Abstract: The present invention provides novel, serum-stable lipid particles comprising one or more active agents or therapeutic agents, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles. More particularly, the present invention provides serum-stable nucleic acid-lipid particles (SNALP) comprising a nucleic acid (e.g., one or more interfering RNA molecules), methods of making the SNALP, and methods of delivering and/or administering the SNALP (e.g., for the treatment of cancer). In particular embodiments, the present invention provides tumor-directed lipid particles that preferentially target solid tumors. The tumor-directed formulations of the present invention are capable of preferentially delivering a payload such as a nucleic acid to cells of solid tumors compared to non-cancerous cells.

Abstract: Activity-inducible fusion proteins whose activity is post-translationally regulated utilizing a hsp90 binding domain and a drug molecule are described. In the absence of the drug molecule, the activity-inducible fusion proteins are inactivated but can be activated by a relevant physiological parameter in the presence of the drug molecule. Examples of the activity-inducible fusion proteins include chimeric antigen receptors (CAR) wherein the relevant physiological parameter is antigen binding.

Abstract: The present invention provides novel, serum-stable lipid particles comprising one or more active agents or therapeutic agents, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles. More particularly, the present invention provides serum-stable nucleic acid-lipid particles (SNALP) comprising a nucleic acid (e.g., one or more interfering RNA molecules), methods of making the SNALP, and methods of delivering and/or administering the SNALP (e.g., for the treatment of cancer). In particular embodiments, the present invention provides tumor-directed lipid particles that preferentially target solid tumors. The tumor-directed formulations of the present invention are capable of preferentially delivering a payload such as a nucleic acid to cells of solid tumors compared to non-cancerous cells.

Abstract: The disclosure provides, in various embodiments, polypeptides (e.g., antibodies and antigen binding fragments thereof) that specifically bind to a thymic stromal lymphopoietin (TSLP) (e.g., a full-length human TSLP). The disclosure also provides, in various embodiments, fusion proteins comprising one or more of the polypeptides, polynucleotides encoding the polypeptides, vectors and host cells suitable for expressing the polypeptides, and methods for treating a TSLP-associated disease or condition.

Abstract: The present invention provides novel antibodies that specifically bind to GUCY2c and uses thereof in the treatment of cancer. The present invention further provides novel bispecific antibodies comprising such antibodies and uses thereof in the treatment of cancer.

Abstract: The present invention is directed to antibodies that specifically bind to GUCY2c and methods of using such antibodies in the diagnosis and/or treatment of cancer.

Abstract: The present invention provides novel antibodies that specifically bind to GUCY2c and uses thereof in the treatment of cancer. The present invention further provides novel bispecific antibodies comprising such antibodies and uses thereof in the treatment of cancer.

Abstract: A valve assembly, is presented that has a seating member is slidably coupled to a valve body adjacent a valve body bore and has a metal seat located on a seating end thereof that is engagable against a ball valve member. The seating member has a vent port located there through to allow fluid to flow into a fluid chamber within the ball housing. A first piston is slidably located between the seating member and the ball housing and located over the vent port, and a second piston is slidably located between the seating member and the ball housing and is located downhole from the first piston. Sealing members are located between the first and second pistons and engaged against the seating member.

Abstract: A ball valve stopper comprising a spherical contoured body comprising a substantially inelastic first material and having a flow port. A closed face of the spherical contoured body is orthogonal with respect to the flow port and includes a spherical fluid seal area. A rotation support member is aligned orthogonally to the flow port and the fluid seal area. A material discontinuity volume is disposed behind the closed face of the spherical contoured body.

Abstract: An actuator assembly of a downhole tool may include a high pressure chamber and a low pressure chamber. A pressure applied from the surface to the tool may enter both chambers. The low pressure chamber may include an inlet that restricts the flow of pressure and prevents the pressure within the low pressure chamber from increasing quickly. The high pressure chamber may also include an inlet that restricts the flow of pressure to prevent the pressure within the high pressure chamber from increasing quickly. The inlet of the high pressure chamber may also include a check valve that prevents pressure from bleeding off from the high pressure chamber through the check valve. The pressure within the high pressure chamber may actuate a piston to actuate the tool in response to the pressure applied from the surface falling within a predetermined pressure and time range.

