Abstract: The present invention provides a method for stabilizing a protein in a desired conformation by introducing at least one disulfide bond into the polypeptide. Computational design is used to identify positions where crysteine residues can be introduced to form a disulfide bond in only one protein conformation, and therefore lock the protein in a given conformation. Accordingly, antibody and small molecule therapeutics are selected that are specific for the desired protein conformation. The invention also provides modified integrin I-domain polypeptides that are stabilized in a desired conformation. The invention further provides screening assays and therapeutic methods utilizing the modified integrin I-domains of the invention.

Abstract: The present invention provides methods for treating cancer in a subject, as well as related compositions and kits that employ a therapeutic agent, or a nucleic acid sequence encoding a therapeutic agent, selected from apolipoprotein A-1 (ApoA1) or biologically active fragment, an ApoA1 mimetic, an agent that increases expression of ApoA1, or a binding agent specific for oxidized ApoA1. In certain embodiments, the ApoA1 or ApoA1 mimetic is at least partially oxidation resistant.

Abstract: Compositions and methods are provided for modulating cell-cell fusion by using agents that modulate expression, activity, or function of intermediate-conductance calcium-activated potassium (SK4) channel. In some embodiments, the compositions and methods of the invention provide for inhibition of multi-nucleated osteoclastogenesis and cell-cell fusion, especially cell fusion involving macrophages. In such embodiments, the compositions can comprise inhibitory nucleic acids, monoclonal antibodies or small molecule inhibitors of the SK4 channels and find use in preventing and/or treating various diseases or disorders including bone loss, autoimmune and inflammatory diseases or disorders, implant and transplant rejection, and cancer metastasis. In other embodiments, the compositions and methods of the invention provide for activation of cell-cell fusion. Also provided are methods to screen for SK4 channel modulators (inhibitors or activators) that modulate cell-cell fusion, particularly macrophage cell fusion.

Abstract: Methods, compounds, compositions, kits and articles of manufacture comprising one or more gap junction modulating agents for treatment of wounds that do not heal at expected rates, including chronic wounds, delayed healing wounds, incompletely healing wounds, and dehiscent wounds in a subject in need thereof.

Abstract: The present invention relates to antibodies which bind to C5aR and which are useful in diagnostic and therapeutic methods. The antibodies of the present invention are reactive with an extracellular loop of C5aR other than the N-terminal domain and are capable of substantially reducing or inhibiting the binding of C5a to C5aR and functional consequences of neutrophil chemoattractant receptor activation.

Abstract: The present invention relates to methods and compositions for regulating lectin complement pathway (LCP)-associated complement activation. In particular, the invention relates to methods and compositions for inhibiting LCP-associated complement activation in order to inhibit hyperglycemic myocardial damage. The invention also relates to the treatment of cardiomyopathy and/or hypertrophy, such as cardiac hypertrophy. The invention also relates to methods and compositions for inhibiting the loss of cardiac progenitor cells by inhibiting LCP-associated complement activation. The methods include both in vitro and in vivo methods. The methods can be accomplished by contacting a mammalian cell having a surface exposed mannose binding lectin (MBL) ligand, such as a cardiac cell, with an effective amount of a MBL inhibitor to inhibit LCP-associated complement activation.

Abstract: The invention relates to humanized anti-human Factor D monoclonal antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their use in the preparation of compositions and medicaments for treatment of diseases and disorders associated with excessive or uncontrolled complement activation. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.

Abstract: The subject invention relates to monoclonal antibodies (e.g., 8F5 and 8C5) that may be used, for example, in the prevention, treatment and diagnosis of Alzheimer's Disease or other neurodegenerative disorders.

Abstract: The invention provides for inhibition of viral disease by the provision to a mammalian host of antibodies directed against an escort protein like Tsg101. These proteins appear on the surface of a cell, and thus can be bound by circulating antibodies thereto. By binding escort proteins on the cell surface, budding of viral particles is inhibited. The virus infects the initial cells, but cannot escape that cell to infect the body en masse.

Abstract: The present invention relates to immunoglobulins that bind Fc?RIIb+ cells and coengage the antigen on the cell's surface and an Fc?RIIb on the cell's surface, methods for their generation, and methods for using the immunoglobulins.

