Abstract: Methods for controlling and regulating engulfment, uptake and/or transcellular transport at a stage following initial engagement of an agent to the endothelium are provided, based on the identification of CAM-mediated endocytosis and the sphingomyelin/ceramide pathway as active steps in transcellular TEM. Administration of regulators relating to the identified pathways, such as NHE1, sphingomyelinases, acid sphingomyelinase and ceramide, permit control and regulation of uptake and transcellular transport. Control and regulation of uptake and/or transcellular transport is applicable in strategies to modulate inflammation, provide controlled and/or targeted delivery of agents, control pathogenic invasion, recover action of an inhibited CAM-mediated uptake or transendothelial pathway, or provide uptake or transendothelial transport by targeting cell surface markers other than ICAM-1.

Abstract: Compositions are described according to embodiments of the present invention which include a neuronal potassium channel antagonist and a neuronal sodium channel antagonist, the neuronal potassium channel antagonist and the neuronal sodium channel antagonist each conjugated to a transporter moiety to form one or more conjugates. The transporter moiety is capable of crossing the blood/brain or blood/nerve barrier such that the conjugate is delivered to the brain and/or nerve. Inventive methods of treating a demyelinating condition in a subject are described herein which include administering an effective amount of a conjugate composition of the present invention to a subject having a demyelinating condition.

Abstract: The present invention relates to a novel compound of use in the improved delivery of therapeutic drug agents into target cells or tissues, composition comprising the same and uses thereof. The compound is more specifically a conjugate of a peptide moiety and a camptothecin, a derivative or analog thereof which provides numerous benefits, including enhancement in terms of aqueous solubility, pharmacokinetics and tissue distribution, enlargement of the therapeutic index, and limitation of the inter-patient metabolic variability, as well as improvement of delivery of the biologically active ingredient to the target cells or tissues.

Abstract: The pharmaceutical composition includes at least one pharmaceutically acceptable carrier, and an active ingredient including an artificially synthesized peptide includes: (A) an amino acid sequence constituting a cell-penetrating peptide and (B) an amino acid sequence constituting the signal peptide in amyloid precursor protein (APP) or an N-terminal partial amino acid sequence or C-terminal partial amino acid sequence from the amino acid sequence constituting that signal peptide.

Abstract: A method of treating an LCN13-related condition is provided comprising administering to a patient in need thereof a therapeutically effective amount of a lipocalin or a physiologically active fragment thereof.

Abstract: The disclosure provides antigenic peptides of Vascular Endothelial Growth Factor Receptor 2(VEGFR-2)/KDR. Pharmaceutical compositions including the peptides and/or antigen presenting cells that exhibit the VEGFR-2/KDR peptides on their cell surface are also provided. Methods for eliciting an immune response and for inhibiting angiogenesis by administering such pharmaceutical compositions are provided.

Abstract: The present invention concerns medicaments for slowing ageing. The medicaments can include an inhibitor of microbial folate biosynthesis as well as agents capable of reducing folate uptake by an animal. Examples of such medicaments include inhibitors that reduce the activity of an enzyme in the folate biosynthesis pathway, such as sulfonamides including sulfamethoxazole. The invention also concerns a food supplement, additive, functional food, or nutraceutial comprising the inhibitor or agent or composition as discussed above, as well as methods for screening for an agent for use as a medicament for slowing ageing comprising determining whether a test agent inhibits microbial folate biosynthesis, or whether the test agent reduces folate uptake by a non-human animal.

Abstract: A cell penetrating peptide which has following sequence: NYBX1BX2BNQX3, wherein B represents a basic amino acid, X1 represents an amino acid with an aromatic, a hydrophobic or an uncharged side chain, X2 represents any amino acid, and X3 represents N or none is described. A method for delivering a cargo into a subject by administrating a complex comprising the cell penetrating peptide and the desired cargo to the subject is also described.

Abstract: An albumin-free Factor VIII formulation comprising: 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. 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. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 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; and a buffering agent.

Abstract: The present invention discloses methods and materials for delivering a cargo compound into a cancer cell. Delivery of the cargo compound is accomplished by the use of protein transduction domains derived from cupredoxins. The invention further discloses methods for treating cancer and diagnosing cancer.

