Abstract: The present disclosure relates to hIL2 orthogonal ligands (“IL2 orthologs”) that specifically and selectively bind to the extracellular domain (ECD) a transmembrane polypeptide comprising of a modified hCD122 polypeptide. The binding of the hIL2 ortholog to the modified hCD122 polypeptide participates in the transduction pathway of intracellular signaling resulting in a biological activity of the native intracellular signaling patterns associated with hIL2 binding to either the intermediate or high affinity hIL2 receptor but which exhibits selectivity to an engineered cell expressing an hCD122 orthogonal receptor. The hIL2 orthologs of the present invention exhibit significantly reduced binding relative to their binding to the extracellular domain of wild type hCD122, either alone or when hCD122 is present in the form of an endogenous high or intermediate affinity hIL2 receptors.
Type:
Grant
Filed:
December 11, 2020
Date of Patent:
May 16, 2023
Assignee:
Synthekine, Inc.
Inventors:
Paul-Joseph Penaflor-Aspuria, Scott Alan McCauley, Martin Oft, Steve Kauder
Abstract: The present disclosure provides immunomodulatory fusion proteins-metal hydroxide complexes comprising an immunomodulatory domain adsorbed to a metal hydroxide via ligand exchange. The disclosure also features compositions and methods of using the same, for example, to treat cancer.
Type:
Grant
Filed:
April 24, 2020
Date of Patent:
May 9, 2023
Assignee:
Massachusetts Insttute of
Technology
Inventors:
Darrell J. Irvine, Karl Dane Wittrup, Tyson Moyer, Yash Agarwal
Abstract: The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), such as where the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof).
Abstract: The disclosure relates to methods to control trace metals during production of anti-CD38 antibodies, drug substances and drug products generated using the methods, and uses of the generated drug substances and drug products.
Type:
Grant
Filed:
November 13, 2019
Date of Patent:
April 25, 2023
Assignee:
Janssen Biotech, Inc.
Inventors:
Nicole Larmore, Balasubramanian Ramanathan, Richard Yeager
Abstract: The present disclosure provides a cytokine-based bioactivatable drug construct (“VitoKine”) platform that aims to reduce systemic mechanism-based toxicities and lead to broader therapeutic utility for proteins and cytokines such as IL-15 and IL-2 for the treatment of cancer, autoimmune diseases, inflammatory diseases, viral infection, transplantation and various other disorders. The novel VitoKine constructs of the present invention comprise: 1) a tissue or disease site targeting moiety D1 domain (“D1”), 2) a bioactivatable moiety D2 domain (“D2”), and a concealing moiety D3 domain (“D3”). Importantly, because the “active moiety” of the VitoKine construct will remain inert until activated locally by proteases that are upregulated in diseased tissues, this will limit binding of the active moiety to the receptors or to the targets in the peripheral or on the cell-surface of non-diseased cells and tissue to prevent over-activation of the pathway and reduce undesirable “on-target” “off tissue” toxicities.
Abstract: The present disclosure relates to modified IL-2 polypeptides, compositions comprising modified IL-2 polypeptides, methods of making the same, and methods of using the modified IL-2 polypeptides for treatment of diseases. In one aspect, the disclosure relates to the treatment of cancer using the modified IL-2 polypeptides. In some embodiments, the disclosed IL-2 polypeptides exhibit preferential binding characteristics to IL-2 receptor ?? complex (IL-2R?) over IL-2 receptor ??? complex (IL-2R?). In some embodiments, the molecular weight distribution of the modified IL-2 polypeptides is monodispersed.
Type:
Grant
Filed:
January 8, 2021
Date of Patent:
April 25, 2023
Assignee:
Bright Peak Therapeutics AG
Inventors:
Vijaya Raghavan Pattabiraman, Roberto Iacone, Jean-Philippe Carralot, Matilde Arévalo-Ruiz, Jeffrey William Bode, Alexander Mayweg, Fränzi Weibel, Anna Haydn, Régis Boehringer, Görkem Kurtuldu Sahin, Claudia Fetz, Camille Delon, Eric Armentani, Alexander Flohr, Giorgio Ottaviani
Abstract: Disclosed herein are interleukin (IL) conjugates (e.g., IL-2 conjugates) and use in the treatment of one or more indications. Also described herein are pharmaceutical compositions and kits comprising one or more of the interleukin conjugates (e.g., IL-2 conjugates).
Type:
Grant
Filed:
August 3, 2018
Date of Patent:
April 11, 2023
Assignee:
SYNTHORX, INC.
