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Hematopoietic cell
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424 - Drug, bio-affecting and body treating compositions
424172100 - Binds eukaryotic cell or component thereof or substance produced by said eukaryotic cell (e.g., honey, etc.)
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|MODULATING THE KV1.1 VOLTAGE-GATED POTASSIUM CHANNEL IN T-CELLS FOR REGULATING THE SYNTHESIS AND SECRETION OF TUMOR NECROSIS FACTOR ALPHA (tnf-ALPHA) AND TREATING HUMAN DISEASE OR INJURIES MEDIATED BY DETRIMENTALLY HIGH OR LOW LEVELS OF TNF-ALPHA - Blocking the voltage-gated potassium channel Kv1.1 of T-cells causes the robust and exclusive production of TNF-α, and thus can be used for eradication of cancer, improved eradication of infectious organisms, increased permeability of blood vessels and the blood brain barriers to given molecules and cells, and improved neuronal features, regeneration function and development. Blocking the voltage-gated potassium channel Kv1.1 of T-cells causes the robust and exclusive production of TNF-α. Similarly, unblocking of a blocked Kv1.1 channel or opening of a Kv1.1 channel will prevent the T-cells from producing and secreting excess amounts of TNF-α, thus being useful in the treatment of conditions such as rheumatoid arthritis and for treating neurological diseases associated with defected functioning and/or pathological block of the Kv1.1 channel, among them PNH associated with Kv1 Abs; Encephalitis associated with Kv1 Abs; and Episodic-ataxia type 1 (EA-1), in all of which the T-cell blocked Kv1.1 channel may secrete excess TNFa and thereby contribute to the pathology. Blocking of the Kv1.1 channel may be achieved in vivo or ex vivo by contact with a selective Kv1.1 channel blocking molecule such as Dendrotoxin-K or a selective monoclonal antibody against the Kv1.1 channel. Preventing the Kv1.1. block would be achieved by Kv1.1 openers, or by molecules that would prevent the closure of the Kv1.1 channel.
|USE OF ANTI-CS1 ANTIBODIES FOR TREATMENT OF RARE LYMPHOMAS - Uses of anti-CS1 antibodies, alone or in combination with other agents, for the treatment of rare lymphomas, such as NK lymphomas, NK/T-cell lymphomas, and angioimmunoblastic lymphomas.
|B-cell depleting agents, like anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome - The present invention relates in a first aspect to a B-cell depleting anti-CD20 antibody or a CD20-binding antibody fragment thereof for the treatment of chronic fatigue syndrome and myalgic encephalomyelitis. In particular, the present invention relates to the use of anti-CD20 monoclonal antibodies or fragments thereof which are preferably humanized for the treatment of chronic fatigue syndrome/myalgic encephalomyelitis in a subject afflicted with said disease.
|TOLERANCE INDUCTION AND MAINTENANCE IN HEMATOPOIETIC STEM CELL ALLOGRAFTS - Provided are methods and compositions for the induction and maintenance of tolerance in hematopoietic stem cell allografts.
|Methods and Compositions for Treating Prostate Cancer or Inducing a Humoral Immune Response Against Prostate Cancer - The present invention relates to prostate cancer markers, compositions comprising such markers, and methods of using such markers to induce or increase an immune response against prostate cancer. An immune response against the markers correlates with an immune response, in particular a humoral immune response, against prostate cancer cells which immune response is preferably associated with prophylaxis of prostate cancer, treatment of prostate cancer, and/or amelioration of at least one symptom associated with prostate cancer.
|FULLY HUMAN ANTIBODIES TO BTLA - The present invention relates to binding compounds specific for BTLA and uses thereof. More specifically, the invention relates to fully human antibodies that recognize human BTLA and modulate its activity in cancer, inflammatory, and autoimmune disorders.
|FC RECEPTOR BINDING PROTEINS - This disclosure provides, inter alia, proteins that bind to FcRn, e.g., immunoglobulins that inhibit FcRn with high affinity and selectivity. The FcRn-binding proteins can be used to treat a variety of disorders including autoimmune disorders.
|METHODS FOR INDUCING IN VIVO TOLERANCE - The present invention encompasses methods for inducing in vivo tolerance to a foreign tissue.
|Anti-HLA-DR Antibodies Suppress Allogeneic and Xenogeneic Immune Responses to Organ Transplants - Disclosed herein are methods and compositions comprising anti-HLA-DR antibodies for treatment of allogeneic and xenogeneic immune responses occurring in organ transplant rejection and other immune dysfunction diseases. In preferred embodiments, the anti-HLA-DR antibodies are effective to deplete antigen-presenting cells, such as dendritic cells. Most preferably, administration of the therapeutic compositions depletes all subsets of APCs, including mDCs, pDCs, B cells and monocytes, without significant depletion of T cells. In alternative embodiments, administration of the therapeutic compositions suppresses proliferation of allo-reactive T cells, while preserving cytomegalovirus (CMV)-specific, CD8
|FC RECEPTOR BINDING PROTEINS - This disclosure provides, inter alia, proteins that bind to FcRn, e.g., immunoglobulins that inhibit FcRn with high affinity and selectivity. The FcRn-binding proteins can be used to treat a variety of disorders including autoimmune disorders.
|BINDING PROTEINS, INCLUDING ANTIBODIES, ANTIBODY DERIVATIVES AND ANTIBODY FRAGMENTS, THAT SPECIFICALLY BIND CD154 AND USES THEREOF - This invention provides binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein. This invention also provides a chimeric, humanized or fully human antibody, antibody derivative or antibody fragment that specifically binds to an epitope to which a humanized Fab fragment comprising a variable heavy chain sequence according to SEQ ID NO: 1 and comprising a variable light chain sequence according to SEQ ID NO: 2 specifically binds. CD154 binding proteins of this invention may elicit reduced effector function relative to a second anti-CD154 antibody. CD154 binding proteins of this invention are useful in diagnostic and therapeutic methods, such as in the treatment and prevention of diseases including those that involve undesirable immune responses that are mediated by CD154-CD40 interactions.
|Prognostic Marker For Cryoglobulinemic Vasculitis And B Cell Malignancies In HCV Infected Patients - The invention provides methods and compositions for early diagnosis and treatment of a disease associated with a specific antibody by employing the detection of a cross-idiotypic epitope on the specific antibody to detect the cells that produce the antibody before the development of clinical symptoms of the disease.
|HEMATOPOIETIC CELL SELECTIN LIGAND POLYPEPTIDES AND METHODS OF USE THEREOF - The invention feature methods and compositions for treating inflammatory disorders, hematopoietic disorders and non-hematopoietic disorders (e.g., non-hematopoietic cancers) and for isolating cells (e.g., stem cells) in a mammal.
|Diagnostic and Therapeutic Utility of Tribbles-2 in Human Cancers - Provided are methods for the diagnosis and treatment of acute myelogenous leukemia. In particular, the present invention relates to the use of Trib2 polynucleotides and polypeptides for the diagnosis and treatment of acute myelogenous leukemia (AML) by assessing myeloid cells of a patient, or malignancies associated with Trib2, C/EBPαp30 or C/EBPαp42, such as AML or lung cancer, by assessing hematopoietic stem cells of the patient.
|BINDING MOLECULES TO THE HUMAN OX40 RECEPTOR - The present disclosure provides isolated binding molecules that bind to the human OX40R, nucleic acid molecules encoding an amino acid sequence of the binding molecules, vectors comprising the nucleic acid molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using the binding molecules or compositions.
|Antibodies which bind human CXCR3 - Antibodies and antigen-binding fragments of antibodies that bind human CXCR3 are disclosed. In preferred embodiments, the antibodies are human. Nucleic acids and vectors encoding the antibodies or portions thereof, recombinant cells that contain the nucleic acids, and compositions comprising the antibodies or antigen-binding fragments are also disclosed. The invention also provides therapeutic and diagnostic methods which employ the antibodies and antigen-binding fragments.
|Treatment Of Type 1 Diabetes With Inhibitors Of Macrophage Migration Inhibitory Factor - Methods of treating a mammal having type 1 diabetes or a risk for type 1 diabetes are provided. The methods comprise administering to the mammal a pharmaceutical composition comprising an agent that inhibits MIF in the mammal. Also provided are methods of evaluating whether a compound is useful for preventing or treating type 1 diabetes. The methods comprise determining whether the compound inhibits a macrophage migration inhibitory factor (MIF) in a mammal, then, if the compound inhibits the MIF, determining whether the compound inhibits development of type 1 diabetes.
|Method for Selectively Depleting Hypoxic Cells - An improved method for selectively depleting hypoxic cells within the bone marrow is disclosed. The method can be used to enhance engraftment of hematopoietic stem cells (HSCs) in the bone marrow of a host subject. Also disclosed is a method for treating a cancer within the bone marrow of a host subject.
|Compositions and methods for identifying response targets and treating flavivirus infection responses - Cellular receptors are identified that induce plasma leakage and other negative effects when infected with flaviviruses, such as dengue virus or Japanese encephamyelitis virus. Using fusion proteins disclosed herein, the receptors to which a pathogen, such as flavivirus, binds via glycan binding are determined. Once the receptors are determined, the effect of binding to a particular receptor may be determined, wherein targeting of the receptors causing a particular symptom may be targeted by agents that interrupt binding of the pathogen to the receptor. Accordingly, in the case of dengue virus and Japanese encephamyelitis virus, TNF-α is released when the pathogen binds to the DLVR1/CLEC5A receptor. Interrupting the DLVR1/CLEC5A receptor with monoclonal antibodies reduced TNF-α secretion without affecting secretion of cytokines responsible for viral clearance thereby increasing survival rates in infected mice from nil to around 50%.
|METHODS FOR INHIBITING ALLOGRAFT REJECTION - Disclosed herein are methods for treating or inhibiting allograft rejection in a transplant recipient. In some embodiments, the methods include administering to the transplant recipient a first amount of a JAK1/3 inhibitor comprising 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one (Compound I) or a prodrug thereof and administering to the transplant recipient a second amount of a non-JAK1/3 inhibitor immunosuppressant, wherein the combined effect of the first amount and the second amount is greater than the effect of the first amount or the second amount individually, wherein the JAK1/3 inhibitor acts in combination with the non-JAK1/3 inhibitor immunosuppressant to inhibit or treat allograft rejection. In some embodiments at least one of the first amount or the second amount is individually a suboptimal dose for inhibiting or treating allograft rejection. In some examples, the combined effect of the first amount and the second amount to inhibit or treat allograft rejection in the transplant recipient is synergistic.