Abstract: This invention relates to a transdermal delivery system for treating skin related diseases employing protein nanoparticles to deliver drugs to the keratinocytes and basal membrane cells for the treatment of Psoriasis. The current invention presents an effective method for delivering small molecule nucleic acids to the epidermal cells.

Abstract: A nanoparticle-polypeptide complex comprising a bioactive polypeptide in association with a nanoparticle, wherein the bioactive polypeptide is modified by the addition of a chemical moiety that facilitates cellular uptake of the protein. The polypeptide can be a protein or a peptide. In some embodiments, the amino acid sequence of the protein or peptide is derived from the amino acid sequence of a tumor suppressor gene product.

Abstract: Pharmaceutical compositions are provided. The compositions comprise a compound comprising the hyaluronan-containing structure A-(low molecular weight hyaluronan domain)-B. The compositions also comprise a pharmaceutically acceptable excipient. A is hydrogen, a substituent that does not comprise a binding site for tumor necrosis factor stimulated gene-6 (“TSG-6”) protein, a substituent that interferes with binding of TSG-6 protein immediately adjacent thereto, or chondroitin. B is hydroxyl, a substituent that does not comprise a binding site for TSG-6 protein, a substituent that interferes with binding of TSG-6 protein immediately adjacent thereto, or chondroitin. The composition is suitable for administration by injection, inhalation, topical rub, or ingestion.

Abstract: The invention provides agents useful for treating pain. An exemplary agent comprises or consists of the a portion of a retroviral Tat protein. One such agent is the peptide Tat-NR2B9c. This peptide has previously been described as an agent for inhibiting damaging effects of stroke and similar conditions via inhibition of PSD95 interactions with NMDA receptors and/or NOS. The present application provides data showing that the Tat-NR2B9c peptides is effective in alleviation of pain. The alleviation of pain can be obtained at a dose of the peptide below the dose required to inhibit PSD-95 interactions with NMDAR or NOS.

Abstract: Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes (at physiologic pH, but can become active toward cell membranes if the environment is acidified below ca. pH 6.8), coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof.

Abstract: The present invention provides for diagnosis or treatment of neurological or neuropsychiatric disorders involving abnormal dopamine neurotransmission. Methods and agents are provided for modulating dopamine transporter activity and modulating dopaminergic neurotransmission. Agents of the present invention include fragments of D2 receptor or dopamine transporter (DAT) that can disrupt D2-DAT coupling.

Abstract: Disclosed are a fusion protein comprising enzyme N-acetylgalactosamine-6-sulfate sulfatase and a short peptide consisting of 4-15 acidic amino acids attached to the enzyme on its N-terminal side, a pharmaceutical composition containing the fusion protein, and a method for treatment of type A Morquio disease using the fusion protein. Compared with the native enzyme protein, the fusion protein exhibits higher transferability to bone tissues and improved, higher stability in the blood.

Abstract: The present invention refers to uses of crotamine and compositions containing it, based on its characteristic of interaction with genetic material. Under submicromolar quantities, the polypeptide is no longer toxic, presenting the characteristics properties of cell penetration, transport of molecules to the surface, cytoplasm or cell nucleus and particularly, selective cell penetration. The invention also refers to compositions comprising a pharmaceutically effective concentration of crotamine and its use for the treatment of diseases and dysfunctions, based on its characteristics of interaction with genetic material, such as DNA and RNA, and cell selectivity.

Abstract: This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including into and across ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length (for example, SEQ ID NO:86).

Abstract: The present invention provides compounds for targeting endothelial cells, tumor cells or other cells that express the NP-1 receptor, compositions containing the same and methods for their use. Additionally, the present invention includes diagnostic, therapeutic and radiotherapeutic compositions useful for visualization, therapy or radiotherapy.

Abstract: The present invention provides a synthetic LDL nanoparticle comprising a lipid moiety and a synthetic chimeric peptide so as to be capable of binding the LDL receptor. The synthetic LDL nanoparticle of the present invention is capable of incorporating and targeting therapeutics to cells expressing the LDL receptor for diseases associated with the expression of the LDL receptor such as central nervous system diseases. The invention further provides methods of using such synthetic LDL nanoparticles.

