Abstract: The present invention relates to methods of treating or preventing cancer and other diseases using molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds an Fc?R that activates a cellular effector (“Fc?RActivating,” such as Fc?RIIA or Fc?RIIIA) and an Fc?R that inhibits a cellular effector (“Fc?RInhibiting,” such as Fc?RIIA) with an altered Ratio of Affinities relative to the respective binding affinities of such Fc?R for the Fc region of the wild-type immunoglobulin. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by Fc?R is desired (e.g.
Abstract: The invention relates to members of the Fc receptor homolog (FcRH) subfamily, as well as fragments and variants thereof. Each FcRH is a Type I transmembrane receptor, preferably, comprises an extracellular region, a transmembrane region, and a cytoplasmic region. The cytoplasmic region preferably comprises one or more immunoreceptor tyrosine-based inhibitory or activation motifs (“ITIMs” or “ITAMs). The invention provides polypeptides, nucleic acids, vectors, expression systems, and antibodies and antibody fragments related to the FcRHs as well as uses thereof. Such uses include uses in the diagnosis and treatment of a malignancy of hematopoietic cell lineage or an inflammatory or autoimmune disease in a subject and in the modulation of a humoral immune response in a subject.
Abstract: The invention relates generally to compositions and methods for altering the isoelectric point of an antibody, and in some cases, resulting in improved plasma pharmacokinetics, e.g. increased serum half-life in vivo.
Type:
Grant
Filed:
July 29, 2011
Date of Patent:
January 28, 2014
Assignee:
Xencor, Inc.
Inventors:
Bassil I. Dahiyat, Gregory A. Lazar, Matthew J. Bernett
Abstract: Provided are a system and methods for selectively inducing expansion of a population of T cells in the absence of exogenous growth factors, such as lymphokines, and accessory cells for research purposes. The cell based expansion system and methods permit the long-term growth of CTLs, preferably human CTLs. In addition, T cell proliferation can be induced without the need for antigen, thus providing an expanded T cell population that is polyclonal with respect to antigen reactivity. Further provided are methods for using the system and methods to screen and identify antigens related to specific diseases or conditions, tumors, autoimmune disorders, or an infectious disease or pathogen, and to identify target molecule for research purposes, or for developing a vaccine based thereon.
Type:
Grant
Filed:
May 10, 2010
Date of Patent:
January 28, 2014
Assignee:
The Trustees of the University of Pennsylvania
Inventors:
Carl H. June, James L. Riley, Marcela Maus, Anna Thomas, Robert Vonderheide
Abstract: The present invention provides compositions for altering a B cell mediated pathology in a patient. The compositions may comprise at least one and/or two chimeric proteins. Each chimeric protein comprises at least a portion of either the VH or VL region of a immunoglobulin molecule from particular B cells from a patient having a B cell mediated pathology, and an immunoglobulin constant region. The genes encoding VH and/or VL regions and the genes encoding immunoglobulin constant regions are isolated and inserted in an expression vector. The chimeric proteins may be produced by introducing the expression vectors into insect cell lines. Proteins may be further purified and conjugated to a compound such as an immunogenic carrier.
Abstract: The present invention relates to a population of antibodies enriched from an antibody preparation, wherein the enriched population of antibodies has an altered amount of sialylation in the Fab region of the antibodies as compared to the antibody preparation prior to enrichment. Furthermore, the present invention relates to a method of enriching a population of antibodies from an antibody preparation, wherein the enriched population of antibodies has an altered amount of sialylation in the Fab region of the antibodies as compared to the antibody preparation prior to enrichment. The present invention also relates to the population of antibodies of the invention for use in medicine, a pharmaceutical composition comprising the populations of antibodies of the invention and the use of the population of antibodies of the invention in the prevention and/or treatment of atherosclerosis, cancer and infections such as bacterial, viral or fungal infections.
Type:
Grant
Filed:
March 26, 2010
Date of Patent:
January 21, 2014
Assignees:
CSL Behring AG, University of Washington
Inventors:
Fabian Käsermann, Monika Rüegsegger, Sylvia Miescher, Keith Elkon
Abstract: The present invention provides for a modified Fc-fusion protein in which at least one amino acid from the heavy chain constant region selected from the group consisting of amino acid residues 250, 314, and 428 is substituted with another amino acid which is different from that present in the unmodified Fc-fusion protein, thereby altering the binding affinity for FcRn and/or the serum half-life in comparison to the unmodified Fc-fusion protein.
Abstract: The present invention provides humanized, chimeric and human anti-CD19 antibodies, anti-CD19 antibody fusion proteins, and fragments thereof that bind to a human B cell marker. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases. In more particular embodiments, the humanized anti-CD 19 antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels. In a particularly preferred embodiment, the substitutions comprise a Ser91Phe substitution in the hAl9 VH sequence.
Type:
Grant
Filed:
June 17, 2013
Date of Patent:
January 7, 2014
Assignee:
Immunomedics, Inc.
Inventors:
Hans J. Hansen, Zhengxing Qu, David M. Goldenberg
Abstract: The present invention provides reagents, methods and systems for predicting the inhibitory activity of an antibody or variant thereof comprising: determining a binding affinity of the antibody or variant thereof to a Fc activating receptor; determining a binding affinity of the antibody or variant thereof to a Fc inhibitory receptor, and calculating the ratio of said activating binding affinity to said inhibitory binding affinity (A/I ratio), wherein the magnitude of said ratio is less than one (1).