|Chemokine receptor antagonists as therapeutic agents - The present invention provides methods and compositions to reduce immune tolerance at specific sites. In one aspect, the present invention comprises methods and compositions to reduce tumorigenicity. In an embodiment, the present invention reduces recruitment of tolerance-inducing antigen presenting cells (APCs) or their precursors to a tumor and/or tumor draining lymph node by decreasing binding of at least one tumor-associated ligand to a chemokine receptor present on the tolerance-inducing APCs or APC precursors. In an embodiment, the chemokine receptor is CCR6 and the tumor-associated ligand is mip-3α. In another aspect, the present invention comprises methods and compositions to reduce immune tolerance to a virus. In an embodiment, the virus is HIV. The present invention further provides for the development of CCR6 antibodies and antagonists as therapeutic agents to prevent or reduce immune tolerance.
|ENGINEERED ANTI-TSLPR ANTIBODIES - The invention relates to binding compounds that specifically bind to human TSLPR, as well as uses thereof, e.g., in the treatment of inflammatory disorders.
|LIGAND FOR HERPES SIMPLEX VIRUS ENTRY MEDIATOR AND METHODS OF USE - A novel polypeptide ligand, p30, or LIGHT, for herpes virus entry mediator, HVEM, is provided. LIGHT is useful for modulating immune responses and in inhibiting infection and/or subsequent proliferation by herpesvirus. HVEM fusion proteins are also provided. Methods for treating subjects with lymphoid cell disorders, tumors, autoimmune diseases, inflammatory disorders or those having or suspected of having a herpesvirus infection, utilizing p30 and the fusion proteins of the invention, are also provided.
|Toll-Like Receptor 3 Antagonists - Toll Like Receptor 3 (TLR3) antibody antagonists, polynucleotides encoding TLR3 antibody antagonists or fragments thereof, and methods of making and using the foregoing are disclosed.
|BIOLOGICAL MATERIALS AND USES THEREOF - The invention provides binding molecules, including antibody molecules which selectively bind to a cell surface antigen of a target cell, and wherein the binding molecules, on binding the cell surface antigen, induce apoptosis of the target cell. There is also provided methods of and pharmaceutical compositions for apoptosis induction and uses thereof.
|ANTIBODIES THAT SPECIFICALLY BIND TO TIM3 - Provided herein are antibodies specific for TIM3 that can be used to detect cancer cells, in particular, cancer stem cells. The antibodies can also be used in therapeutic compositions for treating cancer and reducing inflammation.
|NOVEL COMPOSITIONS AND METHODS FOR TREATING IgE-MEDIATED DISORDERS - The present invention relates to immunoglobulins that bind IgE and FcγRIIb with high affinity, said compositions being capable of inhibiting cells that express membrane-anchored IgE. Such compositions are useful for treating IgE-mediated disorders, including allergies and asthma.
|Methods and Compositions for Using MHC Class II Invariant Chain Polypeptide as a Receptor for Macrophage Migration Inhibitory Factor - Methods and compositions for using the MHC class II invariant chain polypeptide, Ii (also known as CD74), as a receptor for macrophage migration inhibitory factor (MIF), are disclosed. These include methods and compositions for using this receptor, as well as agonists and antagonists of MIF which bind to this receptor, or which otherwise modulate the interaction of MIF with CD74 or the consequences of such interaction, in treatment of conditions characterized by locally or systemically altered MIF levels, particularly inflammatory conditions and cancer.
|Binding members for interleukin-4 receptor alpha (IL-4Ra)-173 - Binding members, especially antibody molecules, for interleukin (IL)-4 receptor alpha (IL-4Rα), and their therapeutic use e.g. in treating or preventing disorders associated with IL-4Rα, IL-4 and/or IL-13, examples of which are asthma and COPD.
|AGENTS AND METHODS FOR MODULATING MACROPHAGE INHIBITORY CYTOKINE (MIC-1) ACTIVITY - The invention relates to a method and novel types of agents for modulating appetite and/or body weight in a subject. Moreover, the invention relates to a method of screening for agents which interact and modulate the activity of the receptor complex for macrophage inhibitory cytokine-1 (MIC-1).
|Inhibition of HIV-1 Replication by Disruption of the Processing of the Viral Capsid-Spacer Peptide 1 Protein - Inhibition of HIV-1 replication by disrupting the processing of the viral Gag capsid (CA) protein (p24) from the CA-spacer peptide 1 (SP1) protein precursor (p25) is disclosed. Amino acid sequences containing a mutation in the Gag p25 protein, with the mutation resulting in a decrease in the inhibition of processing of p25 to p24 by dimethylsuccinyl betulinic acid or dimethylsuccinyl betulin, polynucleotides encoding such mutated sequences and antibodies that selectively bind such mutated sequences are also included. Methods of inhibiting, inhibitory compounds and methods of discovering inhibitory compounds that target proteolytic processing of the HIV Gag protein are included. In one embodiment, such compounds inhibit the interaction of the HIV protease enzyme with Gag by binding to the Gag proteolytic cleavage site rather than to the protease enzyme. In another embodiment, viruses or recombinant proteins that contain mutations in the region of the Gag proteolytic cleavage site can be used in screening assays to identify compounds that target proteolytic processing.
|ANTIBODIES TO IREM-1 - Anti-IREM-1 antibodies and antigen-binding fragments thereof, as well as pharmaceutical compositions comprising such antibodies and antigen-binding fragments are described. Also described are methods of using such antibodies and antigen-binding regions to bind IREM-1 and treat diseases, such as hematologic malignancies, which are characterized by expression of IREM-1.
|Use of Tri-Substituted Glycerol Compounds for the Treatment of Hematological Malignancies - The present invention relates to the use of a tri-substituted glycerol compound for the manufacture of a medicament for the treatment of hematological malignancies. The invention also refers to a kit-of-parts comprising such a medicament. Finally, the invention also relates to a corresponding method for the treatment of such conditions as well as to an in vitro method for determining the susceptibility of such malignant cells to a medicament as defined in the invention.
|ANTAGONIST OX40 ANTIBODIES AND THEIR USE IN THE TREATMENT OF INFLAMMATORY AND AUTOIMMUNE DISEASES - The present invention relates to antagonist antibodies directed against human OX40 receptor (CD134) and fragments thereof, including the amino acid sequences of antagonist antibodies and the nucleic acids that encode the antibodies. Also included in the present invention are antigen binding regions (CDRs) derived from the light and/or heavy chain variable regions of said antibodies. Another aspect of the present invention is the use of anti-OX40 antagonist antibodies in the treatment of inflammatory and autoimmune diseases. The present invention also relates to humanized sequences of an antagonist antibody A10 and epitope mapping of the binding site of the antibody.
|ANTI-CD33 ANTIBODIES AND METHODS FOR TREATMENT OF ACUTE MYELOID LEUKEMIA USING THE SAME - The present invention relates to antibodies that bind CD33. More particularly, the invention relates to anti-CD33 antibodies, fragments and homologues of these antibodies, humanized and resurfaced versions of these antibodies, functional equivalents and improved versions of these antibodies, immunoconjugates and compositions comprising these antibodies, and the uses of same in diagnostic, research and therapeutic applications. The invention also relates to a polynucleotide encoding these antibodies, vectors comprising the polynucleotides, host cells transformed with polynucleotides and methods of producing these antibodies.
|COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY - The invention encompasses compounds having formula I and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK3, are therapeutically useful.
|Induction of immunosuppression by inhibition of ATM - The present invention is directed to methods of inducing immunosuppression in a patient by administering an inhibitor of the enzyme Ataxia telangiectasia mutated (Atm). The method may be used as a treatment for allergies, autoimmune diseases or lymphomas. It may also be used to prevent organ rejection in transplant patients and to treat or prevent graft versus host disease.
|Compositions and Methods for Regulating NK Cell Activity - The present invention relates to novel compositions and methods for regulating an immune response in a subject. More particularly, the invention relates to specific antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects. The invention also relates to fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly in therapy, to increase NK cell activity or cytotoxicity in subjects.
|Integrin Alpha L I Domain Mutants with Increased Binding Affinity - The present invention provides an isolated polypeptide capable of binding to
|LEUKEMIA STEM CELL MARKERS - The invention provides a test method for predicting the initial onset or a recurrence of acute myeloid leukemia (AML) comprising (1) measuring the expression level of human leukemic stem cell (LSC) marker genes in a biological sample collected from a subject for a transcription product or translation product of the gene as an analyte and (2) comparing the expression level with a reference value; an LSC-targeting therapeutic agent for AML capable of suppressing the expression of a gene selected from among LSC marker genes or a substance capable of suppressing the activity of a translation product of the gene; a method for producing a sample containing hematopoietic cells for autologous transplantation or allogeneic transplantation for AML patients comprising obtaining an LSC-purged sample with at least 1 kind of LSC marker as an index; and a method of preventing or treating AML.
|TOLL-LIKE RECEPTOR 3 ANTAGONISTS FOR THE TREATMENT OF METABOLIC AND CARDIOVASCULAR DISEASES - Toll Like Receptor 3 (TLR3) antibody antagonists, polynucleotides encoding TLR3 antibody antagonists or fragments thereof, and methods of making and using the foregoing are disclosed.
|Multivalent Immunogen - The present invention relates, in general, to HIV and, in particular, to immunogens that present epitopes located in the membrane external proximal region (MPER) of HIV-I envelope gp41 in multivalent form and to methods of using same.
