Chimeric, Mutated, Or Recombined Hybrid (e.g., Bifunctional, Bispecific, Rodent-human Chimeric, Single Chain, Rfv, Immunoglobulin Fusion Protein, Etc.) Patents (Class 530/387.3)
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Patent number: 10471099Abstract: Methods for the in vitro production of enucleated red blood cells and the enucleated red blood cells thus prepared are provided. Such enucleated red blood cells may express a sortaggable surface protein, which allows for surface modification in the presence of a sortase. Also described herein are surface modified enucleated red blood cells, e.g., conjugated with an agent of interest such as a peptide, a detectable label, or a chemotherapeutic agent, and uses thereof in delivering the agent to a subject.Type: GrantFiled: May 9, 2014Date of Patent: November 12, 2019Assignee: Whitehead Institute for Biomedical ResearchInventors: Harvey Lodish, Hidde L. Ploegh, Hsiang-Ying Lee, Jiahai Shi, Lenka Hoffman, Novalia Pishesha
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Patent number: 10457748Abstract: The present disclosure relates to a multi-specific antibody molecule comprising or consisting of three polypeptides: a) a polypeptide chain of formula (I): (Vxx)nVx-Cx-X-V1; and b) a polypeptide chain of formula (II): (Vyy)nVy-Cy c) a polypeptide of formula (III): V2 wherein Vx represents a variable domain, Vxx represents a variable domain, Cx represents a constant region, X represents a linker, V represents a variable domain, Vy represents a variable domain, Vyy represents a variable domain, Cy represents a constant region, V2 represents a variable domain, n independently represents 0 or 1, wherein the polypeptide chain of formula (I) and the polypeptide chain of formula (II) is aligned such that the constant regions Cx and Cy are paired and the variable domains Vx and Vy are paired to form a binding domain and optionally a disulphide bond is present between V and V2, in particular where a disulphide bond is present.Type: GrantFiled: December 20, 2013Date of Patent: October 29, 2019Assignee: UCB BIOPHARMA SPRLInventors: Emma Dave, Sam Philip Heywood, David Paul Humphreys
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Patent number: 10457749Abstract: The invention relates to the purification of bispecific antibodies carrying a different specificity for each binding site of the immunoglobulin molecule from a mixture of monospecific antibodies. The bispecific antibodies are composed of a single heavy chain and two different light chains, one containing a Kappa constant domain and the other a Lambda constant domain. This invention in particular relates to the isolation of these bispecific antibodies from mixtures that contain monospecific antibodies having two Kappa light chains or portions thereof and monospecific antibodies having two Lambda light chains or portions thereof. The invention also provides the methods of efficiently purifying these bispecific antibodies.Type: GrantFiled: March 14, 2016Date of Patent: October 29, 2019Assignee: NovImmune SAInventors: Nicolas Fouque, Jean François Depoisier, Keith Wilson, Judith Vajda, Egbert Müller, Romain Dabre
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Patent number: 10392438Abstract: The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided. The present invention also relates to a humanized antibody that specifically binds human TrkB and methods for producing and using the antibody to, inter alia, treat a hearing loss disorder.Type: GrantFiled: May 13, 2015Date of Patent: August 27, 2019Assignee: PFIZER INC.Inventors: Eric M. Bennett, Nathan Higginson-Scott, Lioudmila Tchistiakova, Kimberly A. Marquette, Janet E. Paulsen, Ruth E. Gimeno
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Patent number: 10377833Abstract: The present invention relates to humanized bispecific anti-HER2 antibodies that comprise one antigen binding site containing variable regions of heavy and light chain of trastuzumab, and another antigen binding site containing variable regions of heavy and light chain of pertuzumab. The bispecific anti-HER2 antibodies is effective for treating cancer, such as breast cancer, gastric cancer, or ovarian cancer. Preferred bispecific anti-HER antibodies of the present invention are afucosylated antibodies. The present invention also relates to Chinese Hamster ovary (CHO) mutant cell line that has a dysfunctional Slc35C1 gene, which is the only dysfunctional gene in the mutant that affects glycan regulation.Type: GrantFiled: July 21, 2017Date of Patent: August 13, 2019Assignee: Beijing Mabworks Biotech Co., Ltd.Inventors: Feng Li, Boyan Zhang, Pei Ye, Jian Zhao, Sijia Huang, Chunyang Jin
