Abstract: The present invention provides nucleic acid-containing lipid nanoparticles containing a lipid (lipid A) which has a hydrophilic unit having a single quaternary ammonium group, and three independent, optionally substituted hydrocarbon groups, a lipid derivative or fatty acid derivative of a water-soluble polymer, and a nucleic acid.

Abstract: This invention provides novel erbB2-binding internalizing antibodies. The antibodies, designated F5 and C1, specifically bind to c-erbB2 antigen and, upon binding, are readily internalized into the cell bearing the c-erbB2 marker. Chimeric molecules comprising the F5 and/or C1 antibodies attached to one or more effector molecules are also provided.

Abstract: The present invention is related to methods and pharmaceutical compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with neurofibrillary tangles. In particular, the invention relates to pharmaceutical composition comprising an antigenic peptide, particularly an antigenic phospho-peptide mimicking a major pathological phospho-epitope of protein tau, for the therapeutic and diagnostic use in the treatment of tauopathies including Alzheimer's Disease.

Abstract: The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis. In particular, the present invention provides novel methods and compositions for eliciting a highly specific and highly effective immune response in an organism, but particularly within an animal, particularly a mammal or a human, which is capable of preventing or alleviating amyloidosis, or the symptoms associated with amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer's Disease (AD), including diseases or conditions characterized by a loss of cognitive memory capacity such as, for example, mild cognitive impairment (MCI).

Abstract: An improved linker which lacks chiral centers between a hydrophobic anchor for coupling to lipid-based particles and a targeting agent has suitable hydrophobic/hydrophilic properties for use in vivo.

Abstract: The present invention is concerned with vaccines and their preparation. An effective long-term immune response, especially in mammals, can be produced using a vaccine comprising an antigen encapsulated in liposomes, a suitable adjuvant and a carrier comprising a continuous phase of a hydrophobic substance. The vaccine is particularly effective in eliciting the production of antibodies that recognize epitopes of native proteins.

Abstract: The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis. In particular, the present invention provides novel methods and compositions for eliciting a highly specific and highly effective immune response in an organism, but particularly within an animal, particularly a mammal or a human, which is capable of preventing or alleviating amyloidosis, or the symptoms associated with amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer's Disease (AD), including diseases or conditions characterized by a loss of cognitive memory capacity such as, for example, mild cognitive impairment (MCI).

Abstract: New synthetic Lipid-A analogs based on monosaccharide (1) and disaccharide (2) derivatives were designed and prepared in the present invention. Both structures (1) and (2) incorporate novel lipid structures (3) and (4) that are not found in nature. Also, novel disaccharide Lipid-A structures (2) that incorporate novel contingents of uniform lipids and where R1, R4 and R5 are the same substitution group of structure (III) were synthesized. Liposome formulations containing totally synthetic components such as synthetic Lipid-A and synthetic lipopeptide derived from tumor-associated MUC1 mucin are described along with their therapeutic utility. Comparative test results of immunostimulating properties and toxicity of Lipid-A analogs (1) and (2) are included.

Abstract: Polyanionic therapeutic compounds, generally nucleic acids, are complexed with calcium phosphate and entrapped within liposomes. For DNA vaccines, the complexation and entrapment process provides improved immune response for gene vaccines delivered intramuscularly.

Abstract: Methods, compositions and apparatus for localized delivery of compounds are provided. In certain embodiments, radiation force is used to direct carriers to a target site, and additional radiation is used to fragment the localized carriers, releasing associate compounds. Ultrasound radiation is preferred as the source for radiation force and for fragmentation. Also encompassed are embodiments in which targeting and fragmentations are combined with imaging of the treatment site. Alternate embodiments are disclosed in which compounds are locally delivered without use of carriers.

Abstract: A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

Abstract: A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

Abstract: This invention provides a method of inhibiting viable cells transplanted into a subject from being destroyed by the subject's immune system which comprises: a) containing the viable cells, or tissue comprising the viable cells, prior to transplantation within a device comprising a semipermeable membrane; and b) treating the subject with a substance which inhibits an immune-system costimulation event in an amount effective to inhibit the subject's immune system from responding to said contained cells or tissue. In one embodiment, the substance which inhibits an immune-system costimulation event is CTLA4.

