June 2019 patents
Innovations in gene editing, forming multiple emulsions, stimulating or inhibiting the immune system, and more
Harvard faculty Ulrich von Andrian, Omid Farokhzad, Jinjun Shi, Michael Chorev, Jose Halperin, David Weitz, David Liu, David Mooney, Dennis Kasper, Dingding An, Richard Blumberg, George Church, and Joanna Aizenberg are among the inventors issued U.S. patents in June 2019.
The innovations recognized are as follows:
Microvessel endothelial cell surface markers and uses thereof
U.S. Patent 10,307,487 (June 4, 2019)
Ulrich H. von Andrian, Aude Thiriot, Omid Farokhzad, and Jinjun Shi
Abstract: Disclosed herein are microvessel endothelial cell surface markers and methods, compositions, agents, and kits relating to those surface markers.
Fusion proteins for treating cancer and related methods
U.S. Patent 10,308,697 (June 4, 2019)
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.
Surrogates of post-translationally modified proteins and uses thereof
U.S. Patent 10,309,973 (June 4, 2019)
Michael Chorev and Jose A. Halperin
Abstract: The present invention provides compounds that are surrogates of post-translationally modified proteins and uses thereof. Numerous diseases are associated with post-translationally modified proteins that are difficult to obtain in homogenous form and in quantities needed for immunization and use as convenient standards, calibrators, and/or reference compounds that facilitate the detection and analysis of endogenous post-translationally modified proteins. The surrogate compounds of the invention typically comprise antigenic epitopes (one of which carries a post-translational modification) that are tethered by a flexible and hydrophilic linker. The resulting compound behaves like a surrogate of the post-translationally modified protein because it preserves the character of the included antigens and allows recognition by specific antibodies targeting the individual antigens. The surrogate compounds may be prepared by covalently joining two or more polypeptide epitopes using one or more linkers, wherein at least one of the epitopes comprises a post-translational modification. In one aspect, the surrogate compounds of the invention comprise a C-terminal epitope and a glycated epitope of human CD59. The inventive methods allow quantification of the levels of glycated CD59 in the serum in human subjects, particularly those with diabetes or pre-diabetes. This technological platform of post-translationally modified protein surrogates can be applied to other diseases associated with post-translationally modified proteins (e.g., autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus). In another aspect, the invention provides antibodies that bind specifically to the compounds of the invention and methods for producing such antibodies.
Method and apparatus for forming multiple emulsions
U.S. Patent 10,316,873 (June 11, 2019)
David A. Weitz, Darren Roy Link, and Andrew S. Utada
Abstract: The present invention generally relates to multiple emulsions, and to methods and apparatuses for making multiple emulsions. A multiple emulsion generally describes larger droplets that contain one or more smaller droplets therein. The larger droplets may be suspended in a third fluid in some cases. These can be useful for encapsulating species such as pharmaceutical agents, cells, chemicals, or the like. In some cases, one or more of the droplets can change form, for instance, to become solidified to form a microcapsule, a liposome, a polymerosome, or a colloidosome. Multiple emulsions can be formed in one step in certain embodiments, with generally precise repeatability, and can be tailored to include one, two, three, or more inner droplets within a single outer droplet (which droplets may all be nested in some cases).
Evaluation and improvement of nuclease cleavage specificity
U.S. Patent 10,323,236 (June 18, 2019)
David R. Liu, John Paul Guilinger, and Vikram Pattanayak
Abstract: Engineered nucleases (e.g., zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and others) are promising tools for genome manipulation and determining off-target cleavage sites of these enzymes is of great interest. We developed an in vitro selection method that interrogates 1011 DNA sequences for their ability to be cleaved by active, dimeric nucleases, e.g., ZFNs and TALENs. The method revealed hundreds of thousands of DNA sequences, some present in the human genome, that can be cleaved in vitro by two ZFNs, CCR5-224 and VF2468, which target the endogenous human CCR5 and VEGF-A genes, respectively. Our findings establish an energy compensation model of ZFN specificity in which excess binding energy contributes to off-target ZFN cleavage and suggest strategies for the improvement of future nuclease design. It was also observed that TALENs can achieve cleavage specificity similar to or higher than that observed in ZFNs.
Continuous cell programming devices
U.S. Patent 10,328,133 (June 25, 2019)
David J. Mooney, Omar Ali, and Glenn Dranoff
Abstract: The present invention comprises compositions, methods and devices for creating an infection-mimicking environment within a polymer scaffold to stimulate antigen-specific dendritic cell activation. Devices of the present invention are used to provide protective immunity to subjects against infection and cancer.
Glycosphingolipids and methods of use thereof
U.S. Patent 10,329,315 (June 25, 2019)
Dennis L. Kasper, Dingding An, Sungwhan Oh, Richard S. Blumberg, Torsten Olszak, and Joana F. Neves
Abstract: The invention provides, inter alia, immunoinhibitory glycosphingolipids and immunoinhibitory alpha-galactosylceramides and compositions and preparations thereof, and methods of use thereof including in the treatment of conditions characterized by increased iNKT cells and/or activity.
Orthogonal Cas9 proteins for RNA-guided gene regulation and editing
U.S. Patent 10,329,587 (June 25, 2019)
George M. Church, Kevin M. Esvelt, and Prashant G. Mali
Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including use of multiple orthogonal Cas9 proteins to simultaneously and independently regulate corresponding genes or simultaneously and independently edit corresponding genes.
Fluid-based gating mechanism with tunable multiphase selectivity and antifouling behavior
U.S. Patent 10,330,218 (June 25, 2019)
Joanna Aizenberg, Xu Hou, Mughees Khan, and Alexander Tesler
Abstract: A gating mechanism that uses a capillary stabilized liquid as a reversible, reconfigurable gate that fills and seals pores in the closed state, and creates a non-fouling, liquid-lined pore in the open state is disclosed. Theoretical modeling and experiments demonstrate that for each transport substance, the gating threshold--the pressure needed to open the pores--can be rationally tuned over a wide pressure range. This enables realizing in one system differential response profiles for a variety of liquids and gases, even letting liquids flow through the pore while preventing gas from escaping. These capabilities allow dynamic modulation of gas-liquid sorting and to separate multi-phase mixtures, with the liquid lining ensuring sustained antifouling behavior. Because the liquid gating strategy enables efficient short-term and long-term operation and can be applied to a variety of pore structures and membrane materials, and to nano, micro as well as macroscale fluid systems, the gating systems is useful in a wide range of applications.