Abstract: The present invention provides, among other things, compositions and methods for treatment of Friedrich's Ataxia based on effective targeting of a therapeutic moiety to mitochondria that can substitute for natural FXN protein activity or rescue one or more phenotypes or symptoms associated with frataxin-deficiency. In some embodiments, the present invention provides a targeted therapeutic comprising a therapeutic moiety, which is a polypeptide having an N-terminus and a C-terminus, a mitochondrial targeting sequence associated with the therapeutic moiety at the N-terminus, and a mitochondrial membrane-penetrating peptide associated with the therapeutic moiety at the C-terminus, wherein the therapeutic moiety is targeted to mitochondria upon cellular entry.

Abstract: Disclosed are methods of identifying an agent that modulates an NFAT regulator protein. One such method comprises contacting at least one test agent with a recombinant cell comprising at least one NFAT regulator protein or fragment or derivative thereof, assessing the effect of the test agent on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, and identifying the test agent that has an effect on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, whereby the identified test agent is characterized as an agent that modulates an NFAT regulator protein.

Abstract: In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.

Abstract: Provided herein are IL-2 muteins and IL-2 mutein Fc-fusion molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also, provided herein are linker peptides that are glycosylated when expressed in mammalian cells.

Abstract: The present invention relates to glucagon receptor agonists and their medical use, for example in the treatment of severe hypoglycemia.

Abstract: Peptides capable of interfering with the Kv2.1-mediated apoptotic K+ current surge that leads to neuronal cell death are described. The disclosed peptides are derived from the C-terminal region of Kv2.1, which mediates binding to the SNARE protein syntaxin. Disruption of Kv2.1 binding to syntaxin inhibits the apoptotic K+ current surge that leads to neuronal cell death. The present disclosure provides methods of inhibiting binding of Kv2.1 to syntaxin in a cell (in vitro or in vivo), such as for neuroprotection following cerebral ischemia, stroke, or traumatic brain injury, or during the course of a neurodegenerative disease, or any other condition associated with neuronal cell death.

Abstract: The present invention relates to regulation of cold sensation and pain. More particularly, the present invention is directed to nucleic acids encoding a member of the transient regulatory protein family, CMR1, which is involved in modulation of the perception of cold sensations and pain. In some embodiments, an isolated or recombinant CMR1 polypeptide is directly or indirectly attached to a detectable label or fused to a second polypeptide. In some embodiments, an isolated or recombinant CMR1 polypeptide is directly or indirectly bound to a solid support.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: The present invention relates to mutant transmembrane proteins which have increased conformational stability when compared to their parent protein, methods of selection and production. In particular the invention relates to mutant transmembrane proteins which are mutated in or in the proximity of the transmembrane alpha helices or in a kinked region or in an alpha-helix adjacent to a kink. The mutant transmembrane proteins have use in crystallization studies and also in screening to identify compounds for use in drug discovery and therapy.

Abstract: In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a truncated, ligand-binding portion of the extracellular domain of endoglin (ENG) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders.

Abstract: The present invention relates to a therapeutic polypeptide and methods for its creation and use for modulating an immune response in a host organism in need thereof. In particular, the invention relates to the administration to an organism in need thereof, of an effective amount of a pre-coupled polypeptide complex comprising a lymphokine polypeptide portion, for example IL-15 (SEQ ID NO: 5, 6), IL-2 (SEQ ID NO: 10, 12) or combinations of both, and an interleukin receptor polypeptide portion, for example IL-15Ra (SEQ ID NO: 7, 8), IL-2Ra (SEQ ID NO: 9, 11) or combinations of both, for augmenting the immune system in, for example, cancer, SCID, AIDS, or vaccination; or inhibiting the immune system in, for example, rheumatoid arthritis, or Lupus. The therapeutic complex of the invention surprisingly demonstrates increased half-life, and efficacy in vivo.

Abstract: The present invention relates to a chromatographic process for obtaining purified fibrinogen and thrombin from human plasma. The purified fibrinogen and thrombin preparations contain plasminogen in amounts less than 1 ug/mL. The low levels of plasminogen eliminates use of a proteolytic inhibitor, such as aprotinin in fibrin sealant kits which are used for human therapeutic applications.

