Abstract: The invention provides a vaccine composition comprising a flavi peptide comprising one or more CD8+ T cell epitopes.

Abstract: The present invention describes the integration of preparative crystallization, crystal separation, crystal washing and freeze-drying processes of insulin and insulin analogues into single continuous process using pressure filtration. The process facilitates time reduction and outlines the novel design of using multiple organic solvent washes and nitrogen gas purging for the removal of imbibed water and achieve final drug substance that meets the quality specifications.

Abstract: A method of producing jellyfish collagen extract by combining hard water, frozen jellyfish, protease enzymes, and sodium bisulfate to form a mixture. Heating the mixture for a period of time to permit the mixture to react. The filter, concentrate, and dry the mixture.

Abstract: The present invention relates to production of Human Insulin methyl ester by enzymatic reaction. The present invention further relates to production and enhancement of purity of Human Insulin Methyl ester.

Abstract: Compositions and methods for modulating injection site pain associated with rapid acting injectable insulin formulations have been developed for subcutaneous injection. The formulations contain insulin in combination with a zinc chelator such as ethylenediaminetetraacetic acid (“EDTA”), a dissolution/stabilization agent such as citric acid, a magnesium salt, and, optionally, additional excipients. New presentations include rapid acting concentrated insulin formulations and a way to enhance the absorption of commercially available rapid acting analog formulations by mixing them with a vial containing dry powder excipients that accelerate their absorption. Devices for mixing excipient and insulin together at the time of administration, while minimizing residence time of the mixture, are also described.

Abstract: A composition comprising chromium and insulin and/or a chromium-insulin complex, its method of preparation, and its use in the prevention and treatment of hypoglycemia and hypoglycemia-related conditions. This composition can be administered in numerous ways, including parenterally, intranasally, and orally. The composition stabilizes serum glucose levels and has a synergistic effect compared to chromium and insulin administered separately.

Abstract: The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the ?-amino group of the N-terminal amino acid residue of the B chain or to the ?-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula: —W—X—Y—Z wherein W, X, Y and Z are as defined in the disclosure.

Abstract: The present invention is method for non-covalently immobilizing an infectious prion protein using a magnetic substrate.

Abstract: Described herein are compounds and methods useful in the detection of, e.g., Zn2+, in vitro and in vivo. The compounds include amino acids and peptides functionalized with a moiety that binds, e.g., Zn2+. The peptides may be further functionalized with a detectable moiety. The peptides may also comprise amino acid sequences known to localize extracellularly or in specific areas within a cell.

Abstract: Conjugates which comprise a drug and a ligand which includes a first saccharide; wherein the conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the conjugate is sensitive to serum concentration of a second saccharide. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: The invention relates to methods of separation and/or purification of impurities yielding a purified heterologous protein product devoid of related impurities or with substantially minimal quantities of such glycosylated impurities. More specifically, the invention relates to the identification of glycosylated forms of insulin analogues such as glargine impurities characterized post expression in yeast based systems such as Pichia pastoris. The invention also relates to methods used to clone gene encoding the protein insulin glargine; inserting the related gene in a suitable yeast host; producing culture of the recombinant strain, stimulating expression of the heterologous polypeptide, its secretion and purification post fermentation and related enzymatic conversions.

Abstract: Nanoparticles having a core and a corona of ligands covalently linked to the core, wherein differing species of peptides are bound to the nanoparticles and incorporated into various dosage forms.

Abstract: New biosynthetic analogues of recombined human insulin of prolonged therapeutical activity, which can find place in prophylactic and treatment of diabetes.

Abstract: The present invention relates to a non-peptidyl polymer-insulin multimer comprising two or more of a non-peptidyl polymer-insulin conjugate prepared by linking a non-peptidyl polymer and insulin via a covalent bond, in which the conjugates are complexed with cobalt ion to form a multimer, a method and kit for the preparation of the multimer, a pharmaceutical composition for the prevention or treatment of diabetes comprising the multimer as an active ingredient, and a method for preventing or treating diabetes by administering the composition to a subject.

Abstract: New biosynthetic analogues of recombined human insulin of prolonged therapeutical activity, which can find place in prophylactic and treatment of diabetes.

Abstract: Nanoparticles having a core and a corona of ligands covalently linked to the core, wherein peptides are bound to or associated with the nanoparticles.