Abstract: The present invention is concerned with vaccines and their preparation. An effective long-term immune response, especially in mammals, can be produced using a vaccine comprising an antigen encapsulated in liposomes, a suitable adjuvant and a carrier comprising a continuous phase of a hydrophobic substance. The vaccine is particularly effective in eliciting the production of antibodies that recognize epitopes of native proteins.

Abstract: The present invention is directed to artificial antigen presenting cells and methods of making artificial antigen presenting cells. Such artificial antigen presenting cells may be used in certain methods of isolating and expanding T cell populations as well as modulating T cell responses. Additionally, the present invention provides novel methods for the identification and isolation of antigen-specific T cells. The methods provide for the construction of liposomes containing MHC:peptide complexes, accessory molecules, co-stimulatory molecules, adhesion molecules, and other molecules irrelevant to T cell binding or modulation that are used in the binding of artificial antigen presenting cells to solid support systems that may be used in the retrieval and identification of antigen-specific T cells.

Abstract: The present invention provides novel adjuvants which comprise oil bodies. The invention also provides vaccine formulations comprising oil bodies and an antigen and methods for preparing the vaccines and the use of the vaccines to elicit an immune response.

Abstract: Methods and compositions are described for the treatment of inflammatory diseases including the use of liposomes to deliver non-steroidal anti-inflammatory drugs. Drugs may be encapsulated in the liposomes during their preparation, or alternatively, are combined with the liposomes following their formation. The composition may include glycolipids such as galactolipids including digalactosyl diglyceride, and the liposomes may be made by a number of procedures. The compositions may be administered to mammals including humans.

Abstract: This invention relates generally to the field of therapeutic compounds designed to interfere between the binding of ligands and their receptors on cell surface. More specifically, it provides products and methods for inhibiting cell migration and activation using lipid assemblies with surface recognition elements that are specific for the receptors involved in cell migration and activation.

Abstract: A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

Abstract: Novel archaeosome compositions and their use in vaccine formulations as adjuvants and/or delivery systems, to enhance the immune response to immunogens in an animal such as a human, are described. Another aspect relates to the use of these archaeosomes to enhance the delivery of compounds such as pharmaceuticals to specific cell types and tissues in animals and other life forms, via various routes of administration such as subcutaneous, intramuscular, and oral. The efficacy of the archaeosomes and also of conventional liposomes can be further improved in these applications, by incorporation of coenzyme Q10 and/or polyethyleneglycol-lipid conjugate into liposomes made from these archaeosomes.

Abstract: Single phase preparations of hydrophilic species, in particular macromolecular compounds such as proteins or glycoproteins in a hydrophobic solvent such as an oil can be obtained by preparing a hydrophile/amphiphile array in which the hydrophilic head groups of the amphiphile are orientated towards the hydrophilic species and bringing the array into contact with the hydrophobic solvent. The preparations of the invention can be used alone or can be combined with an aqueous phase to form emulsions in which the hydrophilic species is present in the hydrophobic phase. The compositions of the present invention are versatile and have application in the pharmaceutical, food, cosmetic, chemical and agricultural industries.

Abstract: Polymerized liposome particles which are linked to a targeting agent and may also be linked to a contrast enhancement agent and/or linked to or encapsulating a treatment agent. The targeting imaging enhancement polymerized liposome particles interact with biological targets holding the image enhancement agent to specific sites providing in vitro and in vivo study by magnetic resonance, radioactive, x-ray or optical imaging of the expression of molecules in cells and tissues during disease and pathology. Targeting polymerized liposomes may be linked to or encapsulate a treatment agent, such as, proteins, drugs or hormones for directed delivery to specific biological sites for treatment.

