Abstract: Improved compounds have been developed which are structured to be sequestered with very high specificity in acidic areas of tissues. When the compounds contain a radioisotope effective to report the presence of the compound the compounds are for detecting tumors containing hypoxic/acidic areas. When the compounds contain radioisotopes effective to kill cells the compounds are for treating tumors containing hypoxic/acidic areas. Methods for detecting and treating tumors with such compounds are also disclosed.

Abstract: This invention relates to novel compounds suitable for labeling by positron emitting isotopes, such as 18F, 11C, 13N and 15O, through appropriate labeling reagents, such as 18F reagents and methods of preparing such a compound, compositions comprising such compounds, kits comprising such compounds or compositions and uses of such compounds, compositions or kits for diagnostic imaging by positron emission tomography (PET).

Abstract: The amino acid sequence of the heavy chain polypeptide and the light chain polypeptide of the STRO-1 antibody is disclosed. Also disclosed are methods for detecting and isolating cells expressing the STRO-1 cell surface protein.

Abstract: A method for identifying a molecule that binds an irradiated tumor in a subject and molecules identified thereby. In some embodiments, the method includes the steps of (a) exposing a tumor to ionizing radiation; (b) administering to a subject a library of diverse molecules; and (c) isolating from the tumor one or more molecules of the library of diverse molecules, whereby a molecule that binds an irradiated tumor is identified. Also provided are targeting ligands that bind an irradiated tumor and therapeutic and diagnostic methods that employ the disclosed targeting ligands.

Abstract: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.

Abstract: Methods and compositions are described for targeting therapeutic and diagnostic molecules to particular types of cells using targeting antibodies or other targeting moeities.

Abstract: The invention provides compositions and methods for delivering a therapeutic or diagnostic agent to a disease site in a mammal, the method comprising administering to the mammal a therapeutically or diagnostically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises the therapeutic or diagnostic agent coupled to an albumin binding peptide and a pharmaceutically acceptable carrier.

Abstract: New and improved compounds for use in diagnostic imaging or therapy having the formula M-N—O—P-G, wherein M is a metal chelator having the structure: wherein R1-R5 and FG are as defined herein (in the form complexed with a metal radionuclide or not), N—O—P is the linker containing at least one non-alpha amino acid with a cyclic group, at least one substituted bile acid or at least one non-alpha amino acid, and G is the GRP receptor targeting peptide. In the preferred embodiment, M is an Aazta metal chelator or a derivative thereof. Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided.

Abstract: The present invention relates to a method for complexation of a chelate with a radionuclide, advantageously gallium, the complexation being carried out advantageously at ambient temperature without heating, by adding the radionuclide to the chelate in a buffer solution, the buffer of this solution comprising between two and five functions for coordination with the radionuclide, each coordination function being independently chosen from a carboxylic acid function and a hydroxyl function, on the condition that the buffer comprises at least one carboxylic acid function and at most two carboxylic acid functions. It also relates to the injectable solution obtained.

Abstract: Disclosed are processes for preparing glycopeptide phosphonate derivatives having an amino-containing side chain. Several of the process steps are conducted in a single reaction vessel without isolation of intermediate reaction products, thereby generating less waste and improving the overall efficiency and yield of the process.

Abstract: This invention provides a polyvalent vaccine comprising at least two conjugated antigens selected from a group containing glycolipid antigen, polysaccharide antigen, mucin antigen, glycosylated mucin antigen and an appropriate adjuvant. This invention also provides a multivalent vaccine comprising at least two of the following: glycosylated MUC-1-32mer, Globo H, GM2, Ley, Tn(c), sTN(c), and TF(c). This invention provides the vaccine above, wherein the adjuvant is saponin-based adjuvant. This invention provides a method for inducing immune response in a subject comprising administering an effective amount of the vaccine above to the subject. Finally, this invention provides a method for treating cancer in a subject comprising administering an appropriate amount of the vaccine above to the subject.

Abstract: The present invention concerns compositions comprising and methods of identification and use of targeting peptides selective for cancer tissue, particularly prostate or ovarian cancer tissue. The method may comprise identifying endogenous mimeotopes of such peptides, such as GRP78, IL-11R? and hsp90. Antibodies against such targeting peptides or their mimeotopes may be used for detection, diagnosis and/or staging of prostate or ovarian cancer. In other embodiments, the compositions and methods concern a novel type of gene therapy vector, known as adeno-associated phage (AAP). AAP are of use for targeted delivery of therapeutic agents to particular tissues, organs or cell types, such as prostate or ovarian cancer. In still other embodiments, targeting peptides selective for low-grade lipomas may be used for detection, diagnosis and targeted delivery of therapeutic agents.

Abstract: A process for producing a sustained-release composition which comprises mixing an aqueous solution containing a physiologically active substance and an acid or base in a molar amount of 1.5 or more times that of the physiologically active substance with a solution of a biodegradable polymer and then drying the mixture is provided.