Abstract: The invention relates to a vaccine composition comprising at least one type of anti-HIV vaccine composition containing at least one type of stabilized Tat antigen and to the use thereof for preventing and/or treating a human HIV infection.

Abstract: The present invention aims to provide a tool etc. capable of detecting a methylated region of a DNA in a short time, in a labor-saving manner and without being limited by nucleotide sequences, and further capable of quantifying the methylation. The present invention provides a peptide containing a metal finger motif and a tyrosine derivative in a helix forming part of the motif, which recognizes and binds to a methylated region of a double stranded DNA.

Abstract: Protection of proteins against fibrillation may be afforded by introduction of certain histidine substitutions into the protein, such that a pair of histidines are present with sufficient spacing as to allow the histidines to coordinate with zinc. In the case of insulin, introduction of histidine residue substitutions at residues A4 and A8 together or a histidine residue substitution at residue B1, provides increased resistance to fibrillation while maintaining at least a majority of the activity of the insulin analogue. Introduction of a histidine residue substitution at residue A8 restores at least a portion of fibrillation resistance that may have been harmed by substitutions present on the B-chain such as those present in fast-acting insulins. Proteins protected by such histidine substitutions may be used to provide a pharmaceutical composition. A method of treating a patient includes administering a physiologically effective amount of the pharmaceutical composition to the patient.

Abstract: The present invention provides methods and materials by which glycosylation of glycoproteins can be regulated. Methods include the monitoring and regulation of parameters such that a glycoprotein having a desired product quality is obtained.

Abstract: The present invention relates to pharmaceutical formulations comprising insulin, an insulin analog, an insulin derivative, or a combination of any of the foregoing, and a salt of protamine, to methods of preparing such formulations, and to uses of such formulations in the treatment of diseases and conditions for which use of the insulin peptide(s) contained in such formulations is indicated. The present invention further relates to methods for increasing the stability and/or solubility of insulin in insulin-containing formulations at a pH less than 7.0 by adding a salt of protamine to the insulin-containing formulations.

Abstract: A composition comprising chromium and insulin and/or a chromium-insulin complex, its method of preparation, and its use in the prevention and treatment of hypoglycemia and hypoglycemia-related conditions. This composition can be administered in numerous ways, including parenterally, intranasally, and orally. The composition stabilizes serum glucose levels and has a synergistic effect compared to chromium and insulin administered separately.

Abstract: Nanoparticles having a core and a corona of ligands covalently linked to the core, wherein peptides are bound to or associated with the nanoparticles.

Abstract: A radiolabelled insulin analogue is provided. The analogue comprises a radiolabel linked to an insulin analogue at an amino acid at the terminal end of the B chain of the insulin analogue.

Abstract: The invention claims a process for making an insulin-oligomer conjugate IN-105. IN-105 precursor having formula G-A-V-R-[B-Chain]-R-D-A-D-D-R-[A-Chain] is cloned and expressed in Pichia. The biosynthetic precursor is then conjugated with an activated oligomer. The IN-105 precursor-oligomer conjugate is then treated with protease and purified to afford active insulin-oligomer conjugate of formula insulin-OC—CH2—CH2—(OCH2CH2)3—OCH3.

Abstract: The presently disclosed subject matter provides compositions comprising a first substrate-binding domain (a peptide or a polymer) having binding affinity for a tissue or a medical device, a second substrate-binding domain having binding affinity for a target molecule, and the target molecule. In some embodiments, the first and second substrate-binding domains are covalently linked. The first and second substrate-binding domains are covalently coupled to at least one hydrophobic interaction tag, negatively charged interaction tag, or positively charged interaction tag. When the substrate-binding domains are combined and coated onto the tissue or medical device, the hydrophobic interaction tags interact with each other and the charged interaction tags interact with the oppositely charged interaction tags or the oppositely charged substrate binding polymers, to form a macromolecular network of non-covalently coupled substrate-binding domains to load the target molecule onto the tissue or medical device.

Abstract: An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y—PAG-Z—R2??(Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—.

Abstract: An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y-PAG-Z—R2 ??(Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—.

Abstract: The invention provides a pharmaceutical formulation and a method for preparing the formulation.

