Abstract: An object is to provide an antibody capable of specifically recognizing a human NRG1 protein isoform, and suppressing signal transduction in which the isoform is involved. An antibody capable of binding to a region at positions 221 to 234 of a human NRG1-? protein or an antibody capable of binding to a region at positions 213 to 239 of a human NRG1-?1 protein was successfully obtained. Further, it was also found that these antibodies had an activity of suppressing cleavage of the NRG1 protein, an activity of suppressing phosphorylation of an ErbB3 protein in a cancer cell, and an activity of suppressing in vivo tumor proliferation.
Type:
Grant
Filed:
February 7, 2014
Date of Patent:
April 3, 2018
Assignee:
MEDICAL & BIOLOGICAL LABORATORIES CO., LTD.
Abstract: In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a truncated, ligand-binding portion of the extracellular domain of endoglin (ENG) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders.
Type:
Grant
Filed:
April 19, 2012
Date of Patent:
April 3, 2018
Assignee:
Acceleron Pharma, Inc.
Inventors:
Asya Grinberg, Roselyne Castonguay, Eric Werner, Ravindra Kumar
Abstract: The present disclosure provides chimeric proteins having an N-terminus coupled to a C-terminus, wherein the N-terminus comprises an N-terminal portion of fibroblast growth factor (FGF) 2 and the C-terminus comprises a portion of an FGF1 protein, wherein the chimeric protein comprises at least 95% sequence identity to SEQ ID NO: 9, 10, 11, 12 or 13. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.
Type:
Grant
Filed:
April 6, 2016
Date of Patent:
March 27, 2018
Assignee:
Salk Institute for Biological Studies
Inventors:
Jae Myoung Suh, Michael Downes, Ronald M. Evans, Annette Atkins, Senyon Choe, Witek Kwiatkowski
Abstract: The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF21 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the ?Klotho-FGF receptor complex involving the use of chimeric proteins of the present invention.
Abstract: The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF19 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the ?Klotho-FGF receptor complex involving the use of chimeric proteins of the present invention.
Abstract: Two types of antibodies (35-1 antibody and 292 antibody) capable of binding to phenylalanine at position 115, isoleucine at position 117, glycine at position 140, glutamic acid at position 141, and arginine at position 142 of a human HB-EGF protein were successfully obtained. Then, it was also found that these antibodies had an activity of suppressing cleavage of the human HB-EGF protein, and an activity of suppressing EGFR phosphorylation that would occur when the human HB-EGF bound to the EGFR. Further, determined were amino acid sequences of light chain and heavy chain variable regions of these antibodies and sequences of CDRs of each of the variable regions.
Type:
Grant
Filed:
April 17, 2014
Date of Patent:
March 20, 2018
Assignee:
MEDICAL & BIOLOGICAL LABORATIVES CO., LTD.
Abstract: Skin inflammation in a human subject is reduced by administering to the subject a pharmaceutical composition that includes a pharmaceutically acceptable carrier and a therapeutically effective amount of an agent that selectively binds IL-1?.
Abstract: The present invention relates to antibodies that specifically bind to the human c-Met receptor protein and that act as strict antagonists of hepatocyte growth factor (HGF)-mediated activation of the c-Met receptor and also inhibit HGF-independent activation of the human c-Met protein.
Type:
Grant
Filed:
December 6, 2013
Date of Patent:
February 6, 2018
Assignee:
ARGEN-X N.V.
Inventors:
Anna Hultberg, Michael Saunders, Johannes De Haard, Els Festjens, Natalie De Jonge, Paolo Michieli, Cristina Basilico, Torsten Dreier
Abstract: The invention relates to constructs comprising a transmembrane protein pore subunit and a nucleic acid handling enzyme. The pore subunit is covalently attached to the enzyme such that both the subunit and enzyme retain their activity. The constructs can be used to generate transmembrane protein pores having a nucleic acid handling enzyme attached thereto. Such pores are particularly useful for sequencing nucleic acids. The enzyme handles the nucleic acid in such a way that the pore can detect its component nucleotides by stochastic sensing.
Type:
Grant
Filed:
August 8, 2014
Date of Patent:
February 6, 2018
Assignee:
Oxford Nanopore Technologies Limited
Inventors:
Lakmal Jayasinghe, John Hagan Pryce Bayley, Stephen Cheley, Brian McKeown, James White, James Anthony Clarke
Abstract: The present invention is directed to antibodies and fragments thereof and humanized versions thereof having binding specificity for IL-6. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the VH, VL and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-IL-6 antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-IL-6 antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-IL-6 antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with IL-6.
Type:
Grant
Filed:
November 18, 2014
Date of Patent:
February 6, 2018
Assignee:
ALDERBIO HOLDINGS LLC
Inventors:
Leon F. Garcia-Martinez, Anne Elisabeth Carvalho Jensen, Katie Olson Anderson, Benjamin H. Dutzar, Ethan Wayne Ojala, Brian R. Kovacevich, John A. Latham, Jeffrey T. L. Smith
Abstract: 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:
Grant
Filed:
April 24, 2013
Date of Patent:
February 6, 2018
Assignee:
ThromboGenics NV
Inventors:
Claudia Fromond, Hoa Thu Ngo, Richard Zwaal, Sofie Notebaert
Abstract: In certain embodiments, this disclosure relates to pharmaceutical formulations for polypeptide and lipophilic moiety conjugates suitable for injection into humans and other animals and methods of preparation. In certain embodiments, the disclosure relates to a method of preparing the formulation comprising lyophilizing, solubilizing in ammonium acetate, filtering to create mono-disperse particles, re-lyophilizing, and solubilizing the micelles in a dextrose solution for injection.
