Patents Issued in April 18, 2019
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Publication number: 20190112338Abstract: The present invention relates to decoy peptide or polypeptide consisting of a peptide sequence represented by the following Formula I: X1-Ala-X2-X3-Ile-Glu-X4 (I). It is noteworthy that the decoy peptide or polypeptide of the present invention significantly elevates phosphorylation levels of PLB by inhibiting PP1-mediated dephosphorylation. In addition, the decoy peptide or polypeptide provides cardio-protective effects by restoring of SERCA2a activity and inotropic effect of enhancing myocardial contractility. The present invention will contribute greatly to the prevention or treatment of diseases associated with PLB.Type: ApplicationFiled: December 18, 2018Publication date: April 18, 2019Inventors: Woo Jin PARK, Roger J. HAJJAR, Jae Gyun OH
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Publication number: 20190112339Abstract: The present invention concerns peptides and nucleic acids encoding the peptides, and their use for modulating large conductance Ca2+ activated K+ (BK) channel activity in cells; for treating conditions such as presbycusis (age-related hearing loss), audiogenic seizures, alcohol addiction, cancer, and neurodegenerative disease; and for delivering a cargo moiety to the brain of a subject through the blood-brain barrier.Type: ApplicationFiled: December 17, 2018Publication date: April 18, 2019Inventors: Luisa Lynn Scott, Joseph Paul Walton
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Publication number: 20190112340Abstract: Embodiments of a recombinant Respiratory Syncytial Virus (RSV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also disclosed are nucleic acids encoding the RSV F ectodomain trimer and methods of producing the RSV F ectodomain trimer. Methods for inducing an immune response in a subject are also disclosed. In some embodiments, the method can be a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the recombinant RSV F ectodomain trimer to the subject.Type: ApplicationFiled: March 29, 2017Publication date: April 18, 2019Applicant: The United States of America, as represented by the Secretary, Department of Health and HumanInventors: Peter Kwong, Barney Graham, John Mascola, Li Ou, Aliaksandr Druz, Man Chen, Wing-Pui Kong, Ivelin Stefanov Georgiev, Emily Rundlet, Michael Gordon Joyce, Yaroslav Tsybovsky, Paul Thomas, Marie Pancera, Mallika Sastry, Cinque Soto, Joseph Van Galen, Guillaume Stewart-Jones, Yongping Yang, Baoshan Zhang, Ulrich Baxa
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Publication number: 20190112341Abstract: A method of producing a picornavirus-like particle (PVLP) in a plant is provided. The method comprises introducing a first nucleic acid and a second nucleic acid into the plant, portion of the plant, or a plant cell. The first nucleic acid comprising a first regulatory region active in the plant operatively linked to a nucleotide sequence encoding a polyprotein. The second nucleic acid comprises a second regulatory region active in the plant and operatively linked to a nucleotide sequence encoding one or more protease. The plant, portion of the plant, or plant cell is incubated under conditions that permit the expression of the nucleic acids, thereby producing the PVLP. A PVLP comprising the polyprotein is also provided.Type: ApplicationFiled: December 20, 2018Publication date: April 18, 2019Inventors: MARC-ANDRE D'AOUST, PIERRE-OLIVIER LAVOIE, MANON COUTURE, LUCIE POULIN, LOUIS-PHILIPPE VEZINA
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Publication number: 20190112342Abstract: Embodiments concern methods and compositions for treating or preventing a bacterial infection, particularly infection by a Staphylococcus bacterium. Aspects include methods and compositions for providing a passive immune response against the bacteria. In certain embodiments, the methods and compositions involve an antibody that binds Coagulase (Coa). Further aspects relate to immunogenic compositions comprising at least one Staphylococcal coagulase R Domain, wherein the R Domain is 80% identical in sequence to a R Domain.Type: ApplicationFiled: February 10, 2017Publication date: April 18, 2019Inventors: Dominique Missiakas, Olaf Schneewind, Carla Emolo, Lena Thomer, Molly McAdow, Jeroen Geurtsen, Mark De Been
