Abstract: Disclosed are compounds of Formula 1, including all N-oxides, stereoisomers, and salts thereof, wherein Q1, Q2, R1, R2, Y, J and R7 are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling undesired vegetation comprising contacting the undesired vegetation or its environment with an effective amount of a compound or a composition of the invention.
Type:
Application
Filed:
May 2, 2016
Publication date:
August 2, 2018
Inventors:
Matthew James Campbell, Thomas Martin Stevenson, Andrew Duncan Satterfield
Abstract: The invention relates generally to compounds that modulate the activity of TGF?R-1 and TGF? R-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.
Type:
Application
Filed:
July 21, 2016
Publication date:
August 2, 2018
Inventors:
Lalgudi S. HARIKRISHNAN, Brian E. FINK, Robert M. BORZILLERI, Gopikishan TONUKUNURU, Hasibur RAHAMAN, Jayakumar SANKARA WARRIER, Balaji SESHADRI
Abstract: The invention relates generally to compounds that modulate the activity of TGF?R-1 and TGF?R-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.
Type:
Application
Filed:
July 27, 2016
Publication date:
August 2, 2018
Inventors:
Lalgudi S. HARIKRISHNAN, Brian E. Fink, Robert M. Borzilleri, Gopikishan Tonukunuru, Jayakumar Sankara Warrier
Abstract: Disclosed are compounds of Formula I: or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein R4, X3, X4, X5, X6, X7 and Ring A are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.
Type:
Application
Filed:
December 21, 2017
Publication date:
August 2, 2018
Inventors:
Guoxian Wu, Aaron Albers, John Buell, Elizabeth A. Burton, Phuongly Pham, Hannah Powers, Songyuan Shi, Wayne Spevak, Jeffrey Wu, Jiazhong Zhang
Abstract: The disclosure provides compounds of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the disclosure are useful for treating immunological and oncological conditions.
Type:
Application
Filed:
December 22, 2017
Publication date:
August 2, 2018
Inventors:
Eric C. Breinlinger, Andrew Burchat, Justin D. Dietrich, Michael Friedman, David Ihle, David Kinsman, Kelly Mullen, Augustine T. Osuma, Anil Vasudevan, Noel S. Wilson
Abstract: The invention provides novel compounds having the general formula (I) wherein R1, R2, Y, W, m, n, p and q are as defined herein, compositions including the compounds and methods of using the compounds.
Type:
Application
Filed:
March 23, 2018
Publication date:
August 2, 2018
Applicant:
Hoffmann-La Roche Inc.
Inventors:
Patrick Di Giorgio, Jerome Hert, Daniel Hunziker, Patrizio Mattei, Markus Rudolph, Petra Schmitz, Christoph Ullmer
Abstract: The present invention relates to inhibitors of bromo and extra terminal (BET) bromodomains that are useful for the treatment of cancer, inflammatory diseases, diabetes, and obesity, having Formula I: wherein W, X, Y, Z, R1, R2, R5, and R8 are as described herein.
Type:
Application
Filed:
March 27, 2018
Publication date:
August 2, 2018
Inventors:
Kenneth W. Bair, Torsten Herbertz, Goss S. Kauffman, Katherine J. Kayser-Bricker, George P. Luke, Matthew W. Martin, David S. Millan, Shawn E.R. Schiller, Adam C. Talbot
Abstract: Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
Abstract: The present invention relates to a new process for the preparation of thieno-indole derivatives of formula (Ia) or (Ib), exploiting an asymmetric synthesis for the preparation of key (8S) or (8R) 8-(halomethyl)-1-alkyl-7,8-dihydro-6H-thieno[3,2-e]indol-4-ol intermediates, and to useful intermediate compounds of such process. Thieno-indole derivatives are described and claimed in GB2344818, WO2013/149948 and WO2013/149946, which also disclose processes for their preparation. Thieno-indole enantiopure derivatives can now be advantageously prepared through a new asymmetric synthesis of the key 8-(halomethyl)-7,8-dihydro-6H-thieno[3,2-e]indol intermediates, which, avoiding the chiral resolution step, provides benefits in terms of reducing time and costs of the whole process for their preparation.
Type:
Application
Filed:
July 12, 2016
Publication date:
August 2, 2018
Applicant:
NERVIANO MEDICAL SCIENCES S.R.L.
