Abstract: The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen-recognizing receptor and a co-stimulatory ligand and methods of use therefore for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.
Abstract: The present invention relates to stable formulations of antibodies against human programmed death receptor PD-1, or antigen binding fragments thereof. The present invention further provides methods for treating various cancers and chronic infections with stable formulations of antibodies against human programmed death receptor PD-1, or antigen binding fragments thereof.
Type:
Grant
Filed:
March 29, 2012
Date of Patent:
December 29, 2015
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Manoj K. Sharma, Chakravarthy Nachu Narasimhan, Kevin James Gergich, Soonmo Peter Kang
Abstract: The disclosure relates to a protein composed of a first polypeptide or polypeptide domain having a first specific binding activity for Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) expressed on a T-cell cell surface and a second specific binding activity for Glucose Transporter 2 (GLUT2) or an extracellular ectodomain thereof expressed on a pancreatic ?-cell surface, wherein binding of the first polypeptide or polypeptide domain to CTLA-4 induces a CTLA-4 specific agonist response in the T-cell, and binding of the second polypeptide or polypeptide domain to GLUT2 or an ectodomain thereof does not inhibit GLUT2 glucose transporter function, wherein said agonist response in the T-cell induces a response that reduces immunoreactivity against pancreatic ?-cells.
Type:
Grant
Filed:
March 15, 2013
Date of Patent:
December 29, 2015
Inventors:
Bellur S. Prabhakar, Chenthamarakshan Vasu, Palash Bhattacharya
Abstract: Provided are antibodies that specifically bind to Programmed Death-1 (PD1, Pdcd-1, or CD279) and inhibit PD1-mediated cellular signaling and activities in immune cells, antibodies binding to a set of amino acid residues required for its ligand binding, and uses of these antibodies to treat or diagnose cancer, infectious diseases or other pathological disorders modulated by PD1-mediated functions.
Abstract: The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates ?CD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon ?CD3/?GITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed. In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed.
Abstract: 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:
Grant
Filed:
May 13, 2013
Date of Patent:
December 15, 2015
Assignee:
Bristol-Myers Squibb Company
Inventors:
John Cogswell, Stacie M. Goldberg, Ashok K. Gupta, Maria Jure-Kunkel, Xi Tao Wang, John M. Wigginton
Abstract: The present invention relates to antibodies and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to B7-H1 or PD-1. In some embodiments such molecules are additionally capable of modulating the ability of B7-H1 or B7-DC to bind to PD-1 or are capable of affecting the signaling activity of the B7-H1 or PD-1. The invention additionally concerns the uses of such molecules in the diagnosis and treatment of cancer and other diseases.
Type:
Grant
Filed:
April 19, 2012
Date of Patent:
December 8, 2015
Assignee:
MedImmune, LLC
Inventors:
Solomon Langermann, Linda Liu, Shannon Marshall, Sheng Yao
Abstract: A method of treating a pathological syndrome includes the step of administering a pharmaceutical agent. The pharmaceutical agent contains an activated form of monoclonal, polyclonal or natural antibodies to an antigen. The activated form is prepared by repeated consecutive dilution and external treatment, predominantly based on homeopathic technology. The antigen is a substance or a drug acting as a direct cause of the pathological syndrome or involved in regulation of mechanisms of its formation. Thus, activated antibodies are raised against antigens of exogenous or endogenous origin, against autologous antigens, against fetal antigens and against anti-idiotypic antibodies.
Abstract: The present invention provides anti-human ICOS antibodies with increased effector function. The invention further relates to pharmaceutical compositions, immunotherapeutic compositions, and methods using therapeutic antibodies that bind to the human ICOS antigen and that may mediate ADCC, CDC, and/or antibody-dependent phagocytosis (opsonization) for the treatment and prevention of T cell-mediated diseases and disorders, such as, but not limited to, chronic infection, autoimmune disease or disorder, inflammatory disease or disorder, graft-versus-host disease (GVHD), transplant rejection, and T cell proliferative disorder.