|ANTI-CD33 ANTIBODIES AND METHOD FOR TREATMENT OF ACUTE MYELOID LEUKEMIA USING THE SAME - The present invention relates to antibodies that bind CD33. More particularly, the invention relates to anti-CD33 antibodies, fragments and homologues of these antibodies, humanized and resurfaced versions of these antibodies, functional equivalents and improved versions of these antibodies, immunoconjugates and compositions comprising these antibodies, and the uses of same in diagnostic, research and therapeutic applications. The invention also relates to a polynucleotide encoding these antibodies, vectors comprising the polynucleotides, host cells transformed with polynucleotides and methods of producing these antibodies.
|NOVEL MEMORY CTL INDUCTION POTENTIATOR - The present invention relates to a memory CTL induction enhancer comprising a combination of substance (b) with substance (a) and/or substance (c), wherein substance (a) is an activator of antigen-presenting cells, substance (b) is an inducer of homeostatic proliferation after induction of lymphopenia, and substance (c) is a suppressor of regulatory T cells.
|IL-16 antagonist peptides and DNA encoding the peptides - The present invention has found that a series of peptides having sequences that substantially correspond to specific regions of the C-terminus of IL-16 can inhibit the activity of IL-16. The present invention has demonstrated that such IL-16-inhibiting peptides can be as short as 4 amino acids in length. Based on these discoveries, the present invention provides IL-16 antagonist peptides and the use thereof for the treatment of IL-16 mediated disorders such as certain inflammatory diseases.
|METHOD FOR REGULATING SURVIVAL AND MEMORY OF T HELPER 1 CELLS - The present invention provides a method of inhibiting survival of T helper 1 (Th1) memory cells by contacting or administering a population of Th1 cells with an agent that inhibits CD44 receptor expression or activation. The invention further provides a method of stimulating memory Th1 cell survival comprising contacting or administering Th1 cells with an agent that increases CD44 receptor activation or expression in the cells. The invention additionally provides a method of screening for agents capable of modulating Th1 cell survival.
|METHODS FOR PREDICTING DEVELOPMENT OF AUTO-IMMUNE DISEASES AND TREATMENT OF SAME - The present invention provides a new method for the prediction of, or diagnosis of, auto-immune diseases, thereby alerting the subject to the presence of, or propensity to develop, an auto-immune disease so that preventative or therapeutic regiments may be initiated or changed so as to treat, modulate or prevent expansion of the CD4
|Thrombopoietic compounds - The invention relates to the use of compounds, especially peptides or polypeptides, that have thrombopoietic activity, and pegylated forms thereof. The peptides and polypeptides of the invention may be used to increase platelets or platelet precursors (e.g., megakaryocytes) in a mammal.
|Stimulation of Toll-Like Receptors on T Cells - The present invention relates to compositions and methods for modulating Toll-like receptors (TLRs) for enhancing survival of activated CD4+ T cells. The enhanced survival of activated CD4+ T cells provides a means for regulating an immune response.
|Methods for Inducing Mixed Donor-Recipient Chimerism in an Allograft Transplant Recipient - A method is provided for obtaining mixed donor-recipient chimeric cells, comprising the steps of (a) administering to an allograft recipient a short-term immunosuppressive regimen that depletes about 50% to about 99.9% of recipient T cells circulating in the peripheral blood of the recipient; (b) implanting an allograft from a donor into the recipient; (c) allowing the development of mixed donor-recipient chimeric cells in the recipient after completion of the immunosuppressive regimen; and (d) harvesting the chimeric cells from the recipient. The invention further provides method for compiling a library of chimeric cells and using the library to select of chimeric cells for the induction of tolerance to an allograft in a naïve or previously transplanted recipient.
|CD19-LIGAND AND USE - Provided herein are CD19-ligand (CD19-L) polypeptides and polynucleotides encoding such CD19-L polypeptides. Methods related to diagnosing and treating a disorder associated with CD19 positive B-cells in a patient using a CD19-L polypeptide are also provided.
|Apo-2L receptor agonist and CPT-11 synergism - Methods of using synergistically effective amounts of Apo-2L receptor agonists and CPT-11 to induce apoptosis and suppress growth of cancer cells, are provided.
|COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY - The invention encompasses compounds having formula I-V and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK3, may be therapeutically useful.
|METHOD FOR TREATING PROSTATITIS UTILIZING PORE-FORMING PROTEIN PROAEROLYSIN - The present disclosure includes methods and compositions for treating any condition involving prostatitis and similar diseases and/or conditions. These methods and compositions involve the use of targeted modified pore-forming proteins, including variant proaerolysin proteins.
|ANTIBODIES AGAINST HUMAN IL-21 RECEPTOR AND USES THEREFOR - The present application provides human antibodies and antigen binding fragments thereof that specifically bind to the human interleukin-21 receptor (IL-21R). The antibodies can act as antagonists of IL-21R activity, thereby modulating immune responses in general, and those mediated by IL-21R in particular. The disclosed compositions and methods may be used for example, in diagnosing, treating or preventing inflammatory disorders, autoimmune diseases, allergies, transplant rejection, cancer, and other immune system disorders.
|Method for Identifying a MHC Class H-Dependent Tumor Associated T Helper Cell Antigen - The present invention is a method for identifying MHC class II-dependent disease-associated antigens. The instant method involves expressing a library of disease-derived proteins in lytic bacteriophage for subsequent presentation by antigen presenting cells to T helper cells. Disease-associated antigens are provided as are the use of such antigens in vaccines for inducing an immune response and preventing or treating disease. Moreover, the present invention provides antibodies, which specifically bind to MHC class II-dependent disease-associated antigens or epitope peptides thereof, and their diagnostic and therapeutic use.
|Agonistic binding molecules to the human OX40 receptor - The present invention provides binding molecules, such as human binding molecules, that bind to and stimulate the human OX40-receptor. The invention also provides nucleic acids encoding such binding molecules. Methods for producing such binding molecules are also provided by the present invention. The binding molecules and nucleic acids are useful in the stimulation of human T-cells and can be used to enhance antigen-specific immune responses.
|COMBINATION THERAPY OF A TYPE II ANTI-CD20 ANTIBODY WITH INCREASED ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY (ADCC) - The present invention is directed to a pharmaceutical composition comprising: (A) a type II anti-CD20 antibody with increased antibody dependent cellular cytotoxicity (ADCC); and (B) a chemotherapeutic agent selected from the group consisting of: cyclophosphamide, vincristine and doxorubicine.
|Method of Administering an Antibody - Disclosed is a method for treating a human having a disease associated with leukocyte infiltration of mucosal tissues, comprising administering to said human an effective amount of a human or humanized immunoglobulin or antigen-binding fragment thereof having binding specificity for α4β7 integrin. Preferably, no more than 8 mg immunoglobulin or fragment per kg body weight are administered during a period of about one month.
|FC RECEPTOR HOMOLOG ANTIBODIES AND USES THEREOF - Provided herein are antibodies having the same epitope specificity as an antibody produced by the hybridoma cell line deposited with the American Type Culture Collection as hybridoma 4-2A6, 1-5A3, or 1-3B4. Further provided herein are methods of identifying and selecting cells that express FcRH1 or FcRH4. Methods of diagnosing and treating a subject with a malignancy of a hematopoietic cell lineage or an autoimmune disease and methods of modulating a humoral immune response in a subject are also provided herein. Further provided herein are polypeptides comprising one or more complementary determining regions of the disclosed antibodies and nucleic acids that encode the disclosed polypeptides.
|Receptor Modulators - Method of identifying a modulator of CD28 comprising comparing a structural model of a candidate modulator with a structural model of CD28 to thereby determine whether the modulator will bind to CD28, wherein the structural model is derived from, or comprises, structural coordinates of a crystal of: (i) CD28, (ii) a fragment of CD28, or (iii) a homologue of (i) or (ii). The crystal of CD28 in a soluble form complexed with the Fab fragment of a mitogenic (superagonistic) antibody has been obtained and used for the determination of the 3D-structure of the receptor. The application also relates to modulators of superagonistic signalling for any receptor of the CD28 family, i.e. to superagonistic antibodies and chimeric proteins thereof, and to the screening of the superagonistic modulators. In the methods of screening, the binding of the candidate modulators to a portion of the receptor proximal to the cell membrane is investigated.
|TM4SF4 AND MODULATORS THEREOF AND METHODS FOR THEIR USE - The present invention relates to methods for modulating a β-cell population using a TM4SF4 modulator or a modulator of a TM4SF4 homolog. More particularly, the invention relates, inter alia, to methods and compositions for generating, expanding, and maintaining a β-cell population and treatment of diseases associated with the loss of β-cells using a TM4SF4 modulator or a modulator of a TM4SF4 homolog.
|Neutralizing Antibodies And Methods Of Use Thereof - This invention provides monoclonal antibodies that recognize the Toll-like Receptor 4/MD-2 receptor complex, and monoclonal antibodies that recognize the TLR4/MD2 complex as well as TLR4 when not complexed with MD-2. The invention further provides methods of using the monoclonal antibodies as therapeutics. This invention also provides soluble chimeric proteins, methods of expressing and purifying soluble chimeric proteins, and methods of using soluble chimeric proteins as therapeutics, in screening assays and in the production of antibodies.
|Immunomodulatory Methods And Systems For Treatment And/Or Prevention Of Atherosclerosis And Related Proteins, Peptide And Compositions - Immunostimulatory methods and systems for treating or preventing atherosclerosis and/or a condition associated thereto in an individual.
|BINDING MEMBER WHICH BINDS TO BOTH LEWIS-Y AND LEWIS-B HAPTENS, AND ITS USE FOR TREATING CANCER - The invention relates to the use of a binding member which binds to Lewis
|METHODS AND COMPOSITIONS FOR MODULATING T CELL AND/OR B CELL ACTIVATION - The present invention provides methods of reducing or enhancing T cell activation and/or B cell activation in a subject, comprising administering to a subject an effective amount of an inhibitor or enhancer, respectively, of Semaphorin 6D (Sema6D) activity on T cells and/or B cells.
