Abstract: The use of compounds that block complement component C5 or its active fragments C5a and/or C5b (such compounds collectively referred to as “C5 blockers”) to treat established joint inflammation (arthritis) is disclosed. Administration of such C5 blockers has been found to: 1) arrest and/or reduce inflammation in joints which are already inflamed, and 2) inhibit the spread of inflammation to unaffected joints.

Abstract: The present invention provides heteropolymer compositions and peptide compositions, and methods of making and using therapeutic compositions comprising amino acid heteropolymers for treatment of a subject for an autoimmune or an inflammatory disease, the heteropolymer compositions made by solid state synthesis. The invention also provides kits for assaying binding of a composition to a water-soluble MHC protein.

Abstract: The invention relates to methods and products for regulating lectin complement pathway associated complement activation. The methods include both in vitro and in vivo methods for inhibiting lectin complement pathway associated complement activation. The methods are accomplished by contacting a mammalian cell having surface exposed MBL ligand with an effective amount of a mannan binding lectin inhibitor to inhibit lectin complement pathway associated complement activation. The mannan binding lectin inhibitor may be administered to a subject to prevent cellular injury mediated by lectin complement pathway associated complement activation. The products of the invention include compositions of a mannan binding lectin inhibitor. The mannan binding lectin inhibitor is an isolated mannan binding lectin binding peptide that selectively binds to a human mannan binding lectin epitope and that inhibits lectin complement pathway associated complement activation.

Abstract: A complex comprising an HLA Class 1 molecule and attaching means for selectively attaching the HLA class 1 molecule to a target cell is disclosed, and a method is provided for producing or enhancing an immunological response against a target cell, by attaching said complex to the target cell. Where the target is a diseased, foreign or malignant cell, this method may be used to promote the lysis of the targeted cell by T cells in the immune system. Where the target cell is an antigen presenting cell, this method may be used to promote the proliferation of specific T cell clones. The invention is of potential use in the prevention and treatment of malignant diseases including cancer and leukemia, infectious diseases including viral infections such as HIV, bacterial infections including tuberculosis, and parasitic infections including malaria.

Abstract: Two-domain MHC polypeptides useful for manipulation of antigen-specific T-cells are disclosed. These polypeptides include MHC class II-based molecules that comprise covalently linked ?1 and ?1 domains, and MHC class I-based molecules that comprise covalently linked ?1 and ?2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, and to treat conditions mediated by antigen-specific T-cells.

Abstract: Heparinase enzymes can be used as a medical treatment to reduce localized inflammatory responses. Treatment of activated endothelium with heparinase inhibits leukocyte rolling, adhesion and extravasation. Most of the heparin and heparan sulfate on endothelial cell surfaces and in basement membranes is degraded by exposure to heparinase. In addition, immobilized chemokines, which are attached to heparin/heparan sulfate on activated endothelium are solubilized by heparinase digestion. Heparinase can be infused into the vascular system to inhibit accumulation of leukocytes in inflamed tissue and decrease damage resulting from localized inflammations. Targeting of heparinase to activated endothelium can be accomplished through localized administration and/or use of genetically engineered heparinase containing endothelium ligand-binding domains.

Abstract: This invention provides an anti-HLA-DR monoclonal antibody. This invention relates to an antibody binding to HLA-DR or a functional fragment thereof having (a) life-extending effects in nonhuman animals bearing HLA-DR-expressing cancer cells and (b) activity of suppressing immune responses lower than that of L243, or an antibody binding to HLA-DR or a functional fragment thereof exhibiting immunosuppressive activity equivalent to or higher than that of the mouse anti-HLA-DR monoclonal antibody L243 (ATCC HB-55).

Abstract: Isolated peptides are disclosed which, when processed, generate a coordinated immune response.

Abstract: Peptide constructs including a first peptide segment which includes an amino acid sequence associated with autoimmune disease, asthma, allergy or xeno- or allograft transplantation rejections bonded directly or via a linker or spacer to a second peptide which binds to T cells and which will redirect the immune response from a harmful Th1 response to a less harmful Th2 response, or which will bind to T cells to initiate, but not complete, an immune response causing the T cells to which the first peptide binds, to undergo anergy and apoptosis, are useful in treating autoimmune conditions. For instance, the peptide construct NGQEEKAGVVSTGLIGGGDSAFDVLSFTAEEKAGVYK (SEQ ID NO:14) wherein Th2 stimulating Peptide G (SEQ ID NO:15) is covalently linked, via spacer GGG, to cardiac myosin molecule My1 (SEQ ID NO:16), can be used for treatment or prevention of myocarditis.

Abstract: The present invention is directed to a composition and method for enhancing the complement-mediated cytotoxicity of therapeutic antibodies for their target cells (i.e. those cells displaying the target epitope). More particularly the present invention enhances the efficacy of such therapies by providing a supplemental source of complement.

