Abstract: The invention relates to the field of chemistry and diagnosis, more in particular to diagnosis of current and/or past and/or symptomless infections or of a history of exposure to a gram-negative-bacterium (such as an enterobacteriaceae or a legionella). Even more in particular, the invention relates to the screening of animals or animal products for the presence of un-wanted/undesired microorganisms. The invention further relates to a method for screening samples for the presence of antibodies directed against unwanted/undesired microorganisms and preferably such a method is performed with help of a biosensor. The invention also relates to a method for immobilising polysaccharides to solid surfaces. The invention furthermore provides solid surfaces with immobilised polysaccharides as well as applications of such surfaces.

Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a therapeutic agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract: The present disclosure relates to the use of AHSP to stabilize the ? subunit of rHb. AHSP may be co-expressed with the hemoglobin genes. AHSP stabilization may be used to increase the production of intact rHb in various systems, such as E. coli, other microorganisms, or animal erythroid cells. This intact rHb may then be used as part of a blood substitute product.

Abstract: The present invention provides PEGylated hemoglobins and PEGylated albumins comprising polyethylene glycol (PEG) conjugated to hemoglobin or to albumin, wherein the PEG is a maleimide PEG, an alkylamide PEG, an iodoacetamide PEG, a p-nitro thio-phenyl PEG, a vinyl sulfone PEG, or a mixed disulfide PEG; and PEGylated albumins and PEGylated hemoglobins comprising polyethylene glycol (PEG) attached to a thiolated amino group of albumin or hemoglobin, wherein the amino group is thiolated using dithio sulfo succinimidyl propionate (DTSSP) or dithiosuccinimidyl propionate (DTSP) or dithiobispropionimidate. The invention also provides methods of preparing PEGylated hemoglobins and PEGylated albumins comprising a) reacting hemoglobin or albumin with a thiolating agent and with a PEGylating agent, and b) capping unPEGylated reactive thiols of hemoglobin or albumin with N-ethyl maleimide.

Abstract: The present invention relates to methods for enhancing the hemodynamic stability of an individual undergoing surgery by administering a composition comprising a hemoglobin-based oxygen carrier. In one embodiment, the present invention relates to the use of polyalkylene oxide modified hemoglobins with reduced cooperativity and a high oxygen affinity to enhance oxygen offloading as a preventative measure to avoid hemodynamic stability-related complications during surgery.

Abstract: This invention encompasses antibodies specific for IBC-1 (Invasive Breast Cancer-1), methods for diagnosis and prognosis of metastatic breast cancer and degenerative neural conditions, methods of identifying and manufacturing therapeutic compounds, and methods of treating patients with invasive and metastatic breast cancer or degenerative neural conditions.

Abstract: The invention is directed to blood proteins produced in monocot seeds and isolated therefrom for use in therapeutic compositions, and to methods of making these isolated blood proteins and to therapeutic compositions comprising them.

Abstract: A method of removing carbon monoxide from an oxygen carrier including setting a carbon monoxide bonded oxygen carrier solution across a separation membrane from an oxygen-dissolved solution; and exposing the setting part to the light and a method of removing carbon monoxide from an oxygen carrier including setting a carbon monoxide oxygen carrier solution across a hollow fiber separation membrane from an oxygen-dissolved solution; and exposing the setting part to light.

Abstract: NO preferentially binds to the minor population of the hemoglobin's vacant hemes in a cooperative manner, nitrosylates hemoglobin thiols, or reacts with liberated superoxide in solution. The distribution of minor forms of hemoglobin can be tested and the results can be used to predict whether a composition of hemoglobin will scavenge, load, eliminate, or donate NO. Hemoglobin thus serves to regulate the chemistry of NO. SNO-hemoglobin transfers NO equivalents to the red blood cell anion transport protein AE1, which serves to export NO from red blood cells. Regulation of AE1 function is the basis for methods of therapy to affect levels of NO or its biological equivalent.