|REGULATORY B CELLS AND THEIR USES - The present invention relates to a phenotypically distinct CD1d
|METHODS OF DIAGNOSING MYELODYSPLASTIC SYNDROME (MDS) OR LEUKEMIA USING NUCLEIC ACIDS OR FRAGMENTS ENCODING FLT3 KINASE - To provide a nucleic acid encoding a receptor protein kinase, wherein the nucleic acid has tandem duplication in a nucleotide sequence of a juxtamembrane and is useful for diagnosis of leukemia; a polypeptide encoded by the nucleic acid; an antibody capable of specifically binding to a region encoded by the nucleic acid having tandem duplication occurring in a nucleotide sequence of a juxtamembrane; a nucleic acid capable of specifically binding to the nucleic acid having tandem duplication occurring in a nucleotide sequence of a juxtamembrane; a method for detection of the nucleic acid encoding a receptor protein kinase; and a kit therefor. A nucleic acid encoding a receptor protein kinase, wherein the nucleic acid has tandem duplication in a nucleotide sequence of a juxtamembrane; a polypeptide encoded by the nucleic acid; an antibody capable of specifically binding to the portion of the polypeptide; a nucleic acid capable of specifically binding to the nucleic acid; a method for detection of the nucleic acid; and a kit for detection.
|METHODS OF USING BTL-II PROTEINS - The invention provides isolated BTL-II proteins, nucleic acids, antibodies, antagonists, and agonists and methods of making and using the same. Diagnostic, screening, and therapeutic methods using the compositions of the invention are provided. For example, the compositions of the invention can be used for diagnosis and treatment of inflammatory bowel diseases and for enhancing a mucosal immune response to an antigen.
|CD37-Binding Molecules and Immunoconjugates Thereof - Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to CD37 are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.
|HEMATOPOIETIC CELLS THAT EXPRESS MOSC-1 - The present invention relates to ex-vivo cells belonging to the hematopoietic system, characterized by the presence of MOSC-1 protein on cell surface, methods for isolating them and uses thereof.
|Method for Predicting the Response of a Patient to Treatment with an Anti-TNF Alpha Antibody - The present invention relates to a method for predicting the response of a patient to treatment with an anti-TNFα therapy, in particular an anti-TNFα antibody, the method comprising: (a) providing an in vitro sample of T cells from the patient; (b) exposing said T cells to an anti-TNFα therapy; and (c) determining whether regulatory T cells are induced in said sample of T cells wherein the induction of regulatory T cells indicates that the patient is likely to respond to treatment with said anti-TNFα therapy.
|OLIGONUCLEOTIDES OR THEIR FUNCTIONAL HOMOLOGUES, A COMPOSITION COMPRISING THE SAME AND A METHOD OF TREATING B CELL NEOPLASM - The invention provides nine oligonucleotides with sequences of SEQ ID NO: 1-9 or their functional homologues or a composition comprising the same and a method for treating B cell neoplasm by using the oligonucleotides or their functional homologues or the composition comprising the oligonucleotides. The oligonucleotides induce the apoptosis of B cell neoplastic cells, up-regulate CD40 on B cell neoplastic cells and stimulate the production of IL-10 from B cell neoplastic cells.
|ANTI-KIR ANTIBODIES, FORMULATIONS, AND USES THEREOF - A novel IgG4 isotype anti-KIR antibody, novel formulations of this and other IgG4 anti-KIR antibodies, and methods of using such formulations are provided. Also described are compositions, formulations, dosages, and administration regimens suitable for NK cell activation and therapeutic applications of anti-KIR antibodies, as well as kits comprising one or more anti-KIR antibodies with instructions for use in treating cancer.
|COMPOSITIONS COMPRISING SOLUBLE CD84 OR ANTI-CD84 ANTIBODIES AND METHODS FOR DIAGNOSING AND TREATING B-CLL - A method of diagnosing B-CLL in a subject in need thereof is provided. The method comprising determining in a biological sample of the subject a level of CD84 isoform C (SEQ ID NO: 30), wherein an increase in the level of the CD84 isoform C (SEQ ID NO: 30) beyond a predetermined threshold with respect to a level of the CD84 in a biological sample from a healthy individual is indicative of the B-CLL.
|IMMUNE MODULATION VIA C-TYPE LECTIN - The invention relates to the regulation of the immune system, and in particular to the finding that the CLEC9a molecule is a marker for dendritic cells which are capable of cross-presenting extracellular antigens via the MHC class I pathway. This makes them particularly suitable for generation of cytotoxic T lymphocyte responses. Materials and methods are provided both for the induction of immune responses against target antigens, and for the inhibition or suppression of undesirable immune responses in which these cells are involved.
|Treatment of MS with goat serum - A serum composition from a goat immunised with HIV contains anti-HLA antibody and is suited for palliative improvement of the condition of an animal.
|Human Anti-Kir Antibodies - Compositions and methods for regulating an immune response in a subject are described. More particularly, described are human antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects, and antibodies having antigen-binding properties similar to those of human monoclonal antibody 1-7F9 or 1-4F1. Described also are also fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly for use in therapy, to increase NK cell activity or cytotoxicity in subjects.
|IMMUNOGLOBULIN SINGLE VARIABLE DOMAIN DIRECTED AGAINST HUMAN CXCR4 AND OTHER CELL ASSOCIATED PROTEINS AND METHODS TO GENERATE THEM - The invention relates to immunoglobulin single variable domains directed against specific human CXCR4 epitopes (herein also referred to interchangeably as "compounds of the invention", "amino acid sequences of the invention", or "building blocks of the invention") and polypeptides comprising them (herein also referred to as "polypeptides of the invention", "compounds of the invention", or "constructs of the invention").
|Methods of modulating immune function - The invention relates to methods for modulating the immune function through targeting of CLIP molecules as well as gamma delta T cells. The result is wide range of new therapeutic regimens for treating, inhibiting the development of, or otherwise dealing with, a multitude of illnesses and conditions, including autoimmune disease, transplant and cell graft rejection, cancer, bacterial infection, HIV infection, and AIDS, as well as novel methods of diagnosis and of introducing a treatment regimen into a subject.
|CTLA4 PROTEINS AND THEIR USES - The present disclosure relates to CTLA4 proteins and uses of such proteins, for example to treat diseases associated with the dysregulation of immune responses.
|METHODS AND COMPOSITIONS TO ENHANCE VACCINE EFFICACY BY REPROGRAMMING REGULATORY T CELLS - The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) is expressed by a subset of murine plasmacytoid DCs (pDCs) in tumor-draining LNs, where it can potently activate Foxp3 regulatory T cells (Tregs). We now show that IDO functions as a molecular switch in tumor-draining LNs, maintaining Tregs in their normal suppressive phenotype when IDO was active, but allowing inflammation-induced conversion of Tregs to a polyfunctional T-helper phenotype similar to proinflammatory TH17 cells when IDO was blocked. In vitro, conversion of Tregs to the TH17-like phenotype was driven by antigen-activated effector T cells, and required IL-6 produced by activated pDCs. IDO regulated this conversion by dominantly suppressing production of IL-6 in pDCs, in a GCN2-kinase dependent fashion. In vivo, using a model of established B16 melanoma, the combination of an IDO-inhibitor drug plus anti-tumor vaccine caused upregulation of IL-6 in pDCs and in situ conversion of a majority of Tregs to the TH17 phenotype, with marked enhancement of CD8
|Identification and Engineering of Antibodies with Variant Fc Regions and Methods of Using Same - The present invention relates to 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 FcγRIIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
|METHODS FOR INDUCING IN VIVO TOLERANCE - The present invention encompasses methods for inducing in vivo tolerance to a foreign tissue.
|Anti-cd16 binding molecules - The present invention relates to binding molecules that specifically bind to the human Fc gamma receptor expressed on the surface of natural killer (NK) cells and macrophages (i.e. FcγRIIIA), and in particular binding molecules that specifically bind the A form FcγRIII but do not bind to the B form of FcγRIII, as well as to the use of such binding molecules in the diagnosis and treatment of disease. The invention further extends to polynucleotides encoding such binding molecules, host cells comprising such polynucleotides and methods of producing binding molecules of the invention using such host cells.
|Optimized Anti-Cd30 Antibodies - An antibody that targets CD30, wherein the antibody comprises at least one modification relative to a parent antibody and the antibody binds with altered affinity to an FcgR or alters effector function as compared to the parent antibody. Also disclosed are methods of using the anti-CD30 antibody.
|Multispecific deimmunized CD3-binders - The present invention provides a cytotoxically active CD3 specific binding construct comprising a first domain specifically binding to human CD3 and an Ig-derived second binding domain. Furthermore, a nucleic acid sequence encoding a CD3 specific binding construct of the invention is provided. Further aspects of the invention are vectors and host cells comprising said nucleic acid sequence, a process for the production of the construct of the invention and composition comprising said construct. The invention also provides the use of said constructs for the preparation of pharmacutical compositions for the treatment of particular diseases, a method for the treatment of particular diseases and a kit comprising the binding construct of the invention.
|Humanized Anti-Human NKG2A Monoclonal Antibody - The present invention relates to agents that are non-competitive antagonists of the CD94/NKG2A receptor such as certain anti-NKG2A antibodies, in particular humanized versions of murine anti-NKG2A antibody Z199, as well as methods of producing and using such agents and antibodies.
|METHODS AND COMPOSITIONS FOR USING MHC CLASS II INVARIANT CHAIN POLYPEPTIDES AS A RECEPTOR FOR MACROPHAGE MIGRATION INHIBITORY FACTOR - Methods and compositions for using the MHC class II invariant chain polypeptide, Ii (also known as CD74), as a receptor for macrophage migration inhibitory factor (MIF), are disclosed. These include methods and compositions for using this receptor, as well as agonists and antagonists of MIF which bind to this receptor, or which otherwise modulate the interaction of MIF with CD74 or the consequences of such interaction, in treatment of conditions characterized by locally or systemically altered MIF levels, particularly inflammatory conditions and cancer.
|Selective Histamine H4 Receptor Antagonists for the Treatment of Vestibular Disorders - The invention relates to Histamine H4 receptor antagonists or inhibitors of Histamine H4 receptor gene expression for the treatment and/or the prevention of vestibular disorders.
|DETECTION OF HUMAN IMMUNODEFICIENCY VIRUS CO-RECEPTOR TROPISM IN AVIREMIC SUBJECTS - Methods for detecting human immunodeficiency virus (HIV) co-receptor tropism or replication-competent virus in aviremic subjects, and methods of selecting optimal therapies for aviremic subjects.