Abstract: The invention provides a method for preventing allergic disease in an individual susceptible to such disease, comprising administering an allergen to which the individual has not been sensitized previously. The allergen is administered in a dose and form effective to establish a stable population of allergen-specific T-helper-1-like memory lymphocytes capable of inhibiting activity or amplification of allergen-specific T-helper-2-like lymphocytes responsible for stimulating production of IgE antibodies specific for the allergen. Compositions for use in the method of the invention are also disclosed.

Abstract: Provided are methods for preparing improved biologically active micelle and crystalline products comprising a biologically active amphipathic compound in association with a micelle or crystalline product. Methods for producing the micelle or crystalline products as well as methods of using the micelle or crystalline products in therapeutic, diagnostic, and cosmetic, applications are also provided.

Abstract: Reagents for use in preparing a therapeutic liposome composition sensitized to a target cell are described. The reagents include a liposomal composition composed of pre-formed liposomes having an entrapped therapeutic agent and a plurality of targeting conjugates composed of a lipid, a hydrophilic polymer and a targeting ligand. The therapeutic, target-cell sensitized liposome composition is formed by incubating the liposomal composition with a selected conjugate.

Abstract: This invention provides liposomes containing one or more N-acylated phosphatidylethanolamines, such liposomes being useful for localizing the delivery of bioactive agents to cells.

Abstract: This invention includes the conception of T-independent conjugate-vaccines and its application in the induction of antigen specific IgA response. We demonstrated that 1) &agr;(1,6)dextran can elicit a markedly enhanced IgA response in T-cell free mice (20-50 fold higher than in normal mice); 2)co-injection of the molecule with other antigens can enhance the IgA response to the co-antigen; and 3)a dextran-Gag conjugate can elicit the Gag-specific IgA. Thus, the invention identified &agr;(1,6)dextran as a carrier molecule for producing the T-independent conjugates and as an adjuvant for the enhancement of IgA production. The T-independent property of these conjugates makes it especially useful in vaccinations against HIV and other infectious and non-infectious diseases associated with T-cell deficiency.

Abstract: The invention concerns a method for administering bioactive substances to patients at selected sites in the body and remotely promoting delivery of said media to selected organs or tissues in the body. The method comprises providing an administrable formulation comprising, dispersed in an aqueous carrier liquid, liposomes filled with bioactive substances and gas-filled microspheres, injecting said formulation into the circulation of a patient so that it is directed to a site of interest, and applying ultrasound pulses to said site so as to make the gas-filled microbodies explode and the gas confined therein to expand in the carrier liquid, the energy of expansion of said confined gas causing the liposome vesicles to open and release the trapped substances at said site.

Abstract: Liposome encapsulated antibiotic therapy has limited application against infectious organisms, which can sequester in non-phagocytic cells. Virulence factors of these infectious organisms, for example bacterial components, when used in the formulation of liposomes can enhance the effectiveness of liposomes as delivery systems in the treatment of disease. In this manner, multi-functional liposomes can be developed to treat target diseases. In addition to serving as antibiotic delivery systems, such liposomes also have an immunization effect. Thus, the liposomes can be used for both the prevention and treatment of diseases.

Abstract: The present invention provides for immunoliposomes that optimizes internalization of a drug into target cells bearing a characteristic cell surface marker. The immunoliposomes comprise an Fab′ domain of an antibody that specifically binds the characteristic marker, an amphipathic vesicle-forming lipid, and a polyethylene glycol derivatized lipid. The invention also provides for growth-inhibiting immunoliposomes that lack growth-inhibiting therapeutic agents and yet are capable of inhibiting the growth and proliferation of target cells.

Abstract: The present invention provides compositions comprising colorimetric assay liposomes. The present invention also provides methods for producing colorimetric liposomes and calorimetric liposome assay systems. In preferred embodiments, these calorimetric liposome systems provide high levels of sensitivity through the use of dopant molecules. As these dopants allow the controlled destabilization of the liposome structure, upon exposure of the doped liposomes to analyte(s) of interest, the indicator color change is facilitated and more easily recognized.

