Abstract: The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

Abstract: A method of treating a pulmonary disease such as, for instance idiophathic pulmonary fibrosis (IPF) and asthma, comprising administering an aerosolized interferon such as interferon ?, interferon ? or interferon ? in a therapeutically effective amount is provided herein. Also, pharmaceutical compositions of one or more aerosolized interferon(s) are provided.

Abstract: The present invention relates to methods and compositions for the prevention and treatment of herpes virus infections. The invention provides antigenic peptides, and pharmaceutical compositions comprising complexes of antigenic peptides and adjuvants that can activate an immune response against herpes viruses. The invention also provides methods of making the antigenic peptides and complexes of antigenic peptides and adjuvants. Methods of use of the pharmaceutical compositions are also provided.

Abstract: Embodiments of this invention provide novel peptidomimetics that contain a macrocycle. Such compounds are neuroprotective and have utility as therapeutic agents for treatment of diseases, injuries and other conditions characterised by neuronal degeneration and/or death. Compounds are also useful for manufacture of medicaments useful for treatment of such conditions.

Abstract: The present invention relates to a pharmaceutical composition comprising, (i) a cytokine and, (ii) a compound of the general formula (Ih) or pharmaceutically acceptable salts thereof with an acid or a base, or pharmaceutically acceptable prodrugs or a stereoisomer thereof. Exemplary cytokines are selected from the following group of cytokine families, (i) the four ?-helix bundle family, which consists of, (a) the IL-2 subfamily, (b) the interferon (IFN) subfamily and, (c) the IL-10 subfamily, (ii) the IL-1 family, (iii) the IL-17 family and, (iv) chemokines.

Abstract: Embodiments of this invention provide methods for therapeutic use of cyclic G-2-allylProline (cG-2-allylP) to treat peripheral neuropathies, including toxin-induced peripheral neuropathy and diabetic as well as manufacture of medicaments including tablets, capsules, and other orally active compositions containing cG-2-allylP, as well as injectable solutions that are useful for treatment of such conditions.

Abstract: Implantable devices comprise at least one or more targeting molecules that form a primary coating layer for selectively recruiting, isolating, activating, and/or eliminating any cells of interest, such as T cells, monocytes, and stem cells. The implantable devices can be utilized for selectively removing a particular subset of cells from bodily fluids of a patient. Various non-selective pharmaceutical agents and biological agents can be incorporated into the implantable devices so that cells of interest can be isolated for elimination or for activation/differentiation. Cell-type selectivity is conferred by the presence of cell-type-specific targeting molecules incorporated into the implantable device, preferably at the surface level to permit direct or indirect interaction between the cells of interest and targeting molecules of the implantable device. Related therapeutic methods for utilizing the implantable devices are also provided.

Abstract: The invention provides methods for treating tumours, such as solid tumours, in a host. The methods may involve infecting the tumour with an amount of one or more strains of oncolytic virus. The virus will generally be selected to be effective to cause a lytic infection of tumour cells within the tumour. In various embodiments, the host neutrophil response to the lytic infection may be modulated, so that during the course of the lytic infection, the host has an initial neutrophil response and a secondary neutrophil response, these two responses being different in some material respect. For example, the secondary neutrophil response may mediate a greater degree of apoptotic killing of tumour cells than does the initial neutrophil response.

Abstract: The present invention relates generally to novel recombinant polypeptides having avian cytokine properties and to genetic sequences encoding same. More particularly, the present invention is directed to recombinant avian Type III interferon polypeptides, and genetic sequences encoding same, together with cellular expression systems and uses for same. Even more particularly, the present invention is directed to avian interferon-? (IFN-?) and functional derivatives, homologues and fragments thereof and to methods of use thereof. The molecules and cells of the present invention are useful in a wide range of applications including, but not limited to, providing a means for the treatment and prophylaxis of disease conditions, in particular avian disease conditions, or for use as an immune response modulator. Also provided are diagnostic means for screening for immune response and screening means for identifying modulators of IFN-? protein or nucleic acid functionality.

Abstract: The invention relates to a method of treating cancer, comprising administering to a subject in need thereof an effective amount of a HSV-2 virus, wherein the virus lacks protein kinase activity of ICP10. The invention further relates to pharmaceutical compositions comprising HSV-2 virus, wherein the virus lacks protein kinase activity of ICP10.

