Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encodings the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the intention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Abstract: Systems and methods are provided for producing a protein of interest that is typically not amenable to expression in soluble form in in vitro expression systems. In some aspects, the invention provides methods of synthesizing proteins using in vitro protein synthesis systems that include a scaffold protein such as apolipoprotein or an amphipathic alpha helix containing (“AAHC”) protein, in which higher yields of soluble protein are produced than in the absence of the scaffold protein. The scaffold proteins may be provided in an in vitro protein synthesis system associated with lipid or not associated with lipid. The scaffold protein may be provided as a protein per se or may be encoded by a nucleic acid template and co-expressed with the protein of interest. The invention also provides compositions and kits for synthesis of proteins in soluble form, in which the compositions and kits include cell extracts for protein expression and isolation.

Abstract: The present invention provides isolated apolipoprotein E (apoE) stable folding intermediates. The invention further provides methods for identifying compounds that alter the structure or level or activity of an apoE stable folding intermediate, as well as methods of inhibiting the formation or activity of stable folding intermediates of apoE. The invention further provides methods for reducing the level and/or activity of an apoE stable folding intermediate, and methods for treating disorders relating to apoE4 in a subject.

Abstract: An artificial invasin complex is prepared from purified or recombinantly prepared invasins and gram negative bacteria lipopolysaccharides. Typically, IpaB is mixed with IpaC to form a IpaB:IpaC complex. This invasin protein complex is then mixed with the lipopolysaccharide to form an artificial invasin complex. Additional bioactive molecules can be incorporated into the complex during manufacture. This artificial invasin complex is similar in function to native Invaplex 24 or Invaplex 50. The artificial invasin complex has superior immunogenicity properties relative to the native complex and can be taylor made. Its method of preparation lends itself to scale up. The artificial invasin complex can facilitate transport of biomolecules, therapeutics and antibiotics across cell membranes in a manner similar to native Shigella Invaplex.

Abstract: In one aspect, the present invention provides isolated oxidation resistant mutant apoA-I polypeptides comprising an amino acid sequence substantially homologous to SEQ ID NO:4, the mutant apoA-I polypeptide comprising a combination of: (1) a conservative amino acid substitution at residue Tyr192; and (2) at least one conservative amino acid substitution at residue Met86, Met112, or Met148, wherein the mutant apoA-I polypeptide is resistant to modification by an oxidizing agent. In another aspect, the invention provides a method of promoting cholesterol efflux activity in a mammalian subject in need thereof, the method comprising the step of administering an effective amount of an oxidation resistant apoA-I agonist to the subject to promote cholesterol efflux.

Abstract: Apolipoprotein A-I-rich Lhigh-density Lipoprotein 2 (HDL2) and Apolipoprotein A-I (ApoA-I) was discovered to inhibit angiogenesis in an in vitro human angiogenesis model, the human placental vein angiogenesis model. Apolipoprotein A-I was able to destroy a pre-existing angiogenic response as well as prevent the development of new vessels. Application of Apolipoprotein A-I will be effective in inhibiting tumor growth dependent on angiogenesis, and in decreasing existing blood vessels formed by tumors. It will also be effective in treating non-cancerous diseases which symptoms include an increase in angiogenesis, e.g., psoriasis, retinopathy of prematurity, neovascular glaucoma, diabetic retinopathy, obesity, and psoriasis.

Abstract: Complexes of a protein selected from the group consisting of VEGF-B167, VEGF-C, VEGF-D and processed VEGF-B186 and analogs thereof and the neuropilin-1 (NP-1) receptor, the extracellular domain or a ligand-binding fragment or analogue thereof; the use of such complexes in assays for growth factor proteins having substantially the same binding affinity for a cell surface receptor as VEGF-B167, VEGF-C, VEGF-D or processed VEGF-B186 and/or in promoting or antagonizing a cellular response mediated by VEGF-B167, VEGF-C, VEGF-D and/or processed VEGF-B186; and specific binding partners, e.g. antibodies, for such complexes.

Abstract: The invention is based on the discovery that the human protein referred to herein as INSP153 protein is a lipocalin.

