Abstract: The present invention is directed to methods and compositions employing 9-(4-hydroxy-2-(hydroxymethyl)butyl)guanine (“H2G”) or derivatives or analogs thereof for the treatment of viral diseases, as well as for the treatment of other conditions, including, but not limited to, cancer, chronic fatigue syndrome, Alzheimer's disease, multiple sclerosis and Graves' disease. The H2G or derivative or analog thereof can be administered in a pharmaceutical composition and can be administered with an additional antiviral therapeutic agent or another agent for the treatment of other conditions.

Abstract: The present invention relates to the field of anti-mycobacterial therapeutics, in particular the treatment of tuberculosis, especially including pulmonary multidrug-resistant tuberculosis (MDR-TB), with applications in extensively drug-resistant tuberculosis (XDR-TB) and extremely drug-resistant tuberculosis (XXDR-TB), preferably in combination therapy.

Abstract: Provided are methods for enhancing hippocampal plasticity and hippocampal-mediated learning and memory, and/or enhancing the synaptic maturation of neurons, and/or optimizing or enhancing neuronal synaptic transmission, and/or enhancing intracellular oxygen delivery or utilization, and/or enhancing ATP synthesis, comprising administration, to a subject in need thereof of a sufficient amount over a sufficient time, of an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures (e.g., nanobubbles) having an average diameter of less than 100 nm (e.g., in at least one subject group selected from but not limited to normal subjects, subjects recovering from neurological trauma (e.g., accidents or injury to the brain, stroke, oxygen deprivation, drowning, and asphyxia), and subjects with learning disorders (e.g.

Abstract: The present invention provides for the treatment of multiple sclerosis through the use of chimeric and humanized versions of anti-CD19 antibodies that may mediate ADCC, CDC, and/or apoptosis.

Abstract: The invention features methods of diagnosis by assessing B7-H1 expression in a tissue from a subject that has, or is suspected of having, cancer, methods of treatment with agents that interfere with B7-H1-receptor interaction, methods of selecting candidate subjects likely to benefit from cancer immunotherapy, and methods of inhibiting expression of B7-H1.

Abstract: An inhibitory agent for body cavity fluid accumulation exerts a drug efficacy on body cavity fluid accumulation that is resistant to administration of diuretics, and is capable of exerting therapeutic effects even by systemic administration. The inhibitory agent for body cavity fluid accumulation includes, as an active ingredient, a covalent conjugate of interferon with polyalkylene glycol.

Abstract: Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKK?/? and I?B?, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.

Abstract: The present invention discloses compounds of formula I or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention describes method of treating bacterial infections, including MRSA. In various embodiments, the methods can use interferon beta, which is found to have antimicrobial activity. In certain embodiments, the interferon beta can be human interferon beta. In other embodiments, the interferon beta can be mouse interferon beta. In further embodiments, the interferon beta can be human interferon beta containing amino acid substitutions to make the human interferon beta more cationic in neutral pH.

Abstract: Liquid interferon compositions having a pH between 4.0 and 7.2 are described. The compositions comprise interferon-beta and a stabilizing agent at between about 0.3% and 5% by weight which is an amino acid selected from the group consisting of acidic amino acids, arginine and glycine. If needed, salt is added to provide sufficient ionic strength. The liquid composition has not been previously lyophilized or previously cavitated. The liquid is preferably contained within a vessel having at least one surface in contract with the liquid that is coated with a material inert to adsorption of interferon-beta. A kit for parenteral administration of a liquid interferon formulation and a method for stabilizing liquid interferon compositions are also described.

Abstract: Disclosed are compounds of formula (I) for use as antiviral agents, particularly as anti-hepatitis virus C agents, wherein A, B, U, R1-R7, m, n, and q are as described herein. Also disclosed are pharmaceutical compositions and methods of treating or preventing viral infection in a host by the use of these compounds, either alone or in combination with other pharmaceutically active agents. Further disclosed are methods of preparing such compounds.

Abstract: Disclosed are compounds of formula (I) for use as antiviral agents, particularly as anti-hepatitis virus C agents, wherein R-R 6 and q are as described herein. Also disclosed are pharmaceutical compositions and methods of treating or preventing viral infection in a host by the use of these compounds, either alone or in combination with other pharmaceutically active agents. Further disclosed are methods of preparing such compounds. (I).

Abstract: Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The antibodies show novel and useful diagnostic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal or benign pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. Preferably, the antibodies bind to pancreatic cancer mucins such as MUC1 or MUC5ac and are of use for the detection and diagnosis of early stage pancreatic cancer. In more preferred embodiments, the anti-pancreatic cancer antibodies can be used for immunoassay of serum samples, wherein the immunoassay detects a marker for early stage pancreatic cancer in serum. Most preferably, the serum is extracted with an organic phase, such as butanol, before immunoassay. Alternatively, immunoassay with PAM4 and anti-CA19.9 antibodies may be utilized to improve sensitivity for pancreatic cancer.