Abstract: A chemoembolic agent is disclosed that includes an injectable, recombinantly synthesized silk-elastin like protein copolymer and one or more chemotherapeutic agents. Upon injection, the chemoembolic agent blocks the tumor vasculature, including the capillary bed, and may optionally release chemotherapeutic agents. The chemoembolic agent may be used to treat cancer, including hepatocellular carcinoma.

Abstract: The present invention relates to the newly identified timerization initiating and stagger determining capacity of the NC2 domain of collagen IX. The invention further relates to a hexavalent molecular building block wherein the linkage of additional moieties to the amino and carboxyl terminals of monomers comprising the NC2 domain of collagen IX promotes the directed association of those moieties via the trimerization initiating and stagger determining capacity of the NC2 domain of collagen IX.

Abstract: The invention relates to three isolated DNA molecules that encode for proteins, BigL1, BigL2 and BigL3, in the Leptospira sp bacterium which have repetitive Bacterial-Ig-like (Big) domains and their use in diagnostic, therapeutic and vaccine applications. According to the present invention, the isolated molecules encoding for BigL1, BigL2 and BigL3 proteins are used for the diagnosis and prevention of infection with Leptospira species that are capable of producing disease in humans and other mammals, including those of veterinary importance.

Abstract: The invention relates to compositions and methods to prevent enteric infection in a subject at risk of such infection. In particular, the invention relates to the prevention of recurrence of infection by Clostridium difficile.

Abstract: The present invention relates to methods and compositions for the prevention and treatment of renal damage. The invention provides protein-based renal therapeutic agents for administration to subjects in order to prevent or treat renal degeneration or damage.

Abstract: Compositions and methods of use are provided for intrabodies that bind and alter the effects of poly-glutamate protein aggregation in poly-glutamate associated diseases, such as in Huntington's disease. Intrabodies are provided that prevent poly-glutamate aggregation, gene dysregulation, and negative effects of Huntington's disease.

Abstract: The present disclosure relates to antibodies and polynucleotides encoding the same, that may be used to prevent, control, or reduce the activity of the complement pathway. In addition, the disclosure is directed to compositions and methods for diagnosing and treating diseases mediated by or involving complement C5. Specifically, the disclosure is related to C5 antibodies.

Abstract: An object is to provide an antibody capable of specifically recognizing a human NRG1 protein isoform, and suppressing signal transduction in which the isoform is involved. An antibody capable of binding to a region at positions 221 to 234 of a human NRG1-? protein or an antibody capable of binding to a region at positions 213 to 239 of a human NRG1-?1 protein was successfully obtained. Further, it was also found that these antibodies had an activity of suppressing cleavage of the NRG1 protein, an activity of suppressing phosphorylation of an ErbB3 protein in a cancer cell, and an activity of suppressing in vivo tumor proliferation.

Abstract: The present invention relates to compounds that bind to human vascular endothelial growth factor A (VEGFA) and human angiopoietin-2 (Ang2), and may be useful for treating angiogenic eye diseases, such as diabetic and other proliferative retinopathies, and for cancer, especially solid tumors driven by VEGFA and Ang2, including gastric, lung, hepatocellular carcinoma, ovarian, colorectal, and breast cancers.

Abstract: Mice having a restricted immunoglobulin heavy chain locus are provided, wherein the locus is characterized by a single polymorphic human VH gene segment, a plurality of human DH gene segments and a plurality of JH gene segments. Methods for making antibody sequences that bind an antigen (e.g., a viral antigen) are provided, comprising immunizing a mouse with an antigen of interest, wherein the mouse comprises a single human VH gene segment, a plurality of human DH gene segments and a plurality of JH gene segments, at the endogenous immunoglobulin heavy chain locus.

Abstract: Chimeric and humanized anti-CD37 antibodies and pharmaceutical compositions containing them are useful for the treatment of B cell malignancies and autoimmune and inflammatory diseases that involve B cells in their pathology.

