July 2015 patents: Antibiotics, sub-diffraction imaging, drug delivery and more
Professors Andrew Myers, George Church, Gregory Verdine, David Mooney, George Whitesides, Xiaowei Zhuang, and John Collier were among the faculty members issued U.S. patents this July. The patents include:
Synthesis of tetracyclines and intermediates thereto
U.S. Patent 9,073,829 (July 7, 2015)
Andrew G. Myers, David A. Kummer, Derun Li, Evan Hecker, Amelie Dion, and Peter M. Wright
The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously thought susceptible to tetracycline antibiotics. The recent development of a modular synthesis of tetracycline analogs through a chiral enone intermediate has allowed for the efficient synthesis of novel tetracycline analogs never prepared before. The present invention provides more efficient routes for preparing the enone intermediate and allows for substituents at positions 4a, 5, 5a, and 12a of the tetracycline ring system.
Stabilized MAML peptides and uses thereof
U.S. Patent 9,074,009 (July 7, 2015)
James Bradner, Raymond Moellering, and Gregory L. Verdine
Stably cross-linked a polypeptides related to human MAML are described. These cross-linked polypeptides contain at least two modified amino acids that together form an internal cross-link or tether that can help to stabilize the alpha-helical secondary structure that is thought to be important for binding of MAML peptides to the Notch transcription complex, a complex that includes ICN and CSL.
Mutant Cas9 proteins
U.S. Patent 9,074,199 (July 7, 2015)
Alejandro Chavez, Frank Poelwijk, and George M. Church
Methods of making mutant Cas9 proteins are described.
Sub-diffraction limit image resolution in three dimensions
U.S. Patent 9,077,975 (July 7, 2015)
Xiaowei Zhuang, Wilfred M. Bates, Bo Huang, and Wenqin Wang
The present invention generally relates to sub-diffraction limit image resolution and other imaging techniques, including imaging in three dimensions. In one aspect, the invention is directed to determining and/or imaging light from two or more entities separated by a distance less than the diffraction limit of the incident light. In some cases, the position of the entities can be determined in all three spatial dimensions (i.e., in the x, y, and z directions), and in certain cases, the positions in all three dimensions can be determined to an accuracy of less than about 1000 nm. In some cases, the z positions may be determined using one of a variety of techniques that uses intensity information or focal information (e.g., a lack of focus) to determine the z position. Non-limiting examples of such techniques include astigmatism imaging, off-focus imaging, or multi-focal-plane imaging.
Method for delivering agents into cells using bacterial toxins
U.S. Patent 9,079,952 (July 14, 2015)
Robert J. Collier and Brad L. Pentelute
The invention provides compositions and methods for delivering a bioactive moiety comprising at least one non-natural component into a cell cytosol of an 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.
Active scaffolds for on-demand drug and cell delivery
U.S. Patent 9,089,512 (July 28, 2015)
David J. Mooney and Xuanhe Zhao
The invention provides a composition whose porosity, pore size, pore connectivity, swelling agent concentration, and/or specific volume undergoes a change from a first value to a second value in response to an electromagnetic signal, the composition having a matrix material in which is distributed a magnetic material.
Alginate hydrogel fibers and related materials
U.S. Patent 9,090,868 (July 28, 2015)
Charles R. Mace, Jabulani Barber, Anna Laromaine Sague, George M. Whitesides, and Rebecca Cademartiri
Alginate hydrogel fibers and related materials as well as methods for preparing such materials are provided. An alginate hydrogel fiber includes water in an amount of more than about 92% by weight of the fiber and a cross-linked alginate in an amount of about 0.1% to about 8% by weight of the fiber, wherein the cross-link is a cation. An alginate hydrogel paper includes one or more alginate hydrogel fibers, which form a non-woven matrix. Three-dimensional cellular arrays are also provided, wherein the alginate hydrogel making up the alginate paper is substantially index-matched with a predetermined culture medium. A method for making alginate hydrogel fiber and a method for index-matching alginate hydrogel paper with culture medium are provided. A kit for conducting biochemical, diagnostic, cellular, and/or non-cellular analysis comprises alginate hydrogel paper index-matched to culture medium.