Inventors:
Italo BERIA, Michele CARUSO, Daniele DONATI, Paolo ORSINI
Abstract: Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, X, W, Y1, Y2, Z1, Z2, or Z4 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
Type:
Application
Filed:
August 4, 2017
Publication date:
August 2, 2018
Inventors:
Haolun Jin, Scott E. Lazerwith, Hyung-Jung Pyun
Abstract: Inhibitor compounds are disclosed. The compounds are effective in the treatment of diseases or conditions in which interleukin 1 ? activity is implicated. Methods of synthesis of the compounds, as well as pharmaceutical compositions comprising the compounds are also disclosed.
Type:
Application
Filed:
July 28, 2016
Publication date:
August 2, 2018
Inventors:
David Brough, Stuart McRae Allan, Sally Freeman, Alex George Baldwin
Abstract: Probes for formaldehyde (FA) including a homoallylamine trigger group attached to a detectable moiety are provided. Aspects of the probes include luminogenic or fluorogenic probes, such as a probe including a quencher in energy-receiving proximity to a fluroophore. Also provided are methods of using the probes for sensitive and bio orthogonal detection of FA in a sample. Aspects of the methods include selectively reacting the probe with the formaldehyde in the sample to a release (e.g., via a 2-aza-Cope rearrangement) a reporter group comprising a detectable moiety. Aspects of the methods detecting formaldehyde in a cell, tissue, organ or fluid in a subject. Also provided are compositions and kits including the subject probes that find use in practicing various embodiments of the subject methods.
Type:
Application
Filed:
August 18, 2016
Publication date:
August 2, 2018
Inventors:
Christopher J. Chang, Thomas Francis Brewer, Jefferson Chan
Abstract: Methods of fractionating lignocellulosic biomass using hydrotropic sulfonic acids are provided. Also provided are methods of forming lignin particles, furans, sugars, and/or lignocellulosic micro- and nanofibrils from the liquid and solid fractions produced by fractionation process. The fractionation can be carried out at low temperatures with short reaction times.
Type:
Application
Filed:
January 29, 2018
Publication date:
August 2, 2018
Inventors:
Junyong Zhu, Lineng Chen, Roland Gleisner
Abstract: The present application provides a pharmaceutical composition for use in inhibiting recurrence, aggravation or metastasis of liver cancer, in which the pharmaceutical composition comprises at least one compound having a structure of formula (I) and a pharmaceutically acceptable vehicle.
Abstract: A hemi-sulfate salt of the structure: to treat a host infected with hepatitis C, as well as pharmaceutical compositions and dosage forms, including solid dosage forms, thereof.
Abstract: The present disclosure relates to complexes for intracellular imaging and also to methods and kits for intracellular imaging or cell labelling. Certain embodiments of the present disclosure provide a complex comprising a transition metal carbonyl compound, a conjugated bidentate ligand and a tetrazolato compound comprising a saccharide group.
Abstract: The invention relates to a 17?-alkynyl-androst-5-ene-3?,7?,17?-triol compound essentially free of steroid side-product lacking an oxygen substituent at position 7 and processes for preparing the same.
Abstract: Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein R1a and R1b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.
Type:
Application
Filed:
September 7, 2017
Publication date:
August 2, 2018
Inventors:
Gabriel Martinez Botella, Boyd L. Harrison, Albert J. Robichaud, Francesco G. Salituro
Abstract: Formula (I) The invention relates to C-3 novel triterpenone with C-28 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
Type:
Application
Filed:
February 9, 2016
Publication date:
August 2, 2018
Inventors:
Bandi PARTHASARADHI REDDY, Gazula Levi DAVID KRUPADANAM, Adulla PANDURANGA REDDY, Kasireddy BHASKAR REDDY, Lanka VL SUBRAHMANYAM, Kura RATHNAKAR REDDY
Abstract: The present invention relates to compounds characterized by having a structure according to the following Formula I: or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.
Abstract: The present invention has an object of providing a peptide synthesis method using a carrier capable of reversibly repeating the dissolved state and the insolubilized state, wherein the problem of an amino acid active species existing in the reaction system in de-protection reaction can be easily solved. The present invention provides a peptide synthesis method comprising the following steps: a step of condensing an N-Fmoc protected amino acid with a peptide having a C-terminal protected with a carrier which is crystallized according to a change of a composition of a dissolving solvent, in the presence of a condensing agent, to obtain an N-Fmoc-C-carrier protected peptide, a step of adding an alkylamine having 1 to 14 carbon atoms or hydroxyl amine to the reaction system, a step of de-protecting the N-terminal, and a step of changing the composition of the solvent dissolving the C-carrier protected peptide, to crystallize and separate the peptide.