|MODIFIED ANTIBODIES WITH ENHANCED BIOLOGICAL ACTIVITIES - The present inventors generated modified antibodies in which several Fc domains are linked in tandem to the C terminus of the heavy chain, and modified antibodies in which Fc domains are linked in tandem via spacers, and measured the affinity for Fc receptors, CDC activity, and ADCC activity. A previous report indicated that CDC activity is not enhanced by linking multiple Fcs. However, the modified antibodies of the present invention exhibited enhanced ADCC activity. The methods of the present invention enable provision of antibody pharmaceuticals having a marked therapeutic effect.
|GRANULYSIN AND USES THEREOF - Disclosed are uses of granulysin in methods of diagnosing or treating autoimmune disorders.
|ADENYLYL CYCLASE-ASSOCIATED PROTEIN (CAP1) AND USES THEREOF AS A TARGET FOR IMMUNO-MODULATION - The present invention relates to the use of Adenylyl Cyclase-Associated Protein (CAP1) as a target for immuno-modulation. More specifically, the invention relates to the use of compounds that interact and bind CAP1, specifically, anti-CAP1 antibodies, and/or to CAP1 molecule or any fragments thereof, for the treatment of immune-related disorders by modulation of the Th1/Th2 balance. The invention further provides screening method for immuno-modulatory compounds that interact with CAP1.
|METHOD FOR IN-VITRO DETECTING PATHOGENIC T HELPER CELLS AND PHARMACEUTICAL COMPOSITIONS FOR TREATING AUTOIMMUNE DISEASES - The invention relates to a method for in-vitro detecting pathogenic T helper cells by incubating a sample of a body fluid or tissue taken from a mammal with substances specifically interacting with at least one gene product encoded by selected genes, which are differentially expressed compared to normal T helper cells, determining specific incubation products, correlating an amount of signal or change in signal with a concentration of the gene product in the sample, and detecting cell pathogenicity by comparing the concentration with another gene product concentration in a sample of non-pathogenic and/or pathogenic cells. Another object if the invention concerns a pharmaceutical composition for prophylaxis and therapy of chronicinflammatory. The invention also relates to a method for screening substances with the property to reduce the pathogenicity of T helper cells along with the symptoms of chronic inflammatory diseases.
|METHOD OF THERAPY - Numerous diseases have been linked to the production of regulator cells. The present invention relates to the observation that the immune system is cycling in these diseases. Based on these observations, the present invention provides methods for treating diseases such as cancer and a HIV infection. The present invention also relates to methods of determining when a therapy to treat a disease characterized by the production of regulator cells should be administered to a patient.
|MODULATION OF TIM RECEPTOR ACTIVITY IN COMBINATION WITH CYTOREDUCTIVE THERAPY - A genetic locus and corresponding family of proteins associated with regulation of immune function and cell survival are provided. These genes encode cell surface molecules with conserved IgV and mucin domains. The locus comprising the TIM family is genetically associated with immune dysfunction, including asthma. Furthermore, the TIM gene family is located within a region of human chromosome 5 that is commonly deleted in malignancies and myelodysplastic syndrome. Polymorphisms in the gene sequences are associated with the development of airway hyperreactivity and allergic inflammation, and T cell production of IL-4 and IL-13. The proteins include the human hepatitis A cellular receptor, hHAVcr-1.
|BTLA Antibodies and Uses Thereof - The invention relates to BTLA antibodies that block BTLA-HVEM interaction and uses thereof.
|Compositions and methods for preventing or treating a viral infection - The present invention is a composition for enhancing the immunogenicity of viral vaccine. The composition encompasses a viral vaccine in combination with at least one toll-like receptor and, in particular embodiments, an anti-CD40 antibody. The compositions of the instant invention find application in the prevention or treatment of a viral infection.
|Canine Anti-CD20 Antibodies - The invention provides canine CD20 specific antibodies, methods of making the antibodies and methods of use of the antibodies.
|EXPRESSION OF KIR IN HUMAN CANCER CELLS AS A BIOMARKER FOR IMMUNO-ESCAPE AND CANCER METASTASIS - The present invention is based on the finding that the level of KIR expression in a cancer cell is significant with regard to tumor invasion and metastasis. Therefore, the present invention concerns methods and compositions for evaluating cancer in a patient based on KIR protein or mRNA expression. The invention also provides methods and compositions for treating cancer using a KIR inhibitor and methods of screening for KIR inhibitors.
|BIOMARKERS FOR PREDICTING RESPONSE TO IMMUNOSUPPRESSIVE THERAPY - The subject invention concerns methods and materials for assessing a patient's likelihood of responsiveness to an immunosuppressive therapy. The subject invention is contemplated for use with patients having an autoimmune disorder. In an exemplified embodiment, the methods of the invention are used for assessing and/or treating a patient with MDS. In one embodiment, a method of the invention comprises analyzing T cells of a patient for dysregulation of CD4
|METHOD OF TREATING AUTOIMMUNE DISEASE WITH MESENCHYMAL STEM CELLS - Methods and compositions for treating an autoimmune disease, such as new onset type 1 diabetes (T1D) in a subject using autologous or allogeneic mesenchymal stem cells administered to the subject prior to autoimmune-induced complete depletion of insulin-producing pancreatic beta cells, e.g., within six months of new onset type 1 diabetes (T1D) diagnosis or prior to the onset of disease in a subject determined to be at high risk for T1D.
|REVERSIBLY INHIBITED ANTIBODIES FOR IMMUNE CELL STIMULATION - The invention provides methods for stimulating the immune system using antibodies capable of activating immune cells, such as T cells, the antibodies having reversibly inhibited antigen binding sites. Selective activation of the antigen binding sites at a site where an immune response is required (e.g. by irradiation) leads to a corresponding activation of the immune response at that site. Surprisingly good results are achieved even though the antibodies do not possess any targeting moiety which causes them to selectively accumulate at the site where immune cell activation is required.
|IMMUNE REGULATORY OLIGONUCLEOTIDE (IRO) COMPOUNDS TO MODULATE TOLL-LIKE RECEPTOR BASED IMMUNE RESPONSE - The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These TROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.
|Anti-CD3 Antibody Fromulations - This invention relates to therapeutic, diagnostic and/or prophylactic formulations and dosages of anti-CD3 antibodies, as well as to methods for using such formulations and dosages.
|HIGH AFFINITY HUMAN ANTIBODIES TO HUMAN IL-4 RECEPTOR - An isolated human antibody or antigen binding fragment thereof which binds to human interleukin-4 receptor alpha (hIL-4Rα) with an affinity constant (K
|METHOD OF INDUCING IMMUNE TOLERANCE TO TYPE I DIABETES - A method for inducing immune tolerance to type I diabetes in a mammal by mucosal delivery of an antigen involved in the induction of type I diabetes such as pro-insulin or insulin is disclosed. The antigen involved in the induction of type I diabetes is delivered together with an IL-10 secreting micro-organism such as
|ANTIBODIES AGAINST T CELL IMMUNOGLOBULIN DOMAIN AND MUCIN DOMAIN 1 (TIM-1) ANTIGEN AND USES THEREOF - The invention described herein is related to antibodies directed to the antigen TIM-1 and uses of such antibodies. In particular, there are provided fully human monoclonal antibodies directed to the antigen TIM-1. Isolated polynucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions (FR's) and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3, are provided. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also provided.
|Combination Immunotherapy for the Treatment of Cancer - Agonists to ICOS in combination with a blocking agent to a T cell inhibitory receptor (e.g., CTLA-4, PD-I, etc.) are demonstrated herein to be useful for the treatment of tumors.
|Modulation of Gamma-Delta T Cells to Regulate Airway Hyperresponsiveness - Disclosed is a method for regulation of airway hyperresponsiveness by modulating the action of γδ T cells in a patient. Also disclosed are methods for identifying compounds that regulate airway hyperresponsiveness by modulating γδ T cell action.
|ANTIBODIES TO CLL-1 - Anti-CLL-1 antibodies and antigen-binding fragments thereof, as well as pharmaceutical compositions comprising such antibodies and antigen-binding fragments are described. Also described are methods of using such antibodies and antigen-binding regions to bind CLL-1 and treat diseases, such as hematologic malignancies, which are characterized by expression of CLL-1.
|Superagonistic Anti-CD28 Antibodies - The present invention relates to one or more nucleic acid(s) encoding a binding molecule specifically binding to a human CD28 molecule, comprising
|Immunostimulatory Combinations - The present invention provides immunostimulatory combinations. Generally, the immunostimulatory combinations include a TLR agonist and a TNF/R agonist. Certain immunostimulatory combinations also may include an antigen.
|T CELL ACTIVATION INHIBITOR, PHARMACEUTICAL COMPOSITION CONTAINING SAME, AND SCREENING METHOD FOR T CELL ACTIVATION INHIBITING SUBSTANCE - Provided is a T cell activation inhibitor containing an RGM inhibiting substance such as an anti-RGM neutralizing antibody and the like as an active ingredient. The T cell activation inhibitor is useful as a pharmaceutical composition for the prophylaxis or treatment of autoimmune diseases such as multiple sclerosis and the like, and other diseases caused by T cell activation. In addition, a T cell activation inhibiting substance can be screened for by contacting a test substance with RGM and selecting a test substance that lowers the activity level of RGM.
|INHIBITION OF LEUKOCYTE ADHESION - This invention relates to the inhibition of intercellular adhesion mediated by L-selectin by administering a newly identified L-selectin ligand, CD34. More particularly, the invention concerns a method for inhibiting leukocyte adhesion to endothelial cells by administering an effective amount of an isolated, purified CD34 polypeptide or an antibody capable of binding native CD34.
|ENHANCEMENT OF LIGHT ACTIVATED THERAPY BY IMMUNE AUGMENTATION USING ANTI-CTLA-4 ANTIBODY - The efficacy of light activated therapy treatment is enhanced by stimulating the immune system of the patient substantially above a normal level. Abnormal tissue that is destroyed by the light activated therapy releases factors that stimulate the immune system, leading to systemic reductions in abnormal tissue (i.e., reduction beyond the region treated using light). By further stimulating the immune system using an anti-CTLA-4 antibody, the systemic destruction of abnormal tissue is enhanced.
