Abstract: The present invention relates to a process for manufacturing (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid with the formula (Id) below and pharmaceutically acceptable salts thereof The compound of formula (Id) is a prodrug of a catecholamine for use in treatment of neurodegenerative diseases and disorders such as Parkinson's Disease. The invention also relates to a new intermediate of said process.

Abstract: The present invention is directed to novel prodrugs of modulators of the NMDA receptor. Separate aspects of the inventions are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat neurological disorders or neuropsychiatric disorders such as depression.

Abstract: The present invention relates to a class of monoclonal antibody that specifically binds the phosphorylated serine 396 residue on pathological hyperphosphorylated (PH F) tau (pS396) with improved affinity, as well as to methods of using these molecules and their tau binding fragments in the treatment of Alzheimer's disease and other tauopathies.

Abstract: The present invention is directed to antibodies and antigen binding fragments thereof having binding specificity for PACAP. The antibodies and antigen binding fragments thereof comprise the sequences of the VH, VL, and CDR polypeptides described herein, and the polynucleotides encoding them. Antibodies and antigen binding fragments described herein bind to and/or compete for binding to the same linear or conformational epitope(s) on human PACAP as an anti-PACAP antibody. The invention contemplates conjugates of anti-PACAP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. Methods of making said anti-PACAP antibodies and antigen binding fragments thereof are also contemplated.

Abstract: The present invention relates to a process for synthesis of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol abbreviated THIP, having the INN name gaboxadol, starting from pyrrolidin-2-one. The process comprises a new direct process to obtain the intermediate dimethyl 5-hydroxy-3,6-dihydropyridine-1,4(2H)-dicarboxylate or the intermediate diethyl 5-hydroxy-3,6-dihydropyridine-1,4(2H)-dicarboxylate.

Abstract: Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Abstract: The present invention is directed to methods of inhibiting or preventing photophobia in subjects in need thereof using anti-CGRP antibodies or antibody fragments that inhibit photophobia, especially CGRP-associated photophobia. These antibodies and fragments are useful in treating different disorders associated with photophobia such as migraine, cluster headaches and the like. The present invention also provides assays using transgenic Nestin/Ramp1 rodents, utilizing a CGRP model light aversive behavior model for identifying therapeutically effective anti-CGRP antibodies and fragments thereof having binding specificity for CGRP which inhibit or prevent photophobia in subjects in need thereof. The present invention is specifically directed to methods for identifying therapeutically effective antibodies and fragments thereof having binding specificity for CGRP that may be used to treat CGRP associated disorders such as migraine.

Abstract: The present invention relates to a mouse antibody denoted m2E6, chimeric ch2E6, as well as to 3 humanized forms (2E6-HLD1, 2E6-HLD2 and 2E6-HLD3) and affinity matured forms of HLD1: 7A10, 5A1, 9D7, 9G11, 7C4, L3, 8D9, 9C12 or 6B6 to create higher affinity antibodies.

Abstract: The present invention provides vortioxetine pyroglutamate salt and pharmaceutical compositions comprising said salt.

Abstract: Provided herein are pharmaceutical formulations comprising a monoacylglycerol lipase (MAGL) inhibitor, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

Abstract: The present invention is directed to antagonistic antibodies and antigen binding fragments thereof having binding specificity for PACAP. These antibodies inhibit, block or neutralize at least one biological effect associated with PACAP, e.g., vasodilation. In exemplary embodiments these antibodies and antigen binding fragments thereof may comprise specific VH, VL, and CDR polypeptides described herein. In some embodiments these antibodies and antigen binding fragments thereof bind to and/or compete for binding to specific epitope(s) on human PACAP. The invention is further directed to using these antagonistic anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, mast cell degranulation, and/or neuronal activation, are therapeutically beneficial, e.g., headache and migraine indications.

Abstract: The present invention relates to prodrugs of 4-((1R,3S)-6-chloro-3-phenyl-2,3-dihydro-1H-inden-1-yl)-1,2,2-trimethylpiperazine in the form of 1a and 1b; and 4-((1R,3S)-6-chloro-3-(phenyl-d5)-2,3-dihydro-1H-inden-1-yl)-2,2-dimethyl-1-(methyl-d3)piperazine in the form of 2a and 2b, wherein X—is a counter ion, or pharmaceutically acceptable salts thereof. The present invention also provides pharmaceutical compositions comprising prodrugs, or pharmaceutically acceptable salts thereof, of the invention.

Abstract: The present invention relates to new solid forms of the compound (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid with the formula (Id) below. The compound of formula (Id) is a prodrug of a catecholamine for use in treatment of neurodegenerative diseases and disorders such as Parkinson's Disease.

Abstract: The present invention relates to a new process for manufacturing (6aR,10aR)-7-propyl-6,6 a,7,8,9,10,10a,11-octahydro-[1,3]dioxolo[4?,5?:5,6]benzo[1,2-g]quinoline with formula (Ib) below, (4aR,10aR)-1-Propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinoline-6,7-diol with formula (I) below and salts thereof. Both compounds are for use in the treatment of neurodegenerative diseases and disorders such as Parkinson's Disease. The invention also relates to new intermediate compounds of said process.

Abstract: Methods for producing heterologous multi-subunit proteins in transformed cells are disclosed. In particular, the present disclosure provides improved methods of producing multi-subunit proteins, including antibodies and other multi-subunit proteins, which may or may not be secreted, with a higher yield and decreased production of undesired side-products. In exemplary embodiments, the transformed cells are a yeast, e.g., methylotrophic yeast such as Pichia pastoris.

Abstract: Methods for producing heterologous multi-subunit proteins in transformed cells are disclosed. In particular, the present disclosure provides improved methods of producing multi-subunit proteins, including antibodies and other multi-subunit proteins, which may or may not be secreted, with a higher yield and decreased production of undesired side-products. In exemplary embodiments, the transformed cells are a yeast, e.g., methylotrophic yeast such as Pichia pastoris.

Abstract: Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Abstract: The present invention relates to a new process for manufacturing (6aR,10aR)-7-propyl-6,6a,7,8,9,10,10a,11-octahydro-[1,3]dioxolo[4?,5?:5,6]benzo[1,2-g]quinoline with formula (Ib) below, (4aR,10aR)-1-Propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinoline-6,7-diol with formula (I) below and salts thereof. Both compounds are for use in the treatment of neurodegenerative diseases and disorders such as Parkinson's Disease. The invention also relates to new intermediate compounds of said process.

Abstract: Provided herein are compounds of the formula: and compositions comprising the same, which are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Abstract: Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.