Abstract: In the present invention, the markers identified for liver fibrosis and cirrhosis and the microarray panel thereof comprise at least one of the following proteins/genes: 8 up-regulated genes such as ANXA2; COL1A2; COL3A1; GSN; LDHB; LUM; PDGFRA and TIMP1. 13 down-regulated genes such as ALB; ANPEP; APOF; AZGP1; BHMT C8A; CFHR4; CFHR5; COL18A1; FTCD; GYS2; ITIH1, and THRAP1. 9 therapeutic targets such as PDGFRA; S100A4; COL3A1; CCL19; DCN; DPT; APP; TNF; and INFG. The present invention is capable of screening markers for the early warning of the occurrence for severe fibrosis or cirrhosis and potentially targets for drug design.

Abstract: Compositions and methods for increasing the receptor mediated transport of basic fibroblast growth factor (bFGF) across the blood brain barrier (BBB). The bFGF is conjugated to a BBB targeting agent using either avidin-biotin technology or genetic engineering. The bFGF conjugate was found to cross the BBB at substantially increased rates while still retaining biological activity. In addition, uptake of the bFGF conjugate by non-brain tissue and organs was limited. The bFGF conjugate may be injected intravenously to provide neuroprotection in patients suffering from cerebral stroke.

Abstract: The present invention is directed to systems, apparatus and methods for creating derivatives of at least one form of HDL without substantially affecting LDL. These derivatives of HDL are particles with reduced lipid content, particularly reduced cholesterol content. These particles have the capacity to bind cholesterol and are administered to a patient to enhance cellular cholesterol efflux and reduce cholesterol levels in cells, tissues, organs, and blood vessels. The present method is useful for treating atherogenic vascular disease and may be combined with other therapies such as statins, inhibitors of cholesterol absorption, niacin, anti-inflammatories, exercise and dietary restriction.

Abstract: Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

Abstract: Heart and brain fatty acid binding proteins (H-FABP, B-FABP) are markers for TSEs, especially CJD. The invention provides a diagnostic assay for either of these markers, preferably by enzyme immunoassay using a specific antibody thereto. Since H-FABP is also a marker for acute myocardial infarction (AMI), to distinguish CJD from AMI requires an assay specific to AMI, e.g. using troponin-1 or CK-MB as a marker, also to be carried out.

Abstract: The present invention is directed to systems, apparatus and methods for creating derivatives of at least one form of HDL without substantially affecting LDL. These derivatives of HDL are particles with reduced lipid content, particularly reduced cholesterol content. These particles have the capacity to bind cholesterol and are administered to a patient to enhance cellular cholesterol efflux and reduce cholesterol levels in cells, tissues, organs, and blood vessels. The present method is useful for treating atherogenic vascular disease and may be combined with other therapies such as statins, inhibitors of cholesterol absorption, niacin, anti-inflammatories, exercise and dietary restriction.

Abstract: The invention provides lipopeptide conjugates in which a cysteine that is double-substituted by a fatty acid is bonded by means of the carboxyl group to a highly soluble, physiologically compatible and non-immunogenic, polymeric conjugate group. The conjugates exhibit an excellent macrophage stimulant action and do not require addition solutizing. They can be used in a wide range of applications, in particular for stimulating macrophages, for stimulating antibody synthesis, for combating infection, as an immunostimulant, in particular in relation to tumors, for preventing and treating septicaemic shock, for would healing and as an adjuvant for vaccines.

Abstract: The present invention provides methods and compositions for treating hypercholesterolemia using therapeutic apoE proteins. A therapeutic apoE protein is a naturally-occurring apoE protein (e.g., apoE1, apoE2, apoE2*, apoE2**, apoE3, and apoE4) that has one or more amino acid substitutions in the carboxy-terminal region which, when administered to a mammal having hypercholesterolemia, reduces the plasma cholesterol levels without inducing hypertriglyceridemia. The invention also provides a method for reducing plasma cholesterol using low doses of naturally-occurring apoE proteins.

Abstract: The invention provides not only a smooth muscle growth inhibitory composition and a composition for inhibiting expression of adhesion molecules in vascular endothelial cells, each comprising the adipose tissue-specific secretory factor apM1 as an active ingredient, but also a method for diagnosis of arteriosclerosis which comprises assaying apM1 in a sample, an antibody against apM1, and a diagnostic kit for arteriosclerosis which comprises the antibody as an active component, all of which contribute to the elucidation of obesity-related genes and corresponding expression products which are useful for the etiologic exploration and establishment of therapeutic modalities for various obesity-related diseases, particularly arteriosclerosis inclusive of angina pectoris and myocardial infarction. By utilizing the information thus obtained, therapeutic and diagnostic methods for various diseases can be established.

