Abstract: This invention relates to targeted delivery of anti-viral compounds through protein bioconjugation. More particularly, it relates to an anti-viral compound conjugated to a protein, such as hemoglobin and to a method of treating a viral infection using said conjugate. The invention also provides a method of targeted drug delivery of an anti-viral nucleoside analogue to macrophages, cells comprising a hemoglobin receptor and to CD163 bearing cells.

Abstract: Methods for classifying a test sample as indicative of Alzheimer's disease use protein and peptide biomarkers that are differentially expressed in the cerebral spinal fluid (CSF) of subjects with Alzheimer's disease relative to age-matched controls. The methods also use protein and peptide signatures indicative of Alzheimer's disease. Microarrays and kits for detecting the protein and peptide biomarkers in CSF samples can be used to classify Alzheimer's disease state from test samples.

Abstract: A mutant of the polypeptide Protein A, wherein immunoglobulin binding properties can be altered by changing temperature under the conditions of pH 5-9, below 60° C. The use of the mutant Protein A include the use thereof as a ligand coupled to an affinity chromatography support for the purification of immunoglobulins by affinity chromatography, wherein the immunoglobulins is eluted by changing temperature and thereby the conformation of the mutant Protein A.

Abstract: Microspheres are produced by contacting a solution of a macromolecule or small molecule in a solvent with an antisolvent and a counterion, and chilling the solution. The microspheres are useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions.

Abstract: Disclosed herein are biomolecule-polymer conjugates of Formula 1, as well as methods of preparing same and kits for preparing same.

Abstract: Methods are described for improvement of the serum half life of therapeutic nucleic acids by 3? conjugation to useful target proteins, or other large molecules with useful function. In one embodiment, a 3? A, C or G overhang is added to ds-DNA and the primary amines conjugated using biocompatible bifunctional linkers to proteins. The resulting nucleic acid-3? conjugates are serum nuclease-resistant and retained in vivo for long periods without rapid kidney clearance. Further, the choice of conjugate imparts additional functionality to the nucleic acid-3? conjugate.

Abstract: The present invention relates to compositions for delivering nitric oxide (NO) to cells using heme proteins as carriers. In one embodiment, the present invention relates to the use of MalPEG surface modified hemoglobin to deliver NO to cells.

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: A composition comprising a glassified, stabilized particle preparation having a low water activity (between about 0.1 and 0.9) is provided. The preparations provide improved products with enhanced storage stability, less expensive cost of processing, and extended shelf life. The glassified, stabilized particle preparations are particularly efficacious in the preparation of perishable products, especially pharmaceutical agents, such as human blood and blood products (e.g., red blood cells). A single emulsion process comprising a 2-phase system for preserving food and pharmaceutical products is also provided. Stabilized biological products as glassified beads are also provided, as well as a method for rehydrating and/or reconstituting the glassified beads to provide useful and fully active reconstituted and/or rehydrated materials is also presented.

Abstract: The present invention is a method for preparing stable HBOC solutions. Specifically, the method comprises the steps of deoxygenating a PEG-Hb conjugate and adding one or more antioxidants during or following the deoxygenating step to form a stabilized PEG-Hb conjugate. The Hb in the PEG-Hb conjugate is not crosslinked and the stabilized PEG-Hb conjugate has a p50 less than that of native SFH from the same animal source when measured under the same conditions. Specifically, the p50 is 6±2 mmHg or less than 10 mmHg.

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 relates to isolated haemoglobin from worms belonging to the Nereididae family and its use in cell culture medium, in preservation solutions and as artificial oxygen carrier for transfusion.

Abstract: The invention provides a high affinity heme-binding agent, which can be provided in the form of a pharmaceutical composition that includes, optionally, a pharmaceutically acceptable carrier. The heme-binding agent can be used in a method of facilitating heme-iron export from a cell. The method comprises contacting a cell with a high affinity heme-binding agent. Also provided is a method of treating a disorder associated with excess iron in cells in a subject. The method comprises administering to the subject an effective amount of the composition of the invention. The subject is typically a mammal, most typically a human or veterinary subject.

Abstract: Described herein is a composition and process for synthesizing a hemoglobin-based oxygen carrier (HBOC) composition that includes a polymerized hemoglobin locked in at least one of the tense or relaxed quaternary state and has a molecular weight of at least about 500 kDa. The PolyHb may have a cross-linker to hemoglobin molar ratio of at least about 20:1. The polymerized hemoglobin is useful for delivering oxygen to cells, such as for treatment of anemic conditions in a subject, perfusion of tissues or organs, and supplementing cell culture media in cell culturing systems.