Abstract: The present invention is directed to bi-specific monovalent diabodies that comprise two polypeptide chains and which possess at least one binding site specific for an epitope of CD3 and one binding site specific for an epitope of gpA33 (i.e., a “gpA33×CD3 bi-specific monovalent diabody”). The present invention also is directed to bi-specific monovalent diabodies that comprise an immunoglobulin Fc Domain (“bi-specific monovalent Fc diabodies”) and are composed of three polypeptide chains and which possess at least one binding site specific for an epitope of gpA33 and one binding site specific for an epitope of CD3 (i.e., a “gpA33×CD3 bi-specific monovalent Fc diabody”). The bi-specific monovalent diabodies and bi-specific monovalent Fc diabodies of the present invention are capable of simultaneous binding to gpA33 and CD3. The invention is directed to pharmaceutical compositions that contain such bi-specific monovalent diabodies or such bi-specific monovalent Fc diabodies.

Abstract: The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing Claudin-6 (CLDN6), including tumor-related diseases such as ovarian cancer, lung cancer, gastric cancer, breast cancer, hepatic cancer, pancreatic cancer, skin cancer, malignant melanoma, head and neck cancer, sarcoma, bile duct cancer, cancer of the urinary bladder, kidney cancer, colon cancer, placental choriocarcinoma, cervical cancer, testicular cancer, and uterine cancer.

Abstract: Methods of treatment to suppress an immune response are provided. The method comprises administering to a subject in need of treatment a naked blocking antibody that binds selectively iNKT cells in an amount effective to suppress the subject's iNKT cell function. Compositions comprising, an isolated, humanized antibody that binds selectively iNKT cells are also provided.

Abstract: The present disclosure relates to amino acid sequences that are directed against (as defined herein) HER3, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences (also referred to herein as “amino acid sequences of the invention”, “compounds of the invention”, and “polypeptides of the invention”, respectively).

Abstract: Toll Like Receptor 3 (TLR3) antibody antagonists, polynucleotides encoding TLR3 antibody antagonists or fragments thereof, and methods of making and using the foregoing are disclosed.

Abstract: The present disclosure relates to compositions and methods for compositions, methods, and kits for treating cancer using chimeric antigen receptor (CAR) modified cells. Some embodiments of the present disclosure relate to an isolated nucleic acid sequence encoding CAR. The CAR may include an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain. The antigen binding domain may bind to an antigen of a non-essential organ.

Abstract: Described herein is the identification of human monoclonal antibodies that bind GPC3 or heparan sulfate (HS) chains on GPC3 with high affinity. The antibodies described herein are capable of inhibiting HCC cell growth and migration. Provided are human monoclonal antibodies specific for GPC3 or HS chains on GPC3, including immunoglobulin molecules, such as IgG antibodies, as well as antibody fragments, such as single-domain VH antibodies or single chain variable fragments (scFv). Further provided are compositions including the antibodies that bind GPC3 or HS chains on GPC3, nucleic acid molecules encoding these antibodies, expression vectors comprising the nucleic acids, and isolated host cells that express the nucleic acids. Methods of treating cancer and/or inhibiting tumor growth or metastasis are also provided. Further provided are methods of detecting cancer in a subject and confirming a diagnosis of cancer in a subject.

Abstract: The present application disclose a method for treating a patient who would benefit from stimulation of the patient's stem cells, comprising administering to the patient an antibody that specifically binds to an epitope of the MUC1 protein expressed on human undifferentiated stem cells.

Abstract: Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

Abstract: The present disclosure relates to a modified Interleukin-1 (IL-1) family member cytokine, with reduced activity via its cytokine receptor, wherein said interleukin-1 family member cytokine is specifically delivered to target cells. Preferably, the IL-1 family member cytokine is a mutant, more preferably it is a mutant IL-1 with low affinity to the IL-1 receptor, wherein said mutant IL-1 is specifically delivered to target cells. The targeting is preferably realized by fusion of the modified IL-1 family member cytokine to a targeting moiety, preferably an antibody or antibody-like molecule. The disclosure relates further to the use of such targeted modified IL-1 family member cytokine to treat diseases.

