Abstract: The invention provides materials, reagents, systems, and methods for identifying agents useful for treating diseases resulting from abnormal (e.g., excessive) FGF receptor signaling. The invention also provides (therapeutic) agents thus identified, and methods of using such agents in treating such diseases. In certain embodiments, the invention relates to the treatment of various craniofacial disorders, or Craniosynostosis, that result from FGFR (e.g. FGFR2) malfunction, such as Crouzon, Apert, Jackson-Weiss, Pfeiffer Syndromes, Crouzon+acanthosis nigricans, Beare-Stevenson cutis gyrata, and non-syndromic craniosynostosis (NS). The methods comprise administering to the individuals a therapeutically effective amount of an inhibitor of the FGFR2c-FRS2 signaling. The inhibitor inhibits signaling by antagonizing FGFR2c-FRS2 interaction, inhibiting the expression and/or subcellular localization of wild-type or mutant FGFR2c and/or FRS2, inhibiting the kinase activity of FGFR2c (e.g.
Type:
Grant
Filed:
May 25, 2005
Date of Patent:
January 18, 2011
Assignee:
Yale University
Inventors:
Veraragavan Palani Eswarakumar, Joseph P. Schlessinger, Irit Lax
Abstract: A device may include a hollow needle, a dilator mounted coaxially on the needle, and a sheath mounted coaxially on the dilator. The dilator may be slideably displaceable relative to the sheath.
Abstract: An apparatus for the treatment of venous stasis includes an elongated intraluminal member shaped and dimensioned for passage through vessels of a subject. The intraluminal member includes a proximal end and a distal end. A conduit extends from proximate the proximal end of the intraluminal member to proximate the distal end of the intraluminal member. The conduit is shaped and dimensioned for fluid communication between the proximal end of the intraluminal member and the distal end of the intraluminal member. The distal end of the intraluminal member includes disruption means proximate thereto for ablating a predetermined vessel wall. A method is also provided for the treatment of venous stasis. The method is achieved by advancing an elongated intraluminal member through a vein to a treatment site, activating the intraluminal member for ablation of the treatment site and injecting sclerosant into the vein at the treatment site.
Abstract: Immunoconjugates for treating diseases associated with neovascularization such as cancer, rheumatoid arthritis, the exudative form of macular degeneration, and atherosclerosis are described. The immunoconjugates typically consist of the Fc region of a human IgG1 immunoglobulin including the hinge, or other effector domain or domains that can elicit, when administered to a patient, a cytolytic immune response or cytotoxic effect against a targeted cell. The effector domain is conjugated to a targeting domain which comprises a factor VII mutant that binds with high affinity and specificity to tissue factor but does not initiate blood clotting such as factor VII having a substitution of alanine for lysine-341 or of alanine for serine-344.
Abstract: The present invention provides methods of using Monoamine Oxidase C (MAO-C), also known as renalase, as a therapeutic protein in its active and inactive forms. Administering inactive renalase protein to individuals with lower renalase levels can be used to provide them with an adequate pool of the protein that can be activated by the body as needed. Active renalase protein can be administered to individuals needing an immediate reduction of catecholamine levels. An inhibitor of renalase may be used to enhance adrenergic action.
Abstract: The glmS riboswitch is a target for antibiotics and other small molecule therapies. Compounds can be used to stimulate, active, inhibit and/or inactivate the glmS riboswitch. The atomic structures of the glmS riboswitch can be used to design new compounds to stimulate, active, inhibit and/or inactivate riboswitches.
Type:
Application
Filed:
September 6, 2007
Publication date:
December 23, 2010
Applicant:
Yale University
Inventors:
Ronald R. Breaker, Jinsoo Lim, Scott A. Strobel, Jesse C. Cochrane
Abstract: The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.
Type:
Application
Filed:
December 22, 2009
Publication date:
December 9, 2010
Applicant:
Yale University
Inventors:
Gil G. Mor, David C. Ward, Patricia Bray-Ward
Abstract: Methods for increasing the patency of biodegradable, synthetic vascular grafts are provided. The methods include administering one or more cytokines and/or chemokines that promote outward tissue remodeling of the vascular grafts and vascular neotissue formation. The disclosed methods do not require cell seeding of the vascular grafts, thus avoiding many problems associated with cell seeding. Biodegradable, polymeric vascular grafts which provide controlled release of cytokines and/or chemokines at the site of vascular graft implantation are also provided.
Type:
Application
Filed:
January 8, 2009
Publication date:
December 2, 2010
Applicant:
Yale University
Inventors:
Christopher Breuer, Themis Kyriakides, Jason Roh
Abstract: The subject invention concerns compositions and methods for blocking cancer cell growth or proliferation and/or inducing cancer cell death. Compositions of the present invention are peptidomimetics that inhibit STAT function. Peptidomimetics of the invention include compounds of the formula RY*L (where Y* represents phosphotyrosine), with the R group at the Y-1 position. Peptidomimetics of the invention disrupt Stat3 activation and function. Peptidomimetics of the invention significantly inhibit tumor cell growth and induce tumor cell death.
Type:
Grant
Filed:
November 19, 2007
Date of Patent:
November 30, 2010
Assignees:
University of South Florida, Yale University
Inventors:
James Turkson, Richard Jove, Said M. Sebti, Andrew D. Hamilton
Abstract: The present invention encompasses methods, assays and kits for the diagnosis, screening and identification of Turner syndrome and other disorders of sexual differentiation in a human using single nucleotide polymorphisms present on the X and Y chromosomes.
