58 results about "Biotherapeutic agent" patented technology

Probiotic Bifidobacterium strain AH1714 is significantly immunomodulatory following oral consumption. The strain is useful as an immunomodulatory biotherapeutic agent.

Protein transduction exploits the ability of some cell-penetrating peptide (CPP) sequences to enhance the uptake of proteins and other macromolecules by mammalian cells. Previously developed hydrophobic CPPs, named membrane translocating sequence (MTS), membrane translocating motif (MTM) and macromolecule transduction domain (MTD), are able to deliver biologically active proteins into a variety of cells and tissues. Various cargo proteins fused to these CPPs have been used to test the functional and/or therapeutic efficacy of protein transduction. For example, recombinant proteins consisting of suppressor of cytokine signaling 3 protein (CP-SOCS3) fused to the fibroblast growth factor (FGF) 4-derived MTM were developed to inhibit inflammation and apoptosis. However, CP-SOCS3 fusion proteins expressed in bacteria were hard to purify in soluble form. To address these critical limitations, CPP sequences called advanced MTDs (aMTD) have been developed in this art. This is accomplished by (i) analyzing previous developed hydrophobic CPP sequences to identify specific critical factors (CFs) that affect intracellular delivery potential and (ii) constructing artificial aMTD sequences satisfied for each critical factor. In addition, solubilization domains (SDs) have been incorporated into the aMTD-fused SOCS3 recombinant proteins to enhance solubility with corresponding increases in protein yield and cell-/tissue-permeability. These recombinant SOCS3 proteins fused to aMTD/SD having much higher solubility/yield and cell-/tissue-permeability have been named as improved cell-permeable SOCS3 (iCP-SOCS3) proteins. Previously developed CP-SOCS3 proteins fused to MTM were only tested or used as anti-inflammatory agents to treat acute liver injury. In the present art, iCP-SOCS3 proteins have been tested for use as anti-cancer agents in the treatment of hepatocellular carcinoma. Since SOCS3 is frequently deleted in and loss of SOCS3 in hepatocytes promotes resistance to apoptosis and proliferation, we reasoned that iCP-SOCS3 could be used as a protein-based intracellular replacement therapy for the treatment of hepatocellular carcinoma. The results support this reasoning: treatment of hepatocellular carcinoma cells with iCP-SOCS3 results in reduced cancer cell viability, enhanced apoptosis and loss of cell migration/invasion potential. Furthermore, iCP-SOCS3 inhibits the growth of hepatocellular carcinoma in a subcutaneous xenografts model. In the present invention with iCP-SOCS3 fused to an empirically determined combination of newly developed aMTD and customized SD, macromolecule intracellular transduction technology (MITT) enabled by the advanced MTD may provide novel protein therapy against hepatocellular carcinoma.