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Publication number: 20190112343Abstract: Compositions and methods for controlling plant pests are disclosed. In particular, novel engineered hybrid insecticidal proteins having toxicity to at least European corn borer are provided. By fusing unique combinations of complete or partial variable regions and conserved blocks of at least two different Bacillus thuringiensis (Bt) Cry proteins or a modified Cry proteins a hybrid insecticidal protein having activity against at least European corn borer is designed. Nucleic acid molecules encoding the novel hybrid proteins are also provided. Methods of making the hybrid proteins and methods of using the hybrid proteins and nucleic acids encoding the hybrid proteins of the invention, for example in transgenic plants to confer protection from insect damage are also disclosed.Type: ApplicationFiled: December 7, 2018Publication date: April 18, 2019Applicant: Syngenta Participations AGInventors: Hope Hart, Jeng Shong Chen, Cheryl M. Defontes
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Publication number: 20190112344Abstract: The invention concerns novel streptavidin muteins and their use for determination, isolation or purification of proteins under denaturing conditions. In one embodiment such a mutein has an Cys residue at sequence position 127 of the wild-type sequence of streptavidin and comprises at least one mutation in the region of the amino acid positions 115 to 121 with reference to the amino acid sequence of wild type streptavidin.Type: ApplicationFiled: April 25, 2017Publication date: April 18, 2019Applicant: IBA GMBHInventor: Thomas SCHMIDT
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Publication number: 20190112345Abstract: Methods and apparatus for identifying and screening hydrogen bond networks are provided. A computing device can determine a search space for hydrogen bond networks related to one or more molecules, where the search space can include a plurality of energy terms related to a plurality of residues related to the hydrogen bond networks. The computing device can search the search space to identify one or more hydrogen bond networks based on the plurality of energy terms. The computing device can screen the identified hydrogen bond networks to identity one or more screened hydrogen bond networks based on scores for the identified hydrogen bond networks. An output can be generated that is related to the one or more screened hydrogen bond networks. Also provided are polypeptides that can form homo-oligomers with modular hydrogen bond network-mediated specificity.Type: ApplicationFiled: March 31, 2017Publication date: April 18, 2019Inventors: David BAKER, Scott BOYKEN, Zibo CHEN, Chunfu XU, Sherry BERMEO, Robert LANGAN
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Publication number: 20190112346Abstract: The present invention is a novel composition including a fibrous protein having covered antigenicity, and the composition contains a complex prepared by bonding a fibrous protein such as tropomyosin derived from shrimp to a maltooligosaccharide such as maltopentaose or maltoheptaose through a Maillard reaction.Type: ApplicationFiled: March 28, 2017Publication date: April 18, 2019Inventors: Masakatsu Usui, Taiko Miyasaki, Akira Saito
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Publication number: 20190112347Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.Type: ApplicationFiled: December 27, 2018Publication date: April 18, 2019Inventors: Andrea MAHR, Toni WEINSCHENK, Valentina GOLDFINGER, Oliver SCHOOR, Jens FRITSCHE, Harpreet SINGH
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Publication number: 20190112348Abstract: Novel acylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H.Type: ApplicationFiled: December 14, 2018Publication date: April 18, 2019Inventors: Peter Madsen, Thomas Boerglum Kjeldsen, Thomas Hoeg-Jensen, Palle Jakobsen, Tina Moeller Tagmose, Tine Glendorf, Janos Tibor Kodra, Patrick William Garibay, Jacob Sten Petersen
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Publication number: 20190112349Abstract: Disclosed herein are chimeric receptors that comprise an extracellular domain and a cytoplasmic signaling domain, wherein the extracellular domain has a reduced binding activity to a wild-type Fc fragment; nucleic acids encoding such chimeric receptors, and immune cells expressing the chimeric receptors. Also disclosed are methods of using the chimeric receptors to enhance the efficacy of antibody-based immunotherapy, such as cancer immunotherapy.Type: ApplicationFiled: March 17, 2017Publication date: April 18, 2019Applicant: Unum Therapeutics Inc.Inventors: Kathleen McGinness, Charles Wilson, Seth Ettenberg, Heather Huet
