The present invention is directed to antibodies and fragments thereof having binding specificity for ACTH. Another embodiment of this invention relates to the antibodies binding fragments thereof described herein, comprising the sequences of the V.sub.H, V.sub.L and/or CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-ACTH antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention further contemplates methods of making said anti-ACTH antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-ACTH antibodies and binding fragments thereof for the diagnosis, assessment, prevention and treatment of diseases and disorders associated with ACTH, such as Cushing's Disease, Cushing's Syndrome, Parkinson's disease, obesity, diabetes, sleep disorders depression, anxiety disorders, cancer, muscle atrophy, hypertension, hyperinsulinemia, cognitive dysfunction, Alzheimer's disease, galactorrhea, stress related conditions, cardiac conditions, metabolic syndrome, hyperaldosteronism, Conn's syndrome and familial hyperaldosteronism.

The present invention is directed to antibodies and fragments thereof having binding specificity for ACTH. Embodiments of this invention relate to the binding fragments of antibodies described herein, comprising the sequences of the V.sub.H, V.sub.L and/or CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates anti-ACTH antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention further contemplates methods of making said anti-ACTH antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-ACTH antibodies and binding fragments thereof for the diagnosis, assessment, prevention and treatment of diseases and disorders associated with ACTH, such as CAH, FGD, Cushing's Disease, Cushing's Syndrome, Parkinson's disease, obesity, diabetes, sleep disorders, depression, anxiety disorders, cancer, muscle atrophy, hypertension, hyperinsulinemia, cognitive dysfunction, Alzheimer's disease, galactorrhea, stress related conditions, cardiac conditions, metabolic syndrome, hyperaldosteronism, Conn's syndrome and familial hyperaldosteronism.

The present disclosure is directed to the treatment of diseases or conditions involving the buildup of fatty tissues, such as obesity, metabolic syndrome, type II diabetes, etc. A composition containing a monoclonal antibody directed against gastric inhibitory polypeptide is administered. This results in a reduced rate of weight gain and a marked decrease in lipid synthesis and accumulation.

A compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and one or more monovalent cations such as Na.sup.+ useful for the treatment of hypertension and/or heart failure.

A compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and one or more monovalent cations such as Na+ useful for the treatment of hypertension and/or heart failure.

The invention relates to novel compositions including an aldosterone antagonist and administered according to a predetermined dosage for treating heart deficiency in non-human mammals.

Provided herein are methods for treating subjects having conditions related to adrenocortical activity and/or excessive steroid production. In particular, provided herein are methods for treating subjects having conditions related to adrenocortical activity and/or excessive steroid production through administration of at least one of the following agents: 1) an agent capable of inhibiting cholesterol efflux related to ABCA1 and/or ABCG1; 2) an agent capable of inhibiting MDR1 related cortisol secretion and/or MDR1 P-glycoprotein multiple drug transporter activity; and 3) an agent capable of inhibiting mitochondrial activity.

Provided herein are methods for treating subjects having conditions related to adrenocortical activity and/or excessive steroid production. In particular, provided herein are methods for treating subjects having conditions related to adrenocortical activity and/or excessive steroid production through administration of at least one of the following agents: 1) an agent capable of inhibiting cholesterol efflux related to ABCA1 and/or ABCG1; 2) an agent capable of inhibiting MDR1 related cortisol secretion and/or MDR1 P-glycoprotein multiple drug transporter activity; and 3) an agent capable of inhibiting mitochondrial activity.

Novel crystalline forms of trisodium [3-((1S,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl) propionate-(S)-3-methyl-2-(pentanoyl{2-(tetrazol-5-ylate)biphenyl-4-ylmethyl}amino)butyrate] hydrate, methods for their preparation, pharmaceutical compositions comprising these new forms, and use of them for treating or delaying progression or onset of diseases or disorders related to activity of angiotensin receptor 1 (AT1) blockage and neprilysin (NEP) inhibition, such as heart failure, are disclosed.

The present invention related to a novel and improved process for preparing (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula (I) ##STR00001##