Abstract: Disclosed is a method of diagnosing and treating myeloproliferative or lymphoproliferative cell disorders, such as cancer, with chlorotoxin and/or derivatives, analogs or fragments thereof, which are effective to bind to an inhibit abnormal myeloid or lymphoid cell growth.

Abstract: A polypeptide or multimeric polypeptide construct having the ability to bind to cMet or a complex comprising cMet and HGF, and methods for use are disclosed.

Abstract: The present invention provides compositions and methods for treating disorders associated with epithelial tissues.

Abstract: The present invention relates to methods for the treatment, the prognostic assessment and the detection of breast cancer.

Abstract: The present invention relates to complexes comprising one or more markers and one or more biomolecules for use as a contrast agent in positron emission tomography based imaging. The complexes according to the present invention preferably accumulate in a target compartment, such as the kidney. The present invention further relates to methods for generating the complexes and methods for using the complexes such as for evaluation of different aspects of kidney functionality e.g. for calculation of total and/or regional glomerular filtration rate in the kidney without the need for sampling blood or urine.

Abstract: Tracers are disclosed comprising an amphiphilic comb-like nanostructure conjugated with an oligopeptide such as a fragment of a natriuretic peptide, and a signaling moiety such as a positron-emitting radionuclide. A fragment of a natriuretic peptide comprises Arg-Ile-Asp-Arg-Ile (SEQ ID NO:1). Further disclosed are methods of imaging distribution of C-type atrial natriuretic peptide receptors and methods of imaging angiogenesis and atherosclerosis by PET scanning or MRI using a tracer.

Abstract: Methods are disclosed for using agents and treatments that cause the release of melanin from melanin-containing melanomas to increase the efficacy of therapy and imaging of the melanomas with radiolabeled anti-melanin antibodies and peptides.

Abstract: Provided herein are methods for introducing fluorine atom onto a biomolecule comprising: (i) providing a linker comprising a thiol-reactive terminus and an azido/alkyne-reactive terminus; (ii) reacting the thiol-reactive terminus of the linker with a biomolecule comprising at least one thiol group or a reactive derivative thereof; and (iii) subsequently reacting the azido/alkyne-reactive terminus of the linker with a fluorine-substituted azide or alkyne respectively. Also provided are compositions and method of synthesis of bifunctional linkers and bioconjugates as well as radio-diagnostic agents comprising fluorine-labeled biomolecules.

Abstract: The present invention concerns compositions comprising and methods of identification and use of targeting peptides for placenta or adipose tissue. In certain embodiments, the targeting peptides comprise part or all of SEQ ID NO:5-11, SEQ ID NO:13-22 or SEQ ID NO:144. The peptides may be attached to various therapeutic agents for targeted delivery. Adipose-targeting peptides may be used in methods for weight control, inducing weight loss and treating lipodystrophy syndrome. Adipose-targeting may also be accomplished using other binding moieties selectively targeted to adipose receptors, such as a prohibitin receptor protein complex. Placenta-targeting peptides may be used to interfere with pregnancy, induce labor and/or for targeted delivery of therapeutic agents to placenta and/or fetus. In other embodiments, receptors identified by binding to placenta-targeting peptides may be used to screen compounds for potential teratogenicity.

Abstract: The present invention relates to compounds that are useful as metal ligands and which either contain a molecular recognition moiety or can be bound to a molecular recognition moiety and methods of making these compounds. Once the compounds that contain a molecular recognition moiety are coordinated with a suitable metallic radionuclide, the coordinated compounds are useful as radiopharmaceuticals in the areas of radiotherapy and diagnostic imaging. The invention therefore also relates to methods of diagnosis and therapy utilising the radiolabelled compounds of the invention.

Abstract: This invention provides novel compositions and methods for the specific and/or preferential delivery of an effector (e.g. a drug or label) to an epithelial cell (e.g. a pulmonary epithelium). The compositions comprise an adipocyte differentiation-related protein (ADRP) attached to an effector thereby forming a chimeric moiety. The chimeric moiety is preferentially delivered to epithelial cells.

Abstract: The present invention is about bifunctional chelating agents (BCA) conjugated mannosyl human serum albumin (MSA) and its radioisotope labeled compounds for imaging immune system such as macrophages, Kupffer cells, reticuloendothelial system (RES), and lymphatic system. The present invention comprises BCA-MSA conjugates, their radiolabeled compounds, and kits for radiolabeing. The present invention improved radiolabeling procedure, showed higher lymphatic system uptake, and enabled image by positron emission tomography (PET).

