The present invention relates to the field of pharmaceutical products, specifically the glycosidic derivatives of treprostinil. The glycosidic treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

The present invention relates to compounds of formula (I) or formula (II) or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein said compound of formula (I) and said compound of formula II each comprises at least one ONO.sub.2 or ONO moiety; R.sub.1 is C.sub.1-C.sub.3alkyl; R.sub.2 is H, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.2alkoxy, C.sub.2-C.sub.4alkenyl; R.sub.3 is C.sub.1-C.sub.4alkyl optionally substituted with C.sub.1-C.sub.2alkoxy, C.sub.3-C.sub.4cycloalkyl, C.sub.2-C.sub.4alkenyl; R.sub.4 and R.sub.5 are each independently H or C.sub.1-C.sub.6alkyl optionally substituted with F, OH, ONO, ONO.sub.2, COOH, C.sub.1-C.sub.3alkoxy, C.sub.3-C.sub.6cycloalkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine, homo-piperazine, 2,5-diazabicyclo[2,2,1]heptane and 3,7-diazabicyclo[3,3,0]octane, wherein said heterocyclic ring is optionally substituted with independently one or more R.sub.6; R.sub.6 is C.sub.1-C.sub.6alkyl optionally substituted with independently one or more halogen, OH, ONO, ONO.sub.2, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, COOR.sub.7, NR.sub.8R.sub.9, C═NR.sub.10; R.sub.7 is H, or C.sub.1-C.sub.4alkyl optionally substituted with F, OH, ONO, ONO2, NR.sub.8R.sub.9; R.sub.8 and R.sub.9 are independently H, or C.sub.1-C.sub.4alkyl optionally substituted with ONO, ONO.sub.2; R.sub.10 is C.sub.1-C.sub.4alkyl optionally substituted with F, ONO, ONO.sub.2; C.sub.3-C.sub.6cycloalkyl; pharmaceutical compositions thereof, and their use in methods of treating or preventing a disease alleviated by inhibition of PDE5 in a human or in a non-human mammal

##STR00001##

The invention relates to composition comprising a pharmaceutically effective amount of one or more functional vasoactive intestinal peptide (VIP) fragments, and the use of those compositions in the treatment of fibrosis, hypertension and other disorders.

The present disclosure is directed to a class of fluorinated copolymers, such as a PTFE copolymers, that can be dissolved in low toxicity solvents, such as Class III Solvents, and that enable the creation of stable water-in-solvent emulsions comprising the fluorinated copolymers dissolved in a low toxicity solvents and a hydrophilic agent (e.g., a therapeutic agent) dissolved in an aqueous solvent, such as water or saline.

The disclosure provides methods of preventing or treating Sengers syndrome in a mammalian subject, reducing risk factors associated with Sengers syndrome, and/or reducing the likelihood or severity of Sengers syndrome. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to increase expression of AGK in subjects in need thereof.

A calcitonin gene-related peptide (CGRP) compound can be selected from N-alpha-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)-butyrylamino]ethoxy}ethoxy)acetyl][Ser1]alpha-human CGRP peptide (α-CGRP-analogue), or derivatives thereof; or N-alpha-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butyryl-amino]-ethoxy]ethoxy}acetyl][Ser1]beta-human CGRP peptide (β-CGRP-analogue), or derivatives thereof. The CGRP compound can be used to induce myocardial perfusion recovery, in connection with AMI, by activating any CGRP family of receptors with a larger CGRP compound: CGRP potency ratio in the coronary artery than in the mesenteric artery.

A calcitonin gene-related peptide (CGRP) compound can be selected from N-alpha-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)-butyrylamino]ethoxy}ethoxy)acetyl][Ser1]alpha-human CGRP peptide (α-CGRP-analogue), or derivatives thereof; or N-alpha-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butyryl-amino]-ethoxy]ethoxy}acetyl][Ser1]beta-human CGRP peptide (β-CGRP-analogue), or derivatives thereof. The CGRP compound can be used to induce myocardial perfusion recovery, in connection with AMI, by activating any CGRP family of receptors with a larger CGRP compound: CGRP potency ratio in the coronary artery than in the mesenteric artery.

Engineered multivalent and multispecific binding proteins, methods of making, and their uses in the prevention, diagnosis, and/or treatment of disease are provided.

The present invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective ROCK inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating cardiovascular, smooth muscle, oncologic, neuropathologic, autoimmune, fibrotic, and/or inflammatory disorders using the same.

##STR00001##

The present invention provides a method of measuring the levels of BCMA in a biological sample, specifically upon the B cell surface. The diagnostic assays are useful in predicting an individual's likelihood of developing or currently suffering from an autoimmune disease, such as SLE, and for methods for treating an individual clinically diagnosed with an autoimmune disease. This diagnostic test serves to predict a patient's likelihood to respond to a specific drug treatment, in particular treatment with BLyS antagonists, either singly or in combination with other immune suppressive drugs.