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Patent number: 10357571Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a masked monoclonal antibody (mAb) is provided, which includes a therapeutic mAb and a mask, the mask comprising protein A and protein L attached by a protease cleavable linker.Type: GrantFiled: November 23, 2015Date of Patent: July 23, 2019Assignees: Thomas Jefferson University, City of HopeInventors: John C. Williams, Cindy Zer, Kendra N. Avery, Ulrich Rodeck, Joshua M. Donaldson, Csaba Kari
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Patent number: 10351630Abstract: This disclosure provides a robust, sensitive, and specific assay for the detection and measurement of DPP-4 levels in samples obtained from human patients. The disclosure further provides novel anti-DPP-4 monoclonal antibodies that recognize human DPP-4, and assay kits comprising one or more of these antibodies.Type: GrantFiled: January 8, 2016Date of Patent: July 16, 2019Assignee: MEDIMMUNE, LLCInventors: Chien-Ying Chang, Xiaodong Xiao, Partha Chowdhury
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Patent number: 10344067Abstract: The present invention relates to a recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding an IL-12 polypeptide, wherein said IL-12 polypeptide is an IL-12 fusion polypeptide comprising a p35 subunit of an IL-12 and a p40 subunit of an IL-12; to a polynucleotide encoding the same, and to a kit comprising the same. Moreover, the present invention relates to a method for treating cancer in a subject afflicted with cancer, comprising contacting said subject with a recombinant virus of the family Paramyxoviridae of the invention, and thereby, treating cancer in a subject afflicted with cancer.Type: GrantFiled: February 24, 2017Date of Patent: July 9, 2019Assignees: DEUTSCHES KREBSFORSCHUNGSZENTRUM, RUPRECHT-KARLS UNIVERSITAETInventors: Guy Ungerechts, Christine Engeland, Ruta Veinalde
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Patent number: 10342869Abstract: Disclosed herein are compositions and kits which comprise anti-CD38 antibodies and lenalidomide compounds. Also disclosed are methods for treating cancers, such as multiple myeloma, in subjects with the compositions and kits.Type: GrantFiled: December 6, 2013Date of Patent: July 9, 2019Assignees: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, SANOFIInventors: Byron C. Hann, Blake Tomkinson, Thomas G. Martin, III, Blake T. Aftab
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Patent number: 10316084Abstract: The invention provides anti-LgR5 antibodies and methods of using the same.Type: GrantFiled: November 29, 2016Date of Patent: June 11, 2019Assignee: GENENTECH, INC.Inventors: Andrew G. Polson, Weiguang Mao, Ron Firestein
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Patent number: 10294296Abstract: Administration of a mAb that specifically binds IL-1? is useful for treating tumor-associated diseases in human subjects.Type: GrantFiled: August 23, 2011Date of Patent: May 21, 2019Assignee: XBiotech, Inc.Inventor: John Simard
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Patent number: 10273281Abstract: This application relates to CD80 (B7-1) extracellular domain (ECD) polypeptides and CD80-ECD fusion molecules and their use in treatment of cancer, both alone and in combination with other therapeutic agents, such as immune stimulating agents such as PD-1/PD-L1 inhibitors.Type: GrantFiled: November 1, 2016Date of Patent: April 30, 2019Assignee: Five Prime Therapeutics, Inc.Inventors: Thomas Brennan, David Bellovin, David Busha, Barbara Sennino
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Patent number: 10273299Abstract: The present invention is directed to particular antibodies and fragments thereof that find use in the detection, prevention and treatment of diseases and disorders associated with abnormal angiogenesis. In particular, these antibodies detect tumor endothelial marker 8 (TEM8) in its native and cell-surface expressed form. Also disclosed are improved methods for producing monoclonal antibodies, as well as pharmaceutical compositions and kits.Type: GrantFiled: April 4, 2016Date of Patent: April 30, 2019Assignee: The United States of America, as Represented by the Secretary, Department of Health and Human ServicesInventors: Arthur E. Frankel, Yunpeng Su, Brad St. Croix, Stephen H. Leppla
