Abstract: In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a ligand-binding portion of the extracellular domain of activin-like kinase I (ALK1) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders. Additionally, the disclosure demonstrates that inhibitors of ALK1 may be used to increase pericyte coverage in vascularized tissues, including tumors and the retina. The disclosure also identifies ligands for ALK1 and demonstrates that such ligands have pro-angiogenic activity, and describes antibodies that inhibit receptor-ligand interaction.
Type:
Application
Filed:
July 30, 2018
Publication date:
February 14, 2019
Applicants:
Acceleron Pharma Inc., Ludwig Institute for Cancer Research Ltd.
Inventors:
Asya Grinberg, John Knopf, Robert S. Pearsall, Ravindra Kumar, Jasbir Seehra, Kristian Pietras
Abstract: The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.
Type:
Grant
Filed:
May 28, 2015
Date of Patent:
December 18, 2018
Assignees:
Agenus Inc., Memorial Sloan-Kettering Cancer Center, Ludwig Institute for Cancer Research Ltd.
Inventors:
Volker Seibert, Olivier Léger, Marc Van Dijk, Taha Merghoub, David Schaer, Gerd Ritter, Takemasa Tsuji
Abstract: Some aspects of this invention are based on the recognition that reversible protein multimers in which monomeric proteins are conjugated to a carrier molecule via chelation complex bonds are stable under physiological conditions and can be dissociated in a controlled manner under physiological, nontoxic conditions. Accordingly, such protein multimers are useful for a variety of in vitro, ex vivo, and in vivo application for research, diagnostics, and therapy. Some aspect of this invention provide reversible MHC protein multimers, and methods of using such multimers in the detection and/or isolation of specific T-cells or T-cell populations. Because reversible MHC multimers can efficiently be dissociated, the time of MHC binding to T-cell receptors, and, thus, T-cell receptor-mediated T-cell activation can be minimized.
Type:
Application
Filed:
June 14, 2018
Publication date:
December 6, 2018
Applicant:
Ludwig Institute for Cancer Research Ltd.
Inventors:
Immanuel F. Luescher, Julien Schmidt, Philippe Guillaume, Danijel Dojcinovic
Abstract: The instant disclosure provides antibodies that specifically bind to human CTLA-4 and antagonize CTLA-4 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.
Type:
Grant
Filed:
May 27, 2016
Date of Patent:
December 4, 2018
Assignees:
AGENUS INC., LUDWIG INSTITUTE FOR CANCER RESEARCH LTD, MEMORIAL SLOAN KETTERING CANCER CENTER
Inventors:
Marc van Dijk, Cornelia Anne Mundt, Gerd Ritter, David Schaer, Jedd David Wolchok, Taha Merghoub, David Adam Savitsky, Nicholas Stuart Wilson
Abstract: Methods and compositions for modulating blood-neural barrier (BNB) for the treatment of CNS conditions such as edema, and for increased drug delivery efficacy across the BNB. The present invention further relates to improved tPA treatment of ischemic cerebrovascular and related diseases in combination with antagonism of the PDGF signaling pathway. The inventive method and composition is particularly suitable for conjunctive therapy of ischemic stroke using tPA and an anti-PDGF-C antagonist or an anti-PDGFR-? antagonist.
Type:
Application
Filed:
February 12, 2018
Publication date:
August 9, 2018
Applicants:
Ludwig Institute for Cancer Research Ltd, The Regents of the University of Michigan, University of Maryland, Baltimore
Inventors:
Ulf Eriksson, Linda Fredriksson, Daniel Lawrence, Enming Su, Manuel Yepes, Dudley Strickland
Abstract: The invention provides liposomes containing nonglycosidic ceramides within their bilayers, and compositions thereof. These liposomes activate murine iNKT cells and induce dendritic cell (DC) maturation, both in vitro and in vivo at an efficacy that is comparable to their corresponding soluble nonglycosidic ceramides. Also provided are methods for treating diseases using the liposomes and compositions of the invention.
Type:
Grant
Filed:
August 31, 2016
Date of Patent:
August 7, 2018
Assignee:
LUDWIG INSTITUTE FOR CANCER RESEARCH LTD.
Abstract: Specific binding members, particularly antibodies and fragments thereof, which bind to transforming growth factor beta 1 (TGF-?1) are provided, particularly recognizing human and mouse TGF-?1 and not recognizing or binding TGF-?2 or TGF-?3. Particular antibodies are provided which specifically recognize and neutralize TGF-?1. These antibodies are useful in the diagnosis and treatment of conditions associated with activated or elevated TGF-?1, including cancer, and for modulating immune cells and immune response, including immune response to cancer or cancer antigens. The anti-TGF-?1 antibodies, variable regions or CDR domain sequences thereof, and fragments thereof may also be used in therapy in combination with chemotherapeutics, immune modulators, or anti-cancer agents and/or with other antibodies or fragments thereof. Antibodies of this type are exemplified by the novel antibodies hereof, including antibody 13A1, whose sequences are provided herein.
