Abstract: The present disclosure relates to an improved, efficient, scalable process to prepare intermediate compounds, such as 2-isopropyl-4-methylpyridin-3-amine, useful for the synthesis of compounds, such as Compound 9, for the treatment of KRAS G12C mutated cancers.

Abstract: Disclosed herein are methods, devices and compositions for degradable medical devices and/or compositions that provide local and/or systemic delivery of at least one active agent.

Abstract: Multilayer polymeric materials in the form of a cap contain polymeric layers having distinctive anisotropic properties which are beneficially utilized in a subject, e.g., the multilayer polymeric materials are biocompatible and may be used, for example, to replace or supplement cartilage in an articulated joint. The present invention relates generally to multilayer polymeric materials, in particular to biomaterials suitable for implantation into a mammal or other animal, and methods of manufacturing the biomaterial and various uses thereof.

Abstract: The present invention is directed to absorbable polyesters comprising one or more monophosphate functionality; a conjugate comprising the foregoing polyester and a peptide and/or a bioactive agent; microparticles comprising an absorbable polyester; a conjugate comprising the microparticles and a peptide and/or a bioactive agent; an acylated or alkylated polysaccharide having one or more monophosphate functionality; a conjugate comprising the acylated or alkylated polysaccharide and a peptide and/or a bioactive agent; and pharmaceutical compositions thereof.

Abstract: Polymeric materials referred to herein as PEU include a plurality of linking groups selected from urea and urethane groups, and a plurality of segments located between adjacent linking groups, where at least some of the segments of the PEU are polyoxyalkylene, but other exemplary segments include hydrocarbons, polyesters, polycarbonates and polysiloxanes. The polymeric materials are biocompatible and may be used, for example, to replace or supplement cartilage in an articulated joint.

Abstract: A well packing system and method for operating a well packing system wherein an isolation string assembly has a lower circulation valve with lateral flow ports that are operated to an open position without the use of shifters on a wash pipe. The isolation string assembly is incorporated into a well packing assembly within a wellbore and includes an upper sleeve tool that provides selective production of fluids through the frac pack assembly. In addition, the isolation string includes a lower circulation valve having a sliding sleeve that is shiftable from an open position to a closed position upon receipt of a suitable pressure differential. This configuration is particularly valuable for permitting monitoring of pressure or other conditions in the annulus of the wellbore portion being packed during packing operations. Further, the lower circulation valve tool can be used to selectively allow fluid returns during the packing operation.

Abstract: The invention provides compounds of formula I: wherein Y is F, Cl, Br, methyl or methoxy; and pharmaceutically acceptable salt thereof. The compounds are effective antitumor agent. The invention also provides pharmaceutical compositions comprising a compound of formula I or a salt thereof, intermediates useful for preparing a compound of formula I, and therapeutic methods comprising administering a compound of formula I or a salt thereof to a mammal in need thereof.

Abstract: The invention provides compounds of formula I: wherein Y is F, Cl or Br; or a pharmaceutically acceptable salt thereof. The compounds are effective antitumor agents. The invention also provides pharmaceutical compositions comprising a compound of formula I or a salt thereof, intermediates useful for preparing a compound of formula I, and therapeutic methods comprising administering a compound of formula I or a salt thereof to a mammal in need thereof.

Abstract: The invention provides compounds of the formula: wherein A, X, Y, and Z are as defined in the specification. The compounds are effective anti-tumor agents. The invention also provides pharmaceutical compositions comprising a compound of the above formula or a salt thereof, intermediates useful for preparing a compound of the above formula, and therapeutic methods comprising administering a compound of the above formula or a salt thereof to a mammal in need thereof.

Abstract: A frac pack system and method for operating a frac pack system wherein an isolation string assembly has a lower circulation valve with lateral flow ports that are operated to an open position without the use of shifters on a wash pipe. The isolation string assembly is incorporated into a frac pack assembly within a wellbore and includes an upper sleeve tool that provides selective production of fluids through the frac pack assembly. In addition, the isolation string includes a lower circulation valve having a sliding sleeve that is shiftable from an open position to a closed position upon receipt of a suitable pressure differential. This configuration is particularly valuable for permitting monitoring of pressure or other conditions in the annulus of the wellbore portion being packed during frac pack operations. Further, the lower circulation valve tool can be used to selectively allow fluid returns during the frac pack operation.

Abstract: Systems and methods for guiding a seal assembly associated with a string of production tubing, or a tubular member generally, into a receptacle within a wellbore. The muleshoe of a seal assembly is provided with an auto entry guide device in the form of a guide member or kickover lug that is radially moveable with respect to the muleshoe. The kickover lug is collapsible radially inwardly and biased radially outwardly. The auto entry guide device may also include a centralizer bowspring that is mounted upon the muleshoe. Additionally, the muleshoe is mounted for rotational movement with respect to the seal assembly.

Abstract: A polytunnel system comprises a plurality of cover support members (14), a series of leg members (12) and a cover. The cover support members (14) are supported by associated ones of the leg members (12). The cover support members (14) are securable to the leg members (12) at a plurality of different heights.

Abstract: Harvesting apparatus (10) has a support structure (12), a plurality of driven rotatable members (14) by which the support structure (12) can be moved, and a body support element (16) supported by the support structure (12). The body support element (16) is able to support a picker (22) and is slidable relative to the support structure (12) so that, when the harvesting apparatus (10) is moving in a first direction, the body support element (16) can be selectively positioned relative to the support structure (12) to optimise the portion of the picker (22) relative to the occurrence of produce to be picked. Preferably, a conveyor system (18) and collection area (20) are also included on the support structure (12). The conveyor system (18) enables transportation of produce placed thereon by the picker to the collection area (20) for packing. A method is also provided.

Abstract: A support system includes an end frame comprising a pair of uprights (20), and a cross member (22), each upright (20) being secured at its lower end to a base member (26), a diagonal strut (28) interconnecting the base member (26) and the upright (20).

Abstract: The invention provides compounds of formula I: wherein Y is F, Cl, Br, methyl or methoxy; and pharmaceutically acceptable salts thereof. The compounds are effective antitumor agents. The invention also provides pharmaceutical compositions comprising a compound of formula I or a salt thereof, intermediates useful for preparing a compound of formula I, and therapeutic methods comprising administering a compound of formula I or a salt thereof to a mammal in need thereof.

Abstract: A gravel packing method and apparatus are described where to set the packer; a ball is dropped to a seat that it isolated from the effects of formation pressures when trying to set the packer. This is accomplished by isolation of the gravel pack outlet port when setting the packer and locating the ball seat in a position where the effects of formation pressure are irrelevant. Additionally, by positioning the evacuation ports above a seal bore in the screen extension during circulation or squeeze to deposit gravel and further putting check valves in the evacuation ports, the evacuation step after circulation or squeeze can be accomplished without having to reposition the crossover. The crossover is supported from the packer and movement of the crossover away and back to the support from the packer operates a valve to allow squeezing when the valve is closed and circulating and reversing out when the valve is open.

Abstract: A cyclodextrin derivative, wherein at least 60 percent of the free hydroxy groups of said cyclodextrin are acylated with acyl groups where at least one of said acyl groups comprise a free carboxylic group.

Abstract: A cyclodextrin derivative, wherein at least 60 percent of the free hydroxy groups of said cyclodextrin are acylated with acyl groups where at least one of said acyl groups comprise a free carboxylic group.