Abstract: The present invention relates to blood products, and more particularly to compositions comprising a modified oxygenated hemoglobin having a high affinity for oxygen and methods for making such compositions. Such compositions according to the present invention have better stability to auto oxidation and superior oxygen carrying characteristics.

Abstract: There are provided a pre-treatment technique for a glycated hemoglobin-containing sample, which is a simple and convenient treatment, is free from problems in storage stability and environmental aspects, and is capable of exposing an epitope sufficiently in a short time; and an method for an immunological assay of glycated hemoglobin using this technique. A method for pre-treating a glycated hemoglobin-containing sample for an immunological assay of glycated hemoglobin, the method includes treating a glycated hemoglobin-containing sample with a pre-treatment solution containing (A) guanidine or a salt thereof and (B) a nonionic surfactant and/or a nitrite.

Abstract: A method heat treatment of cross-linked hemoglobin solutions including polymeric hemoglobin is disclosed. The method involves contacting the hemoglobin solution with a high temperature short time heat treatment apparatus. The high temperature short time process thermally denatures unmodified tetrameric hemoglobin (hemoglobin dimer form), protein impurities (e.g. immunoglobin-G, serum albumin), bacteria, and viruses so that renal injury, vascular detrimental effects and other toxicity reactions can be avoided.

Abstract: A composition comprising heme iron and/or heme iron polypeptide in combination with ionic iron(s) and/or chelated iron(s). Administration of effective dosages of the present composition provides a method for treating and/or preventing iron deficiency anemia, and the physiological, biochemical, morphological, and behavioral manifestations symptomatic of same.

Abstract: A highly purified and heat stable cross-linked nonpolymeric tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin, uncross-linked tetrameric hemoglobin, and plasma protein impurities effectively. Addition of N-acetyl cysteine after heat treatment and optionally before heat treatment maintains a low level of met-hemoglobin. The heat stable cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. The inventive hemoglobin can also be used to prevent tumor metastasis and recurrence following surgical tumor excision.

Abstract: Disclosed are methods and apparatuses for stabilizing labile biomolecules in an aqueous solution without the use of chemicals. For example, some embodiments involve exposing an aqueous solution of a labile biomolecule, such as a protein, to light energy to stabilize the biomolecule in the solution.

Abstract: A compound of the formula: wherein R1 is independently selected from C1-C10 alkyl or substituted alkyl, R2 is independently selected from the group consisting of —H and C1-C6 alkyl or substituted alkyl, Y? is an anion, m is an integer from 1 to 8 and n is an integer from 1 to 8 is described. Methods of making and using the compound are also described. The compound may comprise a zwitterionic acid-labile surfactant suitable for purification and identification techniques used in proteomics.

Abstract: The present disclosure provides photoactive polypeptides. A subject photoactive polypeptide is useful in a variety of applications, which are also provided.

Abstract: The present invention is a method for preparing a hemoglobin based oxygen carrier to deliver oxygen to tissue. The method comprises mixing a deoxygenated hemoglobin with a maleimide-activated polyakylene oxide (PAO) to obtain an oxygen carrying product. This product is characterized as having 2 to about 8 PAO moieties covalently bound to a deoxygenated hemoglobin and a p50 less than native stroma-free hemoglobin from the same animal source when measured under the same conditions.

Abstract: The present invention relates to the use of a high molecular weight extracellular hemoglobin for the manufacture of a medicament for treating and/or preventing diseases by inhibition of calcium. Advantageously, the extracellular hemoglobin is obtained from Annelids. In particular, the invention concerns the use of a high molecular weight extracellular hemoglobin for the manufacture of a medicament for treating and/or preventing cardiovascular diseases, such as hypertension, angina such as angina pectoris, Raynaud's disease, arteriopathy, tachycardia, vasospasm, ischemia, myocardial infarction, congestive heart failure, arrhythmia or cerebrovacular accident.

Abstract: The present invention discloses a bladder cancer biomarker and a test method using the same. The biomarker contains at least one of the mentioned 69 compounds, such as apolipoprotein A1 (APOA1), apolipoprotein A2 (APOA2), peroxiredoxin 2 (PRDX2), heparin cofactor 2 precursor (HCII), and serum amyloid A-4 protein (SAA4), which exist in the urine specimen of a testee. The expression intensity of the biomarker can facilitate diagnosis of bladder cancer and evaluation of aggressiveness and malignancy of bladder cancer. Thereby, the physician can arrange an optimized treatment to achieve the best therapeutic effect.

