The present disclosure is generally directed to pinch valves, in particular, toward pinch valves for selectively controlling flow through multiple tubes.
In general, internal and/or external valves have been used to selectively control the flow of a fluid (e.g., a gas, a liquid, etc., and/or combinations thereof) through tubing or some other conduit. These valves may be operated to completely or partially block fluid flow. While internal valves are arranged at least partially within a lumen of the tubing, external valves allow fluid flow control from outside of the tubing. In particular, an external valve allows a force to be applied to an external surface of the tubing, or soft conduit, deforming the lumen of the tubing from an unrestricted state to an occluded, or partially occluded, state.
External valves (e.g., pinch valves, etc.) provide the ability to control fluid flow in tubing without requiring the installation of expensive and complex internal valves. Typical pinch valves control fluid flow in tubing by compressing an outer portion of the tubing thereby closing a lumen disposed in an inner portion of the tubing. As can be appreciated, pinch valves offer a sterile fluid flow control for tubing where the components of the pinch valve do not come into direct contact with fluid inside the tubing.
In some examples, a tubing arrangement or system design may require that more than one tube, or section of tubing, be closed at the same time or at different times. In conventional systems, a pinch valve may be positioned at each discrete area where fluid flow control may be desired. Each pinch valve may be independently operated by a respective actuator. In this conventional approach, as the number of the discrete fluid flow control areas increases, so does the number of pinch valves required to service the system. Since each pinch valve includes its own actuator, the cost and complexity of this conventional approach necessarily increases. In addition, the number of components required to perform the fluid control operations under the conventional approach increases the potential for failure and the time required for routine maintenance operations.
It is with respect to the above issues and other problems that the embodiments presented herein were contemplated. Among other things, the present disclosure provides a multiple-tubing, or multi-tubing, pinch valve assembly that is capable of pinching more than one tube, or section of tubing, with a single actuator. In some examples, the multi-tubing pinch valve assembly may be configured to pinch various tubes, or tubing sections, simultaneously. Additionally or alternatively, the multi-tubing pinch valve assembly may pinch a first set of tubes at a first time and pinch a second set of tubes at a different second time. In one example, the multi-tubing pinch valve assembly may allow flow through the first set of tubes while pinching the second set of tubes (e.g., preventing flow, etc.), and vice versa.
In one example, the multi-tubing pinch valve assembly may comprise a compact valve array that is capable of executing a sequence of opening and closing flow paths to each bioreactor in a multiple-bioreactor system. The multi-tubing pinch valve assembly may comprise a valve mechanism that may be built into a bioreactor rocker assembly. This design, among other things, greatly simplifies a disposable set (e.g., tubing set, etc.) used in cell expansion systems, sterile fluid management systems, any suitable system that uses a multi-tubing valving scheme for sterile fluid pathway management, etc. Additionally or alternatively, the multi-tubing pinch valve assembly may integrate with a soft cassette of a disposable set.
In some examples, the multi-tubing pinch valve assembly may correspond to a cam-driven valve array that provides a compact method of opening/closing many parallel tubes in a set sequence. This approach may allow a multiple-bioreactor cell expansion system to execute a “time share” or “duty cycle” method of servicing multiple bioreactors, with the valve array being located on the bioreactor rocker rather than on a static cassette. As can be appreciated, the multi-tubing pinch valve assembly is not limited to use in a multiple-bioreactor system. For instance, the mechanism of the multi-tubing pinch valve assembly may be adapted to any situation where multiple valves may be required to have their positions fixed relative to others.
In a cam-driven approach, the multi-tubing pinch valve assembly may utilize a finger pump type mechanism having the orientation of the tube and fingers rotated 90 degrees relative to the cam. Rather than pumping a single tube, the multi-tubing pinch valve assembly is capable of valving many tubes simultaneously. This multi-tubing pinch valve assembly design can be paired with a soft cassette, as the fingers actuate in a direction normal to the soft cassette plane. The multi-tubing pinch valve assembly allows the occlusion depth to be tightly controlled, which allows for the possibility of intentionally partially occluding tubes (e.g., partial restriction of fluid flow, etc.). Another benefit of the examples described herein include the compact size and simplified electronics of the multi-tubing pinch valve assembly. Among other things, these features allow the valve unit to be mounted to a bioreactor rocker, in some cases, thereby simplifying a disposable set used in cell expansion systems, for example, by reducing the number of tubes that must run from the bioreactors to the static cassette. Further, the multi-tubing pinch valve assembly may ensure that valve positions are locked relative to each other, allowing assurance of correct flow. For example, it can be assured that one of the tubes in the time share model is always open, preventing pressure buildup, or two tubes may always be open or closed relative to each other, assuring a complete fluid path.
