The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, chimeric, humanized antibodies, antibody fragments, etc., that specifically bind a TREM1 protein, e.g., a mammalian TREM1 or human TREM1, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.

The present invention provides novel heterocyclic compounds of the general formula (I), including novel compounds of formula (Ia), and pharmaceutical compositions containing them. Moreover, the compounds of formula (I) or (Ia) and the pharmaceutical compositions containing them are provided for use in the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. The compounds of formula (I) or (Ia) can act as modulators of nervous system receptors sensitive to glutamate, in particular as modulators of metabotropic glutamate receptors (mGluRs), which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. The present invention further provides compounds of formula (I) or (Ia) that are modulators of metabotropic glutamate receptors (mGluRs), particularly positive allosteric modulators of mGluRs, and more specifically positive allosteric modulators of mGluR3. ##STR00001##

The present invention provides a therapy for treating loss of GABA-mediated pre-synaptic inhibition after spinal injury. The therapeutic regimen includes spinal segment-specific upregulation of GAD65 (glutamate decarboxylase) and VGAT (vesicular GABA transporter) to modulate chronic spasticity in patients after spinal traumatic or ischemic injury.

The present invention provides a therapy for treating loss of GABA-mediated pre-synaptic inhibition after spinal injury. The therapeutic regimen includes spinal segment-specific upregulation of GAD65 (glutamate decarboxylase) and VGAT (vesicular GABA transporter) to modulate chronic spasticity in patients after spinal traumatic or ischemic injury.

The invention provides a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine. This invention also provides pharmaceutical compositions comprising the crystalline salt, processes and intermediates for preparing the crystalline salt, and methods of using the crystalline salt to treat diseases.

The present invention relates to a nucleic acid coding for a human DGKk protein lacking a functional Proline Rich Region and/or a functional EPAPE repeated Region, and to its use in the treatment of fragile X syndrome in a patient in need thereof.

Improved anti-CD154 antibodies are provided herein which have improved therapeutic potency, in vivo half-life and ablated FcR binding and/or complement binding/activation. The use of these antibodies for inducing tolerance and treating immune diseases including autoimmunity, inflammation, transplant recipients, fibrosis and allergic disorders is disclosed herein.

A transdermal therapeutic system containing rotigotine base in a self-adhesive layer structure. The system includes a backing layer, and a rotigotine-containing biphasic layer. The biphasic layer has an outer phase having a composition including 75% to 100% of a polymer or a polymer mixture, and an inner phase that forms dispersed deposits in the outer phase. The inner phase includes rotigotine base and a polymer mixture of at least two hydrophilic polymers. The hydrophilic polymers are selected from the group of polyvinylpyrrolidones having a K-Value of at least 80, polyvinylpyrrolidones having a K-Value of less than 80, copolymers of vinyl caprolactam, vinylacetate and ethylene glycol, copolymers of vinylpyrrolidone and vinylacetate, copolymers of ethylene and vinylacetate, polyethylene glycols, polypropylene glycols, acrylic polymers, and modified celluloses. The polymer mixture in the inner phase is present in an amount sufficient so that it forms a solid solution with the rotigotine base.

Disclosed are novel compounds of Formula I that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.

Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.