Abstract: Elastin-like polypeptide (ELP) serves as a vector for thermally-targeted delivery of therapeutics, including cytotoxic chemotherapeutic drugs such as doxorubicin. Examples of an ELP-based delivery vehicle can comprise: (1) a cell penetrating peptide, such as a Tat peptide, (2) ELP, and (3) the lysosomally degradable glycylphenylalanylleucylglycine (GFLG) (SEQ ID NO: 3) spacer and a cysteine residue (SEQ ID NO: 4) conjugated to therapeutic such as doxorubicin, or an analog thereof.

Abstract: This invention describes a protein nanoparticle system for targeting siRNA or other drugs into tumors. The basis of the protein system is elastin-like peptides that self-assemble once exposed to the nucleic acid of the siRNA. Specific targeting peptides are fused to the core ELP structure by standard genetic engineering techniques. These targeting peptides confer specific binding of the nanoparticle to receptors on the surface of tumor cells and allow for uptake of the nanoparticle into the tumor cells.

Abstract: The present invention relates to stabilized RAP variants and methods of use thereof. Conjugates of stabilized RAP variants to therapeutic compounds and stabilized RAP fusion proteins comprising therapeutic polypeptides are also presented.

Abstract: Disclosed are Drug Delivery Molecules (DDMs) which both facilitate functional imaging, as by PET, MRI or SPECT, and create a biological effect and methods of their use. These DDMs which are variously designed to target specific receptors, internalized and then function biologically, as for purposes of cell destruction or therapy.

Abstract: A method of changing or otherwise converting the biological activity of a PKC peptide agonist to a peptide antagonist is described. The method involves substituting one or more amino acid residues so as to effect a change in charge in the peptide and/or to otherwise make the sequence similar to a sequence derived from the PKC binding site on the RACK protein for the respective PKC enzyme. Methods of inhibiting the activity of a PKC enzyme, and various peptide antagonists of ?PKC are also disclosed.

Abstract: A nonaqueous, single-phase vehicle that is capable of suspending an active agent. The nonaqueous, single-phase vehicle includes at least one solvent and at least one polymer and is formulated to exhibit phase separation upon contact with an aqueous environment. The at least one solvent may be selected from the group consisting of benzyl benzoate, decanol, ethyl hexyl lactate, and mixtures thereof and the at least one polymer may be selected from the group consisting of a polyester, pyrrolidone, ester of an unsaturated alcohol, ether of an unsaturated alcohol, polyoxyethylenepolyoxypropylene block copolymer, and mixtures thereof. In one embodiment, the at least one solvent is benzyl benzoate and the at least one polymer is polyvinylpyrrolidone. A stable, nonaqueous suspension formulation that includes the nonaqueous, single-phase vehicle and an active agent, and a method of forming the same, are also disclosed.

Abstract: The object of the present invention is to provide a method for treating muscular dystrophy. The method for treating muscular dystrophy according to the present invention is characterized in comprising a step of administering a caldecrin.

Abstract: The present invention provides a variety of nucleic acid based therapeutics and methods of use thereof which are effective to beneficially reprogram diseased cells such that they exhibit more desirable phenotypes. Also provided are compositions and methods to reprogram normal cells for medical and commercial purposes.

Abstract: The present disclosure provides peptides and peptide compositions, which facilitate the delivery of an active agent or an active agent carrier wherein the compositions are capable of penetrating the stratum corneum (SC) and/or the cellular membranes of viable cells.

Abstract: The peptides described herein can function as carrier peptides. These peptides can associate with (e.g., non-covalently bind) biologically active molecules or imaging agents to transport the biologically active molecules or imaging across the blood-brain barrier. In some cases, such transport may increase the effectiveness of the biological molecules or imaging agents.

Abstract: Methods and compositions are provided for assessing, treating, and preventing diseases, especially cancer, using cancer-associated targets (“CAT”). Methods and compositions are also provided for determining or predicting the effectiveness of a treatment for these diseases or for selecting a treatment, using CAT. Methods and compositions are further provided for modulating cell function using CAT. Also provided are compositions that modulate CAT (e.g., antagonists or agonists), such as antibodies, proteins, small molecule compounds, and nucleic acid agents (e.g., RNAi and antisense agents), as well as pharmaceutical compositions thereof. Further provided are methods of screening for agents that modulate CAT, and agents identified by these screening methods.