In some examples, the multi-tubing pinch valve assembly may be driven by a motor operatively connected to a camshaft comprising two cam profiles. A first anvil assembly may be disposed adjacent a first cam profile of the two cam profiles and a second anvil assembly may be disposed adjacent a second cam profile of the two cam profiles. As the motor rotates the camshaft, the two cam profiles rotate relative to the first anvil assembly and the second anvil assembly. At specific angles of rotation, at least one cam lobe, or protrusion, disposed on the cam profile may contact the first anvil assembly and the second anvil assembly. For instance, a first cam lobe associated with the first cam profile may contact the first anvil assembly at a first angle of rotation of the camshaft. As the first cam lobe contacts the first anvil assembly, the shape of the first cam lobe may cause the first anvil assembly to move in a direction away from the camshaft toward a pinch plate. A first section of tubing may be disposed in a first space between the first anvil and the pinch plate. In this arrangement, as the first anvil assembly moves toward the pinch plate, a first anvil of the first anvil assembly may contact and deform the first section of tubing such that a lumen of the first section of tubing closes. The first section of tubing may remain closed while the first cam lobe is at, or within a predetermined angular range (e.g., 1-5 degrees) of, a highest displacement point of the first cam lobe and the first anvil maintains the first section of tubing in a closed state.
The multi-tubing pinch valve assembly may be configured as an array of independently actuated multiple-tubing pinch valves. For instance, the multi-tubing pinch valve assembly may include a five-valve array of independently actuated four-tube pinch valves. At least one benefit to this independent actuation arrangement includes, but is in no way limited to, operating the multi-tubing pinch valve assembly in any combination of open or closed states.
This present disclosure describes, among other things, a multi-tubing pinch valve assembly comprising an array that is split into discrete multi-tube valves (e.g., an array of five 4-tube pinch valves), each multi-tube valve in the array capable of being driven by a small linear actuator (e.g., a solenoid, piezoelectric actuator, screw-type actuator, pneumatic cylinder, hydraulic cylinder, and/or a stepper motor linear actuator, etc.). This approach allows for any combination of valve states during a protocol (e.g., system operation, etc.). For example, in a cell expansion system, all valves may be opened during loading of a disposable (e.g., tubing set, etc.), valves may cycle continuously on a 10-second duty cycle during a cell feed, and valves may be opened sequentially for longer durations during tasks such as cell harvest, and/or the like.
In some examples, the pinching jaws of each multi-tube valve (e.g., 4-tube valve, etc.) of the multi-tubing pinch valve assembly may be slightly offset from one another. Among other things, this arrangement may reduce the pinch force from the actuator that may be required to occlude the tubing and increase the jaw gap range that results in occlusion. Such an increased jaw gap may provide enhanced cycling life and tubing integrity over time compared to designs including a decreased jaw gap. In one example, a single set of opposing jaws may pinch four tubes at once. Additionally or alternatively, the independent operability of each of the multi-tube valves may allow for disposable design optimization and simplification when compared with designs that require different valving.
The preceding is a simplified summary of the disclosure to provide an understanding of some aspects of the disclosure. This summary is neither an extensive nor exhaustive overview of the disclosure and its various aspects, embodiments, and configurations. It is intended neither to identify key or critical elements of the disclosure nor to delineate the scope of the disclosure but to present selected concepts of the disclosure in a simplified form as an introduction to the more detailed description presented below. As will be appreciated, other aspects, embodiments, and configurations of the disclosure are possible utilizing, alone or in combination, one or more of the features set forth above or described in detail below.
Numerous additional features and advantages are described herein and will be apparent to those skilled in the art upon consideration of the following Detailed Description and in view of the figures.
The accompanying drawings are incorporated into and form a part of the specification to illustrate several examples of the present disclosure. These drawings, together with the description, explain the principles of the disclosure. The drawings simply illustrate preferred and alternative examples of how the disclosure can be made and used and are not to be construed as limiting the disclosure to only the illustrated and described examples. Further features and advantages will become apparent from the following, more detailed, description of the various aspects, embodiments, and configurations of the disclosure, as illustrated by the drawings referenced below.
Before any embodiments of the disclosure are explained in detail, it is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The disclosure is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Further, the present disclosure may use examples to illustrate one or more aspects thereof. Unless explicitly stated otherwise, the use or listing of one or more examples (which may be denoted by “for example,” “by way of example,” “e.g.,” “such as,” or similar language) is not intended to and does not limit the scope of the present disclosure.
The ensuing description provides embodiments only, and is not intended to limit the scope, applicability, or configuration of the claims. Rather, the ensuing description will provide those skilled in the art with an enabling description for implementing the described embodiments. It being understood that various changes may be made in the function and arrangement of elements without departing from the spirit and scope of the appended claims.
Various aspects of the present disclosure will be described herein with reference to drawings that may be schematic illustrations of idealized configurations.
Conventional external valving solutions generally utilize a single pinch valve to control fluid flow in a single tube. When fluid flow control is required for multiple tubes, each tube of the multiple tubes may employ a respective pinch valve. As can be appreciated, this conventional arrangement increases the number of components needed for a multiple-tube fluid flow control application. With the increased number of components, the complexity of the conventional multiple-tube fluid flow control application increases. Additionally or alternatively, control of each pinch valve in a multiple-tube fluid flow control application, where each tube has its own pinch valve, requires complex valve controls, timing, wiring, and programming. In any event, employing a single pinch valve for every tube, or section of tubing, that is to be pinched in a conventional approach results in increased maintenance times, failures, and system complexity.
It is with respect to the above issues and other problems that the embodiments presented herein were contemplated.