Abstract: The present invention provides pegylated hemoglobins comprising a maleimide polyethylene glycol (PEG) conjugated to a thiol moiety of a cysteine residue of hemoglobin, methods of preparing the pegylated hemoglobins, compositions and blood substitutes comprising the pegylated hemoglobins, and methods of treating a subject which comprise administering to the subject blood substitutes comprising vasoinactive pegylated hemoglobins.

Abstract: There are disclosed chemically active poly(ethylene glycols) and other hydrophilic polymers that are suitable for coupling to pharmaceutically or diagnostically active agents such as peptides, oligonucleotides, proteins or non-peptide molecules. The compounds are represented by the formula Poly-(X—NH—CO-A)n wherein, Poly is a hydrophilic polymer having a molecular weight of from about 300 to 100000 Daltons; A together with —NH—CO— forms a reactive group; X is a spacer moiety or a bond; n is an integer comprised between 1 and 50. The active agents of interest which may be conjugated to the disclosed compounds may be selected from hemoglobin, insulin, urokinase, alpha-interferon, G-CSF, hGH, asparaginase, adenosine deaminase, superoxide dismutase and catalase.

Abstract: The invention relates to stannous halide stabilized and/or enhanced alkaline solutions to be used in combination with calorimetric, luminescent and fluorescent assays. The buffered solutions stabilize hydrogen peroxide at a pH greater than 7.0 and preferably greater than 9.0. By stabilizing and/or enhancing hydrogen peroxide in the buffer system, the compositions used in such assays may have a higher shelf-life and provide enhanced detection of the subject analyte.

Abstract: Metadherin, a protein that controls metastasis, and variants of metadherin are described. DNA sequences encoding the same and methods of production are described. Therapies involving the application of metadherin, binding agents that bind to metadherin, such as antibodies, and expression modulating agents, such as siRNA, are described. The use of metadherin or metadherin variants for delivering desired substances to particular lung tissue is described. A method of diagnosing metastatic cells based on the presence of metadherin is described.

Abstract: Red blood cells are purified by defibrinating whole blood and then filtering the defibrinated whole blood, whereby at least a portion of a plasma component is separated from the red blood cells to form a suspension of red blood cells, thereby purifying the red blood cells. Whole blood is defibrinated by, for example, using a chemical coagulating agent or mechanical agitation. Separation of the plasma component from red blood cells can be completed by, for example, diafiltration. The suspension of red blood cells can then be employed to produce a hemoglobin-based oxygen carrier.

Abstract: The present invention provides monoclonal antibodies that react against high molecular weight melanoma-associated antigen. These antibodies may be used for diagnostic and/or therapeutic purposes.

Abstract: A stabilized hemoglobin solution is contacted with polymerizing agent. The stabilized hemoglobin solution includes stabilized tetrameric hemoglobin. At least a portion of the stabilized tetrameric hemoglobin is polymerized by reaction with the polymerizing agent, thereby producing a polymerized hemoglobin solution. In one embodiment, the stabilized hemoglobin solution includes a filtrate formed by filtrating polymerized solution of native hemoglobin through a filter having a molecular weight cut off of about 100 kD.

Abstract: S-nitrosohemoglobin can liberate NO by transfer to a low molecular weight thiol in the circulatory system, allowing the delivery of NO to the tissues. The effect of administering isolated S-nitrosohemoglobin and low molecular weight thiol to a mammal is to increase delivery of oxygen and NO.

Abstract: A process is disclosed for the preparation of an essentially tetramer-free, substantially stroma-free, polymerized, pyridoxylated hemoglobin. Also disclosed is an essentially tetramer-free, substantially stroma-free, polymerized, pyridoxylated hemoglobin product capable of being infused into human patients in an amount of up to about 5 liters.

Abstract: The present invention provides a method for increasing the yield of a protein produced by cultivating eukaryotic cells and adding an ionic substance to the culture medium prior to harvest of the protein. Suitable ionic substances are the salts of the Hofmeister series, amino acids and peptone.

Abstract: The present invention relates to compositions for delivering carbon monoxide (CO) to cells using heme proteins as carriers. In one embodiment, the present invention relates to the use of MalPEG surface modified hemoglobin to deliver CO to cells.