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Publication number: 20190112350Abstract: The present invention provides peptidic TGF-? antagonists capable of inhibiting TGF-? signaling and disrupting the biochemical events that promote fibrosis and the epithelial-mesenchymal transition. The peptidic TGF-? antagonist may contain from 11 to 28 amino acid residues (for instance, may consist of from 12 to 16 amino acid residues) and may have the following structure (II): NH2? ETWIWLDTNMG-Xaa1-Y?COOH (II) wherein Xaa1 is any amino acid and Y is a peptide having from 0 to 9 amino acids. The peptidic TGF-? antagonists can advantageously be used for the prevention, treatment, and/or alleviation of the symptoms of a condition associated with an increase in TGF-? activity, including fibrosis (such as fibrosis of the skin, liver, lungs, and heart, among others) and cancer (including various carcinomas, such as squamous cell carcinoma, sarcomas, and metastatic cancers).Type: ApplicationFiled: August 11, 2017Publication date: April 18, 2019Inventor: Anie Philip
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Publication number: 20190112351Abstract: In order to further increase antigenicity to provide a DNA vaccine which is clinically usable in humans, the inventors of the present invention focused on exosomes, which are garnering attention as tools for DDS, and discovered that an exosome expressing a fusion antigen of an exosome (extracellular microparticle)-constituent protein and a vaccine antigen has excellent cytotoxic T-cell inducibility. Consequently, the present invention provides a nucleic acid constituent including a nucleic acid sequence coding for an exosome marker protein and a nucleic acid sequence coding for a vaccine antigen.Type: ApplicationFiled: April 4, 2016Publication date: April 18, 2019Applicant: National Institutes of Biomedical Innovation, Health and NutritionInventors: Ken Ishii, Kouji Kobiyama, Tomohiro Kanuma
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Publication number: 20190112352Abstract: An isoform of the TGF beta receptor II comprising a sequence of about of 80 amino acids and lacking a transmembrane domain. The isoform comprises the amino acid sequence set forth in SEQ ID No. 12. The isoform may have the amino acid sequence set forth in SEQ ID No. 2 or sequences having at least 85% sequence identity to the sequence set forth in SEQ ID No. 2. A fusion peptide is provided comprising an isoform of the TGF beta II receptor fused to a ligand, wherein a vector comprising the fusion peptide is used to treat cancer and/or hepatic fibrosis. An antibody binding the soluble isoform of the TGF beta II receptor is provided. The antibody binds the amino acid sequence shown in SEQ ID No. 12 and is used in in vitro methods.Type: ApplicationFiled: October 29, 2018Publication date: April 18, 2019Inventors: Ana ROMO, Anabela Belen LA COLLA, Matias Adan PREISEGGER, Marcela Soledad BERTOLIO, Ricardo Alfredo DEWEY, Pamela Daiana VELAZQUEZ, Andrea Nancy CHISARI, Tania Melina RODRIGUEZ, Benito Jorge VELASCO ZAMORA
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Publication number: 20190112353Abstract: Materials and methods for treating a patient with severe combined immunodeficiency (SCID) or Omenn Syndrome, both ex vivo and in vivo, and materials and methods for editing to modulate the expression, function, or activity of an lnterleukin-7 receptor (IL7R) gene in a cell by genome editing.Type: ApplicationFiled: February 17, 2017Publication date: April 18, 2019Inventors: Ying YANG, Chad Albert COWMAN, Ante Sven LUNDBERG, Gregory Joseph COST
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Publication number: 20190112354Abstract: This invention relates to methods and compositions for overcoming the dose-dependent down regulation of interleukin 10 (IL-10) by expressing, in addition to an interleukin 10 (IL-10) peptide, an IL-10 receptor type 1 (IL-10R1) peptide. The methods have use in treating a variety of diseases and symptoms, including but not limited to neuropathic or chronic pain; symptoms and physiological damage associated with multiple sclerosis, spinal cord injury, ALS, neuroinflammation, arthritis and other diseases of the joint; and autoimmune diseases.Type: ApplicationFiled: April 21, 2017Publication date: April 18, 2019Inventors: John Forsayeth, Raymond Chavez, Linda Watkins, Peter Grace