Abstract: Functional Apolipoprotein A-I mutant proteins, having one or more cysteine substitutions and polynucleotides encoding same, can be used to modulate paraoxonase's arylesterase activity. These ApoA-I mutant proteins can be used as therapeutic agents to combat cardiovascular disease, atherosclerosis, acute phase response and other inflammatory related diseases. The invention also includes modifications and optimizations of the ApoA-I nucleotide sequence for purposes of increasing protein expression and optimization.

Abstract: The present invention relates to a process for purifying a hydrophobic or amphiphilic compound, by first mixing a starting material containing the hydrophobic or amphiphilic compound with a first polymeric material, water and at least one of a second polymeric material and a surfactant, wherein the first polymeric material and the second polymeric material and/or surfactant are immiscible in the resulting primary aqueous solution. The process further comprises maintaining the primary aqueous solution for a period of time sufficient for essentially separating the phases formed, and then removing the phase containing the main portion of the hydrophobic or amphiphilic compound and the second polymeric material and/or surfactant. The second polymeric material and/or surfactant are separated from the hydrophobic or amphiphilic compound, and subsequently recycled to the initial mixing step.

Abstract: The invention relates to the use of reconstituted HDL for improving the endothelial function in patients suffering from hypercholesterolaemia and for treating or preventing acute coronary diseases such as unstable angina pectoris.

Abstract: Use of high density lipoprotein and/or derivatives in the manufacture of a medicament for the prevention or treatment of organ dysfunction following ischaemia and reperfusion injury. In particular, the medicament may be for the treatment of end stage organ injury or failure.

Abstract: The invention provides methods and compositions for treating disorders using non-human animal Apolipoprotein A-I (ApoA-I) protein. The invention provides methods and compositions for treating disorders in animals, including humans, associated with dyslipidemia, including hyperlipidemia, hyperlipoproteinemia, hypertriglyceridemia, hypercholesterolemia, HDL deficiency, ApoA-I deficiency, cardiovascular disease, atherosclerosis, restenosis, and other disorders such as septic shock and viral infections.

Abstract: Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.

Abstract: Isolated polynucleotides encoding novel polypeptides which are capable of binding to native and methylated LDL (low density lipoprotein), the isolated polypeptides, called LBPs (LDL binding proteins), and biologically active fragments and analogs thereof, are described. Also described are methods for determining if an animal is at risk for atherosclerosis, methods for evaluating an agent for use in treating atherosclerosis, methods for treating atherosclerosis, and methods for treating a cell having an abnormality in structure or metabolism of LBP. Pharmaceutical compositions and vaccine compositions are also provided.

Abstract: Spheroidal reconstituted HDL particles with a defined phospholipid composition have been formed for the first time. The spheroidal HDL particle are formed from discoidal HDL particles of defined phospholid composition to which is added in multiple stepwise format unesterified cholesterol carried in a solvent, followed by addition of a LCAT. Lysophopholipids are removed and a specific sequence of addition of reagents are found to be beneficial. Additionally it is found that a ratio of phospholipids to apoprotein A-1 of about 100:1 enhances the result.

Abstract: This invention provides isolated nucleic acids encoding mammalian membrane-bound and soluble LOX-1 receptors. The invention also provides methods of identifying agents that inhibit the activity of a mammalian LOX-1 receptor. This invention further provides methods of preventing or treating atherosclerosis, heart disease or stroke in a subject which comprise reducing the activity of membrane-bound LOX-1 receptor.

Abstract: The present invention provides a novel angiogenesis inhibitor, LK68 whose amino acid sequence is identical with the human apolipoprotein (a) kringle domains IV36, IV37 and V38, a cDNA sequence encoding the LK68, a recombinant expression vector comprising the cDNA, a recombinant microorganism transformed with the recombinant expression vector and a novel use of the LK68 as an anticancer agent and a method for treating angiogenesis-mediated disease. LK68, LK6, LK7 and LK8 exhibit inhibitory activities on the cultured endothelial cell proliferation as well as on the endothelial cell migration. LK68 and its single kringles also inhibit the normal development of capillaries in the chick embryo chorioallantoic membrane (CAM). It was also showed that systemic administration of LK68 causes the inhibition of primary tumor growth, which is correlated with a suppression of tumor-induced angiogenesis.