Abstract: Methods for chemoselective modification of a target molecule comprising an amine N-oxide in a biological sample are provided. Aspects of the methods include selectively reacting the amine N-oxide group of the target molecule with a boron agent, where the reacting reduces the amine N-oxide to an amine to produce a modified target molecule. Modification of the target molecule using the subject methods may produce an activated target molecule, e.g., a detectable or bioactive. In some cases, chemoselective modification leads to cleavage of the modified target molecule to produce a first target fragment and a second target fragment. Also provided are compositions useful in practicing various embodiments of the subject methods.
Abstract: A method is provided for the preparation of an N-acyl peptide, N-acyl polypeptide or N-acyl protein comprising reacting a peptide, polypeptide or protein with an acyl halide in the presence of the biologically compatible tertiary amine nicotinamide as catalyst, thus obtaining the desired N-acyl peptide, N-acyl polypeptide or N-acyl protein.
Abstract: A method for purifying an antibody-like protein includes adsorbing an antibody-like protein onto an affinity separation matrix by bringing the antibody-like protein into contact with the affinity separation matrix; and eluting the antibody-like protein by bringing an eluent having a pH of 3.5 or higher into contact with the affinity separation matrix. The affinity separation matrix includes a carrier and a ligand immobilized on the carrier, and the ligand includes an amino acid sequence derived from a sequence selected from the group consisting of SEQ ID Nos: 1 to 5. Gln or Lys in an Fc-binding site of the amino acid sequence is substituted by Ala, Ser, or Thr, and the ligand has a lower antibody-binding capacity in an acidic pH range, as compared to a ligand including the amino acid sequence without the substitution.
Abstract: The present invention relates to chromogenic and fluorogenic substrates that can be used for the highly sensitive and selective detection of the activity of serine proteases. The present invention further relates to methods for the detection of the activity of serine proteases, said methods using the substrates of the present invention. Furthermore, the present invention relates to diagnostic kits and test strips using the above substrates, as well as uses of said substrates.
Type:
Application
Filed:
August 3, 2016
Publication date:
August 2, 2018
Inventors:
Roland Krämer, Dumitru Arian, Job Harenberg
Abstract: Described herein are methods and compositions featuring a first compound that is a linear peptidic NPR-B agonist and a second compound that is a prostaglandin agonist or a ?-adrenergic antagonist, which are useful in the treatment and/or prevention of ophthalmic disorders such as glaucoma.
Abstract: The concurrent administration of chemotherapy and immunotherapy has been considered a contraindication because of the concern that the induced lymphopenia would ablate therapeutic efficacy of immunotherapy. Temozolomide has been shown to be an effective chemotherapeutic for patients with malignant gliomas and to deprive patients with glioblastoma (GBM) patients of this agent in order to treat with immunotherapy is controversial. Despite conventional dogma, we demonstrate that both chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy. In fact, the temozolomide induced lymphopenia may actually be synergistic with a peptide vaccine.
Type:
Application
Filed:
March 28, 2018
Publication date:
August 2, 2018
Applicants:
Duke University, Board of Regents, The University of Texas System
Inventors:
John H. Sampson, Darell D. Bigner, Duane A. Mitchell, Amy Heimberger
Abstract: The disclosure is related to a method of treating a disorder, such as obesity or a condition associated with obesity, such as hyperphagia, in a subject using a melanocortin-4 receptor (MC4R) agonist.
Type:
Application
Filed:
September 29, 2016
Publication date:
August 2, 2018
Applicant:
Rhythm Pharmaceuticals, Inc.
Inventors:
Leonardus H.T. Van Der Ploeg, Bart Henderson, Shubh Sharma
Abstract: Disclosed are agents (e.g., peptides, polypeptides, proteins, small molecules, antibodies, and antibody fragments that target senescent cells) and methods of their use for imaging senescent cells in vivo and for treating or preventing cancer, age-related disease, tobacco-related disease, or other diseases and disorders related to or caused by cellular senescence in a mammal. The methods include administering one or more of the agents of the invention to a mammal, e.g., a human. The agents, which specifically bind to senescent cells, can be labeled with a radioactive label or a therapeutic label, e.g., a cytotoxic agent.