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Publication number: 20190112355Abstract: The invention provides a fusion protein comprising, from N-terminus to C-terminus: a) a first portion of a Family B G-protein coupled receptor (GPCR) that comprises transmembrane helix (TM)-1, TM2 and TM3 of the GPCR; b) a stable protein domain; and c) a second portion of the GPCR comprising TM4, TM5, TM6 and TM7 of the GPCR. The invention also provides a method of crystallising a GPCR comprising providing the fusion protein of the invention and crystallising it to obtain crystals.Type: ApplicationFiled: September 20, 2018Publication date: April 18, 2019Applicant: Heptares Therapeutics LimitedInventors: Seyed Ali Jazayeri-Dezfuly, Fiona Hamilton Marshall
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Publication number: 20190112356Abstract: The present disclosure is directed to high-affinity immunopolymers for use in a variety of immunoassays and other techniques. The immunopolymers comprise a plurality of antibodies, a plurality of coupling proteins, and a plurality of detectable labels. The plurality of antibodies and plurality of coupling proteins are associated by a high-efficiency conjugation moiety, and may be used in highly multiplexed assays. Methods of preparing the high-affinity immunopolymers are provided. Also disclosed are methods of detecting an antigen that include reacting an antigen with a high-affinity immunopolymer of the disclosure. Reagent mixtures and methods for quantitative immunochemical assays are also provided. The mixtures and methods may include the high-affinity immunopolymers disclosed herein.Type: ApplicationFiled: November 6, 2015Publication date: April 18, 2019Inventors: David A. SCHWARTZ, Stephen J. KRON, Amy C. FLOR
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Publication number: 20190112357Abstract: Disclosed are methods for testing the presence and/or activity of glutathione system components and thioredoxin system components during the manufacturing process of disulfide bond-containing proteins. Also disclosed are methods for mitigating reduction of disulfide bonds during the manufacturing process, and for lowering the reduction potential of disulfide bond-containing proteins. Provided are compositions, kits, and methods for mitigating reduction and diminishing reduction potential of disulfide bond-containing proteins during protein manufacturing processes.Type: ApplicationFiled: May 9, 2017Publication date: April 18, 2019Inventors: Sanjeev AHUJA, Wai Keen CHUNG, Deborah Sweet GOLDBERG, Michael HANDLOGTEN, Someet NARANG, Brian RUSSELL, Min ZHU, Suzanne HUDAK, Kenneth HWANG, Jihong WANG
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Publication number: 20190112358Abstract: The present disclosure relates to a method of obtaining a cell where fucosylation pathways are modified, leading to production of partially fucosylated and non-fucosylated protein products, specifically antibodies from the cell. The present disclosure employs the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. The method of the present disclosure targets the Fut8 gene and GMD gene in a cell. Such products are used in developing therapeutics and biomarkers, and in diagnosis and prognosis of diseases.Type: ApplicationFiled: November 13, 2015Publication date: April 18, 2019Inventors: Bhargav Prasad, Divya Unnikrishnan, Jahnabi Hazarika, Kavitha Iyer Rodrigues, Maloy Ghosh, Pavithra M, Pravin Kumar D, Sanghamitra Bhattacharjee, Sathyabalan M, Sankaranarayanan Srinivasan, Sohang Chatterjee, Sunit Maity, Veeresha K, Vivek Halan, Yogendra Manjunath B. M., Anuradha Hora, Bairavabalakumar N, Karthika Nair, Aswini Thanigaivel, Amol Maliwalave, Bharath R Shenoy, Rajeshwari Pendse, Prabhat Kumar Pathak, Anisha Kurup, Sahana Bhima Rao
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Publication number: 20190112359Abstract: Methods of separating triple-light chain (H2L3) antibodies (e.g., anti-CD123 H2L3 antibodies) or antigen-binding fragments thereof from an antibody composition comprising H2L3 antibodies or antigen-binding fragments thereof and double-light chain (H2L2) antibodies (e.g., anti-CD123 H2L2) or antigen-binding fragments thereof are provided.Type: ApplicationFiled: September 21, 2018Publication date: April 18, 2019Inventors: Fang LIU, Xinfang LI