Referring now to
Features of the multiple-tube pinch valve assembly 100 may be described in conjunction with a coordinate system 102. The coordinate system 102, as shown in the figures, includes three-dimensions comprising an X-axis, a Y-axis, and a Z-axis. Additionally or alternatively, the coordinate system 102 may be used to define planes (e.g., the XY-plane, the XZ-plane, and the YZ-plane) of the multiple-tube pinch valve assembly 100. These planes may be disposed orthogonal, or at 90 degrees, to one another. While the origin of the coordinate system 102 may be placed at any point on or near the components of the multiple-tube pinch valve assembly 100, for the purposes of description, the axes of the coordinate system 102 are always disposed along the same directions from figure to figure. In some examples, reference may be made to dimensions, angles, directions, relative positions, and/or movements associated with one or more components of the multiple-tube pinch valve assembly 100 with respect to the coordinate system 102. For example, the width of the multiple-tube pinch valve assembly 100 may be defined as a dimension along the X-axis of the coordinate system 102, the height of the multiple-tube pinch valve assembly 100 may be defined as dimension along the Y-axis of the coordinate system 102, and the depth of the multiple-tube pinch valve assembly 100 may be defined as a dimension along the Z-axis of the coordinate system 102. Additionally or alternatively, the width of the tubing platen 120 may be defined as a dimension along the X-axis of the coordinate system 102, the height of the tubing platen 120 may be defined as dimension along the Y-axis of the coordinate system 102, and the depth of the tubing platen 120 may be defined as a dimension along the Z-axis of the coordinate system 102.
The multiple-tube pinch valve assembly 100 may include a motor 132 having an output shaft 134, a drive body 136, and a cam drive body 140. As the output shaft 134 of the motor 132 rotates, power is transmitted from the drive body 136 to the cam drive body 140. In one example, the drive body 136 and the cam drive body 140 may be configured as respective gears in meshing contact with one another. In one example, the drive body 136 and the cam drive body 140 may correspond to pulleys (e.g., timing belt pulleys, V-pulleys, etc.). In this example, power may be transmitted from the drive body 136 to the cam drive body 140 via a drive belt 138. The drive belt 138 may correspond to a timing belt, a V-belt, a ribbed V-belt, a link V-belt, etc., and/or any other continuous belt. In any of these examples, as the output shaft 134 of the motor 132 rotates, the camshaft 108 is caused to rotate about the longitudinal axis 110. Rotation of the camshaft 108 causes the cam 112 having at least one cam profile shape to rotate about the longitudinal axis 110. The cam 112 may be keyed (e.g., via a key and keyway, a spline, etc.), fixed, formed from, and/or otherwise affixed to the camshaft 108. The cam 112 may rotate through 360 degrees. At various angular rotations, different portions of the cam profile shape of the cam 112 may be presented to an anvil assembly 150. For instance, as a protrusion of the cam 112 contacts the anvil assembly 150, the anvil assembly 150 may lift (e.g., move in the positive Y-axis direction) toward the tubing platen 120 and as a recess, or heel, of the cam 112 contacts the anvil assembly 150, the anvil assembly 150 may lower (e.g., move in the negative Y-axis direction) away from the tubing platen 120. In this manner, the rotation of the camshaft 108 may cause the anvil assembly 150 to pinch the multiple tubes 124 in the tube receiving apertures 128 of the multiple-tube pinch valve assembly 100.
In some examples, the multiple-tube pinch valve assembly 100 may include a bioreactor support frame 144. The bioreactor support frame 144 may comprise a plurality of recesses 142 configured to receive and/or hold a respective bioreactor (e.g., hollow fiber bioreactor, cell expansion system bioreactor, etc.). In some examples, the multiple tubes 124 that are disposed in the tube receiving apertures 128 may be interconnected to the multiple bioreactors that are held, or supported, by the bioreactor support frame 144. Fluid flow control to multiple bioreactors may benefit from altering the timing associated with opening and closing the multiple tubes 124 associated with each bioreactor at a same time or at different times.
As shown in the front elevation view of
The anvil assembly 150, shown in greater detail in
The anvil assembly 150 may comprise at least one cam contact portion disposed on a lower portion of the anvil body 204. The at least one cam contact portion may extend past the anvil body 204. In any event, the at least one cam contact portion may provide a contact surface between the anvil body 204 and the cam 112 of the multiple-tube pinch valve assembly 100. In some examples, the at least one cam contact portion may correspond to a cam follower 210, or other bearing. The cam follower 210, in some cases, may be made to include a hardened steel wheel and a bearing (e.g., roller bearing, ball bearing, etc.). The lower portion of the anvil body 204 may include a tapered surface 220 disposed on either side of a plane running through a center of the anvil body 204 (e.g., along the XY-plane). The tapered surface 220 may provide clearance for portions of the cam 112 and the cam profile shape as the cam 112 moves relative to the anvil body 204 and anvil assembly 150.
In
As shown in
When the camshaft 108 is rotated by a first rotation 320A (e.g., shown as a first clockwise rotation), the cam 112 rotates from the zero-degree reference to the al angular position (e.g., comprising a non-zero angle measured from the zero-degree reference), as shown in
Continuing the rotation from
The cam 112 may also be configured to provide an “all-open” state in which all of the tubes 124 are open and not constricted by the anvil assembly 150. Such an “all open” state improves loading of the bioreactor support frame 144. The cam 112 may also be configured to be removable from the assembly 100 to allow all of the bioreactors to be opened simultaneously.