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Patent number: 10266578Abstract: The present disclosure generally relates to modified relaxin polypeptides, such as modified human relaxin 2 polypeptides, comprising a non-naturally encoded amino acid which is linked to a pharmacokinetic enhancer, and therapeutic uses of such polypeptides, such as for the treatment of cardiovascular conditions (such as heart failure) and/or conditions relating to fibrosis.Type: GrantFiled: February 8, 2018Date of Patent: April 23, 2019Assignee: Bristol-Myers Squibb CompanyInventors: Gene M. Dubowchik, Olafur S. Gudmundsson, Xiaojun Han, R. Michael Lawrence, Dasa Lipovsek, Cort S. Madsen, Claudio Mapelli, Paul E. Morin, Michael C. Myers
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Patent number: 10261083Abstract: The invention relates generally to compositions and methods for detecting protease activity in a subject or a biological sample using activatable antibodies, and the use of these compositions and methods in a variety of diagnostic indications.Type: GrantFiled: January 3, 2014Date of Patent: April 16, 2019Assignee: CytomX Therapeutics, Inc.Inventors: Olga Vasiljeva, Elizabeth-Edna Mary Menendez
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Patent number: 10253091Abstract: By altering amino acid sequences, the present inventors successfully produced constant regions that can confer antibodies with particularly favorable properties for pharmaceutical agents. When used to produce antibodies, the altered constant regions produced according to the present invention significantly reduce heterogeneity. Specifically, the antibody homogeneity can be achieved by using antibody heavy chain and light chain constant regions introduced with alterations provided by the present invention. More specifically, the alterations can prevent the loss of homogeneity of antibody molecules due to disulfide bond differences in the heavy chain. Furthermore, in a preferred embodiment, the present invention can improve antibody pharmacokinetics as well as prevent the loss of homogeneity due to C-terminal deletion in antibody constant region.Type: GrantFiled: April 7, 2015Date of Patent: April 9, 2019Assignee: Chugai Seiyaku Kabushiki KaishaInventors: Tomoyuki Igawa, Taichi Kuramochi, Atsuhiko Maeda, Hirotake Shiraiwa
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Patent number: 10251377Abstract: The present invention relates to humanisation of antibodies in vivo. The invention provides non-human vertebrates, cells, populations and methods useful for humanising chimaeric antibodies in vivo. Using the present invention it is possible straightforwardly and rapidly to obtain antigen-specific antibodies that are fully human (ie, comprising human variable and constant regions) and have undergone recombination, junctional diversification, affinity maturation and isotype switching in vivo in a non-human vertebrate system. Furthermore, such antibodies are humanised (eg, totally human)—and selected—totally in vivo, and as such the present invention harnesses in vivo filtering for expressibility, affinity and biophysical characteristics in the context of the desired human variable and constant region pairings. This is avoids problems of down-grading antibody characteristics when humanising the constant region of chimaeric antibodies in vitro.Type: GrantFiled: September 26, 2014Date of Patent: April 9, 2019Assignee: Kymab LimitedInventor: Jasper Clube
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Patent number: 10239951Abstract: Described herein are isolated bi-specific antigen binding constructs, e.g., antibodies. The bi-specific antigen binding constructs include two antigen binding polypeptide constructs, e.g., a Fab and an scFv. The first antigen-binding polypeptide construct monovalently and specifically binds to extracellular domain 4 (ECD4) of HER2 (human epidermal growth factor receptor 2); the second antigen-binding polypeptide construct monovalently and specifically binds to an extracellular domain (ECD) of HER3 (human epidermal growth factor receptor 3). One antigen binding polypeptide construct is a Fab format and the other antigen binding polypeptide construct is an scFv format. The bi-specific antigen binding constructs includes an Fc having two Fc polypeptides each having a CH3 domain for dimerization. Each Fc polypeptide is linked to the C-terminus of one of the antigen binding polypeptide constructs with or without a linker.Type: GrantFiled: May 8, 2014Date of Patent: March 26, 2019Assignee: Zymeworks Inc.Inventors: Gordon Yiu Kon Ng, Peter Wing Yiu Chan, Grant Raymond Wickman
