57results about How to "Reduced half-life" patented technology

The present invention provides for a modified antibody of class IgG, in which at least one amino acid from the heavy chain constant region selected from the group consisting of amino acid residues 250, 314, and 428 is substituted with another amino acid which is different from that present in the unmodified antibody, thereby altering the binding affinity for FcRn and / or the serum half-life in comparison to the unmodified antibody.

The present invention provides for a modified antibody of class IgG, in which at least one amino acid from the heavy chain constant region selected from the group consisting of amino acid residues 250, 314, and 428 is substituted with another amino acid which is different from that present in the unmodified antibody, thereby altering the binding affinity for FcRn and / or the serum half-life in comparison to the unmodified antibody.

Compositions and methods are described for the delivery of a fully human post-translationally modified (HuPTM) therapeutic VEGF-Trap (VEGF-TrapHuPTM)—to a human subject diagnosed with an ocular disease or condition or cancer associated with neovascularization and indicated for treatment with the therapeutic mAb. Delivery may be advantageously accomplished via gene therapy—e.g., by administering a viral vector or other DNA expression construct encoding the VEGF-TrapHuPTM to a patient (human subject) diagnosed with an ocular condition or cancer indicated for treatment with the VEGF-Trap—to create a permanent depot in a tissue or organ of the patient that continuously supplies the VEGF-TrapHuPTM, i.e., a human-glycosylated transgene product. Alternatively, the VEGF-TrapHuPTM, for example, produced in cultured human cell culture, can be administered to the patient for treatment of the ocular disease or cancer.

Intradermal delivery devices, systems and methods thereof for the administration of a natriuretic or chimeric peptide are described. The described delivery devices, systems and methods provide for the treatment of pathological conditions such as kidney disease alone, heart failure alone, concomitant kidney disease and heart failure, or cardiorenal syndrome by delivery of a natriuretic or chimeric peptide through a microneedle array using a delivery pump. The described delivery devices, systems and methods can provide for greater availability of a natriuretic or chimeric peptide and improved pharmacokinetics.

Methods, compounds, and medicinal formulations utilizing biocompatible polymers for delivery of a drug, particularly for solubilizing, stabilizing and / or providing sustained release of drug from topical, implantable, and inhalation systems. Many of the methods, compounds, and medicinal formulations are particularly suitable for oral and / or nasal inhalation and use polymers of the formula —[X—R1—C(O)]— wherein each R1 is an independently selected organic group that links the —X— group to the carbonyl group, and each X is independently oxygen, sulfur, or catenary nitrogen.

The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which X is a nucleic acid sequence which encodes a cleavage site; and A and B are nucleic acid sequences encoding a first and a second chimeric antigen receptor (CAR), each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens; wherein one of the first or second CARs is an activating CAR comprising an activating endodomain and the other CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain; and wherein: (a) the first and / or second CAR comprises an intracellular retention signal; and / or (b) the signal peptide of the first or second CAR comprises one or more mutation(s) such that it has fewer hydrophobic amino acids.

The present invention relates to the use of a C1 inhibitor (C1INH) with shorter half-life than plasma-derived C1INH for the preparation of a medicament for the transient treatment of an individual. It relates to both therapeutic and prophylactic treatment. The method of the invention allows for the administration of C1INH at certain therapeutic levels for a concise pre-determined time span. Pharmaceutical compositions based on C1INH with shorter half-lives may be used both in situations where transient treatment is merely and advantage. The advantage of the use according to the invention is that an individual is not exposed to C1INH for longer than required, since the levels of the C1INH more rapidly subsides after administration has stopped. In contrast, levels of plasma-derived C1INH would remain elevated for a prolonged period of time.

Control Devices are disclosed including RNA destabilizing elements (RDE), RNA control devices, and destabilizing elements (DE) combined with Chimeric Antigen Receptors (CARs) or other transgenes in eukaryotic cells. Multicistronic vectors are also disclosed for use in engineering host eukaryotic cells with the CARs and transgenes under the control of the control devices. These control devices can be used to optimize expression of CARs in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered after stimulation of the CAR on the eukaryotic cell.

A kit of parts includes a) gemcitabine or a pharmaceutically acceptable salt thereof and b) a cyclic dinucleotide or pharmaceutically acceptable salt thereof, wherein the cyclic dinucleotide or pharmaceutically acceptable salt thereof is an agonist of the receptor known as “stimulator of interferon genes” (STING), for use in the treatment of solid pancreatic cancer.

In vivo methods for making anti-idiotypic antibodies and compositions comprising the antibodies.

The present invention provides methods for inducing tolerance and / or suppressing an immune response to an antigen by passing a cell suspension containing an anucleate cell through a constriction, wherein the constriction deforms the cell thereby causing a perturbation of the cell such that an antigen and / or tolerogenic factor enters the cell. In some embodiments, the anucleate cell is delivered to an individual and the antigen is delivered to and processed in a tolerogenic environment to induce tolerance and / or suppress an immune response to the antigen.