Abstract: The human Occludin protein is identified as an essential Hepatitis C Virus (HCV) cell entry factor. Occludin is shown to render murine and other non-human cells infectable with HCV and to be required for HCV—susceptibility of human cells. Associated methods for inhibiting HCV infection, transgenic animal models for HCV pathogenesis, methods of identifying compounds or agents that prevent or mitigate interaction of HCV with Occludin, and HCV inhibitory agents are also disclosed. Kits and cell culture compositions useful for identifying compounds or agents that prevent or mitigate interaction of HCV with Occludin are also provided.

Abstract: An in vitro or in vivo method for screening for candidate compounds for the preventive or curative treatment of acne, of seborrhoeic dermatitis or of skin disorders associated with hyperseborrhoea, includes determining the ability of a compound to modulate the expression or the activity of the phosphatidylcholine transfer protein (PCTP), and also utilizes modulators of the expression or of the activity of this protein, for the treatment of acne, of seborrhoeic dermatitis or of skin disorders associated with hyperseborrhoea; methods for the in vitro diagnosis of or in vitro prognosis for these pathologies are also featured.

Abstract: The invention is directed to a method of inhibiting bone resorption. The method comprises administering to a human an amount of sclerostin inhibitor that reduces a bone resorption marker level for at least 2 weeks. The invention also provides a method of monitoring anti-sclerostin therapy comprising measuring one or more bone resorption marker levels, administering a sclerostin binding agent, then measuring the bone resorption marker levels. Also provided is a method of increasing bone mineral density; a method of ameliorating the effects of an osteoclast-related disorder; a method of treating a bone-related disorder by maintaining bone density; and a method of treating a bone-related disorder in a human suffering from or at risk of hypocalcemia or hypercalcemia, a human in which treatment with a parathyroid hormone or analog thereof is contraindicated, or a human in which treatment with a bisphosphonate is contraindicated.

Abstract: The present invention relates to antibodies or fragments thereof that specifically bind Fc?RIIB, particularly human Fc?RIIB, with greater affinity than said antibodies or fragments thereof bind Fc?RIIA, particularly human Fc?RIIA. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.

Abstract: The present invention relates to amyloid-beta (A?) binding proteins. Antibodies of the invention have high affinity to A?(20-42) globulomer or any A? form that comprises the globulomer epitope. Method of making and method of using the antibodies of the invention are also provided.

Abstract: Improved methods for treatment of cancer which involve the targeting of slow-growing, relatively mutationally-spared cancer stem line are provided. These methods are an improvement over previous cancer therapeutic methods because they provide for very early cancer treatment and reduce the likelihood of clinical relapse after treatment.

Abstract: Anti-CEACAM6 antibodies and antibody fragments, nucleic acids encoding them, methods of their manufacture, and methods to treat cancer using these compounds are provided.

Abstract: The invention relates to an anti-idiotypical antibody targeting an antibody inhibiting the human factor VIII, said inhibiting antibody targeting the C2 region of the human factor VIII, the variable region of each of the light chains thereof being encoded by a sequence of nucleic acids of which at least 70% is identical to the murine sequence of nucleic acids SEQ ID NO: 1, and the variable region of each of the heavy chains thereof being encoded by a sequence of nucleic acids of which at least 70% is identical to the murine sequence of nucleic acids SEQ ID NO: 2, the constant regions of the light chains and the heavy chains being constant regions from a non-murine species. The invention also relates to the use of said antibody for activating the Fc?RIII receptors of cytotoxic immune cells, and to the production of a medicament especially for the treatment of haemophilia A.

Abstract: Described herein are deposited hybridoma cell lines and the monoclonal antibodies produced by these hybridomas, and antigen binding fragments thereof. These monoclonal antibodies and antigen binding fragments specifically bind marinobufagenin. The disclosure also encompasses the use of these monoclonal antibodies or antigen binding fragments in a method for detecting the presence of marinobufagenin in a biological sample. Also provided are methods for the use of these monoclonal antibodies or antigen binding fragments as prophylactic, therapeutic, and diagnostic agents for the detection, inhibition and treatment of a cardiovascular disease, for example, essential hypertension, hypertension associated with preeclampsia, eclampsia, or renal failure, or myocardial fibrosis in a subject.