Abstract: Lipid conjugates of a poly-(amino acid), a poly-(amino acid derivative) or a poly-(amino acid analogue), such as poly-[N-(2-hydroxyethyl)-glutamine](PHEG), are provided.

Abstract: The invention relates to the use of a lipopeptide or lipoprotein having the following general structure: 1

Abstract: A high-density lipoprotein-reactive peptide or a foam cell-reactive peptide as set forth in the following (a) or (b): (a) a peptide comprising the amino acid sequence represented by SEQ ID NO: 1; and (b) a peptide comprising an amino acid sequence derived from the amino acid sequence as specified in the above (a) by substitution, deletion, addition, or insertion of one or more amino acid residues and being capable of specifically binding to high-density lipoprotein cholesterol or withdrawing cholesterol from foam cells. Thus, peptides having novel amino acid sequences and being capable of specifically binding to HDL cholesterol or withdrawing cholesterol from foam cells are provided. These peptides are useful as drugs for various diseases caused by arteriosclerosis, lipid metabolic errors, and peripheral cholesterosis.

Abstract: Non-naturally occurring lipoprotein particles, process for preparing such particles and uses thereof.

Abstract: This invention relates to a highly efficient artificial low-density lipoprotein (LDL) carrier system for the targeted delivery therapeutic agents across the blood-brain barrier (BBB). In particular, this invention relates to artificial LDL particles comprised of three lipid elements: phosphatidyl choline, fatty-acyl-cholesterol esters, and at least one apolipoprotein. The present invention further relates to compositions, methods and kits comprising artificial LDL particles for targeting drugs to and across the BBB for the prevention and treatment of brain diseases.

Abstract: The present invention concerns the use of methods and/or compositions related to the synthesis and use of fatty asparagine, cysteine and/or serine derivatives. In particular, the invention concerns methods and compositions for the production of liposomes including fatty asparagine, cysteine and/or serine derivatives.

Abstract: The invention provides human lipid-associated molecules (LIPAM) and polynucleotides which identify and encode LIPAM. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of LIPAM.

Abstract: A process for treatment of a purified lipoprotein material to inactivate prions in a manner that does not substantially adversely affect the biological activity of the lipoprotein is provided that includes treating the lipoprotein prion composition with a solution of base at a pH of between 10 and 13 for a sufficient time to cause inactivation.

Abstract: A method of producing separated lipid-rich lipid/protein complex and native proteins from oil seeds, by adding a substance having the ability to aggregate lipids with proteins to a water extract of oil seeds, sedimenting or floating a lipid/protein complex having a lipid content of 45% or more as an aggregate, and recovering it for separation from native proteins.

Abstract: The present invention relates to the use of novel compositions of lipopeptides that are immunomodulators encapsulated as liposomes or free-form for the treatment of neoplasia and in reducing chemotherapeutically induced cellular pathology, including mucositis. These lipopeptides may be administered alone or in combination with a second antineoplastic agent.

Abstract: The present invention relates to a process for purifying a hydrophobic or amphiphilic compound, by first mixing a starting material containing the hydrophobic or amphiphilic compound with a first polymeric material, water and at least one of a second polymeric material and a surfactant, wherein the first polymeric material and the second polymeric material and/or surfactant are immiscible in the resulting primary aqueous solution. The process further comprises maintaining the primary aqueous solution for a period of time sufficient for essentially separating the phases formed, and then removing the phase containing the main portion of the hydrophobic or amphiphilic compound and the second polymeric material and/or surfactant. The second polymeric material and/or surfactant are separated from the hydrophobic or amphiphilic compound, and subsequently recycled to the initial mixing step.

Abstract: The invention relates to methods of treating lung infections and lung tumors and treating and preventing metastases of extrapulmonary tumors by administering lipopeptides or lipoproteins having the following formula (I): 1

Abstract: The invention provides human lipocalins (LIPOC) and polynucleotides which identify and encode LIPOC. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of LIPOC.