The current invention covers an improved meat-packaging procedure and machine for packaging meat cuts for long-term storage at temperatures of between 28° and 32° F. The process includes sealing meat cuts within a master bag containing oxygen scavenger materials capable of reducing the residual oxygen content of the atmosphere within the bag to 0 ppm within 24 hours of sealing. Gas is injected into the master bag to form a nitrogen-rich storage environment of at least 50% nitrogen. A small amount of carbon monoxide gas (0.1% to 5%) is preferred for the storage environment, as this helps to preserve the red coloration of meat under long-term storage conditions. The over-wrap of the meat trays can be perforated so that gas exchange occurs within the master bag between the interior and exterior of the meat tray to absorb the residual oxygen inside the meat trays. For meat trays containing meat with poor color stability, oxygen scavengers are preferably placed within the meat trays. For cuts with good color stability, the oxygen scavengers may be placed outside the meat trays. Meat can be stored by this system for up to 15 weeks and up to nine days of retail display life.

Control Devices are disclosed including RNA destabilizing elements (RDE), RNA control devices, and destabilizing elements (DE) combined with Chimeric Antigen Receptors (CARs) or other transgenes in eukaryotic cells. Multicistronic vectors are also disclosed for use in engineering host eukaryotic cells with the CARs and transgenes under the control of the control devices. These control devices can be used to optimize expression of CARs in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered after stimulation of the CAR on the eukaryotic cell.

The present invention relates to modified forms of IL-12. These modified forms of IL-12 may be engineered to have a shortened in vivo half-life compared and / or enhanced localization of biological effects compared to that of corresponding non-modified form of IL-12. Short half-life and membrane bound forms of IL-12 may provide greater therapeutic control for in vivo therapeutic delivery, in particular when used in combination with ligand inducible delivery of IL-12. Modified forms of IL-12 engineered to have shortened in vivo half-life and / or enhanced localization of biological effects include heterodimeric p35 / p40, single chain and membrane bound forms of IL-12 wherein a naturally occurring IL-12 amino acid sequence is genetically modified to destabilize IL-12 tertiary structure / polypeptide folding and enhance susceptibility of the IL-12 molecule to in vivo proteolytic degradation.

The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which X is a nucleic acid sequence which encodes a cleavage site; and A and B are nucleic acid sequences encoding a first and a second chimeric antigen receptor (CAR), each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens, wherein the spacer of the first CAR is different to the spacer of the second CAR and wherein one of the first or second CARs is an activating CAR comprising an activating endodomain and the other CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain; and wherein: (a) the first and / or second CAR comprises an intracellular retention signal; and / or (b) the signal peptide of the first or second CAR comprises one or more mutation(s) such that it has fewer hydrophobic amino acids.

The present invention provides conjugates containing metal binding ligands, as well as nanocarriers prepared from the conjugates.

The invention features compositions comprising agents that inhibit or reduce self-reactive IgE and / or basophils, and related methods of using the compositions for treating or preventing lupus, lupus nephritis, and lupus-related disorders.

The disclosure relates to antibodies specific to FcRn, formulations comprising the same, use of each in therapy, processes for expressing and optionally formulating said antibody, DNA encoding the antibodies and hosts comprising said DNA.

Compositions and methods related to anucelate cells (e.g., bacterial minicells) for pesticide degradation applications including related cells, polypeptides, and vectors.

The present invention provides methods for stimulating an immune response to an antigen comprising administering to an individual, an anucleate cell-derived vesicle comprising an antigen and / or an adjuvant. In some embodiments, the anucleate cell-derived vesicle comprising the antigen and / or adjuvant is generated by passing a cell suspension containing an input anucleate cell through a constriction, wherein the constriction deforms the input anucleate cell thereby causing a perturbation of the cell to form an anucleate cell-derived vesicle such that an antigen and / or an adjuvant enters the anucleate cell-derived vesicle. In some embodiments, the anucleate cell-derived vesicle comprising the antigen and / or adjuvant is delivered to an individual and the antigen is delivered to and processed in an immunogenic environment to treat a disease, prevent a disease, and / or vaccinate an individual against an antigen.

Short-acting Factor VII peptides are disclosed. A shortened half-life is desirable for treatment of acute bleeding and similar disorders. Modification of the sialylation and / or glycosylation of Factor VII and variants thereof produced peptides useful in treating conditions of acute bleeding.

The present invention provides a nucleic acid construct comprising the following structure: A-X—B in which A and B are nucleic acid sequences encoding a first and a second chimeric antigen receptor (CAR); and X is a nucleic acid sequence which encodes a cleavage site, wherein the first and second CAR recognise different antigens; the first and second CAR comprise or associate with activating endodomains; and (a) the first and / or second CAR comprises an intracellular retention signal; and / or (b) the signal peptide of the first or second CAR comprises one or more mutation(s) such that it has fewer hydrophobic amino acids.

The present invention relates to a stabilized fluoropolymer aqueous dispersion, wherein the stabilizer is polysiloxane polyoxyethylene copolymer preferably having a cloud point of no greater than 25° C.

The present invention relates to an oral applicable therapeutic dosage form, in particular an orodispersible film comprising Enalapril or pharmaceutically acceptable salts thereof for use in the treatment of hypertension in a pediatric population. The pediatric population is defined from 1 to 18 years of age. The present invention also provides a method of manufacturing of such a dosage form.