Abstract: Low levels of antibodies reactive with oxidised Cardiolipin (oxCL) in mammals are related to an increased risk of developing cardiovascular diseases, auto-immune diseases or inflammatory conditions. High levels can have a protective function and in general there is a negative association between manifestations of these conditions and antibodies against oxCL. Thus, based on their relations methods of monitoring, determining and diagnosing as well as methods of immunisation and therapy of these diseases and conditions are provided.

Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody. In more preferred embodiment the cytokine is G-CSF, erythropoietin or INF-?2b.

Abstract: The invention relates to novel regulators of plasminogen activation and their use for regulating cell migration, plasminolysis, angiogenesis, fibrinolysis, for treating cancer and thrombo-embolic diseases such as heart stroke. Furthermore, the present invention relates to novel pharmaceutical compositions form regulating cell migration, plasminolysis, angiogenesis and for treating cancer. In particular, the present invention relates to a method of regulating the activation of plasminogen comprising contacting a solution of pro-urokinase (uPA) or tissue plasminogen activator (tPA) and plasminogen with melanotransferrin (p97) for a time sufficient to effect regulation thereof.

Abstract: This invention is in the field of treating or preventing inflammation in humans and animals and relates to pharmaceutical compositions and methods for treating or preventing various inflammatory conditions. In particular, the invention relates to compositions and methods for treating or preventing inflammatory conditions such as citrulline related inflammatory diseases. The invention provides specific binding molecules directed against citrulline-containing epitopes for use in the therapy and prevention of inflammatory conditions.

Abstract: A targeted iron chelator delivery system that comprises an iron chelator, a targeting agent and a lipid carrier, e.g., a liposome, is provided. The iron chelator delivery system may be used to remove excess iron from specific organs such as, for example, heart and liver tissue. Methods for preparing and administering the targeted iron chelator delivery system are also provided. The iron chelator delivery system may be administered during a blood transfusion to prevent iron overload.

Abstract: The present invention provides monoclonal antibodies that specifically bind to the extracellular domain of human Claudin-1 on the cell surface, thereby inhibiting HCV entry into susceptible cells and preventing HCV infection of these cells; and hybridoma cell lines which produce such monoclonal antibodies. Also provided are reagents that comprise such antibodies, and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing HCV infection by administration of an inventive monoclonal antibody, or a pharmaceutical composition thereof are also described.

Abstract: The invention describes methods for inhibiting angiogenesis in a tissue by administering an antagonist that specifically binds to a proteolyzed or denatured collagen but not to native triple helical forms of the collagen. Antagonists of the invention can target, for example, denatured collagens type-I, type-II, type-III, type-IV, type-V and combinations thereof. Methods utilizing such antagonists for therapeutic treatment of tumor growth, tumor metastasis or of restenosis also are described, as are methods to use such antagonists as diagnostic markers of angiogenesis is normal or diseased tissues both in vivo and ex vivo. Antagonists include monoclonal antibodies referred to as HUI77, HUIV26, and XL313.

Abstract: A method of promoting oligodendrocyte survival in a human suffering from, or at risk of developing, stroke or other neurological diseases utilizes anti-MAG antibodies or functional fragments of such antibodies.

Abstract: A method of treating lymphoma in a subject comprises administering to a subject afflicted with lymphoma an antibody that binds to tenascin in a therapeutically effective amount. Preferably the antibody is monoclonal antibody 81C6 or an antibody that binds to the epitope bound by monoclonal antibody 81C6. Preferably the antibody is labeled with or conjugated to a chemotherapeutic agent, particularly a radioisotope such as 131I.

Abstract: IgG and IgM autoantibody levels against phosphorylcholine in subjects with hypertension (diastolic pressure >95 mmHg) were determined at baseline in order to determine the importance of antibodies for the development of atherosclerosis. The results show that increases in intima-media thickness (IMT) at a follow-up four years after baseline were significantly less prevalent in subjects having high autoantibodies particularly high IgM autoantibodies, to phosphorylcholine. The presence or absence of autoantibodies, particularly IgM autoantibodies, against phosphorylcholine is thus related to an increased or decreased risk of developing ischemic cardiovascular diseases. A method to determining antibodies, particularly IgM antibodies, toward phosphorylcholine is proposed in this invention to identify subjects at risk of developing ischemic cardiovascular diseases.

