Abstract: Embodiments provide swallowable devices, preparations and methods for delivering therapeutic agents (TAs) within the GI tract such as antibodies (AP-antibodies) or other proteins which neutralize PCSK9 molecules. Many embodiments provide a swallowable device e.g., a capsule for delivering TAs into the intestinal wall (IW). Embodiments also provide TA preparations that are configured to be contained within the capsule, advanced from the capsule into the IW and/or peritoneum and degrade to release the TA into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the IW. Embodiments are particularly useful for delivery of AP-antibodies and related TA's for the treatment of cholesterol, lipid and related conditions where such TAs are poorly absorbed and/or degraded within the GI tract.

Abstract: Embodiments of the invention provide shaped masses (SM) comprising one or more drugs such as proteins or polypeptides and methods for forming and delivering such SM's. One embodiment provides a SM comprising a drug e.g., a protein or polypeptide having a biological activity in the body of a mammal. The SM is formed by compression of a precursor material (PM) comprising the drug wherein an amount of biologically active drug in the SM is a minimum level to that in the PM. Drugs which may be incorporated into the SM include insulin, incretins and immunoglobulins e.g., interleukin neutralizing antibodies or TNF-?-inhibiting antibodies. Embodiments of the invention are particularly useful for the oral delivery of drugs which would be degraded within the GI tract, wherein the SM containing the drug is formed as or incorporated into a tissue penetrating member which is inserted into the intestinal wall after oral ingestion.

Abstract: The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

Abstract: The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

Abstract: Various embodiments provide methods and systems for the biphasic iontophoretic transdermal delivery of therapeutic agents. An embodiment of a method for such delivery comprises positioning at least one electrode assembly in electrical communication with a patient's skin. The assembly includes a solution comprising a therapeutic agent which passively diffuses into the skin. A dose of agent is delivered from the assembly into the skin during a first period using a first current having a characteristic e.g., polarity and magnitude, to repel the agent out of the assembly. During a second period, a second current having a characteristic to attract the agent is used to retain the agent in the assembly such that delivery of agent into skin is minimized. A dose of agent may be delivered on demand by an input from the patient. Embodiments may be used for delivery of agents which cause adverse effects from unwanted passive diffusion.

Abstract: Various embodiments provide methods and systems for the biphasic iontophoretic transdermal delivery of therapeutic agents. An embodiment of a method for such delivery comprises positioning at least one electrode assembly in electrical communication with a patient's skin. The assembly includes a solution comprising a therapeutic agent which passively diffuses into the skin. A dose of agent is delivered from the assembly into the skin during a first period using a first current having a characteristic e.g., polarity and magnitude, to repel the agent out of the assembly. During a second period, a second current having a characteristic to attract the agent is used to retain the agent in the assembly such that delivery of agent into skin is minimized. A dose of agent may be delivered on demand by an input from the patient. Embodiments may be used for delivery of agents which cause adverse effects from unwanted passive diffusion.

Abstract: Embodiments of the invention provide compositions comprising bio degradable polymers, medical implants fabricated from these compositions and methods of using such implants. Many embodiments provide medical implants comprising a first polymer backbone having a first rate of biodegradation and a second polymer backbone having a second rate of biodegradation faster than the first rate. In some embodiments, the second backbone is configured to be replaced by a natural tissue layer. The first backbone provides a scaffold for the implant while the second backbone degrades. This scaffold can enhance mechanical properties of the implant including various aspects of mechanical strength such as tensile, bending, hoop and yield strength; and elasticity. The scaffold also serves to maintain a minimum level of structural support of the implant during the period of degradation of the second backbone or for the entire life of the implant so that the implant does not mechanically fail.

Abstract: Various embodiments provide methods and systems for the biphasic iontophoretic transdermal delivery of therapeutic agents. An embodiment of a method for such delivery comprises positioning at least one electrode assembly in electrical communication with a patient's skin. The assembly includes a solution comprising a therapeutic agent which passively diffuses into the skin. A dose of agent is delivered from the assembly into the skin during a first period using a first current having a characteristic e.g., polarity and magnitude, to repel the agent out of the assembly. During a second period, a second current having a characteristic to attract the agent is used to retain the agent in the assembly such that delivery of agent into skin is minimized. A dose of agent may be delivered on demand by an input from the patient. Embodiments may be used for delivery of agents which cause adverse effects from unwanted passive diffusion.

Abstract: Embodiments of the invention provide patches for the transdermal delivery of compositions to treat an individual suffering from hair loss. Many embodiments provide an iontophoretic patch for the transdermal delivery hair growth stimulating agents for the treatment of hair loss by stimulating the growth of new hair in areas of the scalp exhibiting hair loss. The patch comprises an electrode and a reservoir containing a composition comprising iron containing compound, such as a chelated iron compound for the delivery of the therapeutically effective amount of iron. The patch can be shaped to be placed and remain on the head. Various embodiments provide methods of using embodiments of the iontophoretic patch for delivering a hair growth stimulating agent such as a chelated iron compound, minoxidil and finasteride to the scalp and other areas exhibiting hair loss. Such methods can be used for re-growing hair, and/or preventing or slowing hair loss.

Abstract: An embodiment of the invention provides an apparatus for the detection and treatment of atrial arrhythmia comprising an electrical lead having proximal and distal portions. The distal portion is positionable in an atrial chamber and the end of the proximal portion is configured to be coupled to a pacemaker. The lead comprises a plurality of conductive wires clad with an insulative coating and has sufficient flexibility to be positioned in the atria from a percutaneous introductory site. The conductive wires are coupled to a plurality of pairs of bipolar electrodes positioned on a membrane attachable to an endocardial wall. The electrode pairs are distributed in a pattern defining an area for detecting a location of a foci of aberrant electrical activity located within or adjacent the area and sending a pacing signal to that location to prevent or stop an occurrence of atrial fibrillation caused by that foci.