Abstract: Provided is a peptide containing a variable region and improved in production efficiency. The peptide contains a variable region to which an antigen-binding site is to be formed and has an amino acid sequence expressing a specific adsorption function to a solid phase at a site closer to the C-terminal than a heavy-chain variable region or at a site closer to the C-terminal than a light-chain variable region.
Type:
Grant
Filed:
February 12, 2009
Date of Patent:
December 31, 2013
Assignees:
Enplas Corporation, National University Corporation Kyoto Institute of Technology
Abstract: The compositions and methods of the present invention are based, in part, on our discovery that an effector function mediated by an Fc-containing polypeptide can be altered by modifying one or more amino acid residues within the polypeptide (by, for example, electrostatic optimization). The polypeptides that can be generated according to the methods of the invention are highly variable, and they can include antibodies and fusion proteins that contain an Fc region or a biologically active portion thereof.
Type:
Grant
Filed:
December 13, 2010
Date of Patent:
December 31, 2013
Assignee:
Biogen Idec MA Inc.
Inventors:
Graham K. Farrington, Alexey Alexandrovich Lugovskoy, Werner Meier, John K. Eldredge, Ellen Garber
Abstract: Monoclonal antibodies are provided that bind to the N-terminus of human hepcidin-25 and are characterized as having high affinity and selectivity for the polypeptide. The antibodies of the invention are useful for increasing serum iron levels, reticulocyte count, red blood cell count, hemoglobin, and/or hematocrit in a human and for the treatment of various disorders, such as anemia, in a human subject. The antibodies of the invention are also useful as analytical tools, such as in sandwich ELISA.
Type:
Grant
Filed:
July 29, 2009
Date of Patent:
December 17, 2013
Assignee:
Eli Lilly and Company
Inventors:
Donmienne Doen Mun Leung, Peng Luan, Ying Tang, Derrick Ryan Witcher, Pia Pauliina Yachi
Abstract: A method of cell-based therapy for treating an autoimmune disease is disclosed. The method is directed at stimulating leukocytes and/or dendritic cells to interrupt autoimmunity in a host. The method provides a Fc? receptor-specific complex or a complex which results in the co-crosslinking of Fc?-chains for treating the leukocytes and/or dendritic cells which are in turn used to elicit an autoimmune interruption response in a subject with an autoimmune disease. The Fc? receptor-specific complex and/or complex which results in the co-crosslinking of Fc?-chains is used to treat a biological sample comprising leukocytes and/or dendritic cells from a patient, and upon reintroducing said biological sample to the patient, the pre-treated dendritic cells illicit an autoimmune interruption response in vivo.
Type:
Grant
Filed:
January 16, 2007
Date of Patent:
December 3, 2013
Assignee:
Canadian Blood Services
Inventors:
Alan H. Lazarus, Vinayakumar Siragam, Davor Brinc, John Freedman, Andrew R. Crow, Seng Song
Abstract: The present invention relates to modified immunoglobulin-binding proteins, e.g., Staphylococcus protein A, having improved binding specificity for immunoglobulins and methods of making and using the same.
Abstract: The present invention provides antibodies (such as chimeric and humanized antibodies) specifically bind to an epitope on CD43 and CEA expressed on nonhematopoietic cancer cells. In addition, the present invention also provides use of the antibodies described herein for diagnostic and therapeutic purposes.
Abstract: The invention relates to targeted binding agents against human sonic hedgehog homolog (Shh) and uses of such agents. More specifically, the invention relates to fully human monoclonal antibodies directed to Shh. The described targeted binding agents are useful in the treatment of diseases associated with the activity and/or overproduction of Shh and as diagnostics.
Type:
Grant
Filed:
May 23, 2012
Date of Patent:
October 29, 2013
Assignee:
Medimmune, LLC
Inventors:
David Jenkins, Neil Michaud, Naomi Laing, Jaspal Singh Kang
Abstract: Disclosed are processes for producing a variant polypeptide (e.g. antibodies) having modified binding characteristics for human Fc gamma receptor IIA (CD32A) leading to increased inhibition of proinflammatory mediators while retaining binding to a target antigen via its Fv portion, which processes comprise altering the polypeptides by substitution of at least two amino acid residues at EU position 325, 326 or 328 of a human IgG CH2 region for a sequence selected from SAAF, SKAF, NAAF and NKAF. Also disclosed are molecules, particularly polypeptides, more particularly immunoglobulins (e.g. antibodies) that include a variant CDR3 region, wherein the variant CDR3 region includes at least one amino acid modified relative to a wild-type CDR3 region. The polypeptides that can be generated according to the methods of the invention are highly variable, and they can include antibodies and fusion proteins that contain an Fc region or a biologically active portion thereof.
Abstract: The present invention relates to antibodies or fragments thereof that specifically bind Fc?RIIB, particularly human Fc?RIIB, with greater affinity than said antibodies or fragments thereof bind Fc?RIIA, particularly human Fc?RIIA. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.
Abstract: Antibodies that target CD19, wherein the antibodies comprise at least one modification relative to a parent antibody, wherein the modification alters affinity to an FcyR or alters effector function as compared to the parent antibody, and methods of using the antibodies.
Type:
Grant
Filed:
August 14, 2007
Date of Patent:
September 3, 2013
Assignee:
Xencor, Inc.
Inventors:
Matthew J. Bernett, Seung Yup Chu, John R. Desjarlais, Sher Bahadur Karki, Gregory Alan Lazar, Erik WeiKing Pong, John O. Richards, Eugene Alexander Zhukovsky