|NOVEL RECEPTOR THAT BINDS CTLA-8 - Isolated receptors for CTLA-8, DNAs encoding such receptors, and pharmaceutical compositions made therefrom, are disclosed. The isolated receptors can be used to inhibit an immune response.
|Immunomodulating tumor necrosis factor receptor 25 (TNFR25) agonists, antagonists, and immunotoxins - Compositions and methods utilizing immunomodulating agents can either stimulate or indirectly augment the immune system or have an immunosuppressive effect. TNFR25 agonists disclosed herein have an anti-inflammatory and healing effect. They can be used to treat disease caused by asthma and chronic inflammation such as inflammatory bowel diseases including ulcerative colitis and Crohn's Disease. TNFR25 antagonists disclosed herein are capable of inhibiting CD8 T cell-mediated cellular immune responses and can for example, mitigate organ or tissue rejection following a tissue transplantation.
|COMPOSITIONS AND METHODS OF IDENTIFYING TUMOR SPECIFIC NEOANTIGENS - The present invention related to immunotherapeutic peptides and their use in immunotherapy, in particular the immunotherapy of cancer. Specifically, the invention provides a method of identifying tumor specific neoantigens that alone or in combination with other tumor-associated peptides serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumor responses.
|ANTI-CD79B ANTIBODIES AND IMMUNOCONJUGATES AND METHODS OF USE - The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.
|Specific Depletion of CD4+ T Cells - Specific depletion or modulation of activity of CD4
|POLYMORPHISM MARKERS FOR PREDICTING RESPONSE TO INTERLEUKIN-6 RECEPTOR-INHIBITING MONOCLONAL ANTIBODY DRUG TREATMENT - The present invention provides single nucleotide polymorphisms (SNPs) associated with clinical responsiveness of rheumatoid arthritis patients to treatment with an interleukin-6 receptor antibody such as tocilizumab, and methods of using such SNPs for predicting clinical response to treatment with the antibody.
|METHODS OF TREATING PATIENTS WITH IMMUNE-RELATED DISEASES - Provided herein are methods of treating patients with immune-related diseases (e.g., diabetes) with immunotherapy.
|IMMUNOSTIMULATORY COMBINATIONS - The present invention provides immunostimulatory combinations. Generally, the immunostimulatory combinations include a TLR agonist and a TNF/R agonist. Certain immunostimulatory combinations also may include an antigen.
|CONFORMATION SPECIFIC ANTIBODIES - The disclosure provides, inter alia, binding proteins (e.g., antibodies) that bind to an integrin in an activated conformation, e.g., activated LFA-1 ("aLFA-1"), e.g., relative to a non-activated conformation of LFA-1. In one embodiment, the binding proteins inhibit at least one function of an aLFA-1, e.g., inhibit a binding interaction between aLFA-1 and a cognate ligand of aLFA-1, e.g., an ICAM protein. The binding proteins can be used to treat or prevent an inflammatory disorder or other disorder.
|PAINTING THE PIA, ARACHNOID, AND SPINAL CORD PARENCHYMA - A PEG based hydrogel and a procedure for its topical application to the surface of the pia mater of the spinal cord that can be used for intrathecal delivery of diverse drug and biomolecular therapies for the treatment of traumatic central nervous system injuries and disorders including spinal cord injury (SCI), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are provided. This "painting of the pia" with biofunctionalized hydrogel material may be used as a prelude strategy in the therapeutic management of these CNS disorders. The strategy may be designed to create a microenvironment within the damaged regions of the spinal cord that is more conducive to the successful application of subsequent regeneration based treatments such as cell replacement therapies or endogenous regeneration and plasticity stimulation via application of growth factors or gene therapy. Compositions and methods for topical application of the PEG based hydrogel to the arachnoid mater, the intrathecal portions of the spinal nerves, and application directly to the spinal cord parenchyma are also provided.
|TLR AGONIST (FLAGELLIN)/CD40 AGONIST/ANTIGEN PROTEIN AND DNA CONJUGATES AND USE THEREOF FOR INDUCING SYNERGISTIC ENHANCEMENT IN IMMUNITY - Fusion proteins and DNA conjugates are disclosed which contain a TLR/CD40/agonist and optional antigen combination. The use of these protein and DNA conjugates as immune adjuvants and as vaccines for treatment of various chronic diseases such as HIV infection is also provided.
|IMMUNOTHERAPY USING REDIRECTED ALLOGENEIC CELLS - A method of treating a disease, such as cancer, by administering to a subject in need of such treatment an effective amount of allogeneic T cells with a MHC unrestricted chimeric receptor short time after partial lymphodepletion. The method also comprises administering one or more agents that delay egression of the allogeneic T cells from lymph nodes of said subject during adoptive transfer of said allogeneic T cells to the subject by trapping the T cells in the lymph nodes.
|IMMUNOSUPPRESSIVE DRUG COMBINATION FOR A STABLE AND LONG TERM ENGRAFTMENT - A method of treating a subject in need of a cell or tissue transplant is disclosed. The method comprising (a) transplanting a non-syngeneic cell or tissue transplant into the subject, wherein the transplant comprises bone marrow or lymphoid cells; and (b) administering to the subject a therapeutically effective amount of an immunosuppressive regimen comprising a Sphingosine 1-Phosphate Receptor Agonist, a B7 molecule inhibitor and a CD2/CD58 pathway inhibitor, thereby treating the subject.
|ANTI-RHESUS D MONOCLONAL ANTIBODY - The invention relates to an anti-RhD monoclonal antibody, which is a tetrameric IgG1 immunoglobulin composed of two heavy chains and two light chains, the heavy chain comprising the amino acid sequence SEQ ID No. 2, harboring a phenylalanine residue at position 68, and the light chain comprising the amino acid sequence SEQ ID No. 4.
|Tc11 as a Transcriptional Regulator - Methods and compositions for the diagnosis, prognosis and/or treatment of B cell chronic lymphocytic leukemia associated diseases are disclosed.
|ANTIBODIES WITH T-CELL RECEPTOR LIKE SPECIFICITY TOWARDS NATIVE COMPLEXES OF MHC CLASS II AND DIABETES-ASSOCIATED AUTOANTIGENIC PEPTIDES - Provided are isolated complexes comprising a major histocompatibility complex (MHC) class II and a type I diabetes-associated autoantigenic peptide, the isolated complex having a structural conformation which enables isolation of a high affinity entity which comprises an antigen binding domain capable of specifically binding to a native conformation of a complex composed of the MHC class II and the type I diabetes-associated autoantigenic peptide; and isolated high affinity entities comprising an antigen binding domain capable of specifically binding the complex, wherein the isolated high affinity entity does not bind to the MHC class II in an absence of the diabetes-associated autoantigenic peptide, wherein the isolated high affinity entity does not bind to the diabetes-associated autoantigenic peptide in an absence of the MHC class II; and methods and kits using same for diagnostic and therapeutic purposes.
|CYTOKINE-EXPRESSING CELLULAR VACCINE COMBINATIONS - The present invention in all of its associated aspects provides improved methods and compositions for treating cancer in a mammal based on the administration of the combination of a cytokine-expressing cellular vaccine and at least one additional cancer therapeutic agent or treatment to a patient with cancer, wherein administration of the combination results in enhanced therapeutic efficacy relative to administration of the cytokine-expressing cellular vaccine or cancer therapeutic agent or treatment as a monotherapy.
|HUMAN B1 CELLS AND USES THEREOF - The present invention is directed to isolated populations of human natural immunoglobulin-producing B1 lymphocytes, wherein the B1 lymphocytes display surface biomarkers CD20, CD43 and CD27 and are either CD11b+ or GD11b−. The present invention is also directed to a method of isolating human natural immunoglobulin-producing B1 lymphocytes from a blood sample comprising isolating B lymphocytes from the sample that express surface biomarkers CD20, CD43 and CD27, and, optionally, CD11b. In addition, the present invention is directed to a methods for diagnosing a B1 cell disorder in a patient, determining the prognosis of a patient having a B1 cell disorder, and treating a patient having a B1 cell disorder.
|PD-1 MODULATION AND USES THEREOF FOR MODULATING HIV REPLICATION - Methods, uses, compositions and kits for modulating HIV replication based on PD-1 modulation are disclosed. Methods, uses, compositions and kits useful for the elimination of latent HIV reservoirs based on PD-1 inhibition are also disclosed. Methods and kits useful for identifying agents useful for modulating HIV replication are also disclosed.
|Humanized Anti-CD79B Antibodies and Immunoconjugates and Methods of Use - The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.
Patent applications in class Hematopoietic cell


text:
E 83rd St & Pershing Rd has a Walk Score of 14 out of 100. This location is a Car-Dependent neighborhood so almost all errands require a car.
This location is in Raytown. Nearby parks include Twelve Gates Memorial Gardens, C. Lee Kenagy Park and Trace County Park.
Nearby schools include Raytown South High School, Raytown South Senior High School and Herndon Career Center.
The closest grocery stores are Walmart Supercenter, Nohelani Natural Health and Cosentino's Apple Market.
The closest coffee shop is ROC Express. Nearby restaurants include SUBWAY® Restaurants (Wal-Mart), L W Management Inc and Popeye's Chicken & Biscuits.

subset: commoncrawl


text:
Yoga for One
Let's discover your yoga practice, a practice uniquely suited to your needs that becomes part of your life.
Rowan Lommel, E-RYT, Yoga Therapist
"As a longtime yoga practitioner, I know what yoga can do to advance healing. Rowan has the right background, excellent training and personal qualities which make her an ideal yoga teacher. I refer patients to her with great confidence."
Reuben A. Weininger, M.D.