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Patent number: 10233220Abstract: Anti-tumor immune responses to modified self-epitopes. The present invention relates to the use of tumor-associated epitopes in medicine and in particular in the treatment of cancer. The epitopes stimulate an immune reaction against the tumor and have a modification selected from deimination of arginine to citrulline, nitration of tyrosine, oxidation of tryptophan and deamination of glutamine or asparagine. The invention also relates to nucleic acids comprising sequences that encode such epitopes for use in the treatment of cancer.Type: GrantFiled: February 5, 2015Date of Patent: March 19, 2019Assignee: Scancell LimitedInventors: Linda Gillian Durrant, Victoria Anne Brentville, Rachael Louise Metheringham
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Patent number: 10233237Abstract: The present application is directed to heterodimeric antibodies and methods of use.Type: GrantFiled: November 21, 2013Date of Patent: March 19, 2019Assignee: AMGEN INC.Inventors: Gunasekaran Kannan, Monica Florio, Zhi Liu, Wei Yan
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Patent number: 10220081Abstract: The invention provides HVEM cis complexes which include, for example, HVEM/BTLA, HVEM/CD160 and HVEM/gD cis complexes. The invention provides ligands and agents that bind to HVEM cis complexes, such as antibodies. The invention further provides methods of use of the HVEM cis complexes, and the ligands and agents (e.g., LIGHT polypeptide sequence) that bind to the HVEM cis complexes.Type: GrantFiled: February 7, 2014Date of Patent: March 5, 2019Assignee: LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGYInventors: Carl F. Ware, Timothy C. Cheung, Marcos Steinberg
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Patent number: 10196442Abstract: Described herein are antibodies against GPR49 and uses of such antibodies. Various aspects relate to monoclonal, humanized, or fully human antibodies against GPR49, hybridomas or other cell lines expressing such antibodies, nucleic acids and vectors comprising nucleic acids encoding for such antibodies, and methods of treating cancer with such antibodies.Type: GrantFiled: December 11, 2015Date of Patent: February 5, 2019Assignee: Bionomics Inc.Inventors: Christopher L. Reyes, Peter Chu, Xiangyang Tan, Christilyn Graff, Weixing Yang
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Patent number: 10196437Abstract: Provided are: an antibody binding specifically to a surface antigen, pre-S1, of a hepatitis B virus (HBV); a polynucleotide coating the antibody; an expression vector comprising the polynucleotide; a transformation agent comprising the expression vector; and use of the antibody in treating or preventing HBV infection and in detecting an HBV.Type: GrantFiled: November 27, 2015Date of Patent: February 5, 2019Assignee: GENEONE LIFE SCIENCE, INC.Inventors: Hyo Jeong Hong, Jin Hong Kim
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Patent number: 10196453Abstract: Clostridium difficile is the most common hospital acquired pathogen in the United States, and infection is in many cases fatal. Toxins A and B are its major virulence factors, but increasingly a third toxin may be present, known as C. difficile transferase (CDT). An ADP-ribosyltransferase that causes actin cytoskeletal disruption, CDT is typically produced by the major, hypervirulent strains and has been associated with more severe disease. It is disclosed herein that CDT enhances the virulence of two PCR-ribotype 027 strains in mice. The toxin induces pathogenic host inflammation via a novel Toll-like Receptor 2 (TLR2) dependent pathway, resulting in the suppression of a protective host eosinophilic response. Finally, it is disclosed that restoration of TLR2 deficient eosinophils is sufficient for protection from a strain producing CDT. These findings offer an explanation for the enhanced virulence of CDT-expressing C.Type: GrantFiled: May 17, 2017Date of Patent: February 5, 2019Assignee: University of Virginia Patent FoundationInventors: Carrie Adeline Cowardin, William A. Petri, Jr.