Abstract: A direct assay is described using novel three-dimensional polymeric assemblies which change from a blue to red color when exposed to an analyte, in one case a flue virus. The assemblies are typically in the form of liposomes which can be maintained in a suspension, and show great intensity in their color changes. Their method of production is also described.

Abstract: A protein-lipid vesicle that can be used to make an autogenous vaccine comprises patient-specific antigen, adjuvant or immunomodulator, and lipid carrier. In addition, a negatively charged lipid component is desirably included. The autogenous vaccine is useful to treat individuals with chronic diseases, including chronic infectious diseases and neoplasias. The chronic infectious diseases that can be treated include disease caused by infection with human immunodeficiency viruses.

Abstract: A method for loading liposomes with biopolymeric substances functional in humans involves combining a physiologically compatible solution of the biopolymeric substances with one or more dry, liposome-forming lipids, effecting a lipid-containing fraction, combining the lipid-containing fraction with an organic solvent, effecting an organic solvent fraction, and drying the organic solvent fraction, which effects a dry fraction of liposomes loaded with the biopolymeric substances.

Abstract: A human monoclonal antibody specifically binding to a surface antigen of cancer cell membrane, an isolated DNA encoding the antibody, and a hybridoma producing the antibody. An anti-cancer formulation comprising the monoclonal antibody bonded to the surface of a liposome enclosing an anti-cancer agent or toxin is also provided.

Abstract: Novel archaeosome compositions and their use in vaccine formulations as adjuvants and/or delivery systems, to enhance the immune response to immunogens in an animal such as a human, are described. Another aspect relates to the use of these archaeosomes to enhance the delivery of compounds such as pharmaceuticals to specific cell types and tissues in animals and other life forms, via various routes of administration such as subcutaneous, intramuscular, and oral. The efficacy of the archaeosomes and also of conventional liposomes can be further improved in these applications by incorporation of coenzyme Q.sub.10 and/or polyethyleneglycol-lipid conjugate into liposomes made from these archaeosomes.

Abstract: The invention relates to a pharmaceutical composition intended for inducing in a host mammal a protective immune response against an antigen, at a mucosal effector site, which comprises at least two identical or different products each containing an inducing agent for the immune response, selected from the antigen and, provided the antigen is protein in nature, an expression cassette capable of expressing the antigen, for a concomitant or consecutive administration; one of the products being formulated so as to be administered via the nasobuccal route so that the inducing agent is targeted to the inducer site(s) for an immune response in the naso-oropharynx or the salivary glands, the other product being formulated so as to be administered via a suitable mucosal route other than the nasal route, so that the inducing agent is targeted to the inducer site(s) for an immune response at the effector site at which the immune response is sought.

Abstract: A cationic amphipathic compound of formula (I), ##STR1## wherein A is a single bond, an NH--R' grouping or (a), wherein --R'-- is a straight or branched, optionally substituted, saturated or unsaturated C.sub.1-22 aliphatic chain optionally interrupted by one or more O, S or N heteroatoms and one or more saturated, unsaturated or aromatic carbocyclic or heterocyclic radicals; each of R.sub.1, R.sub.2 and R.sub.3, which are the same or different, is a higher acyl or alkyl grouping; each of R.sub.7, R.sub.8 and R.sub.9, which are the same or different, is a (CH.sub.2).sub.n alkylene radical where 1.ltoreq.N.ltoreq.6; each of R.sub.4, R.sub.5 and R.sub.6, which are the same or different, is a hydrogen atom or an optionally substituted C.sub.1-22 alkyl, alkenyl, alkynyl or acyl radical optionally interrupted by one or more heteroatoms selected from), S and N, or one or more saturated, unsaturated or aromatic carbocyclic or heterocyclic radicals, or else at least two of the groupings R.sub.4, R.sub.5 and R.sub.

Abstract: A suspension of microfabricated microdevices for use in therapeutic applications is disclosed. The microdevices have a selected shape, and uniform dimensions preferably in the 100 nm to 10 Am range. Also disclosed are microfabrication methods for making such microdevices.