In principle, protein-based biotherapeutics offers a way to control biochemical processes in living cells under non-steady state conditions and with fewer off-target effects than conventional small molecule therapeutics. However, systemic protein delivery in vivo has been proven difficult due to poor tissue penetration and rapid clearance. Protein transduction exploits the ability of some cell-penetrating peptide (CPP) sequences to enhance the uptake of proteins and other macromolecules by mammalian cells. Previously developed hydrophobic CPPs, named membrane translocating sequence (MTS), membrane translocating motif (MTM) and macromolecule transduction domain (MTD), are able to deliver biologically active proteins into a variety of cells and tissues. Various cargo proteins fused to these CPPs have been used to test the functional and/or therapeutic efficacy of protein transduction. The recombinant proteins consisting of suppressor of cytokine signaling 3 (CP-SOCS3) protein fused to the fibroblast growth factor (FGF) 4-derived MTM were developed to inhibit inflammation and apoptosis. However, CP-SOCS3 fusion proteins expressed in bacteria cells were hard to be purified in soluble form. To address these critical limitations, CPP sequences called advanced MTDs (aMTDs) have been developed in this art. This is accomplished by (i) analyzing previous developed hydrophobic CPP sequences to identify specific critical factors (CFs) that affect intracellular delivery potential and (ii) constructing artificial aMTD sequences satisfied for each critical factor. In addition, solubilization domains (SDs) have been incorporated into the aMTD-fused SOCS3 recombinant proteins to enhance solubility with corresponding increases in protein yield and cell-/tissue-permeability. These recombinant SOCS3 proteins fused to aMTD/SD having much higher solubility/yield and cell-/tissue-permeability have been named as improved cell-permeable SOCS3 (iCP-SOCS3) proteins. Previously developed CP-SOCS3 proteins fused to MTM were only tested or used as anti-inflammatory agents to treat acute liver injury. In the present art, iCP-SOCS3 proteins have been tested for use as anti-cancer agents in the treatment of various cancers likes gastric, colorectal and breast cancer, and glioblastoma. Since SOCS3 is frequently deleted in and loss of SOCS3 in tumors promotes resistance to apoptosis and proliferation, we reasoned that iCP-SOCS3 could be used as a protein-based intracellular replacement therapy for the treatment of various cancers. The results demonstrated in this art support the reasoning: treatment of cancer cells with iCP-SOCS3 results in reduced cancer cell viability, enhanced apoptosis of solid tumors including gastric, colorectal and breast cancer, and glioblastoma and loss of cell migration/invasion potential. Furthermore, iCP-SOCS3 inhibits the growth of gastric and colorectal tumors in a subcutaneous xenografts model. In the present invention with iCP-SOCS3, where SOCS3 is fused to an empirically determined combination of newly developed aMTD and customized SD, macromolecule intracellular transduction technology (MITT) enabled by the advanced MTDs may provide novel protein therapy against various tumors such as gastric cancer, colorectal cancer, glioblastoma, and breast cancer.

In principle, protein-based biotherapeutics offers a way to control biochemical processes in living cells under non-steady state conditions and with fewer off-target effects than conventional small molecule therapeutics. However, systemic protein delivery in vivo has been proven difficult due to poor tissue penetration and rapid clearance. Protein transduction exploits the ability of some cell-penetrating peptide (CPP) sequences to enhance the uptake of proteins and other macromolecules by mammalian cells. Previously developed hydrophobic CPPs—named membrane translocating sequence (MTS), membrane translocating motif (MTM) and macromolecule transduction domain (MTD)—are able to deliver biologically active proteins into a variety of cells and tissues. Various cargo proteins fused to these CPPs have been used to test the functional and/or therapeutic efficacy of protein transduction. Previously, recombinant proteins consisting of suppressor of cytokine signaling 3 (SOSC3) fused to the fibroblast growth factor (FGF) 4-derived MTM were developed to inhibit inflammation and apoptosis. However, this SOCS3 fusion proteins expressed in bacteria cells were hard to be purified in soluble form. To address these critical limitations, CPP sequences called advanced MTDs (aMTDs) have been developed in this art. The development of this art has been accomplished by (i) analyzing previous developed hydrophobic CPP sequences to identify specific critical factors (CFs) that affect intracellular delivery potential and (ii) constructing artificial aMTD sequences that satisfy each critical factor. Furthermore, solubilization domains (SDs) have been incorporated into the aMTD-fused SOCS3 recombinant proteins to enhance solubility with corresponding increases in protein yield and cell-/tissue-permeability. These recombinant SOCS3 proteins fused to aMTD/SD having much higher solubility/yield and cell-/tissue-permeability have been named as improved cell-permeable SOCS3 (iCP-SOCS3) proteins. Previously developed SOCS3 recombinant proteins fused to MTM were only tested or used as anti-inflammatory agents to treat acute liver injury. In the present art, iCP-SOCS3 proteins have been tested for use as anti-angiogenic agents. Since SOCS3 is known to be an endogenous inhibitor of pathological angiogenesis, we reasoned that iCP-SOCS3 could be used as a protein-based intracellular replacement therapy for inhibiting angiogenesis in tumor cells. The results demonstrated in this art support this following reasoning: Cancer treatment with iCP-SOCS3 results in reduced endothelial cell viability, loss of cell migration potential and suppressed vascular sprouting potentials. In the present invention with iCP-SOCS3, where SOCS3 is fused to an empirically determined combination of newly developed aMTD and customized SD, macromolecule intracellular transduction technology (MITT) enabled by the advanced MTDs may provide novel protein therapy against cancer cell-mediated angiogenesis.