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Patent number: 10179819Abstract: The present invention provides antibodies that bind to prostate-specific membrane antigen (PSMA), bispecific antibodies that bind to PSMA and CD3, and methods of using the same. According to certain embodiments, the antibodies of the invention bind human PSMA with high affinity and bind CD3 to induce human T cell proliferation. The invention includes antibodies that bind PSMA and CD3 and induce T cell-mediated killing of PSMA-expressing tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human PSMA. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of prostate tumors expressing PSMA.Type: GrantFiled: July 29, 2016Date of Patent: January 15, 2019Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Jessica R. Kirshner, Alison Crawford, Gavin Thurston, Eric Smith, Lauric Haber, Drew Dudgeon, Ashique Rafique
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Patent number: 10174114Abstract: The present invention concerns compositions and methods of use of humanized anti-HLA-DR antibodies. In preferred embodiments, the antibodies induce apoptosis and inhibit proliferation of lymphoma cells without inducing CDC or ADCC. In more preferred embodiments, the humanized anti-HLA-DR antibodies bind to the same epitope of HLA-DR as, or compete for binding to HLA-DR with, a murine L243 antibody. Most preferably, the humanized anti-HLA-DR antibody exhibits a higher affinity for HLA-DR than the parental murine antibody. The humanized HLA-DR antibody is of use for therapy of various diseases such as cancer, autoimmune disease or immune dysregulatory function, and is of particular use for therapy of B cell lymphomas and leukemias. In most preferred embodiments, the humanized anti-HLA-DR antibody is capable of inducing at least partial remission of lymphomas that are resistant to other B cell antibodies, such as rituximab.Type: GrantFiled: November 16, 2016Date of Patent: January 8, 2019Assignee: Immunomedics, Inc.Inventors: David M. Goldenberg, Hans J. Hansen, Chien-Hsing Chang
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Patent number: 10167334Abstract: 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: GrantFiled: April 3, 2016Date of Patent: January 1, 2019Assignees: XOMA TECHNOLOGY LTD., THE REGENTS OF THE UNIVERSITY OF CALIFORNIAInventors: Amer M. Mirza, Rosemary J. Akhurst, Ou Li
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Patent number: 10138293Abstract: The present invention relates to nucleic acids which encode the heavy chains and light chains of a novel domain exchanged, bivalent, bispecific antibody, and vectors comprising the same.Type: GrantFiled: January 31, 2012Date of Patent: November 27, 2018Assignee: HOFFMANN-LA ROCHE, INC.Inventors: Christian Klein, Wolfgang Schaefer
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Patent number: 10130721Abstract: A bifunctional polypeptide comprising a specific binding partner for a peptide-MHC epitope, such as an antibody or T cell receptor, and an immune effector, such as an antibody or a cytokine, the immune effector part being linked to the N-terminus of the peptide-MHC binding part.Type: GrantFiled: May 19, 2010Date of Patent: November 20, 2018Assignee: Immunocore LimitedInventors: Bent Karsten Jakobsen, Annelise Brigitte Vuidepot, Yi Li
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Patent number: 10117949Abstract: A recombinant fusion protein comprising a human erythropoietin peptide portion linked to an immunoglobulin peptide portion is described. The fusion protein has a prolonged half-life in vivo in comparison to naturally occurring or recombinant native human erythropoietin. In one embodiment of the invention the protein has a half-life in vivo at least three fold higher than native human erythropoietin. The fusion protein also exhibits enhanced erythropoietic bioactivity in comparison to native human erythropoietin. In one embodiment, the fusion protein comprises the complete peptide sequence of a human erythropoietin (EPO) molecule and the peptide sequence of an Fc fragment of human immunoglobulin IgG1. The Fc fragment in the fusion protein includes the hinge region, CH2 and CH3 domains of human immunoglobulin IgG1. The EPO molecule may be linked directly to the Fc fragment to avoid extraneous peptide linkers and lessen the risk of an immunogenic response when administered in vivo.Type: GrantFiled: January 25, 2007Date of Patent: November 6, 2018Assignee: NOVAGEN HOLDING CORPORATIONInventors: Haitao Wang, Yong Du, Rui Zhang, Jing Xu, Longbin Liu