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Publication number: 20190112360Abstract: The present invention relates to an antibody which specifically binds to the envelope glycoprotein of severe fever with thrombocytopenia syndrome virus (SFTSV), the pathogen of severe fever with thrombocytopenia syndrome (SFTS), and is used in order to effectively detect or diagnosis SFTSV and treat SFTS.Type: ApplicationFiled: March 23, 2017Publication date: April 18, 2019Inventors: Junho CHUNG, Ki-Hyun KIM, Hyori KIM, Myoung-don OH, Wan Beom PARK, Seungtaek KIM, Jinhee KIM
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Publication number: 20190112361Abstract: The invention provides anti-Tau antibodies and methods of using the same.Type: ApplicationFiled: September 24, 2018Publication date: April 18, 2019Applicants: GENENTECH, INC., AC IMMUNE SAInventors: Oskar Adolfsson, Gai Ayalon, Isidro Hotzel, Danielle Marie Di Cara
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Publication number: 20190112362Abstract: The invention provides anti-Tau antibodies and methods of using the same.Type: ApplicationFiled: September 24, 2018Publication date: April 18, 2019Applicants: GENENTECH, INC., AC IMMUNE SAInventors: Oskar Adolfsson, Gai Ayalon, Isidro Hotzel, Danielle Marie Di Cara
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Publication number: 20190112363Abstract: The present invention relates to polypeptides comprising at least one single domain antibody directed against vWF, vWF A1 domain, A1 domain of activated vWF, vWF A3 domain, gpIb and/or collagen, homologues of said polypeptides, and/or functional portions of said polypeptides, for the treatment for conditions which require a modulation of platelet-mediated aggregation and which overcomes the problems of the prior art. A further aspect of the invention is methods of production of said polypeptides, methods to coat devices with such polypeptides used in medical procedures (e.g. PCTA, stenting), methods and kits for screening for agents that modulate platelet-mediated aggregation and kits for the diagnosis of diseases related to platelet-mediated aggregation.Type: ApplicationFiled: September 26, 2018Publication date: April 18, 2019Applicant: Ablynx N.V.Inventor: Karen Silence
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Publication number: 20190112364Abstract: Provided herein are antibodies that specifically bind Tau and methods of using the same.Type: ApplicationFiled: October 16, 2018Publication date: April 18, 2019Inventors: Malcolm Ian Roberts, James Martin Staddon, Hettihewage Alfred Rohan De Silva, Jared Spidel, Hirofumi Aoyagi, Shigeru Akasofu, Yutaka Hashizume, Kishan Agarwala
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Publication number: 20190112365Abstract: Provided herein are antibodies that specifically bind Tau and methods of using the same.Type: ApplicationFiled: December 12, 2018Publication date: April 18, 2019Inventors: Malcolm Ian Roberts, James Martin Staddon, Hettihewage Alfred Rohan De Silva, Jared Spidel, Hirofumi Aoyagi, Shigeru Akasofu, Yutaka Hashizume, Kishan Agarwala
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Publication number: 20190112366Abstract: The present disclosure relates, in general, to combination therapy using an inhibitor of transforming growth factor beta (TGF?) and an inhibitor of programmed cell death protein 1 (PD-1) for treating cancer or preventing recurrence of cancer diseases such as lung cancer, prostate cancer, breast cancer, hepatocellular cancer, esophageal cancer, colorectal cancer, pancreatic cancer, bladder cancer, kidney cancer, ovarian cancer, stomach cancer, fibrotic cancer, glioma and melanoma, and metastases thereof.Type: ApplicationFiled: December 17, 2018Publication date: April 18, 2019Inventors: Amer M. Mirza, Rosemary J. Akhurst, Ou Li
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Publication number: 20190112367Abstract: Provided are novel IL-32 binding molecules of human origin, particularly human anti-IL-32 antibodies as well as IL-32 binding fragments, derivatives and variants thereof. In addition, pharmaceutical compositions, kits and methods for use in diagnosis and therapy are described.Type: ApplicationFiled: August 21, 2018Publication date: April 18, 2019Inventors: Adrian Hayday, Kai Kisand, Kai Krohn, Annalisa Macagno, Shimobi Onuoha, Paert Peterson, Mike Rothe, Martin Woodward, Syeda F. Y. Haque
