78 results about "Membrane anchor" patented technology

The invention is related to polynucleotide-based cytomegalovirus vaccines. In particular, the invention is plasmids operably encoding HCMV antigens, in which the naturally-occurring coding regions for the HCMV antigens have been modified for improved translation in human or other mammalian cells through codon optimization. HCMV antigens which are useful in the invention include, but are not limited to pp65, glycoprotein B (gB), IE1, and fragments, variants or derivatives of either of these antigens. In certain embodiments, sequences have been deleted, e.g., the Arg435-Lys438 putative kinase in pp65 and the membrane anchor and endocellular domains in gB. The invention is further directed to methods to induce an immune response to HCMV in a mammal, for example, a human, comprising delivering a plasmid encoding a codon-optimized HCMV antigen as described above. The invention is also directed to pharmaceutical compositions comprising plasmids encoding a codon-optimized HCMV antigen as described above, and further comprising adjuvants, excipients, or immune modulators.

The present invention relates to immunoglobulins that bind IgE and FcγRIIb with high affinity, said compositions being capable of inhibiting cells that express membrane-anchored IgE. Such compositions are useful for treating IgE-mediated disorders, including allergies and asthma.

The present invention relates to immunoglobulins that bind IgE and FcγRIIb with high affinity, said compositions being capable of inhibiting cells that express membrane-anchored IgE. Such compositions are useful for treating IgE-mediated disorders, including allergies and asthma.

The present invention provides compositions and methods for use in enzyme replacement therapy. The inventors disclose a method of producing membrane bound enzymes in an active soluble form by eliminating the glycosylphosphatidylinositol (GPI) membrane anchor. In particular the inventors disclose a soluble active form of the membrane bound enzyme TNSALP which they produced by deleting the GPI anchor single peptide sequence. They have further shown that this composition is useful for treatment of hypophosphatasia. The inventors also disclose oligo acid amino acid variants thereof which specifically target bone tissue.

The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating polypeptides capable of anchoring heterologous polypeptides to a bacterial inner membrane. In the technique, libraries of candidate anchor polypeptides are expressed as fusions with a heterologous polypeptide that is capable of being detected when bound to the inner membrane. In bacteria expressing a functional anchor sequence, the heterologous polypeptide becomes bound to outer face of the inner membrane. Bacteria with the functional anchor sequence can be identified by removing the outer membrane to remove non-anchored heterologous polypeptide followed by detection of anchored heterologous polypeptide. Such bacteria may be detected in numerous ways, including use of direct fluorescence or secondary antibodies that are fluorescently labeled, allowing use of efficient techniques such as fluorescence activated cell sorting (FACS).

The present invention provides a total artificial heart system for auto-regulating flow and pressure balance. In one embodiment the system comprises an atrial reservoir comprising inlets and outlets connectable to a mammalian cardiovascular system and at least first and second continuous pumps connected to the atrial reservoir. In further embodiments, the system comprises an atrial reservoir comprising at least two atrial chambers, and a means for transmitting fluid pressure between the atrial chambers. The means for transmitting fluid pressure include, but are not limited to a diaphragm, an interatrial window, a flexible membrane, a valve, a filter, or combinations thereof. In another embodiment, the means for transmitting fluid pressure comprises an implantable diaphragm comprising an outer rim attachable to biological tissue and a membrane anchored at its periphery by said outer rim.

The present invention provides compositions and methods for use in enzyme replacement therapy. The inventors disclose a method of producing membrane bound enzymes in an active soluble form by eliminating the glycosylphosphatidylinositol (GPI) membrane anchor. In particular the inventors disclose a soluble active form of the membrane bound enzyme TNSALP which they produced by deleting the GPI anchor single peptide sequence. They have further shown that this composition is useful for treatment of hypophosphatasia. The inventors also disclose oligo acid amino acid variants thereof which specifically target bone tissue.

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for the membrane-anchored, 4O.kDa mesothelin polypeptide, which is overexpressed in several tumors, such as pancreatic and ovarian tumors, mesothelioma and lung cancer cells. These antibodies, accordingly, can be used to treat these and other disorders and conditions. Antibodies of the invention also can be used in the diagnostics field, as well as for further investigating the role of mesothelin in the progression of disorders associated with cancer. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.