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Patent number: 10106612Abstract: Herein is reported a method for producing a bispecific antibody comprising the step of incubating (i) an antibody Fab fragment or a scFv antibody comprising within the 20 C-terminal amino acid residues the amino acid sequence LPX1TG (SEQ ID NO: 01), (ii) a one-armed antibody comprising a full length antibody heavy chain, a full length antibody light chain, and an Fc-heavy chain, whereby the full length antibody heavy chain and the full length antibody light chain are cognate antibody chains that thereof forms an antigen binding site, whereby the full length antibody heavy chain and the Fc-heavy chain are covalently linked to each other via one or more disulfide bonds forming an antibody hinge region, and whereby the Fc-heavy chain has an oligoglycine amino acid sequence at its N-terminus, and (iii) a Sortase A enzyme.Type: GrantFiled: December 22, 2014Date of Patent: October 23, 2018Assignee: HOFFMANN-LA ROCHE INC.Inventors: Sebastian Fenn, Erhard Kopetzki, Georg Tiefenthaler
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Patent number: 10100130Abstract: The present invention provides dual specificity antibody fusion proteins comprising an antibody Fab or Fab? fragment with specificity for an antigen of interest, said fragment being fused to at least one single domain antibody which has specificity for a second antigen of interest.Type: GrantFiled: October 24, 2017Date of Patent: October 16, 2018Assignee: UCB BIOPHARMA SPRLInventors: David Paul Humphreys, Emma Dave, Laura Griffin, Sam Philip Heywood
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Patent number: 10077298Abstract: The present invention provides heterodimer pairs that can comprise a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain or fragment thereof. At least one of the heterodimers can comprise one or more amino acid modifications in the CH1 and/or CL domains, one or more amino acid modifications in the VH and/or VL domains, or a combination thereof. The modified amino acid(s) can be part of the interface between the light chain and heavy chain and are typically modified to create preferential pairing between each heavy chain and a desired light chain such that when the two heavy chains and two light chains of the heterodimer pair are co-expressed in a cell, the heavy chain of the first heterodimer preferentially pairs with one of the light chains rather than the other. Likewise, the heavy chain of the second heterodimer typically preferentially pairs with the second light chain rather than first.Type: GrantFiled: November 28, 2013Date of Patent: September 18, 2018Assignee: ZYMEWORKS INC.Inventors: Adam Louis Corper, Dunja Urosev, Stacey A. L. Tom-Yew, Dustin Weyland Blue Bleile, Thomas Spreter Von Kreudenstein, Surjit Dixit, Paula Irene Lario, Mario Sanches
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Patent number: 10066022Abstract: The invention provides anti-Ly6E antibodies, immunoconjugates and methods of using the same. In some embodiments, the anti-Ly6E antibodies comprise heavy chain HVRs comprising the amino acid sequences of SEQ ID NOs: 32-34 and/or light chain HVRs comprising the amino acid sequences of SEQ ID NOs: 29-31.Type: GrantFiled: February 8, 2016Date of Patent: September 4, 2018Assignee: Genentech, Inc.Inventors: Jyoti Asundi, Ron Firestein, Paul Polakis, Chie Sakanaka, Peter Chang, Rayna Takaki Venook
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Patent number: 10059760Abstract: The present invention relates to a class-G immunoglobulin against the anthrax toxin protective antigen (PA), or one of the fragments of same, comprising at least: a variable heavy-chain region comprising an amino acid sequence represented by the sequence SEQ ID NO: 1, or comprising an amino acid sequence having at least 90% identity with the sequence SEQ ID NO: 1, and comprising the amino acids Leucine in position 51 and Glycine in position 67, and a variable light-chain region comprising an amino acid sequence represented by the sequence SEQ ID NO: 2, or comprising an amino acid sequence having at least 90% identity with the sequence SEQ ID NO: 2, and comprising a Leucine amino acid in position 55. The invention also relates to the uses of such an immunoglobulin.Type: GrantFiled: January 16, 2015Date of Patent: August 28, 2018Assignees: LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIES, ETAT FRANCAIS REPRESENTE PAR LE DIRECTEUR CENTRAL DU SERVICE DE SANTE DES ARMEESInventors: Christian Behrens, Philippe Klein, Denis Hoguet