Abstract: Embodiments provide an apparatus and method for detection of aberrant neural-electric activity (ANEA) in the brain causing an epileptic seizure or other neurologic condition. One embodiment provides an apparatus for detection of ANEA comprising an introducer having at least one lumen. The introducer is introduced into brain tissue through an opening in the skull. A reference electrode is positioned at an introducer distal portion. A plurality of electrode members are advanceable within the at least one lumen with each member having an insulated portion and an exposed distal portion. The members have a non-deployed state in the introducer and a deployed state when outwardly advanced out of the introducer. In the deployed state, the members are substantially orthogonal to each other with the exposed distal portions defining a detection volume capable of determining an electric field vector produced by the ANEA and the direction of a foci of the ANEA.

Abstract: Embodiments described herein provide lid structures for medical implant (MI) housing. In one embodiment, the invention provides a lid structure for a MI housing comprising a substrate comprising a dielectric material, a conductive portion fabricated on a substrate surface or interior, a frame at least partially surrounding the substrate perimeter, a plurality of vias projecting at least partially through the substrate, a plurality of conductive pins with at least one pin projecting through a via. The frame is hermetically joined to the substrate and can be hermetically joined to the housing. The conductive portion allows electrical components, including capacitors, inductors, resistor and antennas to be fabricated on or coupled to the substrate surface or interior. The antenna comprises a conductive trace positioned on a substrate top surface and is configured to send and receive signals between an implant within a patient's body and a communication device external to the body.

Abstract: Disclosed are compounds of the formula: and compounds of the formula: wherein R1, R2, R3, R4, R5, u and v are as defined herein. Also disclosed are methods of treating pain (e.g., inflammatory pain, chronic pain, and neuropathic pain), methods of treating diabetes, and methods of inhibiting the absorption of cholesterol using compounds of formula I or IIA.

Abstract: The present invention relates to Azetidinone Derivatives, compositions comprising an Azetidinone Derivative and methods for treating or preventing a disorder of lipid metabolism, pain, diabetes, a vascular condition, demyelination or nonalcoholic fatty liver disease, comprising administering to a patient an effective amount of an Azetidinone Derivative.

Abstract: The present invention relates to methods for treating or preventing a disorder of lipid metabolism, pain, diabetes, a vascular condition, demyelination or nonalcoholic fatty liver disease, comprising administering a compound having the formula or a pharmaceutically acceptable salt, solvate, ester, prodrug or stereoisomer thereof, wherein: R1 and R2 are defined in Tables 1-6 herein, and R3 is -phenyl, -4-chlorophenyl, -2-pyridyl, or -3-pyridyl.

Abstract: Disclosed is a method of treating a disease or condition (e.g., pain, diabetes or disorders of lipid metabolism) comprising administering an azetidine derivative of the formula I selected from the group consisting of the compounds defined by Tables 1, 2, 3a, 3b, 3c, 3d and 4a.

Abstract: Compounds having the structural formula I or a pharmaceutically acceptable salt thereof, wherein R is R1-isoxazolyl, R1-oxadiazolyl, R1-dihydrofuranyl, R1-pyrazolyl, R1-imidazolyl, R1-pyrazinyl or R1-pyrimidinyl; R1 is 1, 2 or 3 substituents selected from H, alkyl, alkoxy and halo; Z is optionally substituted-aryl, or optionally substituted-heteroaryl; are disclosed, as well as their use in the treatment of central nervous system diseases, in particular Parkinson's disease and Extra Pyramidal Syndrome, pharmaceutical compositions comprising them, and combinations with other agents.

Abstract: A filter and processing sequence is described that efficiently combines and performs two or more tasks required to demodulate a composite 3G (third generation) wireless signal formed by a combination of wideband 3.84 MHz (Universal Mobile Telecommunications System, identified, as acronym “UMTS”, or Universal Mobile Telecommunications System Terrestrial Radio Access, identified as acronym “UTRA”) carriers and narrowband 1.2288 MHz CDMA-2000 carriers. The three tasks, applied to each spectral component of the 3G wireless signal and described in the order of a traditional filtering structure are: Spectral translation, Bandwidth Reduction, and Sample Rate Selection. These tasks are traditionally implemented in three distinct pieces of hardware or software modules.

Abstract: A filter and processing sequence is described that efficiently combines and performs two or more tasks required to demodulate a composite 3G (third generation) wireless signal formed by a combination of wideband 3.84 MHz (Universal Mobile Telecommunications System, identiied a acronym “UMTS”, or Universal Mobile Telecommunications System Terrestrial Radio Access, identified as acronym “UTRA”) carriers and narrowband 1.2288 MHz CDMA-2000 carriers. The three tasks, applied to each spectral component of the 3G wireless signal and described in the order of a traditional filtering structure are: Spectral translation, Bandwidth Reduction, and Sample Rate Selection. These tasks are traditionally implemented in three distinct pieces of hardware or software modules.

Abstract: A fractional-spaced equalizer (FSE) is capable of performing joint intersymbol-interference (ISI) cancellation and matched filter (MF) processing. The FSE employs a constrained optimization technique to control the out-of-band frequency response of the equalizer's FIR while, at the same time, controlling the pass-band and roll-off of the FIR to cancel ISI. The format of the constrained optimization technique permits a single bank of multipliers elements to service the inner product computations associated both with the ISI cancellation and MF operations. This time-multiplexing technique promotes a conservation of hardware associated with the MF, and provides for a reduction in the computational complexity leading to an increase in power efficiency.