A method for manufacturing recombinant neuraminidase by culturing in a suitable culture medium host cells which are transformed with a neuraminidase expression vector or infected with a virus which is transformed with a neuraminidase expression vector, wherein the expression vector comprises at least a part of the coding region of a neuraminidase gene of an influenza virus minus the region which codes for the membrane anchor, or a modified version thereof, preceded in phase by a signal sequence; and isolating the expression product neuraminidase from the culture medium. The invention further relates to vectors expressing the neuraminidase.

The present invention relates to the discovery of antibodies that bind to novel epitopes present on membrane-anchored immunoglobulins and which bind to these novel epitopes on the surface of B cells and plasma cells. In addition, the antibodies of the present invention can mediate ADCC and can be useful to deplete those B cells and plasma cells expressing the novel epitopes of the invention. The antibodies of the present invention can be useful for the treatment of B cell-mediated diseases and diseases caused by monoclonal expansion of B cells. Accordingly the present invention also provides compositions and methods for the prevention, management, treatment or amelioration of B cell-mediated diseases and diseases caused by monoclonal expansion of B cells.

The present invention relates to the discovery of antibodies that bind to novel epitopes present on membrane-anchored immunoglobulins and which bind to these novel epitopes on the surface of B cells and plasma cells. In addition, the antibodies of the present invention can mediate ADCC and can be useful to deplete those B cells and plasma cells expressing the novel epitopes of the invention. The antibodies of the present invention can be useful for the treatment of B cell-mediated diseases and diseases caused by monoclonal expansion of B cells. Accordingly the present invention also provides compositions and methods for the prevention, management, treatment or amelioration of B cell-mediated diseases and diseases caused by monoclonal expansion of B cells.

The present invention provides a drug delivery system wherein a "parachute" structure is coupled to a therapeutic compound. The "parachute" structure comprises hydrophilic branched molecules with a defined action diameter. The complex (a parachute structure coupled with a therapeutic compound) is either fixed at a cell membrane or delivered to a defined distance from the membrane within the cell. The membrane-anchoring / localizing effect of the parachute is achieved by hydrophilic structures linked with a branching unit of desired therapeutic compounds. Furthermore, the parachute structures can be connected by a spacer (e.g. beta-amino acids, gamma-amino butyric acid, or poly-amino acids) instead of directly binding to the therapeutic compound, so that the therapeutic compounds can be localized within the cells at a defined distance from the cell membrane. A spacer containing a breaking point can determine the time span, during which the drug exhibits its therapeutic activity. The hydrophilic residues can also carry signals for targeting the parachute-therapeutic complex to a defined tissue type. This can be mediated by an antibody which is specific for a tumor marker. Alternatively, a Biotin can be attached at C6 position of the sugar and then react with an Avidin-labeled tumor-specific antibody. The parachute function may also be achieved by other, more bulky hydrophilic structures such as oligosaccharides connected to the branching unit. Such sugar oligomers have specific attachment points to cell selectins, and therefore do not need additional molecular structures to target a specific tumor tissue. The use of the parachute structure gives the advantages of being able to localize a photosensitizer or chemotherapeutic drug at the site within a cell where it can destroy the tumor cell most effectively. This reduces the level of necessary systemic doses of the drugs, promotes drug excretion, and therefore considerably reduces side effects of the therapy.

A therapeutic composition or a vaccine comprising tumor membrane-anchored cytokines or other immunostimulatory or costimulatory molecules are provided. The therapeutic composition or a tumor vaccine can be used for treating a tumor or other disease such as autoimmune disorder, viral diseases, bacterial diseases, parasitic diseases, and transplant rejection.

The invention provides a polynucleotide comprising a sequence encoding a polypeptide that is capable of high level presentation of antigenic peptides on antigen-presenting cells, wherein the polypeptide comprises a β2-microglobulin molecule that is linked through its carboxyl terminal to a bridge peptide which spans the whole distance to the cell membrane, said bridge peptide being linked to a polypeptide stretch consisting of the full or partial transmembrane and / or cytoplasmic domains selected from the group consisting of a toll-like receptor (TLR) polypeptide, a CD40 polypeptide, and TLR and CD40 polypeptides fused in tandem, that allows the anchorage of the β2-microglobulin molecule to the cell membrane, and through its amino terminal to at least one antigenic peptide comprising an MHC class I epitope, wherein said antigenic peptide is preferably derived from a tumor-associated antigen or from a pathogenic antigen. Antigen presenting cells and DNA and cellular vaccines for treatment of cancer and infectious diseases, are also provided.