Inventors:
Jerod Ptacin, Carolina E. Caffaro, Marcos Milla
Abstract: The present application concerns methods for treating an IL-6-mediated disorder such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic JIA (sJIA), polyarticular course JIA (pcJIA), systemic sclerosis, or giant cell arteritis (GCA), with subcutaneously administered antibody that binds interleukin-6 receptor (anti-IL-6R antibody). In particular, it relates to identification of a fixed dose of anti-IL-6R antibody, e.g. tocilizumab, which is safe and effective for subcutaneous administration in patients with IL-6-mediated disorders. In addition, formulations and devices useful for subcutaneous administration of an anti-IL-6R antibody are disclosed.
Abstract: The present invention provides a combination therapy for treating a tumor in a subject. The combination comprises two elements. The first is a polypeptide construct comprising an attenuated Type 1 interferon (IFN) linked to an antibody which binds to a cell surface-associated antigen expressed on the tumour cell and comprising a functional Fc region. The second is a CD47 antagonist which inhibits the interaction CD47 with the SIRP? receptor.
Type:
Grant
Filed:
July 19, 2017
Date of Patent:
April 4, 2023
Assignee:
Teva Pharmaceuticals Australia Pty Ltd.
Inventors:
Sarah Lee Pogue, David Scofield Wilson, Tetsuya Taura
Abstract: This invention provides fully human monoclonal antibodies that recognize the IL-6/IL-6R complex. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.
Type:
Grant
Filed:
July 31, 2020
Date of Patent:
March 28, 2023
Assignee:
NovImmune S.A.
Inventors:
Walter Ferlin, Marie Kosco-Vilbois, Greg Elson, Olivier Leger, Florence Guilhot
Abstract: The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.
Type:
Grant
Filed:
August 19, 2022
Date of Patent:
March 28, 2023
Assignee:
Altor Bioscience, LLC
Inventors:
Warren D. Marcus, Robert Newman, Bai Liu, Lijing You, Lin Kong, Peter Rhode, Hing C. Wong
Abstract: The present invention includes proteins, nucleic acids and methods of making and using an activatable interleukin-2 (aIL2) comprising an Interleukin-2 (aIL2) fusion protein comprising: an Interleukin-2 (IL2) wild-type or mutein; a first cleavable linker; an interleukin-2 receptor binding region (IL2RB), and a half-life extender, such as an antibody Fc region, wherein cleavage of the cleavable linker releases the IL2 from the interleukin-2 receptor beta binding region.
Abstract: The present invention provides compounds and methods targeting human interleukin-19, including therapeutic antibodies, pharmaceutical compositions and diagnostic applications useful in the field of immune-mediated diseases including psoriasis, atopic dermatitis, psoriatic arthritis, bronchial asthma and diabetic nephropathy.
Type:
Grant
Filed:
June 17, 2020
Date of Patent:
February 28, 2023
Assignee:
Eli Lilly and Company
Inventors:
Richard Earl Higgs, Jr., Robert John Konrad, Brian Jeffrey Nickoloff, Robert William Siegel, II
Abstract: The problem to be solved is to provide a humanized anti-IL-6 receptor antibody MRA-containing formulation which is suitable for subcutaneous administration, wherein dimerization or deamidation is prevented during long-term storage. The present application is directed to a stable antibody-containing liquid formulation characterized by containing arginine and histidine buffer. A method of inhibiting deamidation or dimerization of such an antibody in a concentrated liquid formulation includes histidine buffer in the liquid formulation.
Abstract: The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.
Type:
Grant
Filed:
September 27, 2021
Date of Patent:
February 7, 2023
Assignee:
Altor Bioscience LLC
Inventors:
Warren D. Marcus, Robert Newman, Bai Liu, Lijing You, Lin Kong, Peter Rhode, Hing C. Wong
Abstract: Described herein are immunosuppressive molecules including immunosuppressive variants of IL-2, and use of such molecules to treat inflammatory and autoimmune disorders.
Abstract: The present invention relates to novel therapies for treating autoimmune and inflammatory diseases. More specifically, the present invention relates to a use of low dose interleukin-2 for the treatment of type I diabetes and other autoimmune and/or inflammatory diseases.
Type:
Grant
Filed:
July 10, 2020
Date of Patent:
January 24, 2023
Assignees:
INSERM (Institut National de la Sante et de la Recherche Medicale), ASSISTANCE PUBLIQUE HOPITAUX DE PARIS, SORBONNE UNIVERSITE
Inventors:
David Klatzmann, David Saadoun, Patrice Cacoub, Michèle Rosenzwajg, Eliane Piaggio, Gilbert Bensimon, Claude Bernard
Abstract: This application provides improved cell culture media and cell culture methods comprising N-acetylcysteine. These improved cell culture media and cell culture methods increase cell viability, cellular growth rate and/or reduce cell doubling time of cholesterol auxotrophic cells, myeloma cells, and hybridoma cells.