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Publication number: 20190112368Abstract: Provided herein are methods of producing a polypeptide containing two chains, such as an antibody including a light chain and a heavy chain. In particular, methods are provided for producing heterologous secretory proteins in bacteria through utilization of optimized expression vectors and culture processes.Type: ApplicationFiled: September 21, 2018Publication date: April 18, 2019Applicant: Genentech, Inc.Inventors: James GIULIANOTTI, Dorothea E. REILLY
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Publication number: 20190112369Abstract: Use of antagonists to IL-31Ra and OSMRb are used to treat inflammation and pain by inhibiting, preventing, reducing, minimizing, limiting or minimizing stimulation in neuronal tissues. Such antagonists include soluble receptors, antibodies and fragments, derivative, or variants thereof. Symptoms such as pain, tingle, sensitization, tickle associated with neuropathies are ameliorated.Type: ApplicationFiled: December 20, 2018Publication date: April 18, 2019Inventors: Yue Yao, Janine M. Bilsborough
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Publication number: 20190112370Abstract: The present invention relates to a pharmaceutical composition for treatment and/or prevention of a cancer, which comprises, as an active ingredient, an antibody or fragment thereof having an immunological reactivity with an MRAP2 protein having the amino acid sequence shown in SEQ ID NO: 2, 4, 6, or 8 or an amino acid sequence having 80% or more sequence identity with the amino acid sequence, or with a fragment of the MRAP2 protein comprising 7 or more consecutive amino acids.Type: ApplicationFiled: March 27, 2017Publication date: April 18, 2019Applicant: TORAY INDUSTRIES, INC.Inventors: Takayuki FUJITA, Fumiyoshi OKANO
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Publication number: 20190112371Abstract: A pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS that does not include the autoimmune neuroinflammatory disease, relapsing-remitting multiple sclerosis (RRMS), is provided. The pharmaceutical composition is for administration by a dosage regimen comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session.Type: ApplicationFiled: October 22, 2018Publication date: April 18, 2019Applicant: Yeda Research and Development Co. LtdInventors: Michal Eisenbach-Schwartz, Kuti Baruch, Neta Rosenzweig
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Publication number: 20190112372Abstract: The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease.Type: ApplicationFiled: December 13, 2018Publication date: April 18, 2019Applicant: bluebird bio, Inc.Inventors: Jordan JARJOUR, Alexander ASTRAKHAN, Michael CERTO
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Publication number: 20190112373Abstract: Provided are anti-CD47 monoclonal antibodies (anti-CD47 mAbs) with distinct functional profiles as described herein, methods to generate anti-CD47 mAbs, and to methods of using these anti-CD47 mAbs as therapeutics for the prevention and treatment of solid and hematological cancers, ischemia-reperfusion injury, cardiovascular diseases, autoimmune diseases, inflammatory diseases or as diagnostics for determining the level of CD47 in tissue samples.Type: ApplicationFiled: December 17, 2018Publication date: April 18, 2019Inventors: Pamela T. Manning, Robyn Puro, Juan C. Almagro, Robert W. Karr
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Publication number: 20190112374Abstract: Humanized or chimeric anti-CD47 monoclonal antibodies are provided. The antibodies bind to and neutralize human CD47, and find use in various therapeutic methods. Preferred are non-activating antibodies. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the humanized or chimeric anti-CD47 monoclonal antibodies; and cell lines that produce these monoclonal antibodies. Also provided are amino acid sequences of the antibodies.Type: ApplicationFiled: December 19, 2018Publication date: April 18, 2019Inventors: Jie Liu, Irving L. Weissman, Ravindra Majeti