Abstract: The present invention relates to a method for treating recurrent tumor metastases following liver resection that includes administration of an effective amount of an agonist of A2A adenosine receptors (ARs).

Abstract: The present invention provides vascular endothelial cell growth factor (VEGF) antagonists and methods of using VEGF antagonists. VEGF antagonists contemplated by the invention include VEGF antibodies and VEGF receptor fusion proteins. Methods of treating edema and stroke using VEGF antagonists are also provided.

Abstract: An axon regeneration promoter is disclosed that contains an inhibitor of RGM-like protein as an effective component. Inhibitors of RGM-like protein encompass inhibitors of RGM-like protein such as anti-RGM-like protein antibodies and Y27632, as well as antisense nucleic acids and double-stranded RNAs that can inhibit the transcription or translation of RGM-like protein. The axon regeneration promoter according to the present invention is effective for the regeneration of central nerve axons and thus contributes, for example, to the treatment of patients who have suffered damage to the central nervous system, for example, the spinal cord, due to, for example, a traffic accident or a cerebrovascular disorder.

Abstract: The present disclosure relates to 2-amidothiadiazole derivatives of formula (I) as well as pharmaceutical compositions comprising them, and their use in therapy as agonists of the S1P1 receptors.

Abstract: Monoclonal antibody compositions, methods of production and use. The monoclonal antibodies are specific to conformational epitope(s) of a prefibrillar aggregate(s) which contribute to amyloid fibril formation in human or animal subjects who suffer from amyloid diseases (e.g., Alzheimer's Disease) and the hybridomas and monoclonal antibodies produced therefrom. The monoclonal antibodies are useable for immunization of human or animal subjects against Alzheimer's Disease or other amyloid diseases and/or for the diagnosis or detection of Alzheimer's Disease or other amyloid diseases. The monoclonal antibodies may be administered concomitantly or in combination with anti-inflammatory agents, such as gold or gold containing compounds, to decrease neural inflammation associated with amyloid diseases (e.g., Alzheimer's Disease).

Abstract: Disclosed are compositions and methods for related to monoclonal antibodies specific for single amino acid variation in an antigen.

Abstract: Methods of treating hemorheologic abnormalities in mammals are provided, as well as methods of evaluating circulatory flow mechanics by analyzing hemorheologic determinants or hemorheologic abnormalities in the blood.

Abstract: The invention relates to methods for treating, preventing and diagnosing macular degeneration-related disorders.

Abstract: The present invention relates to compositions containing novel proteins and methods of using those compositions for the diagnosis and treatment of immune related diseases.

Abstract: The present disclosure is directed to methods of treating and preventing colorectal cancer metastasis or recurrence of colorectal cancer with compositions comprising anti-progastrin antibodies.

Abstract: The invention relates to the use of afamin for the manufacture of a pharmaceutical preparation for the prevention or treatment of fertility disorders.

Abstract: The disclosure relates to methods of treating or preventing neurological disorders using docosahexaenoic acid.

Abstract: Recombinant immunotoxins are fusion proteins composed of the Fv domains of antibodies fused to bacterial or plant toxins. RFB4 (Fv)-PE38 is an immunotoxin that targets CD22 expressed on B cells and B cell malignancies. The present invention provides antibodies and antibody fragments that have improved ability to bind the CD22 antigen compared to RFB4. Immunotoxins made with the antibodies and antibody fragments of the invention have improved cytotoxicity to CD22-expressing cancer cells. Compositions that incorporate these antibodies into chimeric immunotoxin molecules that can be used in medicaments and methods for inhibiting the growth and proliferation of such cancers. Additionally, the invention provides a method of increasing the cytotoxicity of forms of Pseudomonas exotoxin A (“PE”) with the mutation of a single amino acid, as well as compositions of such mutated PEs, nucleic acids encoding them, and methods for using the mutated PEs.

