Abstract: Methods for preparing a protein conjugate having a defined number of conjugate groups are provided. The method includes: forming a mixture containing a macrocyclic matrix material and a plurality of proteins; eluting the proteins to obtain a first separated protein fraction and a second separated protein fraction, wherein substantially all of the proteins in the first separated protein fraction have the same number of handle moieties; contacting the handle moieties with a conversion reagent under conditions sufficient to convert the handle moieties in the first separated protein fraction to reactive moieties; and contacting the reactive moieties with a conjugation reagent under conditions sufficient to form a plurality of protein conjugates, wherein substantially all of the protein conjugates in the plurality have the same number of conjugate groups. Methods also include recovering enzymes and other proteins from mixtures for isolation and/or reuse of the enzymes and proteins.
Type:
Grant
Filed:
January 21, 2016
Date of Patent:
August 6, 2019
Assignee:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Inventors:
Richard L. Kwant, Matthew B. Francis, Christian B. Rosen, Meera Rao
Abstract: Methods for inhibiting an autoimmune disease by administering to a subject a therapeutically effective amount of a composition that induces conversion of naive T cells into Foxp3+ regulatory T cells to induce immunosuppression in the subject. Methods for detecting in a subject an autoimmune disease or a predisposition to an autoimmune disease, and methods for assessing the efficacy of a therapy for an autoimmune disease, particularly type 1 diabetes.
Type:
Grant
Filed:
January 13, 2016
Date of Patent:
July 30, 2019
Assignees:
National Jewish Health, The Regents of the University of Colorado, a body corporate
Inventors:
Aaron Michels, John Kappler, Peter A. Gottlieb
Abstract: The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.
Type:
Grant
Filed:
March 31, 2017
Date of Patent:
July 23, 2019
Assignee:
Bristol-Myers Squibb Company
Inventors:
Michael Matthew Miller, Martin Patrick Allen, Ling Li, Michael S. Bowsher, Eric P. Gillis, Eric Mull, Qian Zhao, Li-Qiang Sun, David R. Langley, Paul Michael Scola
Abstract: A peptide and a peptide complex of the present invention exhibit an anti-obesity effect by inhibiting fat accumulation and decomposing already accumulated fat, and exhibit an excellent effect with respect to diabetes by effectively reducing blood sugar. The peptide and the peptide complex of the present invention decrease the expression of PPAR?, ACC, and aP2, which are adipogenic markers, increase the expression of pHSL, AMPK-?1, CGI-58, and ATGL, which are lipolytic factors, and reduce the size of fat cells and blood cholesterol values. The peptide and the peptide complex of the present invention, which have excellent activity and safety, can be advantageously applied to drugs and quasi-drugs.
Abstract: The invention provides anti-fibrotic peptides derived from the C-terminal region of the MET receptor tyrosine kinase. Polynucleotides encoding these peptides, host cells transformed with the polynucleotides, and methods of using these peptides and polynucleotides are included in the invention. Uses of these peptides, polynucleotides and expression vectors include the treatment of fibrosis in a subject.
Type:
Grant
Filed:
July 21, 2016
Date of Patent:
July 9, 2019
Assignee:
MUSC FOUNDATION FOR RESEARCH DEVELOPMENT
Inventors:
Galina S. Bogatkevich, Yuichiro Shirai, Richard M. Silver
Abstract: The present disclosure describes peptide inhibitors of Rho-associtated-kinase (ROCK) and their use in treating disorders including heart failure, the leading cause of combined morbidity and mortality in the United States. An inhibitory polypeptide blocks ROCK1 activity in the presence of 1 mM ATP. The binding epitope on ROCK1 was mapped using chemical cross-linking to the Activation Loop, a novel locus identifying a new class of inhibitory drugs. The peptides described will be useful against a number of important diseases such as heart disease, pulmonary hypertension, arterial hypertension, glaucoma management, insulin resistance, kidney disease, hemolytic anemia, stroke, ischemia reperfusion injury, or acute myeloid leukemia.
Type:
Grant
Filed:
October 1, 2015
Date of Patent:
July 2, 2019
Assignee:
University of Houston System
Inventors:
Robert J. Schwartz, Hua Zhang, John W. Craft, Scott Gilbertson, Kevin MacKenzie, Reza Abbasgholizadeh, Steven Bark, James M. Briggs, Robert Fox
Abstract: The present invention is related to development of the improved cell-permeable (CP)-?SOCS3 recombinant protein which disrupt the interaction of leptin receptor (ObR) and suppressor of cytokine signaling 3 (SOCS3), as protein-based anti-obesity or anti-diabetes agent by utilizing the platform technology for macromolecule intracellular transduction.
Abstract: Provided are cell-penetrating ATF5 polypeptides having a cell-penetrating region and an ATF5 leucine zipper region, compositions comprising the ATF5 polypeptides, and methods of treating a tumor and promoting cytotoxicity in a neoplastic cell using the ATF5 polypeptides.
Type:
Grant
Filed:
February 17, 2018
Date of Patent:
June 11, 2019
Assignee:
Sapience Therapeutics, Inc.
Inventors:
Barry Jay Kappel, Jimmy Andrew Rotolo, Gene Merutka
Abstract: Described herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting bacterial growth.
Abstract: Proteinoid compounds characterized by a molecular weight (Mw) of at least 15,000 Da, processes of preparing such compounds and methods of use thereof, are provided. A method of monitoring the presence and metastases of cancer in a body of an individual is further disclosed.