Abstract: This invention provides multimeric nanocarrier for in vivo delivery of a bioactive agent, comprising at least two peptide monomers reversibly or irreversibly linked with one or more of said bioactive agents, wherein said two or more of said peptide monomers are covalently linked by a biodegradable difunctional moiety, as well as methods of using this nanocarrier.

Abstract: The present invention features methods and compositions for treating a patient who has a neurological deficit. The method can be carried out, for example, by contacting (in vivo or in culture) a neural progenitor cell of the patient's central nervous system (CNS) with a polypeptide that binds the epidermal growth factor (EGF) receptor and directing progeny of the proliferating progenitor cells to migrate en masse to a region of the CNS in which they will reside and function in a manner sufficient to reduce the neurological deficit. The method may include a further step in which the progeny of the neural precursor cells are contacted with a compound that stimulates differentiation.

Abstract: The present invention provides a method for ameliorating inflammatory and/or neuropathic pain in a subject by modifying the activity of N-methyl-D-aspartate (NMDA) receptors in cells of the subject by inhibition of the interaction of the unique domain of the tyrosine kinase Src enzyme and the NMDA receptor complex.

Abstract: The invention provides compositions, methods, and kits for increasing transport of agents across the blood brain barrier while allowing their activity once across the barrier to remain substantially intact. The agents are transported across the blood brain barrier via one or more endogenous receptor-mediated transport systems. In some embodiments the agents are therapeutic, diagnostic, or research agents.

Abstract: The invention provides methods of treating a subject having a disease, disorder or condition of the central nervous system. The methods include administering TGF-? polypeptides, related polypeptides, fragments and mimetics thereof useful in stimulating progenitor cell or stem cell proliferation, migration and differentiation. The methods of the invention are useful to treat and prophylactically ameliorate neurological tissue injury in vivo.

Abstract: Methods of making ligand-decorated polymer conjugates of therapeutic glycoproteins are described. Improved targeting of glycoproteins to specific tissues is achieved by masking the natural carbohydrate and other surface determinants with high molecular weight polymers, such as, e.g., PEG, polysialic acid, etc., which in turn are decorated with target-specific ligands. In some embodiments, acid-labile linkages in such conjugates or rapidly degradable masking groups allow for the intracellular release of the polymer from the glycoprotein, for example, under conditions found in lysosomes.

Abstract: Apolipoprotein A-I (ApoA-I), preferably a variant form such as Apolipoprotein A-I Milano (ApoA-IM), alone or more preferably in combination with a lipid carrier such as phospholipids or other drug, can be administered locally before or during bypass surgery on diseased coronary, peripheral, and cerebral arteries, surgery to implant grafts or transplanted organs, or angioplasty, or to stabilize unstable plaques. In an alternative embodiment, the apolipoprotein is not provided directly, but the gene encoding the apolipoprotein is provided. The gene is introduced into the blood vessel in a manner similar to that used for the protein, where the protein is then expressed. The technique can also be used for delivery of genes for treatment or prevention or restenosis or other cardiovascular diseases.

Abstract: A modified sodium iodide symporter (NIS) protein is provided. The modified NIS protein comprises an amino acid sequence of SEQ ID NO.1 with the proviso that at least one amino acid residue within SEQ ID NO. 1 is changed. The modified NIS protein has an enhanced transport function, and the expression of the modified NIS protein in the cells results in higher intracellular levels of a substrate of a NIS protein than does the expression of the same amount of a wild-type NIS protein.

Abstract: The invention relates to isolated peptides comprising at least the amino acid sequence YDRREY (SEQ ID NO:1) or a derivative thereof, nucleic acid encoding the peptides, pharmaceutical compositions and methods for modulating ? 7 integrin function, including methods for treatment of inflammatory disorders, antibodies directed to the peptides and methods for identification of integrin ?7 functional interactors.

Abstract: The present invention comprises a method for delivering pharmaceutical and/or imaging agents within and/or through the dermal, mucosal and other cellular membranes, and across the blood-brain barrier, utilizing a fusogenic protein. The fusogenic protein is associated with a phospholipid membrane, such as a liposome. The liposome may include dioleoylphosphatidylserine, a negatively charged long-chain lipid. Alternatively, the liposome is comprised of a mixture of negatively charged long-chain lipids, neutral long-chain lipids, and neutral short-chain lipids. Preferred fusogenic proteins include saposin C and other proteins, polypeptides and peptide analogs derived from saposin C. The active agent contained within the liposome may comprise biomolecules and/or organic molecules. This technology can be used for both cosmetic and medicinal applications in which the objective is delivery of the active agent within and/or beneath biological membranes or across the blood-brain barrier and neuronal membranes.