The present invention is directed to an aqueous pharmaceutical composition, particularly an aqueous ophthalmic composition, suitable as an injection, particularly an intravitreal injection. The composition includes a biologic therapeutic agent (e.g., an isolated monoclonal antibody that specifically binds to a C5 protein) that tends to raise the viscosity of the composition and a guanidine and/or guanidine derivative (e.g., L-arginine) that tends to lower the viscosity of the composition.

The present invention provides compound having a structure of Formula I or Formula II. Uses of such compounds for treatment of various indications, including prostate cancer as well as methods of treatment involving such compounds are also provided.

This invention relates to pressure torque sanitary diaphragm valves and methods of using torque sensitive sanitary valves in the production of chemical and biological therapeutics to obtain procedural reproducibility in the production pharmaceutical compounds and intermediates related thereto.

Bifidobacterium strain AH121A is significantly immunomodulatory following oral consumption. The strain is useful as an immunomodulatory biotherapeutic agent.

Embodiments are related to the field of immunology, and provide a highly avid LeY specific biotherapeutic including at least one further binding site having a different specificity to bind an epitope of a glycosylated cell surface molecule of a tumor cell, characterized by EC50 of less than 1 mM to confer immediate cytotoxicity to the tumor cell.

The present study investigated the use of macromolecule intracellular transduction technology (MITT) to deliver biologically active TFF1 protein into gastric cancer cells both in vitro and in vivo. Proteins engineered to enter cancer cells are supposed to suppress cell proliferation and survival, consistent with its role as a tumor suppressor. The invention has developed new hydrophobic CPP-advanced MTDs (aMTDs) for high solubility/yield and cell-/tissue-permeability of the recombinant therapeutic fusion proteins. The TFF1 protein has been fused to aMTD165 and solubilization domains (SDs), and tested their therapeutic applicability as a gastric cancer-specific protein-based anti-cancer agent. Treatment with CP-TFF1 in gastric cancer cells reduced cancer cell viability (60%˜80% in 10 μM treatment), inhibited cell migration (approximately 50%). Furthermore, CP-TFF1 significantly inhibited the tumor growth during the treatment and the effect persisted for at least 3 weeks after the treatment was terminated (90% inhibition at day 42) in a xenografts model which were subcutaneously implanted with tumor block of gastric cancer cells (MKN45). In the present invention, CP-TFF1 recombinant protein showed the potential of novel protein therapies against gastric cancer.

Gastrointestinal track (GIT) including oesophageal and gastric cancers are a leading cause of cancer death worldwide. Limited therapeutic options highlight the need to understand the molecular changes responsible for the disease and to develop therapies based on this understanding. Advances in understanding the molecular changes responsible for GIT cancer etiology and progression are expected to improve disease diagnosis and treatment. The glutathione peroxidase 7 (GPX7) a candidate tumor suppressor implicated in GIT cancers including esophageal and gastric cancers has been implicated as a potential tumor suppressor gene in esophageal and gastric cancers; however, this claim is controversial. The goal of this invention is to develop cell-permeable (CP-) form of GPX7 to utilize the therapeutic potential of GPX7 in the treatment of GIT cancers. Using macromolecule intracellular transduction technology (MITT) enabled by novel hydrophobic cell-penetrating peptide (CPP) called advanced macromolecule transduction domains (aMTDs) which are able to promote protein uptake by mammalian cells and tissues, the first CP-GPX7 protein has been developed to deliver biologically active GPX7 protein into human oesophageal and gastric cancer cells, resulting in suppression of cell phenotypes and induction of changes in biomarker expression consistent with previously described effects of GPX7. CP-GPX7 recombinant protein fused to aMTD also suppresses the growth of human gastric tumors in a mouse xenograft model. The results of this art provide further evidence that GPX7 can function as an anti-cancer molecule and suggest that practical methods to augment GPX7 function could be useful in treating of some types of GIT cancers. The present art with CP-GPX7 recombinant protein illustrates the use of protein-based therapies to target GIT cancers.