Abstract: Materials and methods for forming self-assembled peptoid structures that are extremely stable, crystalline, free-standing and self-repairing are described. Based on the peptoid design, peptoid membranes in a 2D arrangement was able toroll into single-walled nanotubes with tunable sizes, diameters, thicknesses and stiffnesses as well as tailorable functions result. Crystalline nanomaterials made through this facile solution crystallization and anisotropic formation process are highly tailorable and exhibit a number of properties advantageous for applications such as water decontamination, cellular adhesion, imaging, surface coating, biosensing, energy conversion, biocatalysis or other applications.
Abstract: This document provides methods and materials related to the use of nucleic acid coding for viruses to reduce the number of viable cancer cells within a mammal. For example, methods for using infectious nucleic acid to treat cancer, engineered viral nucleic acid, methods for making engineered viral nucleic acid, methods for identifying infectious nucleic acid for treating cancer, methods and materials for controlling virus-mediated cell lysis, and methods and materials for assessing the control of virus-mediated cell lysis are provided.
Type:
Application
Filed:
March 27, 2018
Publication date:
August 2, 2018
Applicant:
Mayo Foundation for Medical Education and Research
Inventors:
Stephen James Russell, Elizabeth J. Kelly, Elizabeth M. Hadac
Abstract: A protein includes an amino acid sequence derived from a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. The amino acid sequence includes a substitution of a hydrophobic amino acid residue in an Fc binding site with a different hydrophobic amino acid residue or a polar uncharged amino acid residue, and the protein has a reduced antibody-binding capacity in an acidic pH range, as compared to a protein including the amino acid sequence without the substitution.
Abstract: A protein includes an amino acid sequence derived from a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. The amino acid sequence includes a substitution of a hydrophobic amino acid residue, an acidic amino acid residue, or a polar uncharged amino acid residue with a basic amino acid residue, and the protein has a reduced antibody-binding capacity in an acidic pH range, as compared to a protein including the amino acid sequence without the substitution.
Abstract: This disclosure provides plants having enhanced traits such as increased yield, increased nitrogen use efficiency and increased water use efficiency; propagules, progeny and field crops of such transgenic plants; and methods of making and using such transgenic plants. This disclosure also provides methods of producing hybrid seed from such transgenic plants, growing such seed and selecting progeny plants with the composition or with enhanced traits.
Type:
Application
Filed:
March 26, 2018
Publication date:
August 2, 2018
Inventors:
Mark S. Abad, Paul S. Chomet, Dhanalakshmi Ramachandra, Tyamagondlu V. Venkatesh, Xiaoyun Wu
Abstract: The present invention provides methods for treating or alleviating one or more symptoms of depression and/or anxiety in a subject comprising administering an effective amount of an NCAM peptide mimetic to the subject. The symptoms of depression and/or anxiety are typically observed in or associated with a neurological condition. The present invention also provides methods for treating a neurological condition such as a psychiatric disorder in a subject comprising administering an effective amount of an NCAM peptide mimetic to the subject.
Type:
Application
Filed:
September 6, 2017
Publication date:
August 2, 2018
Applicant:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
Huda AKIL, Stanley J. WATSON, Cortney TURNER
Abstract: Described herein are compositions relating to engineered hnRNP-E1 variant polypeptides, nucleic acids encoding such polypeptides, engineered hnRNP-E1 compositions, and methods of use thereof. In some embodiments, the engineered hnRNP-E1 polypeptide contains a C293S substitution and retains the ability to bind to a poly(rC)- and poly(U)-rich 5?-UTR element in its cognate mRNA targets in the absence of homocysteine. In some cases, the engineered hnRNP-E1 compositions provided herein are useful to increase the translation of a subset of mRNAs or to treat certain health conditions as described herein.
Abstract: The disclosure features, among other things, polypeptides comprising a Cryptic polypeptide, a functional fragment thereof, or variants of any of the foregoing. Also featured are nucleic acids encoding the polypeptides, methods for producing of the polypeptides, and a variety of diagnostic and therapeutic applications in which the polypeptides are useful. For example, the polypeptides can be used to treat a subject having a condition associated with bone loss.