Abstract: A high integrity liposome comprising at least one stabile lipid and at least one peptide-like therapeutic agent associated with said liposome, adapted for parenteral administration to an animal, including a human, and method according to manufacture and use. Immunizing dosage forms comprising a liposome and an immunogen, wherein said liposome and immunogen are present in an immunization dose. Additionally, a dosage form, including such form particularly adapted to producing an immune response, comprising a salt according to an organic acid derivative of a sterol and an immunogen wherein said organic acid derivative of a sterol and immunogen are present in an immunization dose, and method according to use is disclosed.

Abstract: Methods of and apparatus for preparing temperature activated gaseous precursor-filled liposomes are described. Gaseous precursor-filled liposomes prepared by these methods are particularly useful, for example, in ultrasonic imaging applications and in therapeutic drug delivery systems.

Abstract: A method and composition are provided for treating intracellular pathogens that reside in phagosomes. The compositions include antibiotics which are conjugated with transferrin or other ligands to form conjugates that target membrane-bound pathogens. The conjugates are selectively taken up by infected phagosomes. Conjugates are provided which utilize transferrin as the targeting ligand for treating mycobacterium which reside in membrane-bound phagosomes.

Abstract: The present invention relates to piperazine based amphilic cationic lipids useful for gene therapy, transfection, and introducing immunogenic compounds for the purpose of vaccination. The disclosed compounds have lipophilic moieties linked to the ring nitrogens. In addition, at least one of the ring nitrogens is quatranized and linked to a hydrocarbon having at least one heteroatom.

Abstract: The present invention relates to targeted polymerized liposomes for oral and/or mucosal delivery of vaccines, allergens and therapeutics. In particular, the present invention relates to polymerized liposomes which have been modified on their surface to contain a molecule or ligand which targets the polymerized liposome to a specific site or cell type in order to optimize the immune response to the encapsulated antigen or the efficacy of the encapsulated drug.

Abstract: A composition for transdermal administration of an immunogen is described. The immunogen is entrapped in lipid vesicles having a oil-in-water emulsion in the central core compartment. The vesicles are administered transdermally to elicit an immune response in a subject.

Abstract: According to the present invention the adjuvants comprise an emulsion containing at least one synthetic hydrophobic lipopolysaccharide, which can either or not be provided with anionic groups, while maintaining the overall hydrophobicity, an interface-forming constituent (such as an oil) and optionally an aqueous solute. In particular the adjuvant and vaccines prepared with it contain a lipopolysaccharide which had an HLB value of less then 9, more favorably less than 4.

Abstract: Peptides are used to define epitopes that stimulate HLA-restricted cytotoxic T lymphocyte activity against hepatitis B virus antigens. The peptides are derived from regions of HBV polymerase, and are particularly useful in treating or preventing HBV infection, including methods for stimulating the immune response of chronically infected individuals to respond to HBV antigens.

Abstract: Vaccines capable of eliciting an immune antitumor response for prostate tumors are disclosed. The active ingredient in such vaccines is selected from the group consisting of human PSA and expression system capable of generating in situ human PSA.

Abstract: Methods of isolating and purifying caveolae, microdomains of GPI-anchored proteins, and membranes consisting essentially of caveolae associated with microdomains of GPI-anchored proteins from endothelial cell membranes are disclosed. The methods comprise coating a luminal surface of an endothelial cell membrane with an adherent first ionic material by perfusion from a luminal cavity adjacent to the endothelial cell membrane, forming a pellicle by contacting the first ionic material with a second ionic material, and isolating and purifying the pellicle. The pellicle is then processed to isolate the desired cellular component.

Abstract: A vaccine for the immunocontraception of mammals is described. The vaccine consists of zona pellucida antigens and an adjuvant encapsulated in a liposome delivery system. The liposome delivery system allows for the slow release of antigen resulting in a prolonged immune response. In particular, after a single injection of the vaccine, levels of anti-zona pellucida antibodies were detected for up to 22 months in seals. Thus, the vaccine according to the present invention is effective after a single dose and is therefore very useful in immunocontraceptive protocols.