Novel antimicrobial agents that can serve as replacements to conventional pharmaceutical antibiotics are disclosed. The antimicrobial agents comprise conjugatively transmissible plasmids that kill targeted pathogenic bacteria, but are not harmful to donor bacteria. Two types of lethal transmissible plasmids are disclosed. One type kills recipient bacteria by unchecked (“runaway”) replication in the recipient cells and is prevented from occurring in donor cells. Another type kills recipient bacteria by expressing a gene that produces a product detrimental or lethal to recipient bacterial cells, that gene being prevented from expression in donor cells.

The invention relates to an application of Lactobacillus paracasei to CAR (chimeric antigen receptor)-T cell therapy, belongs to the technical field of microorganisms and particularly discloses Lactobacillus paracasei MIT-16 and an application of the Lactobacillus paracasei to the immunological therapy process of canine tumors. The Lactobacillus paracasei MIT-16 with higher acid-producing abilityis separated and screened from an intestinal tract of a mouse, has good acid resistance, stronger bactericidal capacity and remarkable immune regulation functions, particularly plays an important rolein immune response regulation in tumor therapy and can be used as an immune regulation biotherapy agent.

Systems and methods for inspecting particles in a liquid beneficial agent are provided. Inspecting particles in a liquid beneficial agent includes selectively illuminating at least a portion of a liquid beneficial agent contained within a container using an excitation beam configured to excite photoluminescent particles in the liquid beneficial agent to emit an emission light and produce scattered excitation light, filtering the illuminated portion of the liquid beneficial agent to transmit the emission light and block the scattered excitation light, obtaining an image of the filtered emission light, analyzing image data representing the image of the filtered emission light to detect regions of the image representing the intrinsic photoluminescence of the photoluminescent particles, measuring an intensity of the regions of the image representing the intrinsic photoluminescence of the photoluminescent particles, and determining a size or number of the photoluminescent particles from the measured intensity of the regions.

The present invention relates to methods of treating cancer in a human subject in need thereof. In particular, the present invention relates to treating a cancer by administering a recombinant virus which expresses one or more biotherapeutic agents in a subject, and administering to the subject a nucleotide analogue or nucleotide precursor analogue chemotherapeutic agent. The invention further relates to method for treating cancer by administering a nucleotide analogue or nucleotide precursor analogue chemotherapeutic agent and a caspase inhibitor, and, optionally, also administering a recombinant virus expressing one or more biotherapeutic agents in the subject. The invention also relates to a method for treating cancer by administering purified interferon gamma to a subject and administering to the subject a nucleotide analogue or nucleotide precursor analogue chemotherapeutic agent. Also provided are pharmaceutical compositions, including controlled release pharmaceutical compositions containing: a nucleotide analogue or nucleotide precursor analogue chemotherapeutic agent and a recombinant virus; a nucleotide analogue or nucleotide analogue precursor chemotherapeutic agent and a caspase inhibitor; or a purified interferon gamma and a nucleotide analogue or nucleotide precursor analogue chemotherapeutic agent.

This invention pertains to the identification of antibody mediated epitope mimics and applications of the identification of said mimic peptides in the design of biotherapeutics and vaccines.

The present invention relates to a more efficient and accurate method for the identification and quantification of comparatively low abundant glycopeptides, compared with general peptides, using mass spectrum obtained by using high resolution mass spectrometer. Therefore, the method of the present invention can be effectively used for the techniques for identification of biotherapeutics and diagnosis of cancer or disease by screening glycopeptide, the disease marker (Biomarker), from various samples.