Although described as rotating in a clockwise direction, it should be appreciated that the camshaft 108 may be rotated in a counterclockwise direction, a clockwise direction, and/or combinations thereof. In some examples, the motor 132 may be rotated in any rotational direction causing the rotation of the camshaft 108. Additionally or alternatively, while described as having a cam heel 308, cam transitions 312, and a cam lobe 316, it should be appreciated that the cam 112 may include greater or fewer protrusions, shapes, dwells, lobes, and recesses than are shown and described in
Referring to
The linear actuator 410 may be mounted to a mount body 408 that is fixed relative to the base 404 of the multi-tubing pinch valve assembly 400. As the linear actuator 410 is actuated, a translation rod 412 may move between a retracted state and an extended state, or vice versa. Extending the translation rod 412 may move the hinge plate 416 toward the clamp platen 420. In this extended position, the multiple tubes 124 disposed in the tube receiving aperture 128 may be pinched by one or more features of the hinge plate 416 and the clamp platen 420.
The clamp platen 420 may be fixed relative to the base 404. As the linear actuator 410 is actuated, the translation rod 412 may move the hinge plate 416 from an open state to a closed state, or vice versa. In the open state, at least one portion of the hinge plate 416 may be separated further from the clamp platen 420 than when in the closed state. When in the open state, the multiple tubes 124 may be loaded and/or removed from the tube receiving aperture 128. Stated another way, the multiple tubes 124 may not be clamped, or pinched, when in the open state. However, when in the closed state, the multiple tubes 124 may be pinched between the hinge plate 416 and the clamp platen 420. Additional detail regarding the construction of the hinge plate 416 and the clamp platen 420 and the fluid flow control (e.g., pinching) arrangement is described in conjunction with
In some examples, the multi-tubing pinch valve assembly 400 may comprise an array of valves arranged adjacent to one another. As shown in the plan view of
The linear actuator 410 may be attached to a mount body 408. The mount body 408 may be fixed relative to the base 404. The linear actuator 410 may include a translation rod 412 that moves relative to the mount body 408 (e.g., in a direction toward or away from the mount body 408). The translation rod 412 may comprise a clevis pin 504 that engages with a clevis of the hinge plate 416. In some examples, the hinge plate 416 may comprise a clevis slot 508 in which the clevis pin 504 may be disposed.
A reagent attachment point is at 838. A regent line extends through a reagent valve 840 to the cell inlet line. An IC media attachment point is at 842. An IC media line extends through IC media valve 844 to the reagent line.
An EC media attachment point is at 850. From the EC media attachment point 850, an EC line extends through EC media valve 852. A wash connection point is at 854, and a wash valve is at 856. A distribution valve is along a line connecting the EC loop 812 and the IC loop 810. The EC loop 812 includes an EC inlet pump 870, which is downstream from an EC fluid detector 872. The EC loop 812 further includes a GTM chamber 880, an EC inlet pressure sensor 882, an EC circulation pump 884, and an EC outlet pressure sensor 886. An EC waste valve 888 is on an EC waste line extending to waste 828. An IC waste valve 890 and an IC outlet pressure sensor 894 are upstream of waste 828 on the IC side.
The base 1110 further includes a plurality of support posts 1150. The support posts 1150 are configured to cooperate with the bioreactor support frame 1310 as explained below to support the bioreactor support frame 1310 on the base 1110 and over the hinge plates 1112A-1112E. A strap 1152 is included to hold the bioreactor support frame 1310 on the base 1110.
The multitube pinch valve assembly 1100 further includes a rocker assembly 1160. The rocker assembly 1160 includes a rocker rod 1162, which cooperates with the base 1110 at an aperture 1164 defined by the base 1110. The rocker assembly 1160 includes a motor configured to rotate the rocker rod 1162. The rocker rod 1162 is mounted to the base 1110 in any suitable manner such that rotation of the rocker rod 1162 rocks the base 1110 and the bioreactors 704A-704E mounted thereto. In come configurations, the rocker assembly 1160 may be configured to invert the bioreactors 704A-704E.
With particular reference to
The bioreactor support frame 1310 further includes a plurality of receptacles 1340, each of which are configured to cooperate with the support posts 1150 of the base 1110. The support posts 1150 support the bioreactor support frame 1310 on top of the base 1110 and position the support frame 1310 such that the tubes 124 are arranged opposite to, and extend perpendicularly across, the hinge pinch protrusions 1114 of the hinge plates 1112A-1112E. Actuation of the different hinge plates 1112A-1112E moves the hinge pinch protrusions 1114 towards tubes to pinch the tubes 124 and restrict fluid flow through the tubes 124 and to the bioreactors 704A-704E in generally the same manner illustrated in
Opposite to the rail 1520, and seated within a housing 1530, are a plurality of actuation plates 1540A, 1540B, 1540C, 1540D, and 1540E. In the example illustrated, five actuation plates 1540A-1540E are included. The base 1510 may include any suitable number of actuation plates, however. Each one of the actuation plates 1540A-1540E includes a pinch protrusion 1542.