Abstract: The present invention includes compositions containing carboxamidomethylated cross-linked hemoglobin where the cysteine moiety of the hemoglobin includes a thiol protecting group and where the hemoglobin has a reduced ability to bind with nitric oxide. Preferably, the hemoglobin is deoxygenated, endotoxin free, and stroma free. The present invention also includes method of preparation, process of preparation and the method of use including supplementing blood volume in mammals and treating disorders in mammals where oxygen delivery agents are of benefit.

Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a target agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract: The present invention includes compositions containing carboxymethylated cross-linked hemoglobin where the cysteine moiety of the hemoglobin includes thiol protecting group and where the hemoglobin is incapable of binding with the nitric oxide. Preferably, the hemoglobin is deoxygenated, endotoxin free, and stroma free. The present invention also includes method of preparation, process of preparation and the method of supplementing blood in mammals.

Abstract: Construct-complexes of a hemoglobin, a hepatocyte modifying substance bound to the hemoglobin, and a haptoglobin bound to the hemoglobin, are provided, for administration to mammalian patients. The construct-complex may be formed ex vivo, or a hemoglobin-hepatocyte modifying substance combination may be administered to the patient so that haptoglobin in the mammalian body bonds thereto to form the construct-complex in vivo. Disorders of the liver may be diagnosed and treated using construct-complexes described herein.

Abstract: The invention relates to catalytic systems which are used to generate colours on a support. The inventive means are characterised in that they comprise one or more deactivated oxidation catalysts. The invention can be used to colour organic or inorganic supports.

Abstract: A stabilized hemoglobin solution is contacted with polymerizing agent. The stabilized hemoglobin solution includes stabilized tetrameric hemoglobin. At least a portion of the stabilized tetrameric hemoglobin is polymerized by reaction with the polymerizing agent, thereby producing a polymerized hemoglobin solution. In one embodiment, the stabilized hemoglobin solution includes a filtrate formed by filtrating polymerized solution of native hemoglobin through a filter having a molecular weight cut off of about 100 kD.

Abstract: A hemoglobin solution packaged in a flexible oxygen-impermeable container system. The container system includes a multi-layer film having at least a product contact layer, an oxygen and moisture barrier layer and an exterior layer. The flexible container system further includes an interface port for filling the flexible container with the hemoglobin solution and delivering the hemoglobin solution. The hemoglobin solution comprises a substantially stroma and tetramer free, cross linked, pyridoxylated hemoglobin solution including preservatives such as ascorbic acid, glycine and dextrose.

Abstract: The present invention relates to a biological tissue examination agent comprising hemoglobin labeled with 15O2 and a method for producing the same. More specifically, the present invention relates to a biological tissue examination agent for diagnosing a cause or condition of a disease by detecting oxygen metabolism in a biological tissue using hemoglobin labeled with 15O2, and a method for producing the same. The present invention also relates to a method for detecting oxygen metabolism in a biological tissue.

Abstract: The present invention relates to a cardio myopeptidin which is isolated from the hearts of non-human healthy mammals. The molecular weight of the cardio myopeptidin is less than 10000 Dalton, the peptide content thereof being 75%˜90%, the free amino acid content 6%˜15%, the ribonucleic acid content less than 2%, and the deoxyribonucleic acid content less than 7.5%. The present invention further provides a method of producing the cardio myopeptidin and the use thereof in producing pharmaceuticals for treating cardiac disorders, specifically the use in producing pharmaceuticals for treating myocardial ischemic and reperfusion injury. The cardio myopeptidin of the present invention can work directly on myocytes, promoting the repair of injuries caused by various reasons, and providing a new way to relieve ischemic and reperfusion injury, and to promote the repair of injured myocardium.

Abstract: The invention provides methods and compositions for in vivo incorporation of non-naturally encoded amino acids into polypeptides by Pseudomonas species and strains derived therefrom. Also provided are compositions including proteins with non-naturally encoded amino acids made by Pseudomonas species and strains derived therefrom.