Abstract: Methods for treating a disease condition in a subject are provided. The subject methods are characterizing by enhancing at least one symptom of the disease condition in a manner effective to cause the subject to mount a compensatory response effective to treat the disease condition. Also provided are compositions, kits and systems for practicing the subject methods.

Abstract: Disclosed are methods of using proteasome inhibitors (PI) in combinations with other pharmaceutically active agents for treating viral hepatitis infections, for example, for treating therapy-resistant and -refractory viral hepatitis infections. Also disclosed are pharmaceutical compositions and kits of pharmaceutical compositions which can be used for treating viral hepatitis infections, for example, for treating therapy-resistant and refractory viral hepatitis infections.

Abstract: This invention discloses the use of an E-selectin antagonist and a mobilizer of hematopoietic stem cells or progenitor cells in methods and compositions for treating or preventing immunocompromised conditions resulting from medical treatment. The present invention is particular relevant for prophylaxis and/or treatment of hematopoeitic disorders including neutropenia, agranulocytosis, anemia and thrombocytopenia in individuals receiving or proposed to receive treatments that target rapidly dividing cells or that disrupt the cell cycle or cell division.

Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the bispecific immunocytokine DNL construct comprises an IgG antibody attached to a Fab antibody fragment and a cytokine, wherein the IgG and the Fab bind to different target antigens which may be expressed on the same target cell. The bispecific immunocytokine DNL construct exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or even other types of cytokine-antibody DNL constructs. In a most preferred embodiment the construct comprises an anti-CD20 IgG antibody conjugated to an anti-HLA-DR Fab and IFN?2b, although other combinations of antibodies, antibody fragments and cytokines may be used to form the subject DNL complexes.

Abstract: This invention provides compositions that include a protein and at least two protease inhibitors, method for treating diabetes mellitus, and methods for administering same, and methods for oral administration of a protein with an enzymatic activity, including orally administering same.

Abstract: Use of interferon-beta (IFN-?) and/or IFN-? for treating rhinovirus (RV) infection in elderly people, particularly elderly people who are, or have been long-term smokers, especially those who have a clinical history of recurrent RV infections, and may have other medical conditions, such as cardiac or circulation problems, and who are liable to suffer severe complications/high mortality from poor innate ability to fight such a viral infection.

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: This invention is in the field of immunology and relates to the discovery that adhesins are potent activators of dendritic cells.

Abstract: A class of macrocyclic compounds of formula (I), wherein R1, R3, R4, Ra, Rb, A, B, Z, M, W and n are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also provided are processes for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection.

Abstract: This invention discloses the use of an E-selectin antagonist in methods and compositions for treating or preventing immunocompromised conditions resulting from medical treatment. The present invention is particular useful for prophylaxis and/or treatment of hematopoietic disorders including neutropenia, agranulocytosis, anemia and thrombocytopenia in individuals receiving or proposed to receive treatments that target rapidly dividing cells or that disrupt the cell cycle or cell division.

Abstract: The invention relates generally to the field of immunology, in particular, to bispecific antibodies. Methods for designing a bispecific antibody for use in treating diseases relating to the immune system are disclosed. Specific examples relate to bispecific antibodies which recognize an activating receptor and an inhibiting receptor.

Abstract: The present invention relates to a polypeptide possessing a CDase activity, characterized in that it is derived from a native CDase by addition of an amino acid sequence with the proviso that said polypeptide has no UPRtase or Thymidine Kinase activity.

Abstract: The present invention provides to immunogene therapy protocols for the treatment of tumors. In particular, the present invention provides combinations of immune-modulating proteins that induce systemic immunity against tumors. In addition, the present invention provides humanized animal models suitable for the evaluation of anti-human tumor immunity and permit the identification of combinations of immune-modulating genes which when delivered to human tumor cells induce an effective anti-tumor response, including a systemic anti-tumor response.

Abstract: Treatment of lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related muscular degeneration, and angiomas. A conjugate is used comprising a molecule that exerts a biocidal or cytotoxic effect on target cells in the lesions and an antibody directed against an extracellular matrix component which is present in such lesions. The antibody may be directed against fibronectin-2 (IL-2), doxorubicin, interleukin-12 (IL-12), Interferon-? (IFN-?), Tumor Necrosis Factor ? (TNF?) or Tissue Factor protein (which may be truncated).