Abstract: A high temperature-stable and highly purified cross-linked (optionally ?70% ?-? linked) tetrameric hemoglobin with high efficiency of oxygen delivery suitable for use in mammals without causing renal injury and vasoconstriction is provided. The dimeric form of hemoglobin is degenerated and purification processes are performed on red blood cells from whole blood. Controlled hypotonic lysis in an instant cytolysis apparatus prevents lysis of white blood cells. Nucleic acids from white blood cells and phospholipids impurities are not detected. Blocking of reactive sulfhydryl groups by a sulfhydryl reagent is performed in an oxygenated environment. Flowthrough column chromatography removes different plasma protein impurities. N-acetyl cysteine is added to the cross-linked tetrameric hemoglobin to maintain a low level of met-hemoglobin. The stabilized hemoglobin is preserved in an infusion bag with aluminum overwrap to prevent formation of inactive met-hemoglobin from oxygen intrusion.

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 application relates to a composition comprising a hyperbranched polymer attached to a core and a biologically active moiety. The biologically active moiety is attached to the core by means of a substantially non-enzymatically cleavable linker L. The composition can be used to deliver the biologically active moiety to its target.

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

Abstract: Described herein are composite materials and methods of using them for hydrophobic interaction chromatography (HIC). In certain embodiments, the composite material comprises a support member, comprising a plurality of pores extending through the support member; and a macroporous cross-linked gel, comprising a plurality of macropores, and a plurality of pendant hydrophobic moieties. In certain embodiments, the composite materials may be used in the separation or purification of a biological molecule or biological ion.

Abstract: A highly purified and heat stable cross-linked nonpolymeric tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin, uncross-linked tetrameric hemoglobin, and plasma protein impurities effectively. Addition of N-acetyl cysteine after heat treatment and optionally before heat treatment maintains a low level of met-hemoglobin. The heat stable cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. Another application is heart preservation in situations where there is a lack of oxygen supply in vivo, such as in heart transplant or oxygen-deprived heart.

Abstract: The present invention describes novel neuroprotective and multifunctional intra- and inter-molecular redox coupled polynitroxylated pegylated carboxy hemoglobins as high therapeutic index agents for un-met medical needs or diseases, which require acute or chronic alleviation of oxidative stress and correction of inadequate blood flow resulting from physical injury, ischemia, reperfusion injury, and inflammation injury in either or both pre-hospital and in-hospital transfusion and critical care medicine. These hemoglobins are triple-modified with a focus on therapeutic activities rather than oxygen carrying ability.

Abstract: Described herein are systems and methods for assaying a sample to quantitatively determine the percentage of glycated hemoglobin in the sample.

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: Disclosed is a novel use of an immunoglobulin Fc fragment, and more particularly, a pharmaceutical composition comprising an immunoglobulin Fc fragment as a carrier. The pharmaceutical composition comprising an immunoglobulin Fc fragment as a carrier remarkably extends the serum half-life of a drug while maintaining the in vivo activity of the drug at relatively high levels. Also, when the drug is a polypeptide drug, the pharmaceutical composition has less risk of inducing immune responses compared to a fusion protein of the immunoglobulin Fc fragment and a target protein, and is thus useful for developing long-acting formulations of various polypeptide drugs.

Abstract: This disclosure relates to methods of using nitrite to detoxify stroma-free hemoglobin based blood substitutes. In particular, methods are described for using a blood substitute comprised of about equimolar amounts of nitrite and hemoglobin (e.g., nitrite-metHb) to treat, prevent, or ameliorate diseases of the blood in a subject, or as a blood replacement in a subject.

Abstract: The disclosure relates to recombinant adult human apohemoglobin (apo-rHb) in which the stability has been increased by replacement of an amino acid with a counterpart from another organism, such as a deep sea diving mammal. This mutated apo-rHb may be more stable and/or give higher production yields than unmutated adult human apo-rHb. The mutated apo-rHb may be produced in microorganisms, such as E. coli or yeast cells, or animal erythroid cells. Some apo-rHb of the present disclosure may be used as part of a blood substitute.

Abstract: The present invention includes a method for diagnosing cancer comprising detecting the presence of survivin in the biological fluid of a patient. The present invention also provides kits comprising one or more agents that detect survivin polypeptide or survivin nucleic acid and a container for collecting biological fluid for testing.

Abstract: The present invention relates generally to a modified hemoglobin with an allosteric effector conjugated which is capable of dynamically regulating the efficiency of oxygen release. The hemoglobin composition provided in the present invention is utilizing maleimide-Polyethylene glycol-N-hydroxysuccinimidyl as a linker to crossbridge the peptide comprising SEQ ID NO: 1 to the surface of a hemoglobin, and hence, it is able to decrease the oxygen affinity through the characteristic of the peptide which could enter into the central cavity formed between ?- chains of hemoglobin under an appropriate oxygen concentration.