Abstract: The invention relates to human neutralizing anti-KIT antibodies and uses thereof. More particularly, the invention relates to an antibody comprising a heavy chain variable region comprising SEQ ID NO: 2 in the H-CDR1 region, SEQ ID NO: 3 in the H-CDR2 region and SEQ ID NO: 4 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 6 in the L-CDR1 region, SEQ ID NO: 7 in the L-CDR2 region and SEQ ID NO: 8 in the L-CDR3 region. The invention also relates to an antibody comprising a heavy chain variable region comprising SEQ ID NO: 10 in the H-CDR1 region, SEQ ID NO: 11 in the H-CDR2 region and SEQ ID NO: 12 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 14 in the L-CDR1 region, SEQ ID NO: 15 in the L-CDR2 region and SEQ ID NO: 16 in the L-CDR3 region.

Abstract: The invention provides antibodies which bind to the extracellular domain of the Tyrosine-protein kinase transmembrane receptor Matriptase. Nucleic acid molecules encoding the antibodies, expression vectors, host cells and methods for expressing the antibodies are also provided. The antibodies may be used for the treatment of cancer, including gastric cancer, colorectal cancer, prostate cancer, breast cancer, ovarian cancer lung cancer, preferably SCLC, esophageal cancer, head and neck cancer, pancreatic cancer, lymphoma preferably non-Hodgkin's lymphoma and skin cancer.

Abstract: A bispecific antigen binding protein complex comprising a first polypeptide comprising a first antigen binding site at an N terminus; a second polypeptide comprising a second antigen binding site at an N terminus; and a linker connecting the first polypeptide and the second polypeptide; wherein the linker comprises a tag at one terminus thereof, and wherein the tag is connected to a C-terminus of the first polypeptide or to an N-terminus of the second polypeptide, and comprises a cleavable amino acid sequence; as well as related compositions and methods.

Abstract: The present invention concerns compositions and methods of use of bispecific antibodies comprising at least one anti-TNF-? antibody or antigen-binding fragment thereof and at least one anti-IL-6 antibody or antigen-binding fragment thereof. Preferably, the bispecific antibody is in the form of a DNL® complex. The anti-TNF-? or anti-IL-6 antibodies may comprise specific CDR sequences disclosed herein. The compositions and methods are of use to treat autoimmune disease, immune system dysfunction or inflammatory disease, as disclosed herein.

Abstract: The present invention relates to methods of degrading or converting a cellulosic material pretreated with a composition comprising one or more GH61 polypeptides.

Abstract: The present invention relates to a method for producing a formyl group-containing porous base matrix, comprising the steps of introducing a spacer in a formyl group-containing porous particle; and then oxidizing the spacer with periodic acid and/or a periodate, to transform the part of the spacer into a formyl group; wherein the formyl group content in the porous particle after introduction of the spacer is not more than 3 ?mol per 1 mL of the porous particle. Also, the present invention relates to a method for producing an adsorbent, comprising the step of immobilizing an amino group-containing ligand on the formyl group-containing porous base matrix. According to the present invention, a formyl-group containing porous base matrix and an adsorbent produced from the porous base matrix of which adsorption amount is high and which is has high strength and of which ligand is difficult to be leaked are provided.

Abstract: The present invention concerns the preparation of chemically modified derivatives of chitosan with acrylic groups and their use in the field of enamel-dentin adhesives. Chitosan derivatives have physical-chemical features (hydrophilicity, presence of electrical charges on the chain) which allow them to interact with the organic part of the demineralized tooth. At the same time, the acrylic groups incorporated in the polymer chain allow the formation of a covalent bond with the restorative material used in the dental field that is typically composed of acrylic resins. By combining the adhesion to the tooth surface and the bond with the restorative material, the chemically modified chitosan described herein is able to increase the lifespan of the dental restoration and can thus find use in the field of adhesives, in particular enamel-dentin adhesives.

Abstract: The present invention is to provide a compound that can provide a modified polymer exhibiting excellent rigidity, wear resistance, and low heat build-up when used in a rubber composition; a modified polymer obtained by subjecting a polymer to modification with the compound; a rubber composition including the modified polymer; and a tire and a conveyor belt that are produced by using the rubber composition. The compound of the present invention is represented by Formula (M) below.