Abstract: The present invention provides compositions and methods for the separation of metals or molecules such as polypeptides, nucleic acids, or endotoxins using a metal-modified solid support. The metals or molecules are isolated from a starting material using the modified solid supports of the invention. Also provided by the invention are kits that can be used in connection with the inventive methods.

Abstract: A substantially tetramer free hemoglobin solution and a method for producing a substantially tetramer free hemoglobin solution. The method includes polymerizing a solution of hemoglobin, treating the polymerized hemoglobin solution to partially degrade the polymer to tetramer and removing tetramer from the hemoglobin solution.

Abstract: An artificial red blood cells are disclosed comprising a thin film encapsulating a core, the core comprising hemoglobin, wherein the film comprises a plurality of layers of polypeptides, opposing layers comprising alternating oppositely charged polypeptides, and wherein at least half of the amino acid residues in the oppositely charged polypeptides have the same charge. In one embodiment, a first layer comprises a first layer polypeptide comprising one or more first amino acid sequence motifs, wherein the one or more amino acid sequence motifs consist of n amino acids, at least x of which are positively charged, or at least x of which are negatively charged, wherein x is greater than or equal to approximately one-half of n.

Abstract: The invention provides methods and compositions for increasing Na ion transport and/or epithelial fluid transport in a vertebrate by administering an effective amount of haptoglobin or haptoglobin and hemoglobin. The invention also provides a new therapeutic approach for treating disorders associated with insufficient epithelial Na ion and/or fluid transport, the use of an effective amount of haptoglobin, or haptoglobin and hemoglobin in the preparation of medicament for increasing epithelial Na ion transport in a vertebrate as well as a method of screening a candidate compound for its ability to modulate haptoglobin or haptoglobin and hemoglobin stimulation of epithelial Na ion transport.

Abstract: The invention relates to stannous halide stabilized and/or enhanced alkaline solutions to be used in combination with colorimetric, luminescent and fluorescent assays. The buffered solutions stabilize hydrogen peroxide at a pH greater than 7.0 and preferably greater than 9.0. By stabilizing and/or enhancing hydrogen peroxide in the buffer system, the compositions used in such assays may have a higher shelf-life and provide enhanced detection of the subject analyte.

Abstract: The present invention includes compositions containing carboxamidomethylated cross-linked hemoglobin where the cysteine moiety of the hemoglobin includes a thiol protecting group and where the hemoglobin has a reduced ability to bind with nitric oxide. Preferably, the hemoglobin is deoxygenated, endotoxin free, and stroma free. The present invention also includes method of preparation, process of preparation and the method of use including supplementing blood volume in mammals and treating disorders in mammals where oxygen delivery agents are of benefit.

Abstract: A novel heme peptide and a method for producing the same are disclosed. The invention provides a peptide with a potent NO-scavenging ability which can be used in capturing/quantifying NO and can be used as a diagnostic agent, prophylactic agent or therapeutic agent for diseases in which NO is involved, as a research reagent, as a reagent for measuring NO concentrations in the environment, and as a treating agent for removing NO in the environment.

Abstract: The functional characteristics of heme proteins can be modified to produce hemoglobins that can be used as blood substitutes in different therapeutic applications. Stable polymers of tetrameric hemoglobin, and of myoglobin molecules, are provided for use in the blood substitutes.

Abstract: The present invention provides agents for alleviating symptoms resulting from inflammation, which have an activity to alleviate inflammatory symptoms caused by bacterial infection, particularly accumulation of body fluid such as bronchocavemous plasma exudation, ascites, etc., at the inflammatory site, or excessive increase of blood neutrophils; symptoms resulting from inflammation caused by bacterial infection, particularly accumulation of body fluid such as bronchocavemous plasma exudation ascites, etc., at the inflammatory site, or excessive increase of blood neutrophils, can be alleviated effectively by ingesting or administering orally or parenterally a composition containing human-type lactoferrin as an effective component.

