turned over by the proteasome and can be visualized and specifically captured by a bioorthogonal reaction (e.g., [3+2] cycloaddition). The methods of the present invention have broad applicability for imaging protein synthesis and for identifying proteins synthesized under various physiological and pathological conditions in vivo.
Protein matrix vaccines and methods of making and administering such vaccines
U.S. Patent 9,216,223 (December 22, 2015)
John J. Mekalanos
Abstract: The invention relates to vaccine compositions having a carrier protein and an antigen of interest entrapped in a complex, methods of making such vaccines, and methods of vaccine administration.
Participant grouping for enhanced interactive experience
U.S. Patent 9,219,998 (December 22, 2015)
Gary King, Eric Mazur, and Brian Lukoff
Abstract: Representative embodiments of a method for grouping participants in an activity include the steps of: (i) defining a grouping policy; (ii) storing, in a database, participant records that include a participant identifier, a characteristic associated with the participant, and/or an identifier for a participant's handheld device; (iii) defining groupings based on the policy and characteristics of the participants relating to the policy and to the activity; and (iv) communicating the groupings to the handheld devices to establish the groups.
Device and method for combined microfluidic-micromagnetic separation of material in continuous flow
U.S. Patent 9,220,831 (December 29, 2015)
Donald E. Ingber, Shannon Xia, Tom P. Hunt, and Robert M. Westervelt
Abstract: A miniaturized, integrated, microfluidic device pulls materials bound to magnetic particles from one laminar flow path to another by applying a local magnetic field gradient. The device removes microbial and mammalian cells from flowing biological fluids without any wash steps. A microfabricated high-gradient magnetic field concentrator (HGMC) is integrated at one side of a microfluidic channel. When magnetic particles are introduced into one flow path, they remain limited to that flow path. When the HGMC is magnetized, the magnetic beads are pulled from the initial flow path into the collection stream, thereby cleansing the fluid. The microdevice allows large numbers of beads and materials to be sorted simultaneously, has no capacity limit, does not lose separation efficiency as particles are removed, and is useful for cell separations from blood and other biological fluids. This on-chip separator allows cell separations to be performed in the field outside of hospitals and laboratories.
Supercharged proteins for cell penetration
U.S. Patent 9,221,886 (December 29, 2015)
David R. Liu, Brian R. McNaughton, James Joseph Cronican, and David B. Thompson
Abstract: Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to "supercharge" the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof. The inventive complexes or pharmaceutical compositions thereof may be used to treat proliferative diseases, infectious diseases, cardiovascular diseases, inborn errors in metabolism, genetic diseases, etc.