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: A pharmaceutical composition comprising a conjugate of a cytokine and a tumor targeting moiety (TTM) and a pharmaceutically acceptable excipient, wherein the cytokine is present in an amount which does not induce a negative feedback mechanism.

Abstract: Fibrosis arises as part of a wound healing response that maintains organ integrity following catastrophic tissue damage, but can also contribute to a variety of human pathologies, including liver cirrhosis. The invention demonstrates that cellular senescence acts to limit the fibrogenic response to tissue damage, thereby establishing a role for the senescence program in pathophysiological settings beyond cancer. Accordingly, the methods of the invention relate to modulating cellular senescence in disease tissue that have elevated numbers of senescent cells, such as in fibrotic tissues.

Abstract: A method of immunotherapy to treat cancer or a synergistic anti-cancer treatment by administering an effective amount of natural cytokine mixture (NCM), an effective amount of cyclophosphamide (CY), or an effective amount of indomethacin (INDO), wherein the NCM, CY, or INDO are administered singly or in communications thereof. An anti-metastatic treatment method by promoting differentiation and maturation of immature dendritic cells in a lymph node; allowing presentation thereof; and preventing development of metastasis. A method of using NCM as a diagnostic skin test for predicting treatment outcome. A method of pre-treating dendritic cells (DC) and a method of treating monocyte defects characterized by sinus histiocytosis or a negative NCM skin test. Compositions and method for eliciting an immune response to endogenous or exogenous tumor antigens.

Abstract: A method for increasing a biological activity of a cytokine or lymphokine and a method of treating a neoplastic disease, autoimmune disease, or infectious disease, and a method for expanding a hematopoietic cell population, is provided by administering an antibody capable of binding a cytokine or by administering a cytokine complexed with an antibody or by administering a cytokine complexed with a cytokine receptor to a mammalian subject in need thereof.

Abstract: Methods for analyzing one or more elements, markers, ligands or other characteristics of the immune system of a body (e.g., of a human or other animal), and based on the analysis, determine a location of disease, identify immune system failure, and/or determine treatments based on disease location or immune system failure. All or a part of the immune system process may be analyzed to identify specific features of the immune system, e.g., which may indicate that the disease will evade the immune system and produce a negative outcome. Therapy may be employed to correct immune system failure rather than addressing the disease directly.

Abstract: The present invention relates to anti-cancer compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides analogs of the known anti-cancer compound amonafide, and structurally and functionally related compounds, and methods of using such compounds as therapeutic agents to treat a number of conditions associated with hyperproliferation.

Abstract: Novel biodegradable compositions are disclosed. The biodegradable compositions include at least one hydroxyl-terminated component and at least one bioactive peptide in a linear chain. The compositions may be utilized as medical devices including drug delivery devices, tissue adhesives and/or sealants.

Abstract: The present invention provides a pharmaceutical composition formulated for oral delivery, comprising a particulate non-covalently associated mixture of pharmacologically inert silica nanoparticles having a hydrophobic surface, a polysaccharide, and a biologically active protein or peptide suspended in an oil. The present invention further provides methods of manufacturing same and therapeutic methods utilizing same for oral delivery of a therapeutic protein or peptide.

Abstract: An immunity-inducing agent comprising as an effective ingredient a specific polypeptide is disclosed. These polypeptides were isolated, by the SEREX method using a cDNA library derived from canine testis and serum from a cancer-bearing dog, as a polypeptide which binds to an antibody existing specifically in serum derived from a cancer-bearing living body. The polypeptides can induce immunity in a living body and cause regression of a tumor in a cancer-bearing living body. Therefore, these polypeptides are especially effective as a therapeutic and/or prophylactic agent for a cancer(s).

Abstract: The present invention relates to methods for extending the in vivo half-life of an exogenous soluble therapeutic molecule administered to a subject, by administering to said subject the exogenous soluble molecule and a monovalent antibody that binds to the exogenous soluble molecule, as well as method for treating a disease or disorder associated with an insufficient level of an endogenous soluble molecule in a subject, by administering to said subject a monovalent antibody that binds to the endogenous soluble molecule.