Abstract: The invention relates to novel nucleic acids encoding a mammalian PCADM-1 gene, and proteins encoded thereby, whose expression is increased in certain diseases, disorders, or conditions, including, but not limited to, prostate cancer. The invention further relates to methods of detecting and treating prostate cancer, comprising modulating or detecting PCADM-1 expression and/or production and activity of PCADM-1 polypeptide. Further, the invention relates to novel assays for the identification of DNA-binding proteins and the double-stranded oligonucleotide sequences that specifically bind with them. Finally, the invention relates to DNAZYMs or DNA enzymes which specifically bind PCADM-1 mRNA to inhibit PCADM-1 gene expression and thereby destroy tumor cells and tumor tissue.

Abstract: Provided are hemoglobins having at least two chemical modifications that lower oxygen affinity, hemoglobins chemically modified by the addition of glyceraldehyde-3-phosphate, and hemoglobins having at least two specific chemical modifications. PEGylated versions of these hemoglobins are also provided, as are certain tetraPEGylated and diPEGylated hemoglobins. Methods of modifying a hemoglobin are additionally provided, as are methods of making a hemoglobin. Pharmaceutical compositions and blood substitutes using these hemoglobins are further provided, as are methods of treating a subject using these pharmaceutical compositions and blood substitutes.

Abstract: The present invention includes a method for diagnosing cancer and predicting recurrent cancer comprising detecting the presence of survivin in the biological fluid of a patient. The present invention also provides kits comprising one or more agents that detect survivin polypeptide or survivin nucleic acid and a container for collecting biological fluid for testing.

Abstract: A new method of diagnosing postprandial hyperglycemia by indirectly measuring a blood glucose level is provided. Postprandial hyperglycemia is detected by measuring a glycation degree of lysine in hemoglobin, in which a side chain amino group of lysine is glycated (GHbLys %). Measurement of GHbLys % can be performed by cleaving hemoglobin by protease, treating a glycated part of a lysine residue in the obtained cleavage product of hemoglobin with fructosyl amino acid oxidase, and measuring a redox reaction between the glycated part and fructosyl amino acid oxidase.

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: The present invention relates to novel methods of using blood substitutes to treat acute blood loss and novel pharmaceutical compositions comprising blood substitutes. Blood substitutes useful for the methods of the present invention can (1) induce expression of erythropoietin as tested in a cell culture under normoxic conditions, and/or (2) induce erythropoiesis under normoxic conditions as measured by (a) a decrease in the doubling time of the subject's hematocrit or hemoglobin, and/or (b) an increase in the subject's circulating erythropoietin level. Blood substitutes useful for the pharmaceutical compositions of the present invention can (1) stabilize HIF-1 alpha expression, and/or (2) down regulate NF-kappa B.

Abstract: The present invention relates to a chromatographic method of separating biological material comprising, providing chromatographic media comprising inorganic oxide particles having an average diameter of about 2 microns or less and an average pore diameter of 300 ? or more; applying a solvent comprising said biological material to said media, wherein said biological material is reversibly bonded to said media; and eluting said biological material from said media with a solvent in less than about 2 minutes for biological material having a molecular weight of less than about 100,000 Daltons.

Abstract: The present invention relates to a modified porphyrin-based oxygen-carrying protein, such as haemoglobin, which has been found, in its unmodified state to have a low affinity site of electron transfer and a high affinity electron transfer between a reductant and ferryl haem iron via one or more protein amino acids. The invention provides such proteins that comprise a modification to enhance this pathway.

Abstract: An implantable preparation comprises a material which can be obtained from globin that has been modified, especially chemically, to be, at least partially, soluble at physiological pH. The material is biocompatible, and biodegradable in the organism. The material may be soluble at physiological pH, or insoluble at that pH. The preparation may be in the form of a solution, suspension, paste, gel, film, sponge, powder or granules, or a solid implant. The preparation can be used for the healing, protection or filling of external skin wounds, the filling of wrinkles and skin flaws, the filling of tissue, as a device for fixing prostheses or biomaterials, or as a device for preventing adhesion.

Abstract: The present invention provides methods for quantitation of glycated protein in a biological sample using a solid support matrix by making a first bound protein measurement total bound protein under conditions where both glycated and non-glycated protein bind to the support in making a second bound protein measurement under conditions where glycated protein is bound to the support and non-glycated protein is not substantially bound. Diagnostic devices and kits comprising the methods of the present invention are also provided.

Abstract: The present invention provides oxygenated hemoglobins in powdered form and methods of preparing a powdered form of a protein, such as hemoglobin, which comprise (a) mixing a solution of the protein with inulin, and optimally with a reducing sugar such as glucose or tagatose, and (b) drying the mixture. Also provided are blood substitutes formed from reconstituted powdered hemoglobins, and methods of treatment using the blood substitutes.