Abstract: Methods are provided for treating a subject having, or at risk of, a lysosomal storage disease, particularly Tay-Sachs, Gaucher disease, Sandhoff disease or Niemann-Pick disease, neuronal ceroid lipofuscinosis, or a condition associated with impaired Phospholipase A2 Group VI (PLA2G6) activity, particularly infantile neuroaxonal dystrophy or PLA2G6 associated neurodegeneration (PLAN), or a sleeping disorder, using a substituted polyunsaturated fatty acid, polyunsaturated fatty acid ester, polyunsaturated fatty acid thioester, fatty acid amide, polyunsaturated fatty acid mimetic, polyunsaturated fatty acid pro-drug, or combinations thereof, where the substituted compound comprises at least one substitution that reduces oxidation of the compound. Preferably, the substituted compound is a deuterated polyunsaturated fatty acid, or an ethyl ester thereof, such as 11,11-D2-linoleic acid, 11,11-D2-linoleic acid ethyl ester, 11,11,14,14-D4-linolenic acid, or 11,11,14,14-D4-linolenic acid ethyl ester.

Abstract: Provided herein is a bulk composition comprising the trihydrate form of (3S, 4R, 3?R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-1-yl]-hexanoic acid 1-azabicyclo[2.2.2]oct-3?-yl ester di-hydrochloride salt. Provided are also pharmaceutical compositions and dosage forms comprising the trihydrate form, and methods and uses for treating a gastrointestinal disorder in a subject with the trihydrate form. In some embodiments, the gastrointestinal disorder is gastroesophageal reflux disease (GERD), dyspepsia (such as functional dyspepsia or functional motility disorder), gastroparesis, paralytic ileus, post-operative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), or esophagitis. In some embodiments, the gastrointestinal disorder is post-operative ileus, chronic grass sickness, constipation, megacolon, gastritis, gastrointestinal stasis, or abomasal emptying defect.

Abstract: A continuously variable transmission device has planetary members (23) in rolling contact with radially inner and outer races (12, 14; 36, 37) each comprising axially spaced relatively axially movable parts, and control means (18) for determining the axial separation of the parts (12, 14) of one of the two races, in which the planetary members (23) are connected for drive transmission to an input or output member (30) of the transmission device by connection means which allows the radial position of the planets to vary in response to variation in the axial separation of the parts (12, 14) of the said one of the two races (37), and in which the generatrix of the curved surface (70, 71) of at least one of the races (37) and/or planetary members (23) is non-circular.

Abstract: The present invention relates to novel piperidine ether derivatives having affinity for the histamine H3 receptor processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

Abstract: A glazing element (12) for an opening defined by opaque boundaries (13) has an edge region (E) shaped to divert light passing through it in a sense such as to enlarge the field of view through the opening. For this purpose the bounding surfaces (33, 34) of the element (12) diverge towards the edge thereof in the edge region (E). The same effect can be achieved by an element (25) adhered to or otherwise held in position to the surface of the element (12) in the edge region (E).

Abstract: The subject invention provides pharmaceutical compounds useful in the treatment of Type II diabetes. These compounds are advantageous because they are readily metabolized by the metabolic drug detoxification systems. Particularly, thiazolidinedione analogs that have been designed to include esters within the structure of the compounds are provided. This invention is also drawn to methods of treating disorders, such as diabetes, comprising the administration of therapeutically effective compositions comprising compounds that have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester-containing thiazolidinedione analogs are also taught.

Abstract: The present invention relates to novel hydroxyethylamine compounds having Asp2 (?-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated ?-amyloid levels or ?-amyloid deposits, particularly Alzheimer's disease.

Abstract: A method for protecting a peptide from peptidase activity in vivo, the peptide being composed of between 2 and 50 amino acids and having a C-terminus and an N-terminus and a C-terminus amino acid and an N-terminus amino acid is described. In the first step of the method, the peptide is modified by attaching a reactive group to the C-terminus amino acid, to the N-terminus amino acid, or to an amino acid located between the N-terminus and the C-terminus, such that the modified peptide is capable of forming a covalent bond in vivo with a reactive functionality on a blood component. In the next step, a covalent bond is formed between the reactive group and a reactive functionality on a blood component to form a peptide-blood component conjugate, thereby protecting said peptide from peptidase activity. The final step of the method involves the analyzing of the stability of the peptide-blood component conjugate to assess the protection of the peptide from peptidase activity.