Type:
Grant
Filed:
September 6, 2012
Date of Patent:
November 24, 2015
Assignee:
MedImmune, LLC
Inventors:
Anthony Coyle, Yihong Yao, Bahija Jallal, Gianluca Carlesso, Michael Bowen
Abstract: The present disclosure relates to anti-CD200 antibodies (e.g., variant anti-CD200 antibodies having decreased or no effector function) and to biomarkers for use in a variety of diagnostic and therapeutic methods, e.g., determining whether a human has been administered one or more of the antibodies at a dose sufficient to induce a desired immunomodulatory effect in the human and/or selecting an appropriate dosing schedule for a patient.
Type:
Grant
Filed:
January 11, 2011
Date of Patent:
November 10, 2015
Assignee:
Alexion Pharmaceuticals, Inc.
Inventors:
Susan Faas McKnight, Roxanne Cofiell, Yan Yan
Abstract: There is disclosed compositions and methods relating to or derived from anti-PD-L1 antibodies. More specifically, there is disclosed fully human antibodies that bind PD-L1, PD-L1-binding fragments and derivatives of such antibodies, and PD-L1-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having PD-L1 related disorders or conditions, including various inflammatory disorders and various cancers.
Type:
Grant
Filed:
May 31, 2013
Date of Patent:
November 3, 2015
Assignee:
Sorrento Therapeutics, Inc.
Inventors:
Heyue Zhou, Randy Gastwirt, Barbara A. Swanson, John Dixon Gray, Gunnar F. Kaufmann
Abstract: Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing a PD1 ligand.
Abstract: Described herein are novel compositions comprising bispecific and multispecific polypeptide agents, and methods using these agents for targeting cells, such as functionally exhausted or unresponsive immune cells, that co-express the inhibitory receptors PD-1 and TIM-3. These compositions and methods are useful for the treatment of chronic immune conditions, such as persistent infections or cancer.
Abstract: Soluble H4 (sH4) levels have been discovered to correlate with the stage or severity of inflammatory disorders including autoimmune disorders. In particular, circulating levels of sH4 can be used as a diagnostic for determining the severity of an inflammatory disorder or the propensity for developing an inflammatory disorder. The severity of an inflammatory disorder can be determined by assaying the levels of sH4 in a subject and comparing the levels of sH4 to reference sH4 concentrations that correlate to specific stages of an inflammatory disorder. The therapeutic efficacy of treatments for inflammatory disorders can also be determined by comparing levels of sH4 before and during treatment. Methods and devices for measuring sH4 are also provided.
Abstract: The invention includes compositions and methods for generating and expanding therapeutic Th17 cells. The invention includes contacting T cells with a composition comprising a first agent that is capable of providing a primary activation signal to T cells and a second agent that is capable of activating ICOS on T cells in the presence of Th-17 polarizing agents.
Type:
Grant
Filed:
February 4, 2011
Date of Patent:
September 15, 2015
Assignee:
The Trustees of the University of Pennsylvania
Inventors:
James L. Riley, Chrystal Paulos, Carl H. June, Bruce Levine
Abstract: The invention relates to the use of a superagonistic monoclonal antibody (mAb), which is specific for a naturally costimulatory receptor expressed on T cells, or a mimicry compound thereto, for producing a pharmaceutical composition for the treatment of diseases occurring with lacking costimulability of T cells, in particular of the B-CLL.
Abstract: The present invention relates to methods of treating cancer, such as melanoma, by administering a CTLA4 antagonist to a subject with a serum C-Reactive Protein (CRP) concentration that is less than or equal to some amount. The invention further relates to methods of treating cancer by determining the level of serum CRP concentration in a subject, and then administering a CTLA4 antagonist if the CRP concentration is less than or equal to a certain amount. The invention further relates to, among other things, the use of serum CRP concentration as a predictive factor for a subject's response to a cancer treatment.
Abstract: Provided are methods of enhancing ex vivo proliferation of a T cell population, the methods comprising contacting the T cell population with IL-7 and anti-CD3/CD28 antibody to activate and expand the T cell population. Further provided are methods of generating an antigen-specific cytotoxic T cell population comprising priming a CD3/CD28-expanded T cell population against an antigen (e.g., a cancer cell) in the presence of at least one of IL-7, IL-12, and IL-15, or a combination thereof. Further provided are methods of treating T cell lymphopenia in a subject, comprising administering a CD3/CD28-expanded T cell population to the subject.