Abstract: The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided.

Abstract: Methods and apparatus for assaying the level of analytes in a sample, related to VLA-4, are disclosed. A method of decreasing the level of an anti-integrin antibody in a subject is described including a) contacting a biological sample from a subject with a detectable capture agent associated with a substrate, wherein the capture agent can bind an anti-integrin antibody in the sample; b) detecting binding of the capture agent with the level of the anti-integrin antibody; and c) treating the subject with plasma exchange until the level of the anti-integrin antibody in the sample reaches a predetermined level.

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

Abstract: Methods, systems and kits for the identification, assessment and/or treatment of a subject having multiple sclerosis are disclosed.

Abstract: The invention provided herein includes isolated polypeptides that specifically block the interaction between neonatal Fc receptor (FcRn) and albumin. Blocking the interaction treats diseases and conditions caused by increased amounts of albumin or modified albumin that possesses pathogenic properties wherein it is deemed desirable to decrease albumin levels. Accordingly, also provided are methods of using these isolated polypeptides to treat various diseases and conditions caused by increased amounts of albumin or modified albumin that possesses pathogenic properties. The invention provided herein also includes isolated polypeptides capable of binding to a non-IgG and non-albumin competitive site on an FcRn alpha 3 domain. These can be useful for tracking FcRn without inhibiting IgG or albumin binding or function. Accordingly, the invention also includes methods and systems to track FcRn without inhibiting IgG or albumin binding or function.

Abstract: A metering device that improves the aseptic transfer of powder and reconstitution fluid into the metering device for medical use. In some implementations, the metering device comprises a housing, containing a metering chamber that defines a volume. The housing also has a connection portion, an extraction portion, and a metering member in fluid communication with the metering chamber. In other embodiments, the metering device additionally includes a dispensing aid that facilitates the dispensing of powder from a first container into the metering chamber through the connection portion. The connection portion is capable of insertion into a second container that contains fluid, thereby allowing a mixture of powder and fluid to form in the metering chamber. The mixture, then ready for use, is removable from the metering chamber through the extraction portion by an extraction device.

Abstract: Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.

Abstract: The invention relates to methods and products for the identification of a clinically significant immune response in subjects treated with a therapeutic protein. A first aspect of the invention relates to methods and compositions for identifying a clinically significant immune response in patients treated with therapeutic amounts of VLA4 binding antibody (e.g., natalizumab). A second aspect of the invention concerns the chronological details of sample collection for determining the titer of antibodies against the therapeutic protein, e.g. the collection of at least two samples at two different time points. A third aspect of the invention relates to the selection of the critical threshold level, which corresponds to the antibody titer of untreated patients increased by the double of the standard deviation of this control antibody titer.

Abstract: Methods and compositions for determining whether a subject is at risk for PML, including subjects being treated with immunosuppressants, by determining whether the subject harbors a JCV variant with reduced binding for sialic acid relative to a normal JCV, are presented. Furthermore, combinations of JCV-VP1 sequence variations that are associated with PML and that can be used as a basis of an assay for identifying subjects susceptible to PML, subjects with PML (e.g., early stage PML), or subjects at risk of developing PML in response to an immunosuppressive treatment are provided.

Abstract: The present invention provides compounds of Formula (I) and (II): wherein R1, R2, R4, R5, R6, X and n are as defined herein, and wherein R3 is hydrogen or a sulfur protecting group. Compounds of Formula (I) and (II), wherein R3 is hydrogen, may be useful in methods for detecting a reactive metabolite in a sample, e.g., wherein the metabolite is generated from the metabolism of a test compound, and wherein the metabolite and the compound of Formula (I) or (II) react to form a detectable adduct, e.g., detectable by mass spectrometry.

Abstract: The present invention pertains to methods of producing polypeptide of interest in cell cultures lacking glutamine. The present invention further pertains to a method of producing a protein of interest in a large scale cell culture, comprising supplementing the cell culture with nucleic acid synthesis precursors and/or corticosteroids.