Abstract: The present invention relates to a compound comprising a PYY peptide or a functional derivative thereof, which is coupled to a reactive group. Such a reactive group is capable of reacting on a blood component so as to form a stable covalent bond therewith. The present invention also relates to a conjugate comprising such a compound which is covalently bonded to a blood component. Moreover, the invention also relates to a method of enhancing, in a patient, the anti-obesity activity of a PYY peptide or functional derivative thereof.

Abstract: The subject invention pertains to novel enantiomerically pure compounds, and compositions comprising the compounds, for the treatment of cardiac arrhythmias. The subject invention further concerns a method of making and purifying the compounds. The enantiomerically purified compounds, and compositions of these compounds, exhibit unexpectedly distinct and advantageous characteristics, such as a markedly superior ability to reduce or inhibit ventricular premature beats, as compared to racemic mixtures of the compounds.

Abstract: Prokayrotic FAB I polypeptides and DNA (RNA) encoding such FAB I and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such FAB I for the treatment of infection, such as bacterial infections. Antagonists against such FAB I and their use as a therapeutic to treat infections, such as staphylococcal infections are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to the presence of FAB I nucleic acid sequences and the polypeptides in a host. Also disclosed are diagnostic assays for detecting polynucleotides encoding FAB I and for detecting the polypeptide in a host.

Abstract: The present invention relates to novel hydroxyethylene compounds having Asp2 (?-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated ?-amyloid levels or ?-amyloid deposits, particularly Alzheimer's disease.

Abstract: The subject invention provides pharmaceutical compounds useful in the treatment of Type II diabetes. These compounds are advantageous because they are readily metabolized by the metabolic drug detoxification systems. Particularly, thiazolidinedione analogs that have been designed to include esters within the structure of the compounds are provided. This invention is also drawn to methods of treating disorders, such as diabetes, comprising the administration of therapeutically effective compositions comprising compounds that have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester-containing thiazolidinedione analogs are also taught.

Abstract: Peptides exhibiting anti-viral and anti-fusogenic activity are modified to provide greater stability and improved half-life in vivo. The selected peptides include fusion inhibitors DP178 and DP107 and related peptides and analogs thereof. The modified peptides are capable of forming covalent bonds with one or more blood components, preferably a mobile blood component.

Abstract: The present invention relates to hydroxyethylene compounds of formula (I), in which Ra represents a group of formula (a) or (b) where R1 represents —SO2R5, W1 represents CO or SO2, and the other variables are as defined in the claims, having Asp2 (?-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, compositions containing them, and their use in the treatment of diseases characterised by elevated ?-amyloid levels or ?-amyloid deposits, particularly Alzheimer's disease.

Abstract: The subject invention provides pharmaceutical compounds useful in the treatment of Type II diabetes. These compounds are advantageous because they are readily metabolized by the metabolic drug detoxification systems. Particularly, thiazolidinedione analogs that have been designed to include esters within the structure of the compounds are provided. This invention is also drawn to methods of treating disorders, such as diabetes, comprising the administration of therapeutically effective compositions comprising compounds that have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester-containing thiazolidinedione analogs are also taught.

Abstract: Novel compounds comprising chemically reactive intermediates which can react with available reactive functionalities on blood components to form covalent linkages, where the resulting covalently-bound conjugates are found to have thrombin inhibition activity are provided. Specifically, the thrombin inhibitor compounds of the present invention are derivatives of the known thrombin inhibitor argatroban, which can be covalently linked to chemically reactive functionalities on various blood components. The conjugated thrombin inhibitors thereby have extended lifetimes in the bloodstream, as compared to the unconjugated parent drug, and are, therefore, capable of maintaining thrombin inhibitory activity for extended periods of time as compared to the unconjugated parent drug. Also provided herein are methods for inhibiting thrombin activity in vivo comprising administering to the bloodstream of a mammalian host the novel compounds of the present invention.