Abstract: The invention provides a complex including a cation and an insulin compound conjugate. The insulin compound conjugate includes insulin compound, such as human insulin or an analog thereof, conjugated to a modifying moiety, such as a polyethylene glycol moiety. The invention also includes solids and pharmaceutical compositions including such complexes, methods of making such complexes, and methods of using such complexes in the treatment of insulin compound deficiencies and other ailments. Further, the invention includes novel insulin compound conjugates and modifying moieties for use in making novel insulin compound conjugates. The invention also includes fatty acid compositions for administration of pharmaceutical agents, such as the novel insulin compound conjugates, and/or the cation-insulin compound conjugate complexes of the invention.

Abstract: The invention features methods of enhancing whole body insulin sensitivity by modulating the endoplasmic reticulum (ER) stress response pathway in adipose cells. In one aspect, the methods involve targeting chaperone proteins important in the ER stress response pathway, for example, BiP and ERO-1. Another aspect features targeting the upstream transcription factors (e.g., CHOP-1 and XBP-1) of the genes encoding the chaperone proteins (and/or other ER proteins). Screening assays for identification of modulators of these ER proteins and/or transcription factors are also featured.

Abstract: The present invention relates to a method for preparing an injectable composition of microparticles for the sustained release of a biologically active agent. The microparticles include a biocompatible polymer and a biologically active agent. The invention provides an improved process for the preparation of microparticles, wherein the physical characteristics of the microparticles, for example, the morphology, density and size, are independent of the process used to prepare the initially formed polymer/drug matrix. The method includes the steps of (a) providing a polymer/biologically active agent matrix; (b) compressing the polymer/biologically active agent matrix, thereby forming a compressed matrix; and (c) fragmenting the compressed matrix, thereby forming an injectable microparticle composition. The polymer/drug matrix can be provided by any suitable method.

Abstract: The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the ?-amino group of the N-terminal amino acid residue of the B chain or to the ?-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula: —W—X—Y—Z wherein W, X, Y and Z are as defined in the disclosure.

Abstract: The present invention is related to insulin derivatives having a side chain attached to an ?-amino group of a Lys residue present in the A-chain or to an ?-amino group of a Lys residue in the B-chain.

Abstract: The protein encapsulation via entrapping protein in CaCO3 microparticles followed by polymeric shell deposition can be used for vaccination based on protein antigen, and in particular rPA 102.

Abstract: A pharmaceutical composition includes at least two of agents I)-iii), wherein agent i) is selected from the group consisting of an insulin, an insulin analog, a physiologically active fragment of said insulin and a physiologically active fragment of said insulin analog, agent ii) is selected from the group consisting of an insulin-related peptide, an insulin-related peptide analog, a physiologically active insulin-related peptide fragment and a physiologically active insulin-related peptide analog fragment, and agent iii) is an insulin sensitizer.

Abstract: Drug formulations for systemic drug delivery with improved stability and rapid onset of action are described herein. The formulations may be administered via buccal administration, sublingual administration, pulmonary delivery, nasal administration, subcutaneous administration, rectal administration, vaginal administration, or ocular administration. In the preferred embodiments, the formulations are administered sublingually or via subcutaneous injection. The formulations contain an active agent and one or more excipients, selected to increase the rate of dissolution. In the preferred embodiment, the drug is insulin, and the excipients include a metal chelator such as EDTA and an acid such as citric acid. Following administration, these formulations are rapidly absorbed by the oral mucosa when administered sublingually and are rapidly absorbed into the blood stream when administered by subcutaneous injection. In one embodiment, the composition is in the form of a dry powder.

Abstract: The present invention relates to an antibody or antibody fragment that binds to 1,4,7,10-tetrazacyclododecane-N,N?,N?,N??-tetraacetic acid (DOTA),which is bound to an alkyl-amino group through one of its pendant carb.oxyl groups.

Abstract: The present invention provides sustained release compositions that can be manufactured easily while providing long duration of the pharmaceutically useful protein being delivered. The compositions comprise insoluble complexes of the pharmaceutically useful protein and a precipitating agent at an appropriate ratio to achieve a desired sustained release profile. The precipitating agent can be selected from a group of various agents including divalent metal cations, Hofmeister series salts and pH adjusters. Particularly provided are compositions comprising insulin that are suitable for pulmonary delivery.