Abstract: A system of optics used to provide illumination through an objective at a precise inclination angle and with uniform intensity across an illuminated field. The system provides annular illumination with a continuously variable diameter at the back aperture of an objective. The resultant illumination field at the imaging plane of the objective includes rays with a single inclination angle with respect to the optical axis of the objective. This incidence angle is determined by the position of an axicon lens. The imaging plane is illuminated from 360 degrees rotation about optical axis of the objective.
Abstract: Riboswitches are targets for antibiotics and other small molecule therapies. Riboswitches and portions thereof can be used to regulate the expression or function of RNA molecules and other elements and molecules. Riboswitches and portions thereof can be used in a variety of other methods to, for example, identify or detect compounds. Compounds can be used to stimulate, active, inhibit and/or inactivate the riboswitch. Riboswitches and portions thereof, both alone and in combination with other nucleic acids, can be used in a variety of constructs and RNA molecules and can be encoded by nucleic acids.
Type:
Application
Filed:
May 29, 2008
Publication date:
November 11, 2010
Applicant:
Yale University
Inventors:
Ronald R. Breaker, Zasha Weinberg, Narasimhan Sudarsan, Joy Xin Wang, Michelle M. Meyer, Adam Roth, Elizabeth E. Regulski
Abstract: A novel tetrodotoxin resistant sodium channel is described, along with isolated nucleotides that encode this receptor. Methods for identifying agents that modulate the Na+ current through the receptor are provided, as well as related therapeutic and diagnostic methods.
Abstract: Disclosed are NgR proteins and biologically active Nogo (ligand) protein fragments. Also disclosed are compositions and methods for modulating the expression or activity of the Nogo and NgR protein. Also disclosed are peptides which block Nogo-mediated inhibition of axonal extension. The compositions and methods of the invention are useful in the treatment of cranial or cerebral trauma, spinal cord injury, stroke or a demyelinating disease.
Abstract: The present invention generally relates to modified miniature proteins, including modified avian pancreatic polypeptides (aPP) and modified pancreatic peptide YYs (PYY). One aspect of the invention is generally directed to various aPPs that have been modified such that they do not substantially form multimers in solution, for example through the addition of a proline switch. Another aspect of the invention is generally directed to modified PYYs, such as YY3. Yet another aspect of the invention is generally directed to composites of modified miniature proteins formed from portions of different miniature proteins such as aPP and/or PYY, optionally with a proline switch. Still other aspects of the invention are generally directed to methods of making such proteins, methods of using such proteins, kits involving such proteins, and the like.
Type:
Application
Filed:
April 16, 2008
Publication date:
October 28, 2010
Applicant:
Yale University
Inventors:
Alanna Shrader Schepartz, Abby M. Hodges, Crystal Zellofrow, Joshua A. Kritzer
Abstract: The present invention provides anti-inflammatory compounds, pharmaceutical compositions thereof, and methods of use thereof for treating inflammatory disorders. The present invention also provides methods of identifying anti-inflammatory compounds and methods of inhibiting NF-?B-dependent target gene expression in a cell.
Type:
Grant
Filed:
April 9, 2009
Date of Patent:
October 12, 2010
Assignee:
Yale University
Inventors:
Michael J. May, Sankar Ghosh, Mark A. Findeis, Kathryn Phillips, Gerhard Hannig
Abstract: The present invention encompasses compositions and compounds as well as methods of their use for the regulation of a VEGF-induced tissue response. A VEGF-induced tissue response may include angiogenesis, inflammation, increased vascular permeability, increased vascular leak, hemorrhage, or mucus metaplasia. As such, the present invention encompasses methods of treating diseases where a VEGF-induced tissue response is part of the disease's clinical presentation. Specifically, the present invention provides compounds and compositions as well as methods for treating acute lung injury (ALI), acute respiratory distress syndrome (ARDS), asthma, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), idiopathic pulmonary fibrosis (IPF), tuberculosis, pulmonary hypertension, pleural effusion, and lung cancer.
Abstract: It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies.
Type:
Grant
Filed:
September 22, 2003
Date of Patent:
September 14, 2010
Assignee:
Yale University
Inventors:
Ronald R. Breaker, Ali Nahvi, Narasimhan Sudarsan, Margaret S. Ebert, Wade Winkler, Jeffrey E. Barrick, John K. Wickiser
Abstract: The present invention includes a method for diagnosing cancer comprising detecting the presence of survivin in the biological fluid of a patient. The present invention also provides kits comprising one or more agents that detect survivin polypeptide or survivin nucleic acid and a container for collecting biological fluid for testing.
Type:
Grant
Filed:
April 18, 2006
Date of Patent:
September 14, 2010
Assignee:
Yale University
Inventors:
Dario Altieri, Robert Weiss, Shannon Smith, Victor Morris, legal representative, Marcia Wheeler, Janet Plescia
Abstract: The present invention provides methods and compositions related to the detection and/or monitoring of the levels of angiogenic factors, specifically VEGF, PlGF and sFlt-1, in urine samples obtained from pregnant women and the effects of such levels on the risk of developing complications of pregnancy, including hypertensive disorders such as preeclampsia, in the first, second, and/or third trimester of pregnancy. The present invention also provides kits for identifying and screening patients at risk of developing a complication of pregnancy, such as preeclampsia.
Type:
Application
Filed:
May 17, 2010
Publication date:
September 9, 2010
Applicant:
Yale University
Inventors:
Catalin S. Buhimschi, Irina Buhimschi, Errol Norwitz