- Private Yoga Lessons
- Yoga Therapy
- Pre- and Post-Natal Yoga
- Special Event Teaching
- Yoga Retreats and Workshops
- Vedic Chanting
- Presentations on Yoga
Seeing everything that goes on in your daily life, your daily activities — when you pick up a pen, when you talk, when you go out for a drive or when you are walking alone in the woods — can you with one breath, with one look, know yourself very simply as you are? - J. Krishnamurti


text:
Thinking about a master of music in vocal performance degree? Is North Park the right place for your voice and to help you meet your career goals? Request more information today; our admissions team is ready to help.
We use a convenient online admissions system to help our students take the next steps toward their degree—whether that's starting an application or asking a question. Filling out a form to request more information helps us know what you're looking for; we'll respond to your request with prompt, personal service. You can expect to receive communication from our admissions office by email as well as printed materials by mail.
Do you have specific questions or want to visit North Park's campus while you make your decision? Do you simply prefer to meet face-to-face with an admissions representative? Meet Dr. Rebecca Ryan, music recruiter and director of operations for the School of Music. She'll be happy to schedule a personal appointment with you to discuss your career goals and how the School of Music can help you meet them.
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text:
I was sitting near the vending machine, and this woman was like, "I don't have my glasses on. Is the Dr. Pepper D1 or B1?" and I was like, "D." And she was like, "Thank you! Here, you keep the quarter." and I was like, "Haha, don't worry about it." and she was like, "Keep it, you might need it one day."
lol, guess who's $0.25 closer to being the proud owner of a Bickel heritage jersey.


text:
sdddddI have a story... which needs to be corrected.
A girl is telling her friends that every year we run competitions in our school .In this competition, Ajay is the only one who has won every time. He is very kind-hearted, and he helps everyone in the school, so everybody likes him.
Akash,the co-participant, who had been losing the competition every time, listened to their words and decided to win this time.
So, in order to win this competition, he asked his friends to throw stones over at Ajay in the race.
The race has started.....
This time Akash has a very good practice .
And he was running faster than Ajay and pulled ahead of B]?[/B] him.
The stones thrown by his friends at hit Akash instead.
He fell down and got hurt. Ajay saw it and came to help Akash..
As soon as, Akash got up, he started running. Ajay also started running but, he was behind Akash.
Finally, Akash won the competition. Ajay went to Akash and congratulated him for the success.
Akask was embarrassed by his praise and he thought that...
I had never praised Ajay like he did to menow.? And, he realized that Ajay would have won the race if he had not helped Akash when he fell down.
Akash thanked Ajay for helping him, And said tohim that,"Though you didn't win the race, you have changed my mind. So, the real winner is you."


text:
Sweet Potato Mini Muffins or Loaves
Community Recipe from
Recipe Time
Prep Time:
Cook Time:
- 3 cup(s) sweet potatoes (2 large) baked and mashed
- 1/3 package(s) silk tofu mashed
- 1 cup(s) brown sugar
- 2 tablespoon(s) honey
- 2 tablespoon(s) canola oil
- 1 teaspoon(s) vanilla extract
- 3 eggs
- 2 cup(s) all-purpose flour
- 1 cup(s) 5 grain flax oatmeal or whole wheat flour
- 2 teaspoon(s) baking soda
- 1 1/2 teaspoon(s) baking powder
- 2 teaspoon(s) cinnamon
- 1 cup(s) pecans (optional) chopped
- Bake potatoes ahead of time and allow to cool.
- Preheat Oven to 350. Lightly grease muffin tins or line with papers. If making loafs, grease pans with canola oil and line bottom with parchment paper.
- Combine potato, tofu, brown sugar, honey, canola oil, vanilla and eggs in large bowl. In another bowl whisk together flour, baking soda, baking powder, and cinnamon. Add dry ingredients to the wet and stir only enough to mix the ingredients.
- Fill mini muffin tins and bake 12 minutes. If making 2 9x5x13 loaves bake 45-60 minutes.
April 2012
This recipe is a personal recipe added by JulieZurolo and has not been tested or endorsed by MyRecipes.
My Notes
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Sweet Potato Mini Muffins or Loaves Recipe at a Glance
- COURSE: Breads
- CONVENIENCE: Kid-Friendly
- MAIN INGREDIENT: Vegetables
- COOKING METHOD: Bake
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Have just had to call a reputable plumber for a serious leak under my bath due to a tap that Aquarius both fitted and were called back to due to my concern that it moved! Or more accurately, it swivelled almost completely round within days of fitting. I was told that it was just the washer underneath which had loosened and it wouldn't present a problem and 'besides it was very awkward to get to anyway' ??? I now have quite considerable water damage under my bath and through to downstairs, a leak which has obviously been ongoing for a considerable time. This, however is just the icing on the cake of a catalogue of errors. First, there is a language barrier with the workmen, making what you want virtually impossible to get across, cut 'half' tiles are placed in the middle of a wall, as the tiler began at both ends??? The sink is now no longer completely secure on the wall and at the end of the day, sad to say but all they seemed interested in is getting their money. By the way, my bathroom has been in a little over 2 years! I think rating them with even one star is one more than they deserve.
Cridhe Dubh - 08/01/2013
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nemar Wrote:
Jul 20, 2012 10:49 PM
smr wrote: "I heard Mark Levin's show last night. Unfortunately, it was pointed out that 80% of the Bush farm bill money went to the burgeoning food stamp program. All of the jokers need to give it a rest. That's why I wanted a Consistent Conservative running. Bush was better than Gore or Kerry by miles, but he still didn't close the border and wanted an amnesty program passed. That's what I call a Middlin' Moderate !"


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This was excellent! I used store bought caramel sauce and mixed cool whip with the pastry cream... it was delicious!
Banana Pecan Dacquoise
Gardnervillian Posted: 12/08/08
Beautiful1 Posted: 01/06/09
I made this exactly as the recipe stated and it could not have been better. I got snowed in and was forced to eat it everyday! What a great recipe. I'll definitely make it again. It's easy to make ahead in pieces than travel somewhere else with it.
LisaDee Posted: 07/15/09
Went over extremely well as the end to a perfect brunch with family and baby! The difference in textures from the crispy chewy meringue and the velvety caramel was sublime. I was a little intimidated by the prep work, but it was much easier than I had anticipated. With all the components ready ahead of time it made me look like Superwoman when it came time to serve.
NWVicky1 Posted: 01/04/11
Horrible, horrible, horrible! Sometimes I think people strive for different when simple would excel. In my opinion, this is the case with this recipe. This is a very involved recipe that has no benefits from the extra efforts. The merinques were dry and tasteless, after much work toasting then chopping the pecans,etc. A simple merinque would have been fantastic here. A fruit pavlova--fruit and simple merinque is one of the most delightful summertime desserts. The banana caramel smelled and tasted of fish??? Added nothing. Again, a simple carmel would have been lovely. The cream patisserie was fine, a little stiff. What a wonderful, simple dessert this would have been with a simple caramel sauce, simple baked meringues, fresh bananas, whipped cream and toasted pecan garnish. Instead it was two hours wasted and a less than impressive result for my guests. Sorry, simple is sometimes better. (A lovely dessert made by my Danish husband's grandmother consisted of simple baked meringues topped with homemade whipped cream and a homemade chocolate. Delicious, simple and in Denmark they call it the King's dessert.)


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Matriz de insumo-produto para a economia turística brasileira: construção e análise das relações intersetoriais
[Input-output matrix for the Brazilian tourism economy: construction and analysis of intersectoral relationships]
AbstractThis study aimed to analyze the tourism contributions to the Brazilian economy, considering the productive framework of 1999. For that, it was aimed to characterize the inter-sectors relations focusing on sectors that form the tourism segment. In order to perform this study, it was needed to share the inputoutput matrix constituted to the country into sectors which were considered touristy and non-touristy. In the analysis, it was used, the linkage index of Hirschmann-Rasmussem, the field of influence, the pure linkage. The linkages inter-sector indexes allowed the identification of key-sectors, considering the input-output model here developed and the level of aggregation used. Among the sectors classified as key-sectors, using the most extensive concept, six (06) were initially considered as compounds of the tourism segment: regular air transport, non-regular air transport, travel agents and agencies, supporting activities of air transport, hotels and other types of temporary accommodation, restaurants and other food establishments. In face of this, it is pointed out the importance of implementing policies and programs to promote the development of the sector of tourism in Brazil, considering that tourism contributes to the growth of the national economy.
Download InfoIf you experience problems downloading a file, check if you have the proper application to view it first. In case of further problems read the IDEAS help page. Note that these files are not on the IDEAS site. Please be patient as the files may be large.
Bibliographic InfoPaper provided by University Library of Munich, Germany in its series MPRA Paper with number 37963.
Date of creation: 2003
Date of revision:
Handle: RePEc:pra:mprapa:37963
Contact details of provider:
Postal: Schackstr. 4, D-80539 Munich, Germany
Phone: +49-(0)89-2180-2219
Fax: +49-(0)89-2180-3900
Web page: http://mpra.ub.uni-muenchen.de
More information through EDIRC
Related researchKeywords: input-output; tourism; key-sectors;
Find related papers by JEL classification:
- D57 - Microeconomics - - General Equilibrium and Disequilibrium - - - Input-Output Tables and Analysis
- R15 - Urban, Rural, Regional, Real Estate, and Transportation Economics - - General Regional Economics - - - Econometric and Input-Output Models; Other Methods
- C67 - Mathematical and Quantitative Methods - - Mathematical Methods; Programming Models; Mathematical and Simulation Modeling - - - Input-Output Models
ReferencesReferences listed on IDEAS
Please report citation or reference errors to , or , if you are the registered author of the cited work, log in to your RePEc Author Service profile, click on "citations" and make appropriate adjustments.:
- Leontief,W., 2009. "Structure, System and Economic Policy," Cambridge Books, Cambridge University Press, number 9780521109062, 9.
- Guilhoto, J. J. M. & Sonis, M. & Hewings, G. J. D., 2005. "Linkages and Multipliers in a Multiregional Framework: Integration of Alternative Approaches," MPRA Paper 38213, University Library of Munich, Germany.
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Cited by:
- Takasago, Milene & Guilhoto, Joaquim José Martins & Mollo, Maria de Lourdes Rollemberg & Andrade, Joaquim Pinto de, 2010.