Type:
Grant
Filed:
November 2, 2016
Date of Patent:
July 31, 2018
Assignee:
LUDWIG INSTITUTE FOR CANCER RESEARCH LTD.
Inventors:
Jacques Van Snick, Catherine Uyttenhove, Thierry Boon
Abstract: Some aspects of this invention are based on the recognition that reversible protein multimers in which monomeric proteins are conjugated to a carrier molecule via chelation complex bonds are stable under physiological conditions and can be dissociated in a controlled manner under physiological, nontoxic conditions. Accordingly, such protein multimers are useful for a variety of in vitro, ex vivo, and in vivo application for research, diagnostics, and therapy. Some aspect of this invention provide reversible MHC protein multimers, and methods of using such multimers in the detection and/or isolation of specific T-cells or T-cell populations. Because reversible MHC multimers can efficiently be dissociated, the time of MHC binding to T-cell receptors, and, thus, T-cell receptor-mediated T-cell activation can be minimized.
Type:
Grant
Filed:
September 30, 2011
Date of Patent:
July 17, 2018
Assignee:
Ludwig Institute for Cancer Research Ltd.
Inventors:
Immanuel F. Luescher, Julien Schmidt, Philippe Guillaume, Danijel Dojcinovic
Abstract: Expression of proteolytically active, high molecular weight ADAM protease is relatively increased in tumor cells that also express the putative tumor stem cell marker CD133. An antibody or antibody fragment such as 8C7 monoclonal antibody may be used to selectively bind to proteolytically active, high molecular weight ADAM10 protease to thereby detect tumor cells and also as a therapeutic agent for treating cancers, tumors and other malignancies inclusive of leukemia, lymphoma, lung cancer, colon cancer, adenoma, neuroblastoma, brain tumor, renal tumor, prostate cancer, sarcoma and/or melanoma.
Type:
Grant
Filed:
February 4, 2015
Date of Patent:
July 17, 2018
Assignees:
Monash University, Memorial Sloan-Kettering Cancer Centre, Ludwig Institute for Cancer Research Ltd.
Inventors:
Martin Lackmann, Peter W. Janes, Lakmali Atapattu Mudiyanselage, Andrew M. Scott, Dimitar B. Nikolov, Nayanendu Saha
Abstract: In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a ligand-binding portion of the extracellular domain of activin-like kinase I (ALK1) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders. Additionally, the disclosure demonstrates that inhibitors of ALK1 may be used to increase pericyte coverage in vascularized tissues, including tumors and the retina. The disclosure also identifies ligands for ALK1 and demonstrates that such ligands have pro-angiogenic activity, and describes antibodies that inhibit receptor-ligand interaction.
Type:
Application
Filed:
February 13, 2018
Publication date:
June 28, 2018
Applicants:
Ludwig Institute for Cancer Research Ltd., Acceleron Pharma, Inc.
Inventors:
Asya Grinberg, John Knopf, Robert S. Pearsall, Ravindra Kumar, Jasbir Seehra, Kristian Pietras
Abstract: The present invention relates to an antibody binding to the transmembrane protein ‘glycoprotein A repetitions predominant’ (GARP) in the presence of TGF-? and uses thereof.
Type:
Grant
Filed:
August 1, 2014
Date of Patent:
June 19, 2018
Assignees:
UNIVERSITÉ CATHOLIQUE DE LOUVAIN, LUDWIG INSTITUTE FOR CANCER RESEARCH LTD
Inventors:
Sophie Lucas, Pierre Coulie, Julia Cuende Villasur, Laure Dumoutier, Jean-Christophe Renauld
Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a mutant Epidermal Growth Factor Receptor (EGFR), and methods of using the dsRNA to inhibit expression of mutant EGFR.
Type:
Grant
Filed:
November 9, 2015
Date of Patent:
May 1, 2018
Assignees:
ALNYLAM PHARMACEUTICALS, INC., LUDWIG INSTITUTE FOR CANCER RESEARCH LTD.
Inventors:
Dinah Sah, Pamela Tan, Webster Cavenee, Frank Furnari, Maria del Mar Inda Perez, Rudy Bonavia
Abstract: Methods and compositions for modulating blood-neural barrier (BNB) for the treatment of CNS conditions such as edema, and for increased drug delivery efficacy across the BNB. The present invention further relates to improved tPA treatment of ischemic cerebrovascular and related diseases in combination with antagonism of the PDGF signaling pathway. The inventive method and composition is particularly suitable for conjunctive therapy of ischemic stroke using tPA and an anti-PDGF-C antagonist or an anti-PDGFR-? antagonist.