The present invention relates to a coccidiosis vaccine to protect poultry against Eimeria infection, comprising a recombinant avian adenovirus vector comprising in frame a (heterologous) promoter linked to a hydrophobic signal sequence for membrane anchoring, or linked to an hydrophobic secretion signal and a cleavage site to allow secretion; a multiple cloning site for in frame insertion of an Eimeria antigen ORF such as derived from the r56, 82 kDa, and / or TFP250 antigens; a polyadenylation signal; and an avian adenovirus genome.

The invention relates to bacterial cell surface display of post-translationally modified heterologous proteins. Provided is an isolated nucleic acid construct encoding a proteinaceous substance comprising, from the N-terminus to the C-terminus, at least (a) an N-terminal a lantibiotic leader sequence; (b) an amino acid sequence of interest to be post-translationally modified to a dehydroresidue- or thioether-bridge containing polypeptide; (c) a hydrophilic cell-wall spanning domain; (d) a sortase recognition motif; (e) a hydrophobic membrane spanning domain and (f) a C-terminal charged membrane anchoring domain. Also provided is a Gram-positive host cell expressing the construct, as well as a library of host cells.

An electroacoustic MEMS transducer, having a substrate of semiconductor material; a through cavity in the substrate; a back plate carried by the substrate through a plate anchoring structure, the back plate having a surface facing the through cavity; a fixed electrode, extending over the surface of the back plate; a membrane of conductive material, having a central portion facing the fixed electrode and a peripheral portion fixed to the surface of the back plate through a membrane anchoring structure; and a chamber between the membrane and the back plate, peripherally delimited by the membrane anchoring structure.

A recombinant DNA construct is provided and includes a first DNA fragment encoding a β-glucuronidase and a second DNA fragment encoding a membrane anchoring domain. The β-glucuronidase may be a human β-glucuronidase or a mouse β-glucuronidase. In one embodiment, an expression vector for delivering a gene of interest or portion thereof into a host cell includes a DNA sequence for the gene of interest, a first DNA fragment encoding a β-glucuronidase, and a second DNA fragment encoding a membrane anchoring domain. In another embodiment, a method of introducing a gene of interest or portion thereof into a host cell is provided, including introducing into the host cell a recombinant DNA construct.

The present invention relates to a TGF-β1 binding protein called r150. This protein has a GPI-anchor contained in r150 itself and not on a tightly associated protein and that it binds TGF-β1 with an affinity comparable to those of the signaling receptors. Furthermore, the released (soluble) form of this protein binds TGF-β1 independent of the types I and II receptors. Also, the soluble form inhibits the binding of TGF-β to its receptor. In addition, evidence that r150 is released from the cell surface by an endogenous phospholipase C is provided. Also, the creation of a mutant human keratinocyte cell line with a defect in GPI synthesis which displays reduced expression of r150 is described. Our results using these mutant keratinocytes suggest that the membrane anchored form of r150 is a negative modulator of TGF-beta responses. These findings, taken together with the observation that r150 forms a heteromeric complex with the signaling receptors, suggest that this accessory receptor in either its membrane anchored or soluble form may antagonize TGF-β responses in human keratinocytes. Experiments with mutants confirmed that TGFβ1 activity can be modulated when the expression of the accessory receptor r150 is silenced. The complete nucleic acid and deduced amino acid sequences are now provided. The r150 cloned nucleic acid was used to study overexpression of r150. When r150 gene is overexpressed, TGFβ responses are increased. r150 and its derivatives or precursors (fragments, variants and nucleic acids encoding the same) will find a broad clinical utility, knowing that TGFβ1 is an important cytokine.

A method for manufacturing a suspended membrane in a single-crystal semiconductor substrate, including the steps of: forming in the substrate an insulating ring delimiting an active area, removing material from the active area, successively forming in the active area a first and a second layers, the second layer being a single-crystal semiconductor layer, etching a portion of the internal periphery of said ring down to a depth greater than the thickness of the second layer, removing the first layer so that the second layer formed a suspended membrane anchored in the insulating ring.