Abstract: An hemoglobin (Hb)-Dextran (Dx) conjugate having a molecular weight between 50 kd and 500 kD provides a blood substitute that results in acceptable erythrocyte sedimentation rate (ESR) and excretion rate (EXC) values. DxHb conjugates of the invention can be used for a variety of purposes as an alternative to blood.

Abstract: Methods for treating a mammal suffering from massive blood loss comprising administering to the mammal a polymerized hemoglobin solution.

Abstract: This invention relates to monovalent and multivalent, monospecific antibodies and to multivalent, multispecific antibodies. One embodiment of these antibodies has one or more identical binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these antibodies has two or more binding sites where these binding sites have affinity towards different epitopes on a target antigen or different target antigens, or have affinity towards a target antigen and a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional antibodies in a host. More specifically, the present invention relates to the tumor-associated antibody designated PAM4. The invention further relates to humanized and human PAM4 antibodies, and the use of such antibodies in diagnosis and therapy.

Abstract: A specific binding member is specific for and binds directly to the ED—B oncofoetal domain of fibronectin (FN).

Abstract: Disclosed herein are immunogenic compositions, methods of designing immunogenic compositions, methods of treatment using immunogenic compositions, methods of evaluating cell-mediated immunity resulting from immunogenic compositions, research models, and methods of making research models, all of which relate to targeting tumor vasculature.

Abstract: This invention relates to monovalent and multivalent, monospecific antibodies and to monovalent and multivalent, multispecific antibodies. One embodiment of these antibodies has one or more identical binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these antibodies has two or more binding sites where these binding sites have affinity towards different epitopes on a target antigen or different target antigens, or have affinity towards a target antigen and a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional antibodies in a host. More specifically, the present invention relates to the tumor-associated antibody designated PAM4. The invention further relates to chimeric PAM4 antibodies, and the use of such antibodies in diagnosis and therapy.

Abstract: The invention provides a conjugate of hemoglobin and a nucleic acid cross-linking agent.

Abstract: The present invention relates to improved antibodies against tumor surface antigens and their use in the treatment of tumors. Of particular interest are highly stable, humanized, high affinity antibodies against carcinoembryonic antigen (CEA), especially the antibody we have termed sm3E, which is derived from the scFv antibody MFE-23. Such antibodies have the potential for improved therapeutic efficacy.

Abstract: Bifunctional inhibitor molecules and methods for their use in the inhibition of protein—protein interactions are provided. The subject bifunctional inhibitor molecules are conjugates of a target protein ligand and a blocking protein ligand, where these two moieties are optionally joined by a linking group. In the subject methods, an effective amount of the bifunctional inhibitor molecule is administered to a host in which the inhibition of a protein—protein interaction is desired. The bifunctional inhibitor molecule simultaneously binds to its corresponding target and blocking proteins to produce a tripartite complex that inhibits the target protein—protein interaction. The subject methods and compositions find use in a variety of applications, including therapeutic applications.

Abstract: A specific region of chromosome 10 (10q23.3) has been implicated by series of studies to contain a tumor suppressor gene involved in gliomas, as well as a number of other human cancers. One gene within this region was identified, and the corresponding coding region of the gene represents a novel 47 kD protein. A domain of this product has an exact match to the conserved catalytic domain of protein tyrosine phosphatases, indicating a possible functional role in phosphorylation events. Sequence analyses demonstrated the a number of exons of the gene were deleted in tumor cell lines used to define the 10q23.3 region, leading to the classification of this gene as a tumor suppressor. Further analyses have demonstrated the presence of a number of mutations in the gene in both glioma and prostate carcinoma cells. Methods for diagnosing and treating cancers related to this tumor suppressor, designated as TS10q23.3, also are disclosed.

Abstract: Neoplasia is treated by administering to a mammalian host a composition comprising ligands for the NKG2D receptor. In addition, other NKG2D ligands, proteins specific for the neoplastic cells and cytokines may be included to enhance the immune response. The composition may be cells comprising expression constructs for the ligands, liposomes or combinations of protein molecules.