Abstract: The present invention provides ocular cells, genetically modified by a CRISPR system targeting the expression of B2M for ocular cell therapy. The invention further provides methods of generating an expanded population of genetically modified ocular cells, for example limbal stem cells (LSCs) or corneal endothelial cells (CECs), wherein the cells are expanded involving the use of a LATS inhibitor and the expression of B2M in the cells has been reduced or eliminated. The present invention also provides cell populations, preparations, uses and methods of therapy comprising said cells.

Abstract: The present invention is related to 6-6 Fused Bicyclic Heteroaryl Compounds of the Formula A2 or A1 and their Use as LATS Inhibitors, or a salt, stereoisomer or pharmaceutical composition thereof; wherein the variables are as defined herein. The present invention further relates to a method of LATS inhibition in a cell population using a compound of Formula A1, or a salt, stereoisomer or pharmaceutical composition thereof. The present invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, their use in the treatment and management of diseases or disorders.

Abstract: The present invention is related to 6-6 Fused Bicyclic Heteroaryl Compounds of the Formula A2 or A1 and their Use as LATS Inhibitors, or a salt, stereoisomer or pharmaceutical composition thereof; wherein the variables are as defined herein. The present invention further relates to a method of LATS inhibition in a cell population using a compound of Formula A1, or a salt, stereoisomer or pharmaceutical composition thereof. The present invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, their use in the treatment and management of diseases or disorders.

Abstract: A microtablet dispenser is provided herein including: a microtablet reservoir disc including a plurality of wells each formed to accommodate at least one microtablet, the wells being arranged in at least one array; a screen plate having at least one opening shaped to expose all of the wells of one of the arrays when aligned therewith; and, a dose selector plate including a plurality of dosing apertures arranged in a plurality of dosing arrays of different patterns. With one of the arrays being aligned with the at least one opening of the screen plate and with a selected dosing array, the microtablets accommodated in the wells aligned with dosing apertures are free to pass through the corresponding dosing apertures so as to be dispensed therefrom, while the wells of the array not aligned with dosing apertures are obstructed by solid portions of the dose selector plate.

Abstract: A multiple dose spoon device for scooping, retaining, and delivering to a patient a specific number of mini-tablets from a container, e.g., bottle, or bulk pile, of mini-tablets. The device comprises a top housing, a bottom housing, and one or two sliders movably positioned between top housing and bottom housing, said: a) top housing having a plurality of nests, and also having a handle with an open window and slider retention notches, and b) one or two sliders with slider tabs, having a plurality of sequential whole number markings equivalent to the plurality of nests, and a plurality minus 1 of tablet blocking ribs, wherein slider movement is regulated by the slider retention notches, and wherein the plurality of nests and the plurality of whole number markings are a same number. Alternatively, the top housing does not have slider retention notches, and the one or two sliders have slider retention notches.

Abstract: A microtablet dispenser is provided herein including: a microtablet reservoir disc including a plurality of wells each formed to accommodate at least one microtablet, the wells being arranged in at least one array; a screen plate having at least one opening shaped to expose all of the wells of one of the arrays when aligned therewith; and, a dose selector plate including a plurality of dosing apertures arranged in a plurality of dosing arrays of different patterns. With one of the arrays being aligned with the at least one opening of the screen plate and with a selected dosing array, the microtablets accommodated in the wells aligned with dosing apertures are free to pass through the corresponding dosing apertures so as to be dispensed therefrom, while the wells of the array not aligned with dosing apertures are obstructed by solid portions of the dose selector plate.

Abstract: The present invention provides ocular cells, genetically modified by a CRISPR system targeting the expression of B2M for ocular cell therapy. The invention further provides methods of generating an expanded population of genetically modified ocular cells, for example limbal stem cells (LSCs) or corneal endothelial cells (CECs), wherein the cells are expanded involving the use of a LATS inhibitor and the expression of B2M in the cells has been reduced or eliminated. The present invention also provides a cell populations, preparations, uses and methods of therapy comprising said cells.

Abstract: A multiple dose spoon device for scooping, retaining, and delivering to a patient a specific number of mini-tablets from a container, e.g., bottle, or bulk pile, of mini-tablets. The device comprises a top housing, a bottom housing, and one or two sliders movably positioned between top housing and bottom housing, said: a) top housing having a plurality of nests, and also having a handle with an open window and slider retention notches, and b) one or two sliders with slider tabs, having a plurality of sequential whole number markings equivalent to the plurality of nests, and a plurality minus 1 of tablet blocking ribs, wherein slider movement is regulated by the slider retention notches, and wherein the plurality of nests and the plurality of whole number markings are a same number. Alternatively, the top housing does not have slider retention notches, and the one or two sliders have slider retention notches.