Abstract: The disclosure provides a drug composition formulated for inhalation comprising a conjugate of a surface active agent and a pulmonary active drug. The surface active agent has an affinity for the human alveolar/gas interface and comprises at least a portion of a mammalian lung surfactant of a mimic thereof. The disclosure also provides a method of treating a subject suffering from or at risk of suffering from a lung disease comprising administering to the subject a conjugate comprising a drug for lung treatment and a surface active agent by inhalation in an amount effective to induce a drug effect in the lungs.

Abstract: The present invention provides humanized, chimeric and human anti-CD74 antibodies, CD74 antibody fusion proteins, immunoconjugates, vaccines and bispecific that bind to CD74, the major histocompatibility complex (MHC) class-II invariant chain, Ii, which is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies, other malignancies in which the cells are reactive with CD74, and autoimmune diseases, and methods of treatment and diagnosis.

Abstract: Immunogenic compositions comprising growth regulatable recombinant intracellular pathogens that have been transformed to express recombinant immunogenic antigens of the same or other intracellular pathogens are provided. Exemplary immunogenic compositions include, but are not limited to, growth regulatable and growth limited recombinant intracellular pathogen immunogenic compositions.

Abstract: The present invention directs to compositions and methods for modulating immune system. One aspect of the present invention relates to a composition comprising FADD-dependent signaling pathway modulators. Another aspect of the 5 present invention relates to biodegradable microparticles, such as a chitosan microparticic, or PLGA/PEI microparticle, designed to deliver nucleic acids and/or proteins, such as FADD-dependent signaling pathway modulators, to boost different pathways of an immune response. Another aspect of the present invention relates to the method of making biodegradable microparticles. The further aspect of the present invention relates to the use of the chitosan and other polycationic microparticles to deliver FADD-dependent signaling pathway modulators to modulate immune system for the prevention and/or treatment infectious diseases and cancers.

Abstract: Modular aAPCs and methods of their manufacture and use are provided. The modular aAPCs are constructed from polymeric microparticles. The aAPCs include encapsulated cytokines and coupling agents which modularly couple functional elements including T cell receptor activators, co-stimulatory molecules and adhesion molecules to the particle. The ability of these aAPCs to release cytokines in a controlled manner, coupled with their modular nature and ease of ligand attachment, results in an ideal, tunable APC capable of stimulating and expanding primary T cells.

Abstract: The present invention provides methods for identifying metastases by detecting nucleic acid hypermethylation of one or more genes in one or more samples, and in particular in the lymph nodes. The invention further relates to DNA methylation as a predictor of disease recurrence and patient prognosis, specifically in the field of cancer biology.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a liposome or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing apoptosis of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates or compositions.

Abstract: The object of the present invention is to elevate the blood levels of a compound of formula I by co-administration with a cytochrome P450 inhibitor.

Abstract: This invention provides compositions and methods for treating a subject suffering from a disease or disorder of the nervous system, associated with an inflammatory response. This invention further provides a pharmaceutical composition comprising, inter alia, an agent which increases brain levels of interferon-?; and an agent which reduces the number of brain T regulatory (Treg) cells, and optionally further comprising an agent which suppresses neurotoxic inflammatory brain responses.

Abstract: The invention relates to a method of treating a host animal to eliminate pathogenic cells. The method comprises the steps of administering to the host animal a hapten-carrier conjugate, administering to the host animal a TH-I biasing adjuvant, and administering to said host animal a ligand conjugated to a hapten herein the ligand-hapten conjugate is administered during the first cycle of therapy with the hapten-carrier conjugate. The invention also relates to the same method wherein the ratio of the hapten-carrier conjugate to the TH-I biasing adjuvant on a weight to weight basis ranges from about 1:10 to about 1:1.

Abstract: The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention.

Abstract: Receptor coupling agents, including multivalent constructs comprising anti-TNF receptor binding moieties, for treating cancer and inhibiting tumor volume in a subject are disclosed.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a carrier such as a polymer, nanoparticle, complex or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing cell death of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate.

Abstract: In certain embodiments, this present invention provides polypeptide compositions (e.g., antibodies and antigen binding portions thereof that bind to FcRn), and methods for modulating FcRn activity. In other embodiments, the present invention provides methods and compositions for treating autoimmune disorders.

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.