Type:
Grant
Filed:
October 6, 2016
Date of Patent:
March 27, 2018
Assignees:
Ludwig Institute for Cancer Research Ltd, The Regents of the University of Michigan, University of Maryland, Baltimore
Inventors:
Ulf Eriksson, Linda Fredriksson, Daniel Lawrence, Enming Su, Manuel Yepes, Dudley Strickland
Abstract: Described herein are methods of evaluating metastatic potential of a cancer based on the phosphorylation state and/or intracellular localization of iASPP. Therapeutic regimens designed based on the results of the diagnostic methods are also provided.
Type:
Grant
Filed:
March 1, 2013
Date of Patent:
January 30, 2018
Assignee:
LUDWIG INSTITUTE FOR CANCER RESEARCH LTD.
Abstract: The invention provides liposomes containing nonglycosidic ceramides within their bilayers, and compositions thereof. These liposomes activate murine iNKT cells and induce dendritic cell (DC) maturation, both in vitro and in vivo at an efficacy that is comparable to their corresponding soluble nonglycosidic ceramides. Also provided are methods for treating diseases using the liposomes and compositions of the invention.
Type:
Application
Filed:
August 31, 2016
Publication date:
April 20, 2017
Applicant:
LUDWIG INSTITUTE FOR CANCER RESEARCH LTD.
Abstract: Specific binding members, particularly antibodies and fragments thereof, which bind to transforming growth factor beta 1 (TGF-?1) are provided, particularly recognizing human and mouse TGF-?1 and not recognizing or binding TGF-?2 or TGF-?3. Particular antibodies are provided which specifically recognize and neutralize TGF-?1. These antibodies are useful in the diagnosis and treatment of conditions associated with activated or elevated TGF-?1, including cancer, and for modulating immune cells and immune response, including immune response to cancer or cancer antigens. The anti-TGF-?1 antibodies, variable regions or CDR domain sequences thereof, and fragments thereof may also be used in therapy in combination with chemotherapeutics, immune modulators, or anti-cancer agents and/or with other antibodies or fragments thereof. Antibodies of this type are exemplified by the novel antibodies hereof, including antibody 13A1, whose sequences are provided herein.
Type:
Grant
Filed:
March 6, 2013
Date of Patent:
December 13, 2016
Assignee:
Ludwig Institute for Cancer Research LTD
Inventors:
Jacques Van Snick, Catherine Uyttenhove, Thierry Boon
Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a mutant Epidermal Growth Factor Receptor (EGFR), and methods of using the dsRNA to inhibit expression of mutant EGFR.
Type:
Application
Filed:
November 9, 2015
Publication date:
July 7, 2016
Applicants:
LUDWIG INSTITUTE FOR CANCER RESEARCH LTD., ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Dinah Sah, Pamela Tan, Webster Cavenee, Frank Furnari, Maria del Mar Inda Perez, Rudy Bonavia
Abstract: Treatments for estrogen receptor and progesterone receptor negative breast cancer or estrogen receptor, progesterone receptor and c-erbB2 negative (triple negative) breast cancer are provided.
Type:
Grant
Filed:
April 22, 2009
Date of Patent:
April 19, 2016
Assignee:
Ludwig Institute for Cancer Research Ltd.
Inventors:
Anita Grigoriadis, Otavia L. Caballero, Andrew John George Simpson
Abstract: The present invention relates to antibodies, particularly antibody 175, and fragments thereof or antibodies derived therefrom, which bind to the EGF receptor, particularly to amplified or overexpressed epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. These antibodies are useful in the diagnosis and treatment of cancer. Recombinant or hybrid antibodies having the variable region heavy or light chain sequence(s) of antibody 175 are also provided. The antibodies of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof.
Type:
Grant
Filed:
August 14, 2008
Date of Patent:
March 15, 2016
Assignee:
Ludwig Institute for Cancer Research Ltd.
Inventors:
Terrance Grant Johns, Elizabeth Stockert, Stephen Stockert, Lloyd J. Old, Andrew M. Scott, Veronika M. Rayzman
Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a mutant Epidermal Growth Factor Receptor (EGFR), and methods of using the dsRNA to inhibit expression of mutant EGFR.
Type:
Grant
Filed:
October 24, 2012
Date of Patent:
December 15, 2015
Assignees:
Alnylam Pharmaceuticals, Inc., Ludwig Institute for Cancer Research Ltd.
Inventors:
Dinah Sah, Pamela Tan, Webster Cavenee, Frank Furnari, Maria del Mar Inda Perez, Rudy Bonavia