Abstract: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Abstract: Rh antibody hybrids for use in testing red blood cells for the presence of one or more Rh factors. The Rh hybrid antibody may also be used in therapeutic procedures which require the use of Rh antisera. The hybrid antibody includes an IgG anti-Rh antibody which has a polymeric tailpiece attached to the carboxy terminal end of each of the IgG antibody heavy chains. A hemagglutinin method is provided for Rh phenotyping in which agglutination of Rh-positive red blood cells is achieved in a one-step process involving addition of the hybrid Rh antisera to the red blood cells being tested.

Abstract: The invention disclosed herein is directed to methods of identifying a polypeptide suitable for epitope liberation including, for example, the steps of identifying an epitope of interest; providing a substrate polypeptide sequence including the epitope, wherein the substrate polypeptide permits processing by a proteasome; contacting the substrate polypeptide with a composition including the proteasome, under conditions that support processing of the substrate polypeptide by the proteasome; and assaying for liberation of the epitope. The invention further relates to vectors including a housekeeping epitope expression cassette and also vectors including epitope cluster regions. The housekeeping epitope(s) can be derived from a target-associated antigen. The housekeeping epitope can be liberatable, that is capable of liberation, from a translation product of the cassette by immunoproteasome processing.

Abstract: The present invention provides peptides having T cell stimulating activity termed recombitope peptides. Recombitope peptides of the invention preferably comprise at least two T cell epitopes derived from the same or from different protein antigens, and more preferably comprise at least two regions, each region preferably having human T cell stimulating activity and each region comprising at least one T cell epitope derived from a protein antigen. Recombitope peptides of the invention can be derived from protein allergens, autoantigens, or other protein antigens. The invention also provides methods of diagnosing sensitivity to a protein allergen or other protein antigen in an individual, methods to treat such sensitivity and therapeutic compositions comprising one or more recombitope peptides. The invention further provides methods for designing recombitope peptides of the invention where the protein antigen to which the individual is sensitive has unknown or ill-defined T cell epitopes.

Abstract: Method of treating a disease or pathological condition with activated protein C or a compound having activated protein C activity by direct regulation of the expression of specific genes associated with the disease or pathological condition.

Abstract: The present invention provides an MHC class II antigen presentation enhancing hybrid polypeptide. The hybrid has an N-terminus comprising the mammalian Ii key peptide LRMKLPKPPKPVSKMR (SEQ ID NO: 1) and modifications thereof which retain antigen presentation enhancing activity, a C-terminus comprising an antigenic epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule, and an intervening chemical structure covalently linking the N-terminal and C-terminal components.

Abstract: Presented are intrinsically fluorescent, self-multimerizing MHC fusion proteins, and complexes assembled therefrom that are capable of detectably labeling antigen-specific T lymphocytes. Also presented are methods for labeling antigen-specific T lymphocytes with the intrinsically fluorescent complexes of the present invention, and methods, particularly flow cytometric methods, for detecting, enumerating, enriching, and depleting antigen specific T lymphocytes so labeled.

Abstract: The present invention provides compositions and methods of inhibiting or inducing activation of T cells in a patient. The methods comprise administering a therapeutically effective dose of pharmaceutical compositions comprising a pharmaceutically acceptable carrier and peptides of between about 4 and about 20 residues, that bind antigen binding sites on MHC molecules encoded by substantially all alleles of a DR locus. These peptides are referred to as pan DR binding peptides. The pan DR binding peptides can be used to inhibit immune responses associated with immunopathologies, such as autoimmunity, allograft rejection and allergic responses. The peptides can also be used in combination with CTL peptides to enhance a CTL response.

Abstract: A human ECM-1 polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for stimulating the differentiation in growth of osteoblasts and osteoclasts, which may be used to promote the healing of bone fractures and de novo bone formation, for osteoporosis, for and to promote angiogenesis. Antagonists to the polypeptide of the present invention are also disclosed which may be utilized to treat osteodystrophy, osteohypertrophy, osteoma, osteoblastoma and cancers. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention.

Abstract: A monoclonal antibody, 3E10, and active fragments thereof that selectively are transported in vivo to the nucleus of mammalian cells without cytotoxic effect are provided. The antibody and other molecules that bind to a variant of myosin IIb heavy chain found in the nucleus of skeletal muscle cells are useful as a non-viral delivery vector to target skeletal muscle in vivo. By contrast, in vitro the monoclonal antibody penetrates and is transported to the nucleus of multiple cell lines derived from different tissue types and can be used in screening tests to identify molecules that modulate growth of cells, such as cancer cells. Non-cytotoxic vectors for delivering a drug, polynucleotide or polypeptide selectively to skeletal muscle cells are also provided.