Abstract: Novel bipyridyl-osmium complex conjugates and their use in electrochemical assays are described. The redox reversible-osmium complexes can be prepared to exhibit unique reversible redox potentials and can thus be used in combination with other electroactive redox reversible species having redox potentials differing by at least 50 millivolts in electrochemical assays designed for use of multiple electroactive species in the same cell and in the same sample without interference between the two or more redox coupled conjugate systems.

Abstract: The invention relates to a formulation comprising a polypeptide selected from at least one of insulin, an insulin metabolite, an insulin analog, and an insulin derivative; at least one surfactant; optionally at least one preservative; and optionally at least one of an isotonicizing agent, a buffer or an excipient, wherein the formulation is free from or low in zinc. The invention also relates to the production of such insulin preparations and their use as pharmaceutical formulations.

Abstract: A method for treating rosacea of the skin of a patient employs topically applying to the affected skin a composition comprising at least one peptide copper complex. In other embodiments, the present invention is directed to such a method where the composition used therefor further comprises certain disclosed active agents, including active drug and active cosmetic substances. In a related aspect, further embodiments of the present invention are directed to compositions comprising at least one peptide copper complex and certain active drug and active cosmetic substances that render the compositions particularly effective in treating rosacea.

Abstract: A method for treating psoriasis of the skin of a patient employs topically applying to the affected skin a composition comprising at least one peptide copper complex. In other embodiments, the present invention is directed to such a method where the composition used therefor further comprises certain disclosed active agents, including active drug and active cosmetic substances. In a related aspect, further embodiments of the present invention are directed to compositions comprising at least one peptide copper complex and certain active drug and active cosmetic substances that render the compositions particularly effective in treating psoriasis.

Abstract: Provided herein is a heretofore unknown insulin analogue, a pharmaceutical composition comprising such an insulin analogue, as well as processes for preparing such an insulin analogue and such a pharmaceutical composition.

Abstract: The present invention provides a monomeric insulin analog formulation stabilized against aggregation in which the buffering agent is either TRIS or arginine. The stable formulations of the present invention are useful for treating diabetes, and are particularly advantageous in treatment regimes requiring lengthy chemical and physical stability, such as, in continuous infusion systems.

Abstract: The present invention relates to protracted human insulin derivatives in which the A21 and the B3 amino acid residues are, independently, any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys; PheB1 may be deleted; the B30 amino acid residue is (a) a non-codable, lipophilic amino acid having from 10 to 24 carbon atoms, in which case an acyl group of a carboxylic acid with up to 5 carbon atoms is bound to the ?-amino group of LysB29; or (b) the B30 amino acid residue is deleted or is any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys, in any of which cases the ?-amino group of LysB29 has a lipophilic substituent; and any Zn2+ complexes thereof with the proviso that when B30 is Thr or Ala and A21 and B3 are both Asn, and PheB1 is present, then the insulin derivative is always present as a Zn2+ complex.

Abstract: The present invention is directed to stabilized insulin composition comprising a mixture of insulin species such as insulin and an insulin analog. As disclosed herein, insulin compositions comprising a mixture of insulin and insulin analog species form heterodimeric complexes having a greater stability than the homodimeric complexes formed in compositions comprising single insulin species. Consequently, the present invention provides methods for stabilizing insulin molecules, methods for identifying stable heterodimeric insulin complexes and stabilized insulin compositions.

Abstract: Monomeric analogues of human insulin have a single substitution of the amino acid in 12th, 16th or the 26th position of the B chain of human insulin and may also have a terminal deletion in the B chain.

Abstract: Provided is a compressed anti-solvent technique for manufacture of insulin-containing powders for pulmonary delivery. The insulin is processed in a cosolvent system including two or more mutually soluble organic solvents. Also provided are powders manufacturable by the manufacture method, including powders of substantially pure insulin and powders including a biocompatible polymer for pulmonary sustained insulin release applications. Also provided are packaged products including insulin-containing powder in a container that is receivable by and operable with a dry powder inhaler to produce an aerosol including dispersed insulin-containing particles when the inhaler is actuated.

Abstract: The present invention is a pharmaceutical composition for polypeptide which are not stably soluble. A preferred polypeptide is monomeric insulin and a preferred formulation consists of a TRIS-phosphate combination buffer, zinc; a phenolic preservative and an isotonicity agent such as glycerol.