Abstract: The invention is based, at least in part, on the finding that a dimeric version of a BBB-transmigrating antibody (e.g., the TMEM30A (CDC-50A) binding antibody, FC5) was found to greatly enhance transport across the BBB as compared to monovalent FC5 VHH. The invention provides, inter alia, molecules that increase transport of pharmacologically active agents across the blood brain barrier, methods for increasing transport across the blood brain barrier, and methods of treatment of disorders or diseases having a neurological component.

Abstract: A novel receptor in the TNF family is provided: BAFF-R. Chimeric molecules and antibodies to BAFF-R and methods of use thereof are also provided.

Abstract: Aspect of the disclosure relate to methods of assessing a bioreactor culture that involve determining a culture parameter of the manufacturing-scale bioreactor culture using a model that relates a Raman spectrum to the culture parameter. Related bioreactor system are also provided.

Abstract: Antibodies that specifically bind to VLA-1 integrin and methods of using these antibodies to treat immunological disorders in a subject. Also included are crystal structures of complexes formed by VLA-1 antibodies and their ligands, and VLA-1 antagonists and agonists identified by using the structure coordinates of these structures.

Abstract: Aspects of the present disclosure provide compositions and methods for increasing protein production in mammalian cells, e.g. methods of increasing mammalian cell expression of a protein of interest, comprising culturing mammalian cells that overexpress a protein of interest and are modified to overexpress a gene encoding Rab 11 or Yap1, as well as mammalian cells that overexpress a protein of interest and which are modified to overexpress a gene encoding Rab 11 or Yap1.

Abstract: A method for using citraconic anhydride and itaconic anhydride as addition cure end caps in reactions for forming polyamic acid oligomers and polyimide oligomers, is provided. Prepregs and high temperature adhesives made from the resulting oligomers, as well as, high temperature, low void volume composites made from the prepregs, are also provided.

Abstract: The invention covers both the sole structure and its related production equipment and technology, especially in relation to a type of flocked shoe sole. Compared with the existing technology, the shoe sole can trap and retain fiber particles via electrostatic or electrostatic spraying, which is not only anti-slippery also with elegant looking and reduce the cost. This set of equipment for making flocked sole is highly automatic, easy to operate, save the labor and reduce the production cost. The production procedure consists of 1) applying prime coating; 2) applying adhesive; 3) natural flock retention or electrostatic flocking; 4) electrostatic separation, cleaning, pairing and packaging. The whole process has been shortened dramatically, simplify the procedure, and reduce the cost. Also the solvent and adhesive used are both environmental friendly, harmless, which helps increase the productivity and yield.

Abstract: Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein i.a. Ring A is phenylene or 5- to 6-membered heteroarylene; Ring B is phenylene, 5- to 6-membered heterocycloalkylene or 5- to 6-membered heteroarylen; R4 is absent, heteroarylene, arylene, C1-3 alkylene, or R4 and R3 taken together with the nitrogen to which they are bound form a 3- to 7-membered heterocycloalkyl ring; R5 is absent, C(O)NR51, NR52 or O; R6 is C2-10 alkylene or alkenylene, wherein one or two of the carbon atoms in the alkylene chain is optionally replaced by an O, S, SO, SO2 or NR61, and wherein two of the carbon atoms in the alkylene chain are optionally connected by a two or three carbon atom alkylene chain to form a 5- to 7-membered ring; R7 is absent, NR71 or O. The compounds are IRAK4 inhibitors useful for the treatment of inflammatory diseases.

Abstract: An arc suppressor fixable to a fusible element to suppress electrical arcs and prevent the spread of electric arc “burn-back.” The arc suppressor includes first and second inner members comprised of pre-cured silicone rubber, and first and second outer members comprised of an arc suppressing material (e.g., melamine). The inner and outer members form a sandwich around a portion of the fusible element, wherein the first inner member is located adjacent to a first surface of the fusible element and the second inner member is located adjacent to an opposing second surface of the fusible element. The first outer member is located adjacent to the first inner member and the second outer member is located adjacent to the second inner member. Mechanical fasteners tightly engage together the first and second inner members, the fusible element, and the first and second outer members.