Abstract: A fusion polypeptide comprising (A)x-M-(A?)y, wherein A and A? are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A? may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.
Type:
Grant
Filed:
October 10, 2014
Date of Patent:
December 12, 2017
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
James P. Fandl, Gang Chen, Nicholas J. Papadopoulos, Thomas H. Aldrich
Abstract: A monoclonal antibody, which recognizes at least two amino acids among amino acids located at position 69, position 79, position 81 and position 102 of human midkine, has been found to have excellent reactivity with and excellent neutralizing activity against human midkine. Moreover, the activity of suppressing the proliferation of tumor has been observed in the antibody having excellent neutralizing activity. The use of the antibody of the present invention makes it possible to treat cancer effectively and to detect or purify midkine efficiently.
Type:
Grant
Filed:
July 30, 2013
Date of Patent:
December 12, 2017
Assignees:
NATIONAL UNIVERSITY CORPORATION NAGOYA UNIVERSITY, MEDICAL & BIOLOGICAL LABORATORIES CO., LTD.
Abstract: The present invention provides human anti-human epidermal growth factor receptor (EGFR) antibodies and their encoding genes and applications thereof. By gene engineering means and phage surface display technology, the present invention screens anti-human EGFR gene engineering single chain antibody from fully synthetic single chain human antibody library, and obtains the antibody variable gene sequence thereof, and based thereon, constructs intact human monoclonal antibody, to further obtain high-purity antibody protein. The binding affinity of the antibody of the present invention with human EGFR is no more than 1 nM, and the mutants affinity thereof is no more than 10 nM; and the identification of the immunity activity and bioactivity of antibodies protein IgG is completed, confirming that the antibody of the present invention has good bioactivity of inhibiting the tumor growth of EGFR expressing cell A431 tumor-bearing model mouse.
Abstract: The present invention is directed to antibodies and fragments thereof and humanized versions thereof having binding specificity for IL-6. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the VH, VL and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-IL-6 antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-IL-6 antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-IL-6 antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with IL-6.
Type:
Grant
Filed:
April 30, 2015
Date of Patent:
December 5, 2017
Assignee:
ALDERBIO HOLDINGS LLC
Inventors:
Leon F. Garcia-Martinez, Ann Elisabeth Carvalho Jensen, Katie Olson Anderson, Benjamin H. Dutzar, Ethan W. Ojala, Brian R. Kovacevich, John A. Latham, Jeffrey T. L. Smith
Abstract: The ratio of concentrations of pro-adrenomedullin (pro-ADM)/pro-endothelin (pro-END) immunoreactivity in body fluids of critically ill patients is used as for the diagnosis, course control and prognosis, including an assessment of the mortality risk, of severe life threatening diseases. Further, a treatment of critically ill patients having high levels of pro-ADM but insufficient levels of pro-END immunoreactivities with a medicament comprising vasoconstrictive endothelin or its precursors, and/or endothelin agonists or adrenomedullin antagonists is provided.
Type:
Grant
Filed:
December 1, 2005
Date of Patent:
November 28, 2017
Assignee:
ADRENOMED AG
Inventors:
Andreas Bergmann, Joachim Struck, Nils G. Morgenthaler
Abstract: The present invention relates to amino acid sequences that are directed against proteins from the group of the Angiopoietin/Tie family such as Tie1, Tie2, Ang1, Ang2, Ang3, Ang4, Angptl1, Angptl2, Angptl3, Angptl4, Angptl5, Angptl6, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more of such amino acid sequences.
Type:
Grant
Filed:
May 18, 2016
Date of Patent:
November 21, 2017
Assignee:
Ablynx N.V.
Inventors:
Maria Gonzalez Pajuelo, Michael John Scott Saunders, Johannes Joseph Wilhelmus De Haard, Peter Vanlandschoot
Abstract: The invention provides IGFBP7 immunoassays with improved clinical performance, particularly when used in the evaluation of renal injuries. The immunoassays rely on the selection and use of antibodies and antibody pairs that exhibit improved assay performance when used in complex clinical specimens such as biological fluids, and particularly when used in rapid assay formats such as lateral flow test devices.
Type:
Grant
Filed:
November 6, 2014
Date of Patent:
November 21, 2017
Assignee:
ASTUTE MEDICAL, INC.
Inventors:
Ravi A. Vijayendran, Srivatsa Venkatasubbarao
Abstract: This disclosure provides peptides, polypeptides, fusion polypeptides, compositions, and methods for enhancing or increasing the stability of a polypeptide (e.g., Taq polymerase). Such peptides, polypeptides, fusion polypeptides, or compositions include polypeptides linked to a peptide tag that enhances the stability of the polypeptide. The peptides, polypeptides, fusion polypeptides, compositions may also enhance the activity, specificity, and/or fidelity of other polypeptides in a reaction mixture. The disclosure also provides methods of using such peptides, polypeptides, fusion polypeptides, compositions.