Abstract: A peptide having affinity for oxidised low density lipoprotein, in cyclised or multimeric form is useful in an enzyme immunosolvent assay, to detect oxLDL which is a marker of coronary heart disease.

Abstract: The present invention relates to novel vaccine therapies, and prophylactic treatments of atherosclerotic diseases. Accordingly there is provided, immunogens comprising specific fragments or derivatives of oxidised Apolipoprotein C-III (ApoCIII). The vaccines of the present invention, comprising said immunogens, are potent in the prevention, or reduction, of atherosclerotic plaque formation over prolonged periods of time, thereby reducing the potential of atherosclerosis leading to coronary or cerebrovascular disease. Also provided are methods of treating or preventing atherosclerosis by active vaccination, or passive vaccination through administration to a patient of an antibody that is capable of binding to the specific fragments of ApoCIII. Specific monoclonal antibodies and their use in therapy of atherosclerosis is provided. There is further provided the use of the immunogens of the present invention in medicine, and methods of their production.

Abstract: The invention uses our knowledge of the mechanisms by which antigen is recognized by T cells to identify and prepare MAGE2/3 epitopes, and to develop epitope-based vaccines directed towards MAGE2/3-bearing tumors. More specifically, this application communicates our discovery of pharmaceutical compositions and methods of use it) the prevention and treatment of cancer.

Abstract: Fatty acid derivatives of sulfhydryl-containing compounds (for example, sulfhydryl-containing peptides or proteins) comprising fatty acid-conjugated products with a disulfide linkage are employed for delivery of the compounds to mammalian cells. This modification markedly increases the absorption of the compounds by mammalian cells relative to the rate of absorption of the unconjugated compounds, as well as prolonging blood and tissue retention of the compounds. Moreover, the disulfide linkage in the conjugate is quite labile in the cells and thus facilitates intracellular release of the intact compounds from the fatty acid moieties.

Abstract: The invention provides human lipid-associated molecules (LIPAM) and polynucleotides which identify and encode LIPAM. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of LIPAM.

Abstract: This invention uses our knowledge of the mechanisms by which antigen is recognized by T cells to identify and prepare p53 epitopes, and to develop epitope-based vaccines directed towards p53-bearing tumors. More specifically, this application communicates our discovery of pharmnaceutical compositions and methods of use in the prevention and treatment of cancer.

Abstract: A method for diagnosing early stage renal disease and/or renal complications of a disease in which intact albumin is an indicator of the renal disease and/or complications. The method includes an isolated intact protein, an anti-intact protein antibody thereto, and methods for preparing the same.

Abstract: The present invention relates to human LIPIN3 polynucleotides, which are involved in the control of mammalian body weight. The invention encompasses LIPIN3 polynucleotide sequences, including altered (mutant) LIPIN3 sequences, and fragments thereof, vectors and host cells comprising LIPIN3 polynucleotides, Lipin3 polypeptides, antibodies that specifically bind to Lipin3 polypeptide, arrays comprising LIPIN3 polynucleotides and polypeptides, and purified cells comprising an altered LIPIN3 polynucleotide. The invention also encompasses methods and compositions for the diagnosis and/or treatment of obesity and obesity related diseases, and for the identification of individuals susceptible to such diseases. The invention also encompasses methods of screening for compounds that alter LIPIN3 expression, preferably reducing LIPIN3 expression, and compounds that modulate the activity of the LIPIN3 gene product.

Abstract: The invention relates to a method for screening therapeutic agents, defined as SCAP antagonists, for use in combating diseases associated with elevated lipid levels, said method comprising detecting or assaying the extent or result of transcriptional activity or binding between a control SCAP antagonist and SCAP, in the presence of and absence of said agent. Also claimed are therapeuic agents which are antagonists of SCAP, identified by such a method and their use in combating diseases associated with elevated lipid levels.

Abstract: The present invention provides epitopes present on cancer cells and important in physiological phenomena such as cell rolling, metastasis, and inflammation. Therapeutic and diagnostic methods and compositions using antibodies capable of binding to the epitopes are provided. Methods and compositions according to the present invention can be used in diagnosis of and therapy for such diseases as cancer, including tumor growth and metastasis, leukemia, auto-immune disease, and inflammatory disease.