Type:
Grant
Filed:
August 10, 2016
Date of Patent:
May 28, 2019
Assignee:
BAR-ILAN UNIVERSITY
Inventors:
Shlomo Margel, Michal Kolitz Domb, Stella Kiel, Elisheva Sason
Abstract: The invention includes methods of suppressing cancer metastasis and local recurrence in a subject. In one aspect, the method comprises removing the tumor by surgery; and implanting a composition of the invention to the site of the primary tumor. In another aspect, the method comprises implanting a composition of the invention to a cancerous site. The composition comprises a pharmaceutically effective amount of collagen type III.
Type:
Grant
Filed:
January 19, 2016
Date of Patent:
May 14, 2019
Assignee:
The Trustees of the University of Pennsylvania
Abstract: Described herein are modified integrin ? and/or ? headpiece polypeptides, and crystallizable integrin polypeptide dimers comprising a modified integrin ? and/or ? headpiece polypeptide and a disulfide bond linking the two integrin headpiece polypeptide subunits. Methods for using the modified integrin ? and/or ? headpiece polypeptides and the integrin polypeptide dimers are also provided herein. For example, methods for characterizing integrin-ligand interaction and identifying integrin ligands are also provided herein. In some embodiments, the identified integrin ligands can be used as inhibitors of integrins.
Type:
Grant
Filed:
February 3, 2017
Date of Patent:
April 30, 2019
Assignee:
The Children's Medical Center Corporation
Inventors:
Timothy Alan Springer, Xianchi Dong, Chafen Lu
Abstract: Disclosed is related to an anti-aging peptide, which has an amino acid sequence of ProAspSerThrGluAlaLys (SEQ ID NO: 1). Also provided are anti-aging compositions comprising the peptide and personal care methods of using the peptide.
Abstract: A method of purifying a desired protein from a preparation includes providing the preparation in a form having less than about 5% of the chromatin residing in the original production medium, contacting the preparation with a nonionic organic polymer in an amount sufficient to cause the desired protein to precipitate or adsorb on a nonionic hydrophilic surface, and adjusting a salt concentration before or during the contacting step, the adjusting step providing a sufficient salt concentration to produce a conductivity greater than physiological conductivity.
Type:
Grant
Filed:
February 27, 2014
Date of Patent:
April 9, 2019
Assignee:
AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH
Abstract: Azaindoline compounds as granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Methods for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.
Abstract: An isolated peptide being no longer than 20 amino acids comprising a sequence at least 95% homologous to the sequence GQLNHILGILGX1PX2QED (SEQ ID NO: 4), wherein X1 and X2 are any amino acid, the peptide being capable of preventing extracellular signal-regulated kinase1/2 (ERK) translocation into the nucleus.
Abstract: This invention relates to compositions of glucagon suitable for administration by manual injection or by an insulin pump or other injection device to treat hypoglycemia. Said compositions comprise glucagon and a sugar, have a final pH between about 1.5 and 3, and are gel-free, chemically-stable at body temperature and pump-able.
Abstract: Provided herein are stabilized ?-CT polypeptides comprising an alpha-helical segment, and wherein the polypeptide is of Formula (I-1) or Formula (I-2): Rf—[XAA]s—XA1—XA2—XA3—XA4—XA5—XA6—XA7—XA8—XA9—XA10—XA11—XA12—XA13—XA14—[XAA]t—Re (I-1) Rf—[XAA]s—XC1—XC2—XC3—XC4—XC5—XC6—XC7—XC8—XC9—XC10—XC11—XC12—XC13—XC14—XC15—XC16—XC17—XC18—XC19—XC20—[XAA]t—Re (I-2) wherein the ?-CT polypeptide binds to the insulin receptor, and wherein the ?-CT polypeptide includes at least one staple (i.e. two cross-linked amino acids) and/or at least one stitch (i.e. three cross-linked amino acids). Further provided are insulin analogs including the stapled or stitched ?-CT polypeptides, pharmaceutical compositions thereof, methods of use, e.g., methods of treating a diabetic condition or complications thereof.
Type:
Grant
Filed:
June 13, 2014
Date of Patent:
March 12, 2019
Assignee:
PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Gregory L. Verdine, Gerard Hilinski, Rebecca Yue Liang, Yvonne Alice Nagel, Minyun Zhou
Abstract: This invention relates to ?A-crystallin protein modulating compounds (e.g., phosphomimetic peptides), compositions comprising such modulating compounds, and their use as therapeutics for the treatment and prevention of conditions involving neurodegeneration and neuroinflammation.
Type:
Grant
Filed:
September 18, 2017
Date of Patent:
March 5, 2019
Assignees:
The Regents of the University of Michigan, Vanderbilt University
Abstract: The present disclosure provides a method of producing enzyme-specific inhibitors or substrate binding partners comprising: identifying active site residues of the substrate in the enzyme substrate complex or in substrate binding partner-substrate complex; randomizing the active site residues to produce a combinatorial library of substrate variants; and selecting substrate variants that inhibit enzyme activity or bind substrate as substrate-specific binding partners. The present disclosure also provides ubiquitin enzyme specific inhibitors and ubiquitin variants that bind ubiquitin interaction motifs.
Type:
Grant
Filed:
June 8, 2011
Date of Patent:
February 26, 2019
Assignee:
THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO
Inventors:
Sachdev Sidhu, Linda Beatty, Andreas Ernst