Abstract: Multifunctional polymers are disclosed having a smart segment and a biodegradable segment. Advantageously, the biodegradable segment includes a hydrophilic segment and a hydrophobic segment. Embodiments include combining the multifunctional polymeric material with a biologically active substance in an aqueous loading environment and administering the composition as a drug delivery vehicle to a human subject.

Abstract: It is disclosed a method for the treatment of hepatitis B (HBV) infection or HBV/hepatitis D (HDV) co-infection, the method comprising administering to a subject in need of treatment a first pharmaceutically acceptable agent that removes the hepatitis B surface antigen from the blood and a second pharmaceutically acceptable agent which stimulates immune function.

Abstract: It is disclosed a method for the treatment of hepatitis B (HBV) infection or HBV/hepatitis D (HDV) co-infection, the method comprising administering to a subject in need of treatment a first pharmaceutically acceptable agent that removes the hepatitis B surface antigen from the blood and a second pharmaceutically acceptable agent which stimulates immune function.

Abstract: The object of the present invention is to provide a glycosylated polypeptide having uniform sugar chain structure which has interferon ? activity. It was found that a glycosylated polypeptide having uniform sugar chain structure as well as having interferon ? activity can be prepared by a method comprising a step of synthesizing a glycosylated peptide fragment and at least two peptide fragments and a step of linking the glycosylated peptide fragment and the at least two peptide fragments.

Abstract: Disclosed are antibody fusion proteins with a modified FcRn binding site and nucleic acid molecules encoding them. The antibody fusion protein include two polypeptide chains, wherein the first polypeptide chain includes a biologically active molecule linked to at least a portion of an immunoglobulin constant region. The second polypeptide chain includes at least a portion of an immunoglobulin constant region. One of the polypeptide chains includes a mutation in the FcRn binding site that reduces binding to FcRn. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins for treating diseases and conditions alleviated by the administration of the fusion proteins.

Abstract: The present invention relates to a tyrosine kinase inhibitor or a mast cell inhibitor, and in particular masitinib or a pharmaceutically acceptable salt thereof, for the treatment of human multiple sclerosis.

Abstract: Compositions and methods relating to 2?-C-methyl nucleoside 5?-monophosphate derivative compounds are provided. In some embodiments, the novel compounds are useful to treat viral infections. In particular, 2?-C-methyl nucleoside 5?-monophosphate derivative compounds, stereoisomers, and pharmaceutically acceptable salts or prodrugs thereof, their preparation, and their uses for the treatment of viral infection are described.

Abstract: The present invention describes peptides comprising phycocyanobilin (PCB), as well as the medical use of said peptides and that of PCB, due to the neuroprotector and/or neuroregenerative effects identified for them. Furthermore, pharmaceutical combinations of said peptides and of PCB with proteins or other peptides with synergic effect justify their use for ischemic or neurodegenerative CNS disease treatment.

Abstract: The present invention relates to tetraaza phenalen-3-one compounds which inhibit poly(ADP-ribose) polymerase (PARP) and are useful in the chemosensitization of cancer therapeutics. The induction of peripheral neuropathy is a common side-effect of many of the conventional and newer chemotherapies. The present invention further provides means to reliably prevent or cure chemotherapy-induced neuropathy. The invention also relates to the use of the disclosed PARP inhibitor compounds in enhancing the efficacy of chemotherapeutic agents such as temozolomide. The invention also relates to the use of the disclosed PARP inhibitor compounds to radiosensitize tumor cells to ionizing radiation. The invention also relates to the use of the disclosed PARP inhibitor compounds for treatment of cancers with DNA repair defects.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The invention features methods, compositions, and kits for the administration of an HSP90 inhibitor, OBAA, flunarizine, aphidicolin, damnacanthal, dantrolene, or an analog thereof, alone, or in combination with, e.g., a TAA, an antigen-binding scaffold (e.g., an antibody, a soluble T cell receptor, or a chimeric receptor) specific for a TAA, a cell (e.g., a white blood cell that targets a cancer cell), and/or an IFN-? receptor agonist or an IFN-? receptor agonist, for the treatment of cancer.

Abstract: The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, esters, or prodrugs thereof: Q-G-A-L-B—Z—W??(I), which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: Provided herein include combination therapies for the treatment of neurological inflammatory diseases, such as, for example, demyelinating autoimmune diseases, such as multiple sclerosis and neuromyelitis optica, etc. In various aspects and embodiments, the methods may include administering to a patient an effective dose of an inhibitor of an angiotensin-converting enzyme (ACE) in combination with one or more second compounds, In one aspect, provided is a method of treating a demyelinating autoimmune disease (such as multiple sclerosis) that includes administering to a patient an effective dose of an inhibitor of an angiotensin-converting enzyme (ACE) in combination with one or more compounds selected from the group consisting of a cytokine, a vitamin B, dimethyl fumarate (DMF, also referred to as BG-12) and fingolimod (Gilenya).