Abstract: Isolated monoclonal antibodies are disclosed herein that specifically bind a cell surface antigen expressed on the human pancreatic endocrine cells or a subset thereof, and/or a precursor thereof. Isolated monoclonal antibodies are also disclosed herein that specifically bind a cell surface antigen expressed on human pancreatic exocrine cells or human ductal cells. Humanized forms of these antibodies, and functional fragments of these antibodies, are also disclosed. The antibodies can be conjugated to an effector molecule, such as a detectable marker, a therapeutic agent, or a toxin. These antibodies are of use to detect and isolate pancreatic cells or a subset thereof. The antibodies can be used for in vitro or in vivo detection and/or isolation of pancreatic endocrine cells. Methods of treating a pancreatic tumor are also disclosed. In several examples, the isolated monoclonal antibodies bind pancreatic endocrine cells and can be used to detect diabetes or a pancreatic endocrine cell tumor.

Abstract: The present application describes therapy with antagonists which bind to B cell surface markers, such as CD20. In particular, the application describes the use of such antagonists to treat autoimmune disease in a mammal who experiences an inadequate response to a TNF?-inhibitor.

Abstract: The invention relates to C2a inhibitors, which bind to C2a and block the functional activity of C2a in complement activation. The inhibitors include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, F(ab?)2 and Fv, small molecules, including peptides, oligonucleotides, peptidomimetics and organic compounds. A monoclonal antibody, which bound to C2a and blocked its ability to activate complement was generated and designated 175-62. The hybridoma producing this antibody was deposited at the American Type Culture Collection, 10801 University Blvd., Manassas, Va. 20110-2209, under Accession Number PTA-1553.

Abstract: Methods of inhibiting tumor growth, methods of treating cancer, and methods of reducing the frequency of cancer stem cells in a tumor are described. Particularly, the methods are directed to tumors or cancers that comprise a K-ras mutation. The methods described comprise administering a DLL4 antagonist (e.g., an antibody that specifically binds the extracellular domain of human DLL4) to a subject. Related polypeptides and polynucleotides, compositions comprising the DLL4 antagonists, and methods of making the DLL4 antagonists are also described.

Abstract: An in vitro or in vivo method for screening for candidate compounds for the preventive or curative treatment of acne, of seborrhoeic dermatitis or of skin disorders associated with hyperseborrhoea, includes determining the ability of a compound to modulate the expression or the activity of the CIDEA protein, and also utilizes modulators of the expression or of the activity of this protein, for the treatment of acne, of seborrhoeic dermatitis or of skin disorders associated with hyperseborrhoea; methods for the in vitro diagnosis of or in vitro prognosis for these pathologies are also featured.

Abstract: The invention provides compositions and methods for treatment of amyloidogenic diseases. Such methods entail administering an agent that induces a beneficial immune response against an amyloid deposit in the patient. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In such methods, a suitable agent is A? peptide, active fragments thereof or an antibody thereto.

Abstract: Described herein is the discovery that cell and tissue survival can be dramatically increased following radiation exposure through inhibition of the interaction between TSP-1 and CD47. This effect is shown using antisense molecules, peptides, and antibodies, which can now be used as radioprotectant agents. These agents find application in minimizing, reducing and/or preventing tissue damage following intentional and accidental radiation exposure, as well as increasing the therapeutic efficacy of radiation therapies by protecting non-target tissue from incidental radiation damage and by increasing tumor ablation following radiation treatment.

Abstract: The present invention relates to a method of diagnosis and therapy of cancers expressing the HER2 receptor. The invention provides antibodies or fragments thereof that recognise an epitope of the HER2 receptor truncated form CTF-611, said epitope being defined by a sequence included in SEQ ID NO: 2, and that are capable of discriminating between CTF-611 and CTF-616 (represented by SEQ ID NO:7), preferably additionally capable of discriminating between CTF-611 and CTF-613 (represented by SEQ ID NO:6). The invention also provides a method of cancer diagnosis using the disclosed antibodies, which comprises the detection of the presence of the HER2 receptor truncated form consisting of the amino acid sequence SEQ ID NO: 1 in a patient sample.