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Publication number: 20190112375Abstract: The present invention provides antibodies, or antigen binding fragments thereof, that bind to human TIGIT (T cell immunoreceptor with Ig and ITIM domains), as well as uses of these antibodies or fragments in therapeutic applications, such as in the treatment of cancer or chronic viral infection. Such method of treatment include combination therapy with inhibitors of other immunomodulatory receptor interactions, such as the PD-1/PD-L1 interaction. The invention further provides polynucleotides encoding the heavy and/or light chain variable region of the antibodies, expression vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies, cells comprising the vectors, and methods of making the antibodies or fragments by expressing them from the cells.Type: ApplicationFiled: December 20, 2018Publication date: April 18, 2019Inventors: Mark F. MAURER, Tseng-hui Timothy CHEN, Brigitte DEVAUX, Mohan SRINIVASAN, Susan H. JULIEN, Paul O. SHEPPARD, Daniel F. ARDOUREL, Indrani CHAKRABORTY
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Publication number: 20190112376Abstract: The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1/PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.Type: ApplicationFiled: December 21, 2018Publication date: April 18, 2019Applicant: Bristol-Myers Squibb CompanyInventors: John P. COGSWELL, Stacie M. Goldberg, Ashok K. Gupta, Maria Jure-Kunkel, Xi-Tao Wang, Jon M. Wigginton
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Publication number: 20190112377Abstract: The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1/PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.Type: ApplicationFiled: December 21, 2018Publication date: April 18, 2019Applicant: Bristol-Myers Squibb CompanyInventors: John P. COGSWELL, Stacie M. Goldberg, Ashok K. Gupta, Maria Jure-Kunkel, Xi-Tao Wang, Jon M. Wigginton
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Publication number: 20190112378Abstract: A method of treating or preventing breast cancer (eg invasive ductal carcinoma) and/or cancer associated with elevated levels of either one or both of the IL-3 receptor (IL-3R) and interleukin-3 (IL-3) is disclosed which comprises administering to a subject an IL-3 -inhibiting agent such as an agent which inhibits (eg by blocking) IL-3R.Type: ApplicationFiled: November 26, 2015Publication date: April 18, 2019Inventors: Angel F. LOPEZ, Claudine S. BONDER, Emma THOMPSON
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Publication number: 20190112379Abstract: Provided are methods for preventing or ameliorating toxicity caused by or due to a therapy, such as an immunotherapy or a cell therapy, by pre-emptive or early administration toxicity-targeting agent(s). In some embodiments, the therapy is a cell therapy in which the cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the methods, including the timing of the administration of the agents or treatments for toxicity, provide various advantages, such as lower toxicity while maintaining persistence and efficacy of the administered cells.Type: ApplicationFiled: March 22, 2017Publication date: April 18, 2019Applicant: SEATTLE CHILDREN'S HOSPITAL (DBA SEATTLE CHILDREN'S RESEARCH INSTITUTE)Inventors: Michael JENSEN, Rebecca GARDNER
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Publication number: 20190112380Abstract: Provided herein is a composition comprising, a cell, comprising nucleic acids encoding a chimeric antigen receptor (CAR) and one or more of signaling proteins selected from K13-vFLIP, MC159-vFLIP, cFLIP-L, cFLIP-p22, HTLV1-Tax and HTLV2-Tax, wherein the CAR comprises an a) extracellular antigen specific domain, b) a transmembrane domain and c) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein c) is located at the C-terminus of the chimeric receptor. In some embodiments, the CAR further comprises one or more co-stimulatory domains. Also provided herein are methods for treating diseases using the compositions described herein.Type: ApplicationFiled: March 29, 2017Publication date: April 18, 2019Inventor: Preet M. Chaudhary
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Publication number: 20190112381Abstract: Provided herein are B cell maturation agent (BCMA) targeting trispecific proteins comprising a domain binding to CD3, a half-life extension domain, and a domain binding to BCMA. Also provided are pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such BCMA targeting trispecific proteins. Also disclosed are methods of using the disclosed BCMA targeting trispecific proteins in the prevention, and/or treatment diseases, conditions and disorders.Type: ApplicationFiled: October 12, 2018Publication date: April 18, 2019Inventors: Holger Wesche, Bryan D. Lemon, Richard J. Austin