Abstract: The effectiveness of interferon for treating multiple sclerosis and other demyelinating diseases is synergistically potentiated by concomitant administration of a compound of Formula (I): wherein R1 is H, alkyl or OH, R2 is hydroxyalkyl or alkyl-O-L1, R3 is H or OH, X is C(?CH2), CH(OH), or spirooxirane-2, Z is CH2CH(OH) or C(=0), and R4 is an optionally substituted L2-alkyl or L2-alkenyl, wherein L2 is an optionally substituted 3-furanyl or 3-fur-3-enyl moiety.

Abstract: The invention relates to a pharmaceutical formulation for sustained delivery of a therapeutic agent, preferably a protein, polypeptide, an antibody or an antibody fragment, comprising one or more gel forming peptides wherein the formulation exhibits sustained delivery for at least two weeks, three weeks, four weeks, five weeks, six weeks, seven weeks, eight weeks, nine weeks, ten weeks, eleven weeks, twelve weeks or more. In one embodiment, the invention relates to a formulation comprising self-assembling peptides that undergo sol-gel transition in the presence of an electrolyte solution such as biological fluids and salts. The formulation can provide sustained release of antibody and antibody fragments, in particular, IgG. Antibody diffusivities can be decreased with increasing hydrogel nanofiber density, providing a means to control the release kinetics.

Abstract: Disclosed are antagonists designed to inhibit or block expression of a mammalian complement such as complement component 6 (C6). The invention has a wide range of uses including use in the preparation of a medicament for the enhancement of nerve regeneration following acute or chronic nerve damage in a mammal. Additional applications include use in the treatment of multiple sclerosis either alone or in combination with another drug.

Abstract: The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: This invention relates to antibodies and antigen binding fragments and conjugates containing same, and/or alternative scaffolds, specific for LSR molecules, which are suitable drugs for immunotherapy and treatment of specific cancer.

Abstract: This invention relates to monovalent and multivalent, monospecific binding proteins and to multivalent, multispecific binding proteins. One embodiment of these binding proteins has one or more binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these binding proteins has two or more binding sites where each binding site has affinity towards different epitopes on a target antigen or has affinity towards either a target antigen or a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional binding proteins in a host. More specifically, the present invention relates to the tumor-associated antigen binding protein designated RS7, and other EGP-1 binding-proteins. The invention further relates to humanized, human and chimeric RS7 antigen binding proteins, and the use of such binding proteins in diagnosis and therapy.

Abstract: Conjugates of hydroxyalkyl starch and a protein are provided herein. The conjugates are formed by a covalent linkage between the hydroxyalkyl starch or a derivative of the hydroxyalkyl starch and the protein. Methods of producing the conjugates and the use of the conjugates also are provided herein.

Abstract: New pyridin-2(1H)-one derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

Abstract: The present invention is directed to antibodies and fragments thereof (especially chimeric and humanized) having binding specificity for HGF and their use in therapy and diagnosis. These antibodies inhibit or block HGF-associated activities including HGF's effects on cell proliferation, invasion, angiogenesis, metastasis and fibrosis. Particularly the antibodies may be used as a monotherapy or in combination therapies in treating cancer, other proliferative disorders and other conditions wherein inhibition of HGF and/or the HGF/HGF-R (c-met) interaction is desired.

Abstract: The invention provides compositions and methods of identifying, modifying and producing modified target molecules, including therapeutic molecules by modification with non-natural amino acids. Certain aspects of the invention include methods of adding a chemical moiety to a target molecule, and the compositions resulting therefrom. Certain aspects of the invention also relate to kits for identifying, modifying and producing modified target molecules described herein.

Abstract: Therapies effective for the treatment and prevention of cancer and other diseases are disclosed. These methods include the administration of therapeutically effective amounts of agents that increase the local production of effector cell-attracting chemokines within tumor lesions, with concomitant suppression of local production of undesirable chemokines that attract regulatory T(reg) cells. These methods include administering to the subject therapeutically effective amounts of a Toll-like receptor (TLR) agonist or other activator of NF-KB pathway in combination with a blocker of prostaglandin synthesis or a blocker of prostaglandin signaling, in combination with a type-1 interferon, or in combination with both a blocker of prostaglandin synthesis or signaling and with a type-1 interferon.

