Abstract: A novel etiological hypothesis for Multiple Sclerosis (MS) is proposed describing autoimmune attack of ATP: Cob(I)alamin adenosyltransferase (ATR) thereby inhibiting synthesis of (5?-deoxy-5?-adenosyl)cobamide (referred to as 5?-deoxyadenosylcobalmin or AdoCbl) from Vitamin B 12 providing a basis for therapeutic design and diagnostic methods. Pharmaceutical compositions for therapy of MS, inflammatory neurological diseases and neurodegenerative diseases utilizing AdoCbl, growth hormones, immunomodulators, interleukins, other therapeutic agents, and physiotherapy are also described.

Abstract: Formulations and methods are provided for improving the stability upon exposure to aqueous media of polypeptides present in non-aqueous suspension vehicles. In particular aspects of the invention, formulations are provided that comprise a complex of a metal ion and a polypeptide suspended in a non-aqueous, biocompatible suspension vehicle. Aggregation of individual polypeptide molecules is reduced when aqueous media is introduced to such formulations, serving to stabilize the polypeptide.

Abstract: This invention relates to methods for the stabilization, storage and delivery of biologically active macromolecules, such as proteins, peptides and nucleic acids. In particular, this invention relates to protein crystals, formulations and compositions comprising them. Provided are methods and compositions for encapsulating proteins, glycoproteins, enzymes, antibodies, hormones and peptide crystals or crystal formulations into compositions for biological delivery.

Abstract: Absorption of a therapeutic agent across a mucosal membrane or the skin can be enhanced using an absorption enhancer comprising a hydroxy fatty acid ester of polyethylene glycol.

Abstract: The present invention relates to novel polypeptides, methods for their synthesis, pharmaceutical compositions comprising the novel polypeptides as well as their use in medicaments for therapeutic applications.

Abstract: The present invention relates to a thermosensitive phosphazene-based polymer having a degradation controllable ionic group, a use thereof, and a use thereof as a material for delivering bioactive substances. The phosphazene-based polymer according to the present invention has the thermosensitivity of showing the temperature-dependent sol-gel phase transition. Thus, it forms a gel phase at the body temperature when it is injected into the body to make it easy to control the release of bioactive substances such as drugs, and has the functional groups capable of making chemical bonds such as ionic bond, covalent bond, coordinate bond, etc. with drugs and thus is excellent in bearing the drugs. Since it can control the degradation rate depending on the kind of ionic group, it can selectively control the release time depending on the characteristics of drugs. Furthermore, it has an excellent biocompatibility and thus is very useful as a material for delivery of bioactive substances such as drugs, etc.

Abstract: The invention provides compositions for oral delivery and methods of treatment using VSP carriers, such as Giardia sp. variable surface proteins (VSP), to deliver therapeutic agents. VSP drug carriers can be combined with bioactive peptides, e.g., insulin, glucagon, or hGH, and be administered orally or mucosally. VSP carriers are resistant to acidic pHs and to proteolytic degradation and protect therapeutic agents from degradation in the gastrointestinal tract.

Abstract: An ocular drug delivery system can include a composition in which a formulation including recombinant human growth hormone (rHGH) is contained in a polymer matrix. The composition is configured for placement in or on the eye of a subject, and provides controlled release of an amount of the rHGH to the eye effective to promote healing of a conjunctival, sclera and or corneal wound.

Abstract: Use of particular substituted heterocycle fused gamma-carboline compounds as pharmaceuticals and pharmaceutical compositions comprising them for the treatment of one or more disorders involving the 5-HT2A, SERT and/or dopamine D2 pathways are disclosed. In addition, the compounds may be combined with other therapeutic agents for the treatment of one or more sleep disorders, depression, psychosis, dyskinesias, and/or Parkinson's disease or any combinations.

Abstract: The present invention relates generally to a novel method of introducing property modifying groups to a protein. In particular, the present invention relates to the derivatization of lysine residues, as well as new conjugates of growth hormones with improved pharmacological properties, and methods for their preparation and use in therapy.

Abstract: Compositions for nasal administration, which comprise a pharmaceutical, a physiologically active peptide, or a peptide-related compound, and as the carrier thereof, crystalline cellulose with a specific particle diameter and/or partially pregelatinized starch are provided. Such compositions improve the in vivo absorption efficiency of pharmaceuticals.