Abstract: The invention provides a method of reducing or preventing mitochondrial permeability transitioning. The method comprises administering an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids; a relationship between the minimum number of net positive charges (pm) and the total number of amino acid residues (r) wherein 3pm is the largest number that is less than or equal to r+1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (pt) wherein 2 a is the largest number that is less than or equal to pt+1, except that when a is 1, pt may also be 1.

Abstract: A method of treating an LCN13-related condition is provided comprising administering to a patient in need thereof a therapeutically effective amount of a lipocalin or a physiologically active fragment thereof.

Abstract: Devices and methods for treating diseases associated with loss of neuronal function are described. The methods are designed to promote proliferation, differentiation, migration, or integration of endogenous progenitor stem cells of the central nervous system (CNS). A therapy, such as an electrical signal or a stem cell enhancing agent, or a combination of therapies, is applied to a CNS region containing endogenous stem cells or a CNS region where the endogenous stem cells are predicted to migrate and eventually reside, or a combination thereof.

Abstract: The present invention relates to a pharmaceutical composition for the treatment and/or prevention of a neurodegenerative disease, comprising the following polypeptide shown in any of (a) to (c): (a) a polypeptide comprising the amino acid sequence represented by Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala-Pro-Ala-Gly-Ala-Ser-Arg-Leu-Leu-Leu-Leu-Thr-Gly-Glu-Ile-Asp-Leu-Pro (SEQ ID NO: 1); (b) a polypeptide comprising an amino acid sequence having a deletion, substitution, insertion, and/or addition of one or several amino acids in the amino acid sequence consisting of Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala-Pro-Ala-Gly-Ala-Ser-Arg-Leu-Leu-Leu-Leu-Thr-Gly-Glu-Ile-Asp-Leu-Pro (SEQ ID NO: 1), and having an activity that inhibits neuronal cell death associated with neurodegenerative disease; and (c) a modified polypeptide from the polypeptide (a) or (b), or a pharmaceutically acceptable salt thereof, as an effective ingredient.

Abstract: The present inventors have demonstrated the presence of H-ferritin receptors on endothelial cells in culture and on rat brain rat brain microvasculature, identifying H-ferritin as a means for transporting iron across the blood brain barrier. The present invention provides a method for treating an iron deficiency disorder in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a ferritin-iron complex. In an embodiment of the invention, the ferritin-iron complex comprises H-ferritin. In another embodiment, the iron deficiency disorder comprises an iron deficiency in the brain.

Abstract: The present invention provides a cell penetrating peptide which has following sequence: NYBX1BX2BNQX3, wherein B represents a basic amino acid, X1 represents an amino acid with an aromatic, a hydrophobic or an uncharged side chain, X2 represents any amino acid, and X3 represents N or none. The present invention also provides a method for delivering a cargo into a subject by administrating a complex comprising the cell penetrating peptide and the desired cargo to the subject.

Abstract: Transcriptional regulatory regions and transcriptional regulatory factors for the human high affinity IgE receptor (Fc?RI) ?-chain gene are specified and are targets for the development of transcriptional regulatory agents for the Fc?RI ?-chain gene. The following are provided: DNA comprising the full length or a portion of the base sequence shown in SEQ ID NO:1, that regulates transcription of the human high affinity IgE receptor (Fc?RI) ?-chain gene; and DNA comprising the full length or a portion of the base sequence shown in SEQ ID NO:2, that regulates transcription of the human high affinity IgE receptor (Fc?RI) ?-chain gene. The present invention is promising for the development of novel agents for the prophylaxis/treatment of allergic diseases, autoimmune diseases, thrombosis, glomerulonephritis, and lupus nephritis.

Abstract: According to the present invention, it is possible to provide a novel cell penetrating peptide that transports proteins into cells and/or into nuclei at higher frequency than conventional cell penetrating peptides, and a pharmaceutical containing the peptide.