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Patent number: 10017567Abstract: Described herein are compositions and methods relating to LAP-binding agents, including, for example, anti-LAP antibodies, and to their use in methods of treatment of cancer. LAP-binding agents affected both systemic and intra-tumor immunity and were shown effective to treat a broad spectrum of cancer types.Type: GrantFiled: July 13, 2017Date of Patent: July 10, 2018Assignee: The Brigham and Women's Hospital, Inc.Inventors: Howard L. Weiner, Galina Gabriely, Andre Pires Da Cunha, Takatoku Oida
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Patent number: 10010625Abstract: The present invention provides heavy chain immunoglobulins of the VHH type or fragment thereof having affinity for a target antigen of interest, including glycoprotein D2 (gD2) of HSV-2 or antigen thereof, and for envelope proteins of HIV-1 or an antigen thereof linked to Pseudomonas exotoxin A or functional fragments thereof. Also included are multimeric forms of the immunoglobulins and their use in the prevention and/or treatment of HSV2 and/or HIV-1.Type: GrantFiled: January 2, 2015Date of Patent: July 3, 2018Assignee: The Johns Hopkins UniversityInventors: Richard Markham, Eileen Geoghegan
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Patent number: 10000574Abstract: The present invention relates to compositions comprising polypeptides, especially polypeptides capable of specifically binding predetermined antigens. The polypeptide in the composition comprises at least two antigen binding sites. These at least two antigen binding sites are located on a single polypeptide chain. One of the at least two antigen binding sites specifically binds the human CD3 antigen. The polypeptide may exist in both monomeric form and multimeric form. The multimeric form of the polypeptide constitutes no more than 5% of the total weight of the combined monomeric and multimeric forms of said polypeptide.Type: GrantFiled: November 26, 2004Date of Patent: June 19, 2018Assignee: AMGEN RESEARCH (MUNICH) GMBHInventors: Robert Hofmeister, Nadja Prang, Andreas Wolf, Frank Hanakam, Thomas Urbig, Christian Itin, Patrick Baeuerle
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Patent number: 9969810Abstract: The invention provides antibodies that specifically bind to OX40 (CD134), referred to as OX40 antibodies, anti-OX40 or anti-OX40 antibodies. Invention antibodies that specifically bind to OX40 include mammalian (human, primate, etc.), humanized and chimeric anti-OX40 antibodies. Invention antibodies and antibody subsequences (fragments) that specifically bind to OX40 include purified and isolated antibodies, as well as pharmaceutical formulations thereof, are useful in various methods including treatment, screening and detection methods.Type: GrantFiled: September 23, 2016Date of Patent: May 15, 2018Assignee: KYOWA HAKKO KIRIN CO., LTD.Inventors: Shinichiro Kato, Rachel Soloff Nugent, Hitoshi Yoshida, Michael Croft
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Patent number: 9963716Abstract: The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.Type: GrantFiled: March 26, 2014Date of Patent: May 8, 2018Assignee: Kymab LimitedInventors: Allan Bradley, E-Chiang Lee, Qi Liang, Dominik Spensberger, Nicholas England
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Patent number: 9951145Abstract: Disclosed are a CH3 domain variant pair of an antibody, a method for preparing same, and a use thereof. A mutation is induced in the CH3 domain so as to improve a yield of forming a heterodimer heavy chain constant region of an antibody. The CH3 domain heterodimer forms a heterodimer heavy chain constant region with a high efficiency of 90 to 95% or more and also has outstanding heat stability. A heterodimer heavy chain constant region including the CH3 domain heterodimer can construct a bispecific monoclonal antibody which simultaneously recognizes two kinds of antigens. The CH3 domain heterodimer and the bispecific antibody or fusion protein of an antibody constant region comprising same can be usefully applied to the treatment or prevention of a disease associated with a target antigen or a target protein.Type: GrantFiled: November 27, 2013Date of Patent: April 24, 2018Assignee: AJOU UNIVERSITY INDUSTRY—ACADEMIC COOPERATION FOUNDATIONInventors: Yong Sung Kim, Hye Ji Choi, Eun Sil Sung
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Patent number: 9920118Abstract: A complex comprising a GDF15 polypeptide is described. Methods of treating individuals with a metabolism disorder, such as, glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.Type: GrantFiled: October 29, 2015Date of Patent: March 20, 2018Assignee: NGM Biopharmaceuticals, Inc.Inventors: Wenyan Shen, Darrin Anthony Lindhout, Raj Haldankar, Hugo Matern