Abstract: Embodiments of this invention include methods for detecting in vitro the presence in peripheral blood mononuclear cells (PBMCs), and in serum or plasma, of antibodies reactive to and of lymphocytes that are responsive to CNS antigens associated with Multiple Sclerosis (MS). These CNS antigens include, but are not limited to whole brain lysate and the myelin antigens myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), MOG peptides (MOGps), proteolipid protein (PLP), and PLP peptides (PLPps). Stimulating PBMCs from patients with MS by CNS antigens cause B-lymphocytes to produce antibodies specific for CNS antigen, and causes T-lymphocytes to produce T-lymphocyte-specific cytokines, including interferon gamma (IFN-y), interleukin-2 (IL-2), or interleukin-17 (IL-17). In contrast, stimulating PBMCs from subjects without MS do not produce such responses.

Abstract: The invention relates to a stable amorphous form of (5-Fluoro-2-methyl-3-quinolin-2-ylmethyl-indol-1-yl)-acetic acid and its use in the treatment of conditions mediated by the action of PGD2 at the CRTH2 receptor.

Abstract: Compounds of formula I wherein: R1 is and R2, R4, and R6-9 are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.

Abstract: The present invention provides a polypeptide construct comprising a peptide or polypeptide signaling ligand linked to an antibody or antigen binding portion thereof which binds to a cell surface-associated antigen, wherein the ligand comprises at least one amino acid substitution or deletion which reduces its potency on cells lacking expression of said antigen.

Abstract: The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated form of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

Abstract: The present invention concerns chimeric or humanized antibodies or antigen-binding fragments thereof that comprise specific CDR sequences, disclosed herein. Preferably, the antibodies or fragments comprise specific heavy and light chain variable region sequences disclosed herein. More preferably, the antibodies or fragments also comprise specific constant region sequences, such as those associated with the nG1m1,2 or Km3 allotypes. The antibodies or fragments may bind to a human histone protein, such as H2B, H3 or H4. The antibodies or fragments are of use to treat a variety of diseases that may be associated with histones, such as autoimmune disease (e.g.

Abstract: This invention is directed to a method for treating a host, especially a human, infected with hepatitis C, flavivirus and/or pestivirus, comprising administering to that host an effective amount of an anti-HCV biologically active pentofuranonucleoside where the pentofuranonucleoside base is an optionally substituted 2-azapurine. The optionally substituted pentofuranonucleoside, or a salt or prodrug thereof, may be administered alone or in combination with one or more optionally substituted pentofuranonucleosides or other anti-viral agents.

Abstract: Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The antibodies show novel and useful diagnostic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal or benign pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. Preferably, the antibodies bind to an epitope located within the second to fourth cysteine-rich domains of MUC5ac (amino acid residues 1575-2052) and are of use for the detection and diagnosis of early stage pancreatic cancer. In more preferred embodiments, the anti-pancreatic cancer antibodies can be used for immunoassay of serum samples, wherein the immunoassay detects a marker for early stage pancreatic cancer in serum. Most preferably, the serum is extracted with an organic phase, such as butanol, before immunoassay.

Abstract: The present invention relates to devices and related methods for treating fistulas such as anal or recto-vaginal fistulas, in particular by the use of a seton to secure a tissue growth promoter such as a growth factor and/or fibrin. The various devices are particularly suitable for positioning tissue growth promoters securely within a fistula. Thus, one device comprises a seton and a tissue growth promoter. Further related aspects of the invention included devices comprising an enclosure provided in between portions of a seton, devices comprising a seton and a plurality of holes for enabling the device to be sutured to tissue, devices comprising a probe and a seton that are releasably connectable end-to-end, devices comprising an attachment device to secure the ends of a seton, and devices comprising a fistula plug adapted to be secured to a section.

Abstract: The present invention concerns compositions and methods of use of humanized anti-HLA-DR antibodies. In preferred embodiments, the antibodies induce apoptosis and inhibit proliferation of lymphoma cells without inducing CDC or ADCC. In more preferred embodiments, the humanized anti-HLA-DR antibodies bind to the same epitope of HLA-DR as, or compete for binding to HLA-DR with, a murine L243 antibody. Most preferably, the humanized anti-HLA-DR antibody exhibits a higher affinity for HLA-DR than the parental murine antibody. The humanized HLA-DR antibody is of use for therapy of various diseases such as cancer, autoimmune disease or immune dysregulatory function, and is of particular use for therapy of B cell lymphomas and leukemias. In most preferred embodiments, the humanized anti-HLA-DR antibody is capable of inducing at least partial remission of lymphomas that are resistant to other B cell antibodies, such as rituximab.

Abstract: In one aspect, the invention provides compounds represented by Formula I, and pharmaceutically acceptable salts, esters, stereoisomers, tautomers, solvates, and combinations thereof, pharmaceutical compositions comprising these compounds and the use of these compounds for treating a viral infection in a subject.

Abstract: The present invention features a method for the treatment of Hepatitis C in a human in need thereof comprising administering a compound of Formulas (II) or (IIB) described herein or a pharmaceutically acceptable salt thereof in combination with one or more alternative Hepatitis C therapeutic agents.