Abstract: A hydraulic line balance manifold includes a housing having first and second open ports for fluidly coupling an upper open line to a downhole tool, first and second close ports for fluidly coupling an upper close line to the downhole tool, and bypass channel for fluidly coupling the second open port with the second close port according to pressure within the upper open line and the upper close line. A sensor piston having first and second positions relative to the housing is slidably disposed within the housing, the second open port fluidly uncoupled from the second close port through the bypass channel when the sensor piston is in the first position, second open port fluidly coupled to the second close port through the bypass channel when the piston is in the second position for reducing fluid resistance to mechanical operation of the slave valve in a mechanical override intervention operation.

Abstract: A ball valve stopper comprising a spherical contoured body comprising a substantially inelastic first material and having a flow port. A closed face of the spherical contoured body is orthogonal with respect to the flow port and includes a spherical fluid seal area. A rotation support member is aligned orthogonally to the flow port and the fluid seal area. A material discontinuity volume is disposed behind the closed face of the spherical contoured body.

Abstract: This disclosure provides a multi-ball valve assembly that lessens the pressure applied from either uphole or downhole directions by directing a portion of the pressure into a sealed fluid chamber area between two balls that are operatively coupled together by one or more control arms. The multi-ball valve assembly may be a floating design where the balls move axially with respect to each other or fixed designs that use either pressure relief valves or biased travel piston valves to divert a portion of the pressure into the fluid chamber area, thereby lessening the distortion of the face of the ball valve against which fluid pressure is being applied.

Abstract: An actuator assembly of a downhole tool may include a high pressure chamber and a low pressure chamber. A pressure applied from the surface to the tool may enter both chambers. The low pressure chamber may include an inlet that restricts the flow of pressure and prevents the pressure within the low pressure chamber from increasing quickly. The high pressure chamber may also include an inlet that restricts the flow of pressure to prevent the pressure within the high pressure chamber from increasing quickly. The inlet of the high pressure chamber may also include a check valve that prevents pressure from bleeding off from the high pressure chamber through the check valve. The pressure within the high pressure chamber may actuate a piston to actuate the tool in response to the pressure applied from the surface falling within a predetermined pressure and time range.

Abstract: A hydraulic line balance manifold includes a housing having first and second open ports for fluidly coupling an upper open line to a downhole tool, first and second close ports for fluidly coupling an upper close line to the downhole tool, and bypass channel for fluidly coupling the second open port with the second close port according to pressure within the upper open line and the upper close line. A sensor piston having first and second positions relative to the housing is slidably disposed within the housing, the second open port fluidly uncoupled from the second close port through the bypass channel when the sensor piston is in the first position, second open port fluidly coupled to the second close port through the bypass channel when the piston is in the second position for reducing fluid resistance to mechanical operation of the slave valve in a mechanical override intervention operation.

Abstract: This disclosure provides a multi-ball valve assembly that lessens the pressure applied from either uphole or downhole directions by directing a portion of the pressure into a sealed fluid chamber area between two balls that are operatively coupled together by one or more control arms. The multi-ball valve assembly may be a floating design where the balls move axially with respect to each other or fixed designs that use either pressure relief valves or biased travel piston valves to divert a portion of the pressure into the fluid chamber area, thereby lessening the distortion of the face of the ball valve against which fluid pressure is being applied.

Abstract: A valve assembly, is presented that has a seating member is slidably coupled to a valve body adjacent a valve body bore and has a metal seat located on a seating end thereof that is engagable against a ball valve member. The seating member has a vent port located there through to allow fluid to flow into a fluid chamber within the ball housing. A first piston is slidably located between the seating member and the ball housing and located over the vent port, and a second piston is slidably located between the seating member and the ball housing and is located downhole from the first piston. Sealing members are located between the first and second pistons and engaged against the seating member.

Abstract: A method, a device and a system for activating a running/setting tool are provided. The method includes: 1) detecting a wellbore condition at the running tool, 2) based on a signal from surface equipment received at the running tool, initiating an isolation of pressure below the running tool from pressure above the running tool, and 3) if the signal is not received at the running tool, initiating the isolation of pressure below the running tool from the above at a predefined time based on the wellbore condition.

Abstract: A method, a device and a system for activating a running/setting tool are provided. The method includes: 1) detecting a wellbore condition at the running tool, 2) based on a signal from surface equipment received at the running tool, initiating an isolation of pressure below the running tool from pressure above the running tool, and 3) if the signal is not received at the running tool, initiating the isolation of pressure below the running tool from the above at a predefined time based on the wellbore condition.

Abstract: The present invention provides novel antibodies that specifically bind to GUCY2c and uses thereof in the treatment of cancer. The present invention further provides novel bispecific antibodies comprising such antibodies and uses thereof in the treatment of cancer.