"O potencial criador de emprego e renda do turismo no Brasil
[The potential to create employment and income from tourism in Brazil]," MPRA Paper 30693, University Library of Munich, Germany.
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N.B. The following are the original transcripts provided by the lecturers. They have not been edited in anyway.
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Categories > Original > Romance > The Forgotten Pieces (A Tom Hiddleston story)
Realise0 Reviews
Dinner with Ethan has caused Lara to realise some things...
Ethan turned out to be a lovely gentleman asking how my injuries were healing up. I started to think that maybe he was not – as he would call it – a jerk. He was smiling all the time and took his time trying to inform me of all the things I could not remember that might help me in healing.
We were in the middle of discussing the music world when my phone started ringing that awful ringtone again. I excused myself whilst taking the phone out of my pocket. It was Tom calling.
"Hey, where are you? I'm at your place," he paused. "Are you okay? You're not lost are you?"
"Oh, I must have forgotten to mention that I went out to help in recovering…" I bit my cheek. "I'm at a café right now with Ethan… my work colleague."
"What?" he sighed in a harsh manner. "Where are you? I'll pick you up, it's late."
"Oh, uhh…" I move the phone from my ear and leaned towards the curious Ethan. "Sorry, but where are we located?"
He chuckled before giving me the address.
I repeated the address to the speaker.
"Alright, I'll be there in ten," and he hung up.
I knew I have upset him by wandering around only a few days after checking out of the hospital with no notification of my whereabouts. He was after all the person who will be looking after me and he has promised my parents over and over that he will take good care of me.
"Sorry about that," I gave the sandy blonde hair man a tight-lipped smile.
"That's alright. If you don't mind me asking, was that Tom Hiddleston on the phone?"
I nodded.
"I'd really like to meet him but I doubt he would give me a chance because of how crowded this place is," he gestured around him.
It was almost 9pm and the streets were still alive with people wandering about.
I nodded in agreement. "He doesn't like crowded places?"
"Well, I wouldn't know. It's just that, you know, his status and everything you would think that he would not step out in a crowded place where anyone would recognise him. It would cause a big scene," he chuckled.
I rubbed my forehead and gazed out the busy street outside the café and contemplated in asking what he meant by what he said. I was not sure if I should ask Ethan by not knowing what consequences might lay underneath that action. Learning from our conversations, Ethan seemed to know about everyone's private life and it would not help if I revealed that I had no idea about Tom and his life other than the fact that the man was English and was my boyfriend.
I looked back at Ethan who was watching me and nodded to him in agreement without saying anything more.
We continued our conversation about the music world. Ethan updated me on the mainstream music that was loved by everybody. I wasn't at all surprised seeing as the mainstream music has not changed in the last three years. It was when Tom called letting me know he was outside that Ethan to the queue to get up and pay the bills in which I tried to object but he ignored me.
We left the café together and faced the black shiny car which I remembered was Tom's. The passenger window went down revealing Tom with a tight smile.
"Hey! Here's your missus all safe and sound," Ethan put a hand on my shoulder.
"Thank you Ethan for looking after her," Tom said.
"It is such an honour to meet you finally, I really love your work – even though I work in the music section of our magazine," he chuckled.
I glanced up at Ethan with a questioning look then delivered the same look to Tom. His status? His work?
"Thank you," he nodded. "Listen Ethan, I'm quite in a hurry so-"
"No, no! That's okay! I'll be on my way, nice meeting you!" Ethan then looked down at me. "And I hope you get well soon."
I thanked him and smiled before climbing into the car.
The car ride was silent and uncomfortable. I wanted to apologise but was afraid that the atmosphere around me will become tenser and swallow me up. Instead I looked out the window and watched the dark lit streets fly passed me. A ridiculous amount of thoughts and questions were cluttered in my mind taking turns to think and question every one which increased my anxiety level. I have never really thought about it. I have never really thought about who this man seated beside me was. I was so consumed by my strategies of gaining my memories back that I have never really thought about the present moment, at all.
I have no even acknowledged Tom entirely and was engulfed by my own problems, trying so hard to retrieve my memories, always doing whatever it took to regain them. I was not concerned about him at all. I did not try to get to know him as well. My eyebrows were knitted at my very thought that I have no tried to get to know him. He was after all, a large part of my life. I obviously did not know how true that was but seeing as he was apparently my steady boyfriend, it would mean that the majority of my life was spent with him. I closed my eyes shut and silently cursed myself. All I was doing was staying about this man to keep my independence.
Finally we arrived to my apartment and the car went to a halt. I sighed and unbuckled my seatbelt before glancing at Tom.
"I'm really sorry for heading out without telling you," I watched to see any signs of response. He only pressed his lips together and avoided looking into my eyes. So I continued, "I honestly did not know I would be out for so long, and when Ethan called I thought-"
"You thought that he could help?" he interrupted. His polite voice was threaded in dismay.
"Well, yes."
"Look, Lara," he shut his eyes and squeezed the bridge of his nose. "I know this is going to make me sound like an aggressive and possessive person but I don't want you to see that man ever again."
I frowned at him in disbelief, "What makes you say that?"
"I would refer to the reason that I am your boyfriend and I have the right to be jealous but that won't work in this case since you don't remember any aspect of our relationship," he spoke quickly and calmly. "But I will say this, he tends to be rather nosy which I don't like and he has bothered you quite a lot. I wouldn't want a repeat of that."
I sighed and glared out the windscreen at the blank white concrete wall.
"I'm just trying to be cautious, I'm sorry."
"It's okay," it really wasn't but I was not ready to argue. I absently fiddled with the hem of my coat and looked back at Tom who was already looking at me.
His brows were furrowed as he studied my face. From that look I knew that he knew that I was lying.
"I should go inside," I broke the silence. I had a faint idea of how to get back to my apartment.
He nodded. I know it's your decision to make but by your intense struggle to try to regain your memories is bothering me, so…" he opened his door. "I'm going to have to spend some quality time with you and help get back those memories."
"You don't need to…" I wasn't sure I liked the idea of spending quality time with this man. He was gorgeous, yes, but that could distract me from my goal.
"I think I do," he grinned at me. "After all, most of the memories you have lost had me in it and it kills me to respect this personal space of yours."
I have a few things to blame for the delayed chapter.
1. Uni
2. Exams
3. Writer's block
I'd appreciate if any of you have any ideas that you would like me to consider, or you know, give me some feedback of how this is going.


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LUBBOCK, TX (KCBD) - Police took two men into custody Wednesday afternoon, after they say one led them on a chase through central Lubbock.
Police say they pulled over Daniel Arguijo, 62, and Jeremiah Arguijo, 25. When they stopped, they say Jeremiah Arguijo ran. Police caught up with him near 35th Street and Flint Avenue around 3:30 p.m.
Police say both men had warrants out for their arrest. They say Jeremiah Arguijo will most likely face additional charges.
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When you think about music as a survival instinct, taking the edge off a long train ride is probably what first comes to mind. But neuroscientist Lawrence Parsons wants you to think a little farther back—way back to our evolutionary beginnings. In this clip, Parsons explains how music has helped early humans survive, and how positive feedback from our brain keeps us coming back for more.
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HI! I'm Michelle. I only recently discovered Tumblr so this blog is not really of one thing or another, but more of several different topics that catch my eye.
I'm a 22 year old college student in NC majoring in International Development and Nonprofit Studies. Aaaaand I'm obsessed with Tumblr.
By other blog is http://puppy-escapades.tumblr.com so make sure to check it out!
If you have any comments, go ahead and message me!
Some of the things I blog about:
American Horror Story (TATE!!)
Cute animal pictures, especially PUGS
Comics such as BATMAN or Thor
Anything DRACO MALFOY
Random Pokemon pics
Game of Thrones
Any other random photo that makes me go LOL
Thanks for looking! Hope you see something you like.
Stuff I like
- Photo via thefuuuucomicsPhoto via thefuuuucomics
Do you ever wonder about how an author would describe you...


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Ummm!!! So that's what happens.
Not for you though!
@mshelent lol I'm keeping them under control :)))
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Instead of carrying your iPhone or iPod with you where you go, this tactical iPod holder arm band is designed to carry it for you. The tactical arm band is designed for durability and security. The polyester knit fabric arm band holds an inner zippered compartment for your valuables, and the iPod holder also features a slot to slide your identification into. So, if you're on the run, strap this iPhone armband onto your arm, or your ankle, and go! Enjoy hands free music or movies with the Black or Camo iPod Arm Band Holder.
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Arizona Youth Ballet
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Come and be a part of the Valley's newest pre-professional ballet company!!! We are a non profit 501(c)3 program that provides pre-professional performance opportunities through strong technical training and a nurturing environment for dancers of all ages. Through dedicated, highly regarded faculty, outstanding supporters and amazing dancers, we strive to be the premier youth dance company in the Southwest.
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Italian designer Valentino Garavani has shaped haute couture fashion for five decades.
Donatella Versace pays tribute to her late brother, Gianni Versace as part of the Atelier Versace couture runway show at the Ritz Carlton in Paris.
The Versace fall/winter couture show was quite an emotional moment for designer Donatella Versace as she unveiled the latest Atelier Versace couture creations at the Ritz Carlton hotel in Paris. Her brother, Gianni Versace, had always staged his shows at the iconic hotel for eight consecutive years before he passed away. Donatella's return to the venue celebrates her late brother's legacy. Actresses Jessica Alba, Milla Jovovich, Elizabeth Banks and actor Pierce Brosnan were amongst those present at this emotional 'homecoming'. Click next to view more on the collection.
fashion guide
For seven consecutive years Louis Vuitton has been named the world's most valuable luxury brand.
American fashion house Ralph Lauren doesn't just sell clothes; it sells an aspirational lifestyle.
Versace has established itself as one of the world's leading fashion houses.
Fashion house Dolce & Gabbana favours bright colours, clashing patterns and animal prints.
One mention of Chanel brings to mind elegance, sophistication and an ageless quality.
One of the longest-running British labels, Burberry embodies tradition, exclusivity and durability.
Yves Saint Laurent's biggest legacy was making it acceptable for women to wear trousers.