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:
Application
Filed:
July 21, 2016
Publication date:
August 2, 2018
Inventors:
Galina S. Bogatkevich, Yuichiro Shirai, Richard M. Silver
Abstract: Methods and kits for the diagnosis of illnesses related to protocadherin 19 (PCDH19) protein deficiency or altered PCDH19 protein function are provided, as well as methods and kits for the identification of a predisposition to such illnesses and methods of screening subjects to identify carriers of such illnesses and methods and kits for the therapeutic or prophylactic treatment of PCDH19 deficiency or altered PCDH19 protein function. Further, nucleotide and amino acid sequences corresponding to a complete PCDH19 open reading frame (ORF), mutant sequences encoding non-functional PCDH19 mRNA or altered PCDH19 mRNA are described along with transformed cells and non-human transgenic animals comprising wild-type or mutant PCDH19 ORF nucleotide sequences.
Type:
Application
Filed:
January 9, 2018
Publication date:
August 2, 2018
Inventors:
Leanne Michelle DIBBENS, Ingrid Eileen SCHEFFER, Samuel Frank BERKOVIC, John Charles MULLEY, Jozef GECZ
Abstract: The present disclosure relates to a method for the treatment of a non-pathogen associated inflammatory disorders in a subject in need thereof, comprising administering to said subject an isolated peptide which specifically binds to an amino acid sequence within the dimer interface of a T cell costimulatory pathway member, particularly the T cell costimulatory pathway members CD28 and CTLA4. The present disclosure also relates to pharmaceutical compositions comprising the isolated peptide and to use of the peptide in treating of a non-pathogen associated inflammatory disorders.
Type:
Application
Filed:
March 27, 2018
Publication date:
August 2, 2018
Inventors:
Raymond KAEMPFER, Anat SHIRVAN, Gila ARAD
Abstract: Provided herein is an isolated tumour necrosis factor receptor (TNFR) polypeptide capable of binding to TNF, or a TNF-binding fragment thereof, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO:1, or an amino acid sequence that has at least 60% identity thereto and wherein the polypeptide or TNF-binding fragment comprises an N-terminal VPAQV motif (SEQ ID NO: 68), with the proviso that the polypeptide is not mouse TNFR p80 isoform. Also provided is a fusion protein comprising said polypeptide, or a TNF-binding fragment thereof, linked to a fusion partner, such as the CH2 and CH3 domains of an immunoglobulin heavy chain constant region. The polypeptides and fusion proteins disclosed herein may be used for diagnostic purposes and in the treatment or prevention of conditions mediated by TNF, particularly in non-human animals such as feline and equine.
Abstract: Provided herein are recombinant masking proteins and recombinant ligand proteins useful in treating cancer, neurodegenerative disease, and cardiovascular disease. The recombinant masking proteins provided herein may, inter alia, be used as non-covalent masks of antagonists of, for example, cellular growth factors (e.g., TNF) or cell surface proteins (e.g., CTLA-4).
Type:
Application
Filed:
July 2, 2015
Publication date:
August 2, 2018
Applicants:
City of Hope, Thomas Jefferson University
Abstract: The invention concerns a detection method to enable the detection of complexes formed between antibodies and antigen which is endogenous to the production cell line, e.g. CHO MIF in a final product.
Type:
Application
Filed:
August 21, 2015
Publication date:
August 2, 2018
Inventors:
Dirk Voelkel, Patrice Douillard, Gerhard Antoine, Randolf Kerschbaumer
Abstract: The present invention relates to monoclonal antibodies which have high anti-RSV neutralizing titers. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. The invention yet further provides for diagnostic, prophylactic and therapeutic methods employing the antibodies and nucleic acids of the invention, particularly as a passive immunotherapy agent in infants and the elderly.
Type:
Application
Filed:
March 22, 2018
Publication date:
August 2, 2018
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Kalpit A. Vora, Kara S. Cox, Aimin Tang, Zhifeng Chen, Daniel DiStefano, Lan Zhang, Hua-Poo Su
Abstract: The present invention relates to monoclonal antibodies which have high anti-RSV neutralizing titers. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. The invention yet further provides for diagnostic, prophylactic and therapeutic methods employing the antibodies and nucleic acids of the invention, particularly as a passive immunotherapy agent in infants and the elderly.
Type:
Application
Filed:
March 22, 2018
Publication date:
August 2, 2018
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Kalpit A. Vora, Kara S. Cox, Aimin Tang, Zhifeng Chen, Daniel DiStefano, Lan Zhang, Hua-Poo Su