Filamentous phage comprising a matrix of cpVIII proteins encapsulating a genome encoding first and second polypeptides of an antogenously assembling receptor, such as an antibody, and a receptor comprised of the first and second polypeptides surface-integrated into the matrix via a filamentous phage coat protein membrane anchor domain fused to at least one of the polypeptides.

The present invention provides a drug delivery system wherein a "parachute" structure is coupled to a therapeutic compound. The "parachute" structure comprises hydrophilic branched molecular fragments, or a cyclodextrin moiety, with a defined action diameter. The complex (a parachute structure coupled with a therapeutic compound) is either fixed at a cell membrane or delivered to a defined distance from the membrane within the cell. The membrane-anchoring / localizing effect of the parachute is achieved by hydrophilic structures linked with a branching unit of desired therapeutic compounds. Furthermore, the parachute structures can be connected by a spacer (e.g. beta-amino acids, gamma-amino butyric acid, or poly-amino acids) instead of directly binding to the therapeutic compound, so that the therapeutic compounds can be localized within the cells at a defined distance from the cell membrane. A spacer containing a breaking point can determine the time span, during which the drug exhibits its therapeutic activity. The hydrophilic residues can also carry signals for targeting the parachute-therapeutic complex to a defined tissue type. This can be mediated by an antibody which is specific for a tumor marker. Alternatively, a biotin can be attached at C6 position of the sugar and then react with an avidin-labeled tumor-specific antibody. The parachute function may also be achieved by other, more bulky hydrophilic structures such as oligosaccharides connected to the branching unit. Such sugar oligomers have specific attachment points to cell selecting, and therefore do not need additional molecular structures to target a specific tumor tissue. The use of the parachute structure gives the advantages of being able to localize a photosensitizer or chemotherapeutic drug at the site within a cell where it can destroy the tumor cell most effectively. This reduces the level of necessary systemic doses of the drugs, promotes drug excretion, and therefore considerably reduces side effects of the therapy.

The invention discloses an odor control and deodorization system of a refuse landfill. The odor control and deodorization system comprises a reservoir region membrane laminating sealed odor control unit, a landfilling working surface leakage-proof membrane sealed odor control unit and an annular field and partitioning membrane anchoring sealed odor control unit, wherein the reservoir region membrane laminating sealed odor control unit is used for carrying out refuse dump odor control in a refuse reservoir region; the reservoir region membrane laminating sealed odor control unit is arranged nearby the landfilling working surface leakage-proof membrane sealed odor control unit or surrounds the landfilling working surface leakage-proof membrane sealed odor control unit; the landfilling working surface leakage-proof membrane sealed odor control unit is used for controlling the odor of a refuse landfilling working surface; the annular field and partitioning membrane anchoring sealed odor control unit is arranged at the periphery of the reservoir region membrane laminating sealed odor control unit. According to the odor control and deodorization system disclosed by the invention, refuselandfilling work is combined with odor control, and the odor control and deodorization are combined; the all-directional and multi-layered odor control and deodorization system is set; operation working time can be arranged and set according to changes of seasonal climates and weather and wind directions; the odor control and deodorization effects are good.

The present invention relates to a method for generating immunoglobulin sequences against cell-associated antigens, more particularly, antigens that are membrane-anchored. The invention also provides immunoglobulin sequences obtainable by the method of the invention. Specifically, the present invention relates to the generation of immunoglobulin sequences by use of DNA vaccination. More specifically, the present invention relates to generation of immunoglobulin sequences in camelids, preferably directed against cell-associated antigens, in particular antigens with multiple transmembrane spanning domains, including GPCRs and ion channels, by DNA vaccination. Furthermore, the present invention relates to said immunoglobulin sequences against cell-associated antigens, more particularly, antigens that are membrane-anchored, such as e.g. GPCRs and ion channels, more preferably ion channels.

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for the membrane-anchored, 29 kDa C4.4a polypeptide, which is over expressed in several tumors, e.g. lung, colorectal, pancreas, prostate, renal and breast cancer. These antibodies, accordingly, can be used to treat these and other disorders and conditions. Antibodies of the invention also can be used in the diagnostics field, as well as for further investigating the role of C4.4a in the progression of disorders associated with cancer. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.