Abstract: A drug delivery device comprising a drug container extending between a distal end and a proximal end and is capable of being compressed into a single plane; a body extending between proximal and distal ends comprising a hollow space for containing the drug container; and a plunger extending between proximal and distal ends, wherein the distal end of the plunger engages telescopically with the proximal end of the body, wherein the plunger comprises at least one pair of protrusions, wherein the protrusion is capable of compressing the drug container as the plunger moves towards the proximal end of the drug delivery device, by applying a force to the drug container that is perpendicular to the movement of the plunger.

Abstract: A force multiplier having a substantially non-rotating input screw to which a force to be amplified is applied relative to an external housing, a substantially non-rotating output screw providing a resulting output force relative to the housing, and a rotating nut disposed to receive and engage each of the input screw and the output screw and disposed to engage the housing and provide a force opposite to the output force, wherein the output screw is movable in a first direction when the input force is applied and is retractable upon relief of the input force, and an advancement ratchet disposed to engage the output screw and receive the output force relative to the housing having an output member providing a monotonically increasing motion in response to a plurality of cycles of force multiplier output screw first direction advancement and retraction. Also included is a mating syringe.

Abstract: The present invention is related to 6-6 Fused Bicyclic Heteroaryl Compounds of the Formula A2 or A1 and their Use as LATS Inhibitors, or a salt, stereoisomer or pharmaceutical composition thereof; wherein the variables are as defined herein. The present invention further relates to a method of LATS inhibition in a cell population using a compound of Formula A1, or a salt, stereoisomer or pharmaceutical composition thereof. The present invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, their use in the treatment and management of diseases or disorders.

Abstract: A drug delivery device comprising a drug container extending between a distal end and a proximal end and is capable of being compressed into a single plane; a body extending between proximal and distal ends comprising a hollow space for containing the drug container; and a plunger extending between proximal and distal ends, wherein the distal end of the plunger engages telescopically with the proximal end of the body, wherein the plunger comprises at least one pair of protrusions, wherein the protrusion is capable of compressing the drug container as the plunger moves towards the proximal end of the drug delivery device, by applying a force to the drug container that is perpendicular to the movement of the plunger.

Abstract: Various embodiments provide drug products and dry powder inhalers. With various embodiments of the present invention, a de-agglomeration chamber and by-pass channel are provided which allow for various de-agglomerating capabilities for dry powder dispensers.

Abstract: Dose counter assemblies are provided herein which allow for the counting of used doses of a medical inhaler. In one aspect, one dose counter ring is utilized. This provides for dose counting but with inherent limitations in the number of doses which may be counted. In a second, and preferred, aspect of the subject invention, two cooperating does counter rings are utilized which allow for adjacent digits to be displayed, thereby allowing an increased number of doses to be counted. Advantageously, with the subject invention, due to mechanical interactions, reliable dose counting can be achieved with the subject invention.

Abstract: A dry powder inhaler is provided herein having a powder housing defined on an exterior by a generally cylindrical wall. Within the interior volume of the wall, a central passageway is provided through which certain components of the dry powder inhaler may pass. In addition, a powder reservoir is defined within the interior volume having a generally crescent-shaped profile formed along a substantial length of the wall. The powder reservoir terminates at end points between which is defined an isolated inhalation channel. With the configuration provided herein, the powder reservoir has a substantial working length exposed at its bottom to permit removal of medication therefrom. Advantageously, with this configuration, a relatively large amount of medication may be maintained, and obtained access to, in the powder reservoir.

Abstract: Disclosed is a method and an apparatus for ablating biological tissues, in which a cannula is configured to affect biological tissue and a heat transmitting end-effecter is coupled to the cannula. A source of electromagnetic energy is provided via an electro-magnetic energy emitter and a wall of the heat transmitting end-effecter is made of an electromagnetic-energy-absorbing material that absorbs electromagnetic waves.

Abstract: Various embodiments of the present invention provide drug products and dry powder inhalers and powder dispensers with multiple reservoirs. Several embodiments provide a drug product comprising a dry powder inhaler and at least one dose of at least one active pharmaceutical agent; wherein the dry powder inhaler comprises at least two reservoirs. Other embodiments provide for a powder dispenser which includes a first powder reservoir having at least one first opening, and a second powder reservoir having at least one second outlet opening, the second outlet opening being spaced from the first outlet opening.

Abstract: A weightlifting apparatus is operative to continuously provide and adjust a force resistant to a torque produced by an exerciser that performs supination of biceps simultaneously with other exercise motions or pronation of triceps simultaneously with other exercise motions.

Abstract: A weightlifting apparatus is operative to continuously provide and adjust a force resistant to a torque produced by an exerciser that performs supination of biceps simultaneously with other exercise motions or pronation of triceps simultaneously with other exercise motions.

Abstract: A force amplifier has a guide track, a non-locking screw threadedly engaging the track to spirally move in response to an axial input force applied to the proximal end of the non-locking screw. The force amplifier includes a compliant component coupled to the non-locking screw by one end and to a self-locking screw by the other end. The compliant component is configured to transmit a torque generated by the non-locking screw to the self-locking screw, which is actuated to move spirally along the track while generating an axial output force greater than the input force.