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Patent number: 9914771Abstract: Methods for making heteromultimeric molecules, such as bispecific antibodies, and compositions comprising these molecules are disclosed. The methods include introducing mutations in amino acids that are in contact at the interface of two polypeptides, such that the electrostatic interaction between the ion pairs is altered.Type: GrantFiled: March 3, 2016Date of Patent: March 13, 2018Assignee: ONCOMED PHARMACEUTICALS, INC.Inventors: Austin L. Gurney, Aaron K. Sato
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Patent number: 9895429Abstract: Embodiments of the invention are directed to compositions and methods related to immunogenic compositions comprising the amino acid sequence of SEQ ID NO:1 and amyloid oligomer specific antibodies that specifically bind an oligomer comprising such a peptide.Type: GrantFiled: July 28, 2015Date of Patent: February 20, 2018Assignee: THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEMInventor: Rakez Kayed
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Patent number: 9890204Abstract: The present invention relates to trivalent, bispecific antibodies, methods for their production, pharmaceutical compositions containing the antibodies, and uses thereof.Type: GrantFiled: August 7, 2012Date of Patent: February 13, 2018Assignee: Hoffmann-La Roche Inc.Inventors: Ulrich Brinkmann, Rebecca Croasdale, Eike Hoffmann, Christian Klein, Ekkehard Moessner, Juergen Michael Schanzer, Claudio Sustmann, Pablo Umana
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Patent number: 9884910Abstract: The invention relates to antibodies binding to the PDGF-C antigen and capable of inhibiting binding of PDGF-C to the PDGFR? receptor and of inhibiting PDGFR? activation by PDGF-C. Applications of such antibodies are also disclosed. These include treatment of cancer.Type: GrantFiled: April 24, 2013Date of Patent: February 6, 2018Assignee: ThromboGenics NVInventors: Claudia Fromond, Hoa Thu Ngo, Richard Zwaal, Sofie Notebaert
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Patent number: 9879095Abstract: The present invention relates to bispecific antibodies, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.Type: GrantFiled: February 21, 2013Date of Patent: January 30, 2018Assignee: HOFFMAN-LA ROCHE INC.Inventors: Ulrich Brinkmann, Alexander Haas, Silke Metz, Juergen Michael Schanzer
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Patent number: 9862779Abstract: Herein is reported a method for producing a polypeptide comprising at least two polypeptide domains comprising the step of cultivating a cell comprising (a) a nucleic acid encoding a soluble S. aureus sortase A with a C-terminal endoplasmic reticulum retention signal, (b) a nucleic acid encoding a first polypeptide domain comprising at its C-terminus a sortase motif followed by an endoplasmic reticulum retention signal, and (c) a nucleic acid encoding a second polypeptide domain comprising at its N-terminus at least a diglycine, whereby the cell secretes the sortase A conjugate of the first polypeptide domain and the second polypeptide domain, thereby producing a polypeptide comprising at least two polypeptide domains.Type: GrantFiled: March 13, 2015Date of Patent: January 9, 2018Assignee: HOFFMANN-LA ROCHE INC.Inventors: Mariel Beck, Georg Tiefenthaler
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Patent number: RE47194Abstract: Cysteine engineered anti-MUC16 antibodies are engineered by replacing one or more amino acids of a parent anti-MUC16 antibody with non cross-linked, reactive cysteine amino acids. Methods of design, preparation, screening, and selection of the cysteine engineered anti-MUC16 antibodies are provided. Cysteine engineered anti-MUC16 antibodies (Ab) are conjugated with one or more drug moieties (D) through a linker (L) to form cysteine engineered anti-MUC16 antibody-drug conjugates having Formula I: Ab-(L-D)p ??I where p is 1 to 4. Diagnostic and therapeutic uses for cysteine engineered antibody drug compounds and compositions are disclosed.Type: GrantFiled: April 7, 2015Date of Patent: January 8, 2019Assignee: Genentech, Inc.Inventors: Jagath R. Junutula, William Mallet
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Patent number: RE47223Abstract: The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.Type: GrantFiled: June 26, 2015Date of Patent: February 5, 2019Assignee: GENENTECH, INC.Inventors: Mark S. Dennis, Paul Polakis, William Mallet