Abstract: A new and improved method for extending the half life of pharmaceutical compounds for use in diagnostic imaging or therapy uses a novel linker to attach a diagnostic or therapeutic moiety to a targeting peptide or another diagnostic or therapeutic moiety. The resulting compound may have the general formula M-N—O—P-Q, wherein M is the diagnostic or therapeutic moiety, N—O—P is the linker of the present invention, and Q is the targeting peptide. In another embodiment the compounds may have the formula M-N—O—P-M, wherein M is independently a diagnostic or therapeutic moiety and N—O—P is the linker of the invention. Methods for imaging or treating a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound are further provided. Methods for radiotherapy of a patient using the compounds are further provided, as are methods for preparing a radiotherapeutic agent from the compounds.

Abstract: The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use, for example, in PET imaging techniques. The labeled molecules may be peptides or proteins, although other types of molecules may be labeled by the described methods. Preferably, the F-18 may be conjugated to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety. Alternatively, the metal may first be conjugated to the chelating group and subsequently the F-18 bound to the metal. In other embodiments, the F-18 labeled moiety may comprise a targetable construct used in combination with a bispecific or multispecific antibody to target F-18 to a disease-associated antigen, such as a tumor-associated antigen. The F-18 labeled targetable construct peptides are stable in serum at 37° C. for a sufficient time to perform PET imaging analysis.

Abstract: A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8.

Abstract: The present invention describes linking a therapeutic agent to a compound which is known to be naturally concentrated in a tissue affected by, or that is causing, a disease, to create a prodrug for treatment of the disease. Embodiments of the present invention include a new class of carotenoid-linked drugs to treat such blinding retinal disease such as age-related macular degeneration, retinoblastoma, and diabetic macular edema. For example, the present invention comprises a method for the treatment of a disorder of the eye comprising linking a therapeutic agent to a xanthophyll carotenoid to create a prodrug, and administering a therapeutically effective amount of the prodrug to an individual in need of treatment. Provided are prodrugs for treatment of retinoblastoma, cystoid macular edema (CME), exudative age-related macular degeneration (AMD), diabetic retinopathy, diabetic macular edema, or inflammatory disorders.

Abstract: A method of diagnosing and treating a human glioblastoma multiforme (GBM) brain tumor in a subject is disclosed. The method includes administering to the subject, an effective amount of composition having a peptide 12-20 amino acid residues in length and selected for its ability to bind preferentially to a subtype of human GBM cells identified as brain tumor initiating cells (BTICs) or highly invasive glioma cells (HIGCs).

Abstract: The invention relates to the fields of materials sciences and medicine and relates to an agent, which can be used, for example, as a contrast medium for the localization of cancer cells. The object of the present invention is to disclose an agent which sensitively and selectively recognizes the site and the type of the molecules or cells to be examined. The object is attained through an agent composed at least of bio-shuttle molecules to which endohedral fullerenes are coupled by way of peptide-based molecules, wherein the endohedral fullerenes are hydrophobic and correspond to the formula A3-xMxZ@C2n in which x=0 to 3 and n?34, A means rare earths and/or transuranic elements, M means metals, Z means non-metals and C means carbon. The object is further attained through a method in which hydrophobic endohedral fullerenes are coupled with bio-shuttle molecules by way of an irreversible Diels-Alder reaction with an inverse electron demand (DARinv).

Abstract: The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.

Abstract: The present invention provides a protein-silane and/or protein-siloxane copolymer obtainable by reacting a protein and a silane compound, the relative amounts of the protein and the silane compound being such that in the range of from 0.1 to 0.4 silane molecule is present for each reactive amino group of the protein. The copolymer is suitable for use in hair treatment compositions and is useful in reducing damage to hair caused by flexure and/or abrasion thereof.

Abstract: The invention discloses a pharmaceutical composition of bioactive nanoparticles composed of chitosan, poly-glutamic acid, and a bioactive agent for oral delivery. The chitosan-based nanoparticles are characterized with a positive surface charge and enhanced permeability for oral drug delivery.

Abstract: In one aspect, the invention provides covalent conjugates between artemisinin-related endoperoxides and iron-carrying proteins. In some embodiments, the covalent conjugates comprise artelinate and holotransferrin. In another aspect, the invention provides methods for administering the covalent conjugates of the invention to treat cancer and infections by pathogens that bind iron-carrying proteins.

Abstract: The present invention relates to novel muteins derived from human lipocalin 2 (hNGAL) and related proteins that bind a given non-natural ligand with detectable affinity. The invention also relates to corresponding nucleic acid molecules encoding such a mutein and to a method for their generation. The invention further relates a method for producing such a mutein. Furthermore, the invention is directed to a pharmaceutical composition comprising such a lipocalin mutein as well as to various uses of the mutein.

Abstract: A polypeptide or multimeric polypeptide construct having the ability to bind to cMet or a complex comprising cMet and HGF, and methods for use are disclosed.

Abstract: A method for purifying a polypeptide by ion exchange chromatography is described in which a gradient wash is used to resolve a polypeptide of interest from one or more contaminants.