Abstract: The present invention relates to a macromolecule for delivering protein, polypeptide or peptide drugs and to a production method for the same, as well as to a slow release composition for protein, polypeptide or peptide drugs comprising the same, and more specifically relates to a polylactic acid derivative compound of Chemical formula 1 of which the numerical average molecular weight is no more than 7000 daltons and to a production method for the same, as well as to a slow release composition for protein, polypeptide or peptide drugs using the same and to a production method for the same.

Abstract: The present disclosure provides a biodegradable drug delivery composition including a vehicle and an insoluble component comprising beneficial agent dispersed in the vehicle. Typically, the composition is not an emulsion, but has a low viscosity and further provides for minimized initial burst and sustained release of the beneficial agent over time. Also provided, are kits including the biodegradable drug delivery composition or components thereof, as well as methods of making and using the biodegradable drug delivery composition.

Abstract: Compositions and methods for identifying patients at increased risk for PIGFD and ISS are disclosed.

Abstract: A method for reducing or substantially preventing formation of a trisulfide derivative of a polypeptide in a liquid medium containing the polypeptide ijn question comprises stripping the liquid medium with a gas, suitably a chemically unreactive gas such as nitrogen or argon.

Abstract: A sustained-release drug composition consisting essentially of microparticles of hyaluronic acid having a high molecular weight or an inorganic salt thereof and a protein or peptide drug encased in said microparticles, wherein the average size of said microparticles ranges from 0.1 to 40 ?m.

Abstract: The present invention relates to novel methods of making soluble proteins having free cysteines in which a host cell is exposed to a cysteine blocking agent. The soluble proteins produced by the methods can then be modified to increase their effectiveness. Such modifications include attaching a PEG moiety to form pegylated proteins.

Abstract: Disclosed herein is preferably a multi-dose type non-aqueous oily injectable formulation including; an active ingredient (drug) expressing therapeutic effects, which is dissolved, dispersed or suspended in a therapeutically effective amount, in oil. The disclosed non-aqueous oily injectable formulation may include; an oil-affinitive preservative, and a hydrophilic excipient non-phase separable from the oil-affinitive preservative when the excipient is mixed with the oil-affinitive preservative.

Abstract: The present invention relates to novel porous matrix composites and formulations for controlled protein delivery and the uses therefor. The present invention also provides methods of synthesizing such protein delivery systems. The composites comprise affinity sites embedded in the matrix where the affinity sites are functionalized with nucleic acid aptamers having high affinity for proteins to be released. The aptamers function as binding affinity sites for the proteins to be released. In certain embodiments, release rates are controlled by tuning the binding affinity of the nucleic acid aptamers to the proteins at a desired level. In yet other embodiments, complementary oligonucleotides that hybridize with the aptamers are employed to trigger accelerated release of the proteins when desired. Various in situ injectable hydro gels functionalized with aptamers are provided for treating a condition and disease in a subject in need of a therapeutic protein.

Abstract: A polypeptide and polynucleotides comprising at least two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a non-human peptide-of-interest are disclosed. Pharmaceutical compositions comprising the non-human polypeptides and polynucleotides of the invention and methods of using both human and non-human polypeptides and polynucleotides are also disclosed.

Abstract: A composition for oral delivery of a poorly absorbed drug is disclosed. The composition includes the drug, an enhancer for increasing absorption of the drug through the intestinal mucosa, a promoter, which further increases the absorption of the drug in the presence of the enhancer, and optionally a protector for protecting the drug from physical or chemical decomposition or inactivation in the gastrointestinal tract. Illustrative enhancers include sucrose fatty acid esters, and illustrative promoters include aminosugars and amino acid derivatives, such as poly(amino acids). Illustrative protectors include methylcellulose, poly(vinyl alcohol), and poly(vinyl pyrrolidone).

Abstract: Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Many embodiments provide a swallowable device for delivering the agents. Particular embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. Embodiments also provide various drug preparations that are configured to be contained within the capsule, advanced from the capsule into the intestinal wall and degrade to release the drug into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the intestinal wall. Embodiments of the invention are particularly useful for the delivery of drugs which are poorly absorbed, tolerated and/or degraded within the GI tract.

Abstract: A stable pharmaceutically acceptable aqueous formulation containing human growth hormone, a buffer, a non-ionic surfactant, and, optionally, a neutral salt, mannitol, or, a preservative, is disclosed. Also disclosed are associated means and methods for preparing, storing, and using such formulations.