Abstract: A process for improving a latex comprising the steps of (a) providing a latex comprising a polymer binder, wherein said polymer binder is formed by polymerization of a monomer mixture comprising one or more ethylenically unsaturated carboxylic acid functional monomer, and (b) passing said latex comprising said polymer binder over a cation exchange resin.

Abstract: Modified fluoropolymers, and methods for manufacturing modified fluoropolymers are provided. According to at least one embodiment, chemically modified fluoropolymers, via radical generation and subsequent reaction, produce fluoropolymers having fluorinated moieties and/or non-fluorinated moieties, disrupting highly coherent polar domains, wherein the non-fluorinated moieties include, for example, at least one of carbonyl, hydroxyl, alkoxy, alkyl, and/or aromatic chemical groups.

Abstract: The present disclosure relates to a method for the emulsion polymerization of itaconic acid containing ester functionality, for example, the alkyl esters of itaconic acid known as alkylitaconate. More specifically, an ester of polyitaconic acid polymer is produced via emulsion polymerization and contains greater than 50% by weight of an ester of itaconic acid along with a selected particle size and levels of molecular weight and syndiotactacticity.

Abstract: The present embodiments provide a system and method for separation within a polymer production process. Specifically, a flashline heater configured according to present embodiments may provide more time than is required for complete vaporization of liquid hydrocarbons that are not entrained within a polymer fluff produced within a polymerization reactor. Such extra time may allow for liquid hydrocarbons that are entrained within the polymer fluff to be vaporized.

Abstract: Disclosed are methods for making partially hydrogenated annulated cyclopentadienyl complexes which can provide efficient synthesis of metallocene catalysts desired for olefin polymerization.

Abstract: A copolymer of polyvinyl alcohol and trifluoro acetaldehyde derivatized to have a substituent that contains fluorine. Such compositions are useful in compatibilizing fluorinated molecules that are to be blended into liquid materials or systems, as well as materials and systems that may be aerosolizable or foamable liquids.

Abstract: Improved reaction processes comprise reacting a mixture to form a product comprising a metal alkyl, metal oxide, or mixture thereof and then passing said product to a post-reactor heat exchanger. The improvement comprises one or more of the following: (1) reacting said metal alkyl compound with an acid to produce a soluble metal ester; or (2) adding an ionic surfactant; or (3) adding a mixture comprising an antioxidant to the product under conditions sufficient to avoid formation of significant amounts of insoluble metal or metal compounds derived from said metal alkyl compound; or (4) purging said post-reactor heat exchanger with an inert gas under conditions to remove metal oxide from the post-reactor heat exchanger.

Abstract: Catalyst systems and methods for making and using the same. A method of methylating a catalyst composition while substantially normalizing the entiomeric distribution is provided. The method includes slurrying the organometallic compound in dimethoxyethane (DME), and adding a solution of RMgBr in DME, wherein R is a methyl group or a benzyl group, and wherein the RMgBr is greater than about 2.3 equivalents relative to the organometallic compound. After the addition of the RMgBr, the slurry is mixed for at least about four hours. An alkylated organometallic is isolated, wherein the methylated species has a meso/rac ratio that is between about 0.9 and about 1.2.

Abstract: The invention relates to a pipe comprising at least one metallocene-catalyzed polyethylene resin, wherein the polyethylene resin has a multimodal molecular weight distribution and comprises at least two metallocene-catalyzed polyethylene fractions A and B, wherein fractions A and B are prepared in different reactors of at least two reactors connected in series, wherein the polyethylene resin comprises: at least 30% by weight and at most 50% by weight of the polyethylene fraction A, based on the total weight of the polyethylene resin, wherein fraction A has a melt index MI2 of at least 50 g/10 min as determined on the fluff of fraction A according to ISO 1133:1997 condition D at a temperature of 190° C. and under a load of 2.16 kg; wherein fraction B has a density of at most 0.9210 g/cm3; and wherein the polyethylene resin has a melt index MI5 of at least 0.10 g/10 min and of at most 1.0 g/10 min as determined according to ISO 1133:1997, condition T, at 190° C.