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Publication number: 20190112382Abstract: A method of treating a medical disorder associated with the presence of pathogenic B cells expressing B cell maturation antigen (BCMA), the method comprising administering to a subject an isolated antibody or antibody fragment comprising specific VH and VL domain complementary determining region (CDR) sequences, wherein the antibody or fragment thereof specifically binds an epitope of the extracellular domain of CD269 (BCMA)Type: ApplicationFiled: October 25, 2018Publication date: April 18, 2019Inventors: Felix Oden, Stephen Marino, Oliver Daumke
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Publication number: 20190112383Abstract: A method of treating B-cell lymphoma comprises administering to a patient a chemotherapeutic regimen, followed by treatment with a radiolabeled anti-CD20 antibody, wherein at the time of said treatment with said radiolabeled antibody said patient is not refractory to said chemotherapeutic regimen and has not relapsed.Type: ApplicationFiled: May 14, 2018Publication date: April 18, 2019Inventors: Werner Krause, Joachim Kalmus, Jens Kuhlmann
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Publication number: 20190112384Abstract: Disclosed are methods and compositions for the detection, diagnosis, prognosis, and therapy of hematological malignancies, and in particular, B cell leukemias, lymphomas and multiple myelomas. Disclosed are compositions, methods and kits for eliciting immune and T cell responses to specific malignancy-related antigenic polypeptides and antigenic polypeptide fragments thereof in an animal. Also disclosed are compositions and methods for use in the identification of cells and biological samples containing one or more hematological malignancy-related compositions, and methods for the detection and diagnosis of such diseases and affected cell types. Also disclosed are diagnostic and therapeutic kits, as well as methods for the diagnosis, therapy and/or prevention of a variety of leukemias and lymphomas.Type: ApplicationFiled: December 17, 2018Publication date: April 18, 2019Inventors: Paul A. ALGATE, Lauren CARTER, Jonathan David CLAPPER, Alexander GAIGER, Jane MANNION, Patricia Dianne MCNEILL, Nadia ORDONEZ, Aijun WANG
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Publication number: 20190112385Abstract: The present invention relates to a human or humanized antibody, or an antibody-based binding protein, modified antibody format retaining target binding capacity, antibody derivative or fragment retaining target binding capacity, which targets Mesothelin (MN). It further relates to bi- or multispecific antibodies, to Immunoligand-Drug Conjugates, to Chimeric Antigen Receptors and to T-cells comprising such Chimeric Antigen Receptors.Type: ApplicationFiled: October 31, 2016Publication date: April 18, 2019Applicant: NBE-THERAPEUTICS AGInventors: Ina HELLMANN, Lorenz WALDMEIER, Ulf GRAWUNDER, Roger BEERLI
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Publication number: 20190112386Abstract: The invention relates to cancer therapeutics, in particular, the system of making cancer cells more susceptible to effector cells by introduction of cellular therapy targets into the cancer cells.Type: ApplicationFiled: August 1, 2018Publication date: April 18, 2019Inventors: Roy Lobb, Paul Rennert
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Publication number: 20190112387Abstract: The present invention relates to an antibody, particularly a monoclonal antibody, which binds a novel epitope of the ERBB2 tyrosine kinase receptor, wherein the unique features of said binding enable interference with receptor-mediated signalling and downstream biological effects in a novel and unanticipated fashion not obtainable with state-of-the-art therapeutic antibodies. The present invention relates to compositions comprising such an antibody and its humanized derivative, as well as methods using such an antibody and derivative, particularly in ERBB2-low/non-amplified breast cancers, particularly in combination with Trastuzumab and Pertuzumab.Type: ApplicationFiled: March 31, 2017Publication date: April 18, 2019Inventors: Leonardo SIBILIO, Patrizio GIACOMINI