The actuation plates 1540A-1540E are individually actuatable by any suitable actuation mechanism. In the example illustrated, each one of the actuation plates 1540A-1540E is actuated by a different actuation mechanism 1550A, 1550B, 1550C, 1550D, 1550E respectively. The actuation mechanisms 1550A-1550E may include any suitable linear actuator, such as any suitable solenoid, linear stepper motor, pneumatic actuator, etc. The actuation mechanisms 1550A-1550E may be individually actuated to control fluid flow through tubes 124 of the bioreactors 704A-704E.
With particular reference to
The tubing platen 1730 further defines a center channel 1740 configured to receive the rail 1520 therein. At a rear of the center channel 1740 is a rear aperture 1742. The center channel 1740 extends perpendicular to the lengths of the bioreactors 704A-704E, and perpendicular to the tubes 124 supported by the tube receiving apertures 1732. At a rear end of the tubing platen 1730 are rear tabs 1750. At a front end of the tubing platen 1730 are front tabs 1752.
To connect the bioreactor support frame 1710 to the base 1510, the latch 1512 is folded downward, the tubing platen 1730 is positioned so that the rail 1520 enters through the rear aperture 1742, and then the tubing platen 1730 is slid onto the rail 1520 so that the rail 1520 extends along the center channel 1740. The tubing platen 1730 is slid along the rail 1520 until the rear tabs 1750 are seated within rear openings 1560 of the base 1510. The latch 1512 is then closed onto the front tabs 1752 so that the front tabs 1752 are seated within recesses 1562 defined on an inner surface of the latch 1512 to lock the tubing platen 1730 into position. The rear tabs 1750 and the front tabs 1752 improve alignment of the tubes 124 relative to the pinch protrusions 1542, and prevent loading the bioreactors backwards. Also, when the assembly 1500 includes a rocker, the tabs 1750, 1752 keep the bioreactors 704A-704E and tubes 124 in the correct position relative to the rod 1520. The tubing platen 1730 is oriented so that the pinch protrusions 1542 are perpendicular to the tubes 124. Actuation of the different actuation plates 1540A-1540E moves the pinch protrusions 1542 towards and into the center channel 1740 to pinch the tubes 124 between the pinch protrusions 1542 and the rail 1520 to restrict fluid flow through the tubes 124 in generally the same manner illustrated in
While the operations and steps above have been discussed and illustrated in relation to a particular sequence of events, it should be appreciated that changes, additions, and omissions to this sequence can occur without materially affecting the operation of the disclosed embodiments, configuration, and aspects.
The exemplary systems and methods of this disclosure have been described in relation to pinch valves and multiple-tubing systems. However, to avoid unnecessarily obscuring the present disclosure, the preceding description omits a number of known structures and devices. This omission is not to be construed as a limitation of the scope of the claimed disclosure. Specific details are set forth to provide an understanding of the present disclosure. It should, however, be appreciated that the present disclosure may be practiced in a variety of ways beyond the specific detail set forth herein.
A number of variations and modifications of the disclosure can be used. It would be possible to provide for some features of the disclosure without providing others.
References in the specification to “one embodiment,” “an embodiment,” “an example embodiment,” “some embodiments,” etc., indicate that the embodiment described may include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same embodiment. Further, when a particular feature, structure, or characteristic is described in conjunction with one embodiment, it is submitted that the description of such feature, structure, or characteristic may apply to any other embodiment unless so stated and/or except as will be readily apparent to one skilled in the art from the description. The present disclosure, in various embodiments, configurations, and aspects, includes components, methods, processes, systems and/or apparatus substantially as depicted and described herein, including various embodiments, subcombinations, and subsets thereof. Those of skill in the art will understand how to make and use the systems and methods disclosed herein after understanding the present disclosure. The present disclosure, in various embodiments, configurations, and aspects, includes providing devices and processes in the absence of items not depicted and/or described herein or in various embodiments, configurations, or aspects hereof, including in the absence of such items as may have been used in previous devices or processes, e.g., for improving performance, achieving ease, and/or reducing cost of implementation.
The foregoing discussion of the disclosure has been presented for purposes of illustration and description. The foregoing is not intended to limit the disclosure to the form or forms disclosed herein. In the foregoing Detailed Description for example, various features of the disclosure are grouped together in one or more embodiments, configurations, or aspects for the purpose of streamlining the disclosure. The features of the embodiments, configurations, or aspects of the disclosure may be combined in alternate embodiments, configurations, or aspects other than those discussed above. This method of disclosure is not to be interpreted as reflecting an intention that the claimed disclosure requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment, configuration, or aspect. Thus, the following claims are hereby incorporated into this Detailed Description, with each claim standing on its own as a separate preferred embodiment of the disclosure.
Moreover, though the description of the disclosure has included description of one or more embodiments, configurations, or aspects and certain variations and modifications, other variations, combinations, and modifications are within the scope of the disclosure, e.g., as may be within the skill and knowledge of those in the art, after understanding the present disclosure. It is intended to obtain rights, which include alternative embodiments, configurations, or aspects to the extent permitted, including alternate, interchangeable and/or equivalent structures, functions, ranges, or steps to those claimed, whether or not such alternate, interchangeable and/or equivalent structures, functions, ranges, or steps are disclosed herein, and without intending to publicly dedicate any patentable subject matter.