Abstract: The present application is directed to radiolabeled cyclic polyazapeptides, pharmaceutical compositions comprising radiolabeled cyclic polyazapeptides, and methods of using the radiolabeled cyclic polyazapeptides. Such polyazapeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

Abstract: Compositions and methods for treating a patient with insulin that combines insulin, a permeation enhancer, and a carrier that maintains an acidic pH, are disclosed.

Abstract: The present application is directed to radiolabeled cyclic polyazapeptides, pharmaceutical compositions comprising radiolabeled cyclic polyazapeptides, and methods of using the radiolabeled cyclic polyazapeptides. Such polyazapeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

Abstract: The invention discloses a pharmaceutical composition of bioactive nanoparticles composed of chitosan, poly-glutamic acid, and a bioactive agent for oral delivery. The chitosan-based nanoparticles are characterized with a positive surface charge and enhanced permeability for oral drug delivery.

Abstract: Unregulated angiogenesis is associated with a variety of pathological conditions. Tumor growth and metastasis is dependent on the development of new blood vessels. The development of new blood vessels in the eye, or ocular neovascularization, has been implicated in a variety of serious ocular diseases. For instance, choroidal neovascularization is linked to age-related macular degeneration, while retinal neovascularization is linked to diabetic retinopathy. The present invention is based on the discovery of a peptide sequence, C16Y, which inhibits ocular neovascularization and tumor growth in vivo. C16Y is a scrambled version of the C16 peptide sequence from the y1 chain of laminin-1. Unlike C16, which is an angiogenic stimulator, C16Y has been shown to inhibit angiogenesis. The present invention discloses methods of treating ocular neovascularization and cancer using both full-length and truncated versions of the C16Y.

Abstract: Methods and compositions for treating sepsis using cell membrane-permeant peptide conjugate covalent compounds having target cell specificity are provided.

Abstract: Methods of modulating interfacial characteristics in a self-assembled, force-transmitting peptide network at a fluid-fluid interface are disclosed. The methods involve exposing a peptide capable of participating in a self-assembled, force-transmitting peptide network, either before or after it interacts with other peptides to form the peptide network to a stimulus that alters the chemical and/or physical properties of the peptide. Use of such methods in applications such as emulsions and foams are also disclosed.

Abstract: A radiolabeled annexin comprising at least 2 up to 20 histidine residues at its N-terminus is disclosed. At least two of said histidine residues are adjacent or separated by no more than one other amino acid. The radiolabeled annexin is a stable complex with a radionuclide such as technetium 99m. The radiolabeled annexin can be used in a method of imaging cell death in a nucleated cell within a region of a mammalian subject in vivo.

Abstract: Methods and compositions for diagnosing, staging disease, monitoring therapeutic effect of drugs and imaging a patient are provided, including radiopharmaceutical formulations. Compositions comprising Ga-AMBA complexed with a radioactive isotope are provided; as are methods of imaging Gastrin Releasing Peptide receptor (GRP-R) bearing tissue and methods of diagnosing or staging disease in patients suspected of having disease associated with aberrant GRP-R function. Further, methods of monitoring therapeutic effect of a drug targeted to a receptor that crosstalks with GRP-R are provided; as are methods of pre-dosing/co-dosing non-target tissues containing GRP-R.

Abstract: The present invention describes the use of angiotensin-(1-7) peptide as an anti-cancer therapeutic. Thus, in one embodiment, the present invention comprises a composition to inhibit the growth of cancer cells in an individual comprising a pharmaceutically effective amount of an agonist for the angiotensin-(1-7) receptor to inhibit cancer cell growth or proliferation. Application of a pharmaceutically effective amount of angiotensin-(1-7) or angiotensin-(1-7) receptor agonist is associated with an increase in the expression of genes involved in tumor suppression, apoptosis, and/or cell cycle inhibition, and a decrease the expression of known oncogenes, protein kinases, and/or cell cycle progression genes. Cancers treated using the methods and compositions described herein include cancers having an angiotensin-(1-7) receptor, including, but not limited to, breast and lung cancer.

Abstract: Provided are therapeutic and diagnostic somatostatin analogs including radiotherapeutic and radiodiagnostic reagents, and methods of making and use thereof.

Abstract: The present invention concerns combination of an amount of a GPR119 agonist with an amount of a dipeptidyl peptidase IV (DPP-IV) inhibitor such that the combination provides an effect in lowering a blood glucose level or in increasing a blood GLP-1 level in a subject over that provided by the amount of the GPR119 agonist or the amount of the DPP-IV inhibitor alone and the use of such a combination for treating or preventing diabetes and conditions related thereto or conditions ameliorated by increasing a blood GLP-1 level. The present invention also relates to the use of a G protein-coupled receptor to screen for GLP-1 secretagogues.