Abstract: We disclose growth hormone [GH] fusion proteins that have increased in vivo stability and activity; nucleic acid molecules encoding said proteins and methods of treatment of growth hormone deficiency that use said fusion proteins. The GH fusion proteins comprise human GH covalently linked to the extracellular domain of Growth Hormone Receptor [GHR] either as a direct in-frame translational fusion or via a flexible peptide linker. The GH/GHR fusion proteins have exceptional pharmacokinetics and are potent growth hormone receptor agonists. The GH/GHR fusion proteins form head to tail dimers.

Abstract: The invention relates to the discovery that the addition of aromatic carboxylate ions inhibit protein instability caused by aromatic preservatives. Thus, the invention relates to compositions, (preferably aqueous compositions, comprising a protein, an aromatic preservative and aromatic carboxylate ions. The proteins remain stable and suitable for storage at ambient temperatures or lower, even in aqueous form. Preferably, the aqueous composition comprises a protein, a phenolic preservative and benzoate ions, wherein the pH of the composition is at least 1 unit greater than the pKa of benzoic acid. The invention also provides methods of reducing protein degradation by aromatic preservatives in an aqueous formulation of a protein susceptible to such degradation, comprising the step of adding aromatic carboxylate ions to the formulation wherein the formulation is maintained at a pH that is at least 1 unit greater than the pKa of the corresponding aromatic carboxylic acid.

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: A microparticle includes an agglomerate of a hydrophilic active substance containing particle, which particle includes an amphiphilic polymer composed of a hydrophobic segment of poly(hydroxy acid) and a hydrophilic segment of polysaccharides or polyethylene glycol, and a hydrophilic active substance. It is characterized by an efficient inclusion of the hydrophilic active substance, and a release of the hydrophilic active substance at an appropriate speed in the human body, and is hence very useful as a DDS pharmaceutical preparation.

Abstract: A liquid composition in an osmotic drug delivery system and a dosage form in an osmotic drug delivery system is disclosed comprising an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent.

Abstract: A method for alleviating a symptom of chemotherapy in a subject comprises identifying a subject undergoing chemotherapy and then administering a therapeutically effective amount of a GH/IGF-1 Axis inhibitory composition to the subject. Typically, the levels of IGF-1 and/or GH in the subject are monitored as well as chemotherapy related symptoms. A method of alleviating oxidative damage, cellular damage including mutations, and insulin resistance in a subject is also provided.

Abstract: The present invention relates to growth hormone (GH) compounds having additional disulphide bridges and at least one additional single point mutation making the compounds resistant to proteolytic degradation.

Abstract: Non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides, are disclosed. The non-natural amino acids, by themselves or as a part of a polypeptide, can include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Methods for making, modifying, and purifying the non-natural amino acid polypeptides are also disclosed. Further, methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses, are disclosed.

Abstract: A method for delivering a biologic to a human, comprising administering said biologic parenterally into the perispina! space of said human without direct intrathecal injection and positioning said human in a Trendelenburg position.

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 is directed to stable liquid growth hormone formulations that remain stable after physical agitation, and after exposure to one or more freeze-thaw events. Formulations of the present invention can be stored long term at a variety of temperatures, even frozen. In the present invention, a combination of buffer and stabilizing agents, including a non-ionic surfactant (e.g., polysorbate 20), a polymer stabilizer (e.g., polyethylene glycol), and other optional stabilizers combine to provide unexpected stability to aqueous formulations of a growth hormone (e.g., human growth hormone).

Abstract: The present invention relates to dosage forms of human growth hormone, the use of an absorption enhancer to allow absorption of human growth hormone into the systemic circulation in a biologically active form, in particular after oral administration, as well as the use of oral dosage forms comprising human growth hormone and an absorption enhancer for the treatment of human growth hormone deficiencies and disorders associated therewith.

Abstract: Methods are disclosed for treating sepsis and septic shock using a combination of ghrelin and growth hormone, and for using ghrelin to reduce organ and tissue injury and improve survival after combined radiation exposure and sepsis.

Abstract: A use of an inhalable powder formulation for preventing or treating an NMDA receptor hypofunction-related disease, a method for preventing or treating an NMDA receptor hypofunction-related disease in a subject, which comprises administering a therapeutically effective amount of an inhalable powder formulation comprising growth hormone (GH) to the subject in need thereof, and an inhalable powder formulation for preventing or treating an NMDA receptor hypofunction-related disease comprising GH as an active ingredient are provided.

Abstract: A polypeptide and polynucleotides encoding same comprising one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to an amino terminus of a growth hormone and two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a carboxy terminus of a growth hormone are disclosed. Pharmaceutical compositions comprising the polypeptide and polynucleotides of the invention and methods of using same are also disclosed.

Abstract: The present invention relates to pre-formulations comprising low viscosity, non-liquid crystalline, mixtures of: a) at least one neutral diacyl lipid and/or at least one tocopherol; b) at least one phospholipid; c) at least one biocompatible, oxygen containing, low viscosity organic solvent; wherein at least one bioactive agent is dissolved or dispersed in the low viscosity mixture and wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with an aqueous fluid. The preformulations are suitable for generating parenteral, non-parenteral and topical depot compositions for sustained release of active agents. The invention additionally relates to a method of delivery of an active agent comprising administration of a preformulation of the invention, a method of treatment comprising administration of a preformulation of the invention and the use of a preformulation of the invention in a method for the manufacture of a medicament.

Abstract: Pharmaceutical compositions comprising pegylated growth hormone at pH 7 or below are provided.

Abstract: We disclose growth hormone [GH] fusion proteins that have increased in vivo stability and activity; nucleic acid molecules encoding said proteins and methods of treatment of growth hormone deficiency that use said fusion proteins. The GH fusion proteins comprise human GH covalently linked to the extracellular domain of Growth Hormone Receptor [GHR] either as a direct in-frame translational fusion or via a flexible peptide linker. The GH/GHR fusion proteins have exceptional pharmacokinetics and are potent growth hormone receptor agonists. The GH/GHR fusion proteins form head to tail dimers.

Abstract: The invention discloses particulate complexes composed of chitosan, poly-glutamic acid, and at least one bioactive agent, wherein equal moles of the positively charged chitosan and the negatively charged poly-glutamic acid substrate form an electrostatic network enabling improved loading the bioactive agent.

Abstract: A formulation of a diluted amino acid segment is prepared by mixing an amino acid segment and a diluting agent to form a mixture. The mixture is serially diluted to produce a diluted formulation. The amino acid segment includes a peptide sequence that is the same as a portion of a longer peptide sequence found in a naturally occurring material. A homeopathic remedy can be prepared using the formulation.

Abstract: The present invention relates to compositions and methods for the preparation, stabilization, and/or storage of active agents, particularly therapeutic proteins and polypeptides such as Interleukin-2.

Abstract: The present invention relates to pharmaceutical formulations comprising a peptide and propylene glycol, to methods of preparing such formulations, and to uses of such formulations in the treatment of diseases and conditions for which use of the peptide contained in such formulations is indicated. The present invention further relates to methods for reducing the clogging of injection devices by a peptide formulation and for reducing deposits on production equipment during production of a peptide formulation.

Abstract: The present disclosure provides a biodegradable drug delivery composition including a vehicle and an insoluble component comprising beneficial agent dispersed in the vehicle. Typically, the composition is not an emulsion, but has a low viscosity and further provides for minimized initial burst and sustained release of the beneficial agent over time. Also provided, are kits including the biodegradable drug delivery composition or components thereof, as well as methods of making and using the biodegradable drug delivery composition.

Abstract: A liquid composition in an osmotic drug delivery system and a dosage form in an osmotic drug delivery system is disclosed comprising an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent.

Abstract: This invention relates to stable non-aqueous single phase viscous vehicles and to formulations utilizing such vehicles. The formulations comprise at least one beneficial agent uniformly suspended in the vehicle. The formulation is capable of being stored at temperatures ranging from cold to body temperature for long periods of time. The formulations are capable of being uniformly delivered from drug delivery systems at an exit shear rate of between about 1 to 1×10?7 reciprocal second.

Abstract: Described herein is a transmucosal delivery device and their use for delivering bioactive agents across a mucosal membrane. The delivery devices contain a pharmaceutically acceptable oxidizing and agents that facilitates the delivery of the blood stream across the mucosal membrane.

Abstract: Injectable depot gel compositions and kits that provide an excipient for modulating a release rate and stabilizing beneficial agents are provided. Methods of administering and preparing such systems are also provided. The gel compositions comprise biodegradable, bioerodible polymers and water-immiscible solvents in amounts effective to plasticize the polymers and form gels with the polymers. Suitable excipients include pH modifiers, reducing agents, and antioxidants.