Exemplary aspects are directed to a multiple-tube pinch valve assembly, comprising: a camshaft extending a length along a longitudinal axis of the camshaft, the camshaft comprising at least one cam disposed along the length, the at least one cam comprising a cam profile shape defined around the longitudinal axis and a periphery of the camshaft and; a platen offset a distance from the longitudinal axis, the distance at least partially defining a space configured to receive multiple fluid flow tubes; and an anvil assembly comprising a cam contact portion disposed on a first side of the anvil assembly and a pinch edge disposed on a second side of the anvil assembly, wherein the anvil assembly is moveable between a retracted state such that the pinch edge is disposed outside of the space and an extended state such that the pinch edge is disposed inside the space adjacent the platen, and wherein the anvil assembly moves between the retracted state and the extended state by a rotation of the camshaft and the at least one cam.
Any one or more of the above aspects include wherein the cam profile shape comprises at least one cam lobe and at least one cam heel, wherein the anvil assembly is in the extended state when the cam lobe is disposed in contact with the cam contact portion, and wherein the anvil assembly is in the retracted state when the cam heel is disposed in contact with the cam contact portion. Any one or more of the above aspects include wherein the cam contact portion comprises at least one cam follower. Any one or more of the above aspects include wherein the space comprises a plurality of tube receiving apertures arranged side-by-side along a direction that is parallel to the longitudinal axis of the camshaft. Any one or more of the above aspects include wherein each tube receiving aperture of the plurality of tube receiving apertures extend in a direction that is perpendicular to the longitudinal axis of the camshaft. Any one or more of the above aspects further comprising: a plurality of tubes removably engaged with the plurality of tube receiving apertures such that a section of each tube of the plurality of tubes is disposed in the space adjacent the platen, wherein, in the retracted state, a lumen of each tube of the plurality of tubes is open along the section of each tube of the plurality of tubes, and wherein, in the extended state, the lumen of each tube of the plurality of tubes is closed at a point along the section of each tube of the plurality of tubes. Any one or more of the above aspects further comprising: a motor comprising an output shaft; a drive body attached to the output shaft of the motor; and a cam drive body attached to the camshaft, wherein rotation of the output shaft of the motor transmits power from the drive body to the cam drive body causing the camshaft to rotate relative to the anvil assembly. Any one or more of the above aspects further comprising: a support frame comprising a plurality of recesses, wherein each recess of the plurality of recesses is configured to hold a respective bioreactor, and wherein each tube of the plurality of tubes is associated with the respective bioreactor. Any one or more of the above aspects include wherein the anvil assembly, when moving between the retracted state and the extended state, translates along a plane that is perpendicular to a plane running through the plurality of tubes, and wherein, in the extended state, the pinch edge of the anvil assembly contacts and closes each tube of the plurality of tubes. Any one or more of the above aspects further comprising: an array of valves disposed along a length of the longitudinal axis of the camshaft, wherein each valve in the array of valves comprises a plurality of tube receiving apertures, and wherein each valve in the array of valves comprises a respective anvil assembly that is capable of moving between the retracted state and the extended state by the rotation of the camshaft and the at least one cam. Any one or more of the above aspects include wherein the respective anvil assembly of each valve in the array of valves is capable of moving between the retracted state and the extended state based on a position of a respective cam connected to the camshaft. Any one or more of the above aspects include wherein a first valve in the array of valves is capable of closing tubing contained within a first set of tube receiving apertures associated with the first valve at a same time or a different time as a second valve in the array of valves closes tubing contained within a second set of tube receiving apertures associated with the second valve. Any one or more of the above aspects include wherein, at a first time as the camshaft rotates, a first valve in the array of valves closes tubing contained within a first set of tube receiving apertures associated with the first valve, wherein, at a second time as the camshaft rotates, a second valve in the array of valves closes tubing contained within a second set of tube receiving apertures associated with the second valve. Any one or more of the above aspects include wherein, at a third time as the camshaft rotates, a third valve in the array of valves closes tubing contained within a third set of tube receiving apertures associated with the third valve, wherein, at a fourth time as the camshaft rotates, a fourth valve in the array of valves closes tubing contained within a fourth set of tube receiving apertures associated with the fourth valve, and wherein at a fifth time as the camshaft rotates, a fifth valve in the array of valves closes tubing contained within a fifth set of tube receiving apertures associated with the fifth valve. Any one or more of the above aspects include wherein the first set of tube receiving apertures, the second set of tube receiving apertures, the third set of tube receiving apertures, the fourth set of tube receiving apertures, and the fifth set of tube receiving apertures each comprise four tube receiving apertures.
Exemplary aspects are directed to a multiple-tube pinch valve assembly, comprising: a motor comprising an output shaft; a drive body attached to the output shaft of the motor; a camshaft extending a length along a longitudinal axis of the camshaft, the camshaft comprising at least one cam disposed along the length, the at least one cam comprising a cam profile shape defined around the longitudinal axis and a periphery of the camshaft and; a cam drive body attached to the camshaft; a platen offset a distance from the longitudinal axis, the distance at least partially defining a space configured to receive multiple fluid flow tubes; and an anvil assembly comprising at least one cam follower disposed on a first side of the anvil assembly and a pinch edge disposed on a second side of the anvil assembly, wherein rotation of the output shaft of the motor transmits power from the drive body to the cam drive body causing the camshaft to rotate relative to the anvil assembly and move the anvil assembly between a retracted state, such that the pinch edge is disposed outside of the space, and an extended state, such that the pinch edge is disposed inside the space adjacent the platen, and wherein the anvil assembly moves between the retracted state and the extended state by rotation of the camshaft and the at least one cam.
Exemplary aspects are directed to a multi-tubing pinch valve assembly, comprising: a hinge plate extending a length from a first point to a second point, the hinge plate comprising: a pivot axis disposed adjacent the first point of the hinge plate; and a pinch protrusion disposed between the first point and the second point, the pinch protrusion extending from a surface of the hinge plate; a platen comprising a body offset a distance from the hinge plate, the platen comprising a tubing contact portion disposed on a surface of the platen; an actuator operatively connected to the hinge plate adjacent the second point, wherein the actuator is moveable between a retracted state and an extended state, wherein, in the retracted state, the hinge plate is pivoted about the pivot axis such that the second point of the hinge plate is separated from the platen by a first distance, wherein, in the extended state, the hinge plate is pivoted about the pivot axis such that the second point of the hinge plate is separated from the platen by a second distance, and wherein the first distance is greater than the second distance.
Any one or more of the above aspects include wherein, in the extended state, the pinch protrusion of the hinge plate is adjacent the tubing contact portion of the platen, and wherein in the retracted state, the pinch protrusion of the hinge plate is offset from the tubing contact portion of the platen creating a receiving space between the hinge plate and the platen. Any one or more of the above aspects include wherein, in the retracted state, the pinch protrusion of the hinge plate is offset from the tubing contact portion of the platen by a first dimension defining a receiving space capable of receiving a plurality of tubes. Any one or more of the above aspects include wherein, in the extended state, the pinch protrusion of the hinge plate is offset from the tubing contact portion of the platen by a second dimension defining a pinched receiving space that is sized to pinch the plurality of tubes disposed between the hinge plate and the platen. Any one or more of the above aspects further comprising the plurality of tubes disposed in between the hinge plate and the platen, wherein the plurality of tubes provide fluid flow paths therethrough when in the retracted state, and wherein the fluid flow paths are restricted by the pinch protrusion of the hinge plate and the tubing contact portion of the platen when in the extended state. Any one or more of the above aspects include wherein the pinch protrusion of the hinge plate and the tubing contact portion of the platen completely restrict fluid flow in the plurality of tubes when in the extended state. Any one or more of the above aspects further comprising: a clevis disposed adjacent the second point of the hinge plate; and a clevis pin engaged with the clevis, the clevis pin being connected to an end of a translation rod of the actuator. Any one or more of the above aspects include wherein the tubing contact portion comprises a platen pinch protrusion extending from a surface of the platen, and wherein the surface of the platen faces the hinge plate. Any one or more of the above aspects include wherein the pivot axis is defined by a hinge pin engaged with the hinge plate and a hinge support block. Any one or more of the above aspects include wherein the actuator is one of a solenoid, a screw-type actuator, and a stepper motor actuated screw. Any one or more of the above aspects include wherein the clevis pin engages with a slot in the clevis.
Exemplary aspects are directed to a multi-tubing pinch valve assembly, comprising: an array of valves disposed adjacent one another, wherein each valve in the array of valves comprises: a hinge plate extending a length from a first point to a second point, the hinge plate comprising: a pivot axis disposed adjacent the first point of the hinge plate; and a pinch protrusion disposed between the first point and the second point, the pinch protrusion extending from a surface of the hinge plate; a tubing contact body offset a distance from the hinge plate; an actuator operatively connected to the hinge plate adjacent the second point, wherein the actuator is moveable between a retracted state and an extended state, wherein, in the retracted state, the hinge plate is pivoted about the pivot axis such that the second point of the hinge plate is separated from the tubing contact body by a first distance, wherein, in the extended state, the hinge plate is pivoted about the pivot axis such that the second point of the hinge plate is separated from the tubing contact body by a second distance, and wherein the first distance is greater than the second distance.
Any one or more of the above aspects include wherein, in the extended state, the pinch protrusion of the hinge plate is adjacent the tubing contact body, and wherein in the retracted state, the pinch protrusion of the hinge plate is offset from the tubing contact body creating a receiving space between the hinge plate and the tubing contact body. Any one or more of the above aspects include wherein each valve in the array of valves is configured to receive a plurality of tubes in the receiving space. Any one or more of the above aspects include wherein each valve in the array of valves is configured to pinch the plurality of tubes in the receiving space in the extended state of the actuator. Any one or more of the above aspects include wherein each valve in the array of valves is independently operable such that each hinge plate of each valve is moveable between the retracted state and the extended state independently. Any one or more of the above aspects include wherein a first valve in the array of valves is operable together with and/or separately from a second valve in the array of valves. Any one or more of the above aspects further comprising: a support frame comprising a plurality of recesses, wherein each recess of the plurality of recesses is configured to hold a respective bioreactor, and wherein each tube of the plurality of tubes is associated with the respective bioreactor.
Exemplary aspects are directed to a multiple-bioreactor assembly comprising the multi-tubing pinch valve assembly of any of the above aspects.
Any one or more of the above aspects/embodiments as substantially disclosed herein.
Any one or more of the aspects/embodiments as substantially disclosed herein optionally in combination with any one or more other aspects/embodiments as substantially disclosed herein.
One or means adapted to perform any one or more of the above aspects/embodiments as substantially disclosed herein.
Any one or more of the features disclosed herein.
Any one or more of the features as substantially disclosed herein.
Any one or more of the features as substantially disclosed herein in combination with any one or more other features as substantially disclosed herein.
Any one of the aspects/features/embodiments in combination with any one or more other aspects/features/embodiments.
Use of any one or more of the aspects or features as disclosed herein.
It is to be appreciated that any feature described herein can be claimed in combination with any other feature(s) as described herein, regardless of whether the features come from the same described embodiment.
As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “include,” “including,” “includes,” “comprise,” “comprises,” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The term “and/or” includes any and all combinations of one or more of the associated listed items.
The term “a” or “an” entity refers to one or more of that entity. As such, the terms “a” (or “an”), “one or more,” and “at least one” can be used interchangeably herein. It is also to be noted that the terms “comprising,” “including,” and “having” can be used interchangeably.
The phrases “at least one,” “one or more,” “or,” and “and/or” are open-ended expressions that are both conjunctive and disjunctive in operation. For example, each of the expressions “at least one of A, B and C,” “at least one of A, B, or C,” “one or more of A, B, and C,” “one or more of A, B, or C,” and “A, B, and/or C” means A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B, and C together. When each one of A, B, and C in the above expressions refers to an element, such as X, Y, and Z, or a class of elements, such as X1-Xn, Y1-Ym, and Z1-Zo, the phrase is intended to refer to a single element selected from X, Y, and Z, a combination of elements selected from the same class (e.g., X1 and X2) as well as a combination of elements selected from two or more classes (e.g., Y1 and Zo).
The term “automatic” and variations thereof, as used herein, refers to any process or operation, which is typically continuous or semi-continuous, done without material human input when the process or operation is performed. However, a process or operation can be automatic, even though performance of the process or operation uses material or immaterial human input, if the input is received before performance of the process or operation. Human input is deemed to be material if such input influences how the process or operation will be performed. Human input that consents to the performance of the process or operation is not deemed to be “material.”
The terms “determine,” “calculate,” “compute,” and variations thereof, as used herein, are used interchangeably and include any type of methodology, process, mathematical operation, or technique.
Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and this disclosure.
It should be understood that every maximum numerical limitation given throughout this disclosure is deemed to include each and every lower numerical limitation as an alternative, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this disclosure is deemed to include each and every higher numerical limitation as an alternative, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this disclosure is deemed to include each and every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.
This application claims the benefit of U.S. Provisional Patent Application No. 63/314,931 filed on Feb. 28, 2022, the entire disclosure of which is incorporated herein by reference.
Number | Name | Date | Kind |
---|---|---|---|
2821434 | Hunter | Jan 1958 | A |
2997077 | Rodrigues | Aug 1961 | A |
3013435 | Rodrigues | Dec 1961 | A |
3067915 | Shapiro et al. | Dec 1962 | A |
3191807 | Rodrigues | Jun 1965 | A |
3283727 | Rodrigues | Nov 1966 | A |
3613729 | Dora | Oct 1971 | A |
3650296 | Johnson | Mar 1972 | A |
3701717 | Ingvorsen | Oct 1972 | A |
4173415 | Wyatt | Nov 1979 | A |
4301010 | Eddleman et al. | Nov 1981 | A |
4301118 | Eddleman et al. | Nov 1981 | A |
4412990 | Lundblad et al. | Nov 1983 | A |
4418691 | Yannas et al. | Dec 1983 | A |
4439901 | Eddleman | Apr 1984 | A |
4478829 | Landaburu et al. | Oct 1984 | A |
4486188 | Altshuler et al. | Dec 1984 | A |
4509695 | Bessman | Apr 1985 | A |
4585654 | Landaburu et al. | Apr 1986 | A |
4618586 | Walker | Oct 1986 | A |
4629686 | Gruenberg | Dec 1986 | A |
4670544 | Schwinn et al. | Jun 1987 | A |
4727059 | Binder et al. | Feb 1988 | A |
4828706 | Eddleman | May 1989 | A |
4897358 | Carrasco | Jan 1990 | A |
4960521 | Keller | Oct 1990 | A |
4988623 | Schwarz et al. | Jan 1991 | A |
5015585 | Robinson | May 1991 | A |
5019054 | Clement et al. | May 1991 | A |
5126238 | Gebhard et al. | Jun 1992 | A |
5130141 | Law et al. | Jul 1992 | A |
5149544 | Gentile et al. | Sep 1992 | A |
5169930 | Ruoslahti et al. | Dec 1992 | A |
5192553 | Boyse et al. | Mar 1993 | A |
5197985 | Caplan et al. | Mar 1993 | A |
5202254 | Amiot et al. | Apr 1993 | A |
5225346 | Matsumiya et al. | Jul 1993 | A |
5226914 | Caplan et al. | Jul 1993 | A |
5240614 | Ofsthun et al. | Aug 1993 | A |
5240861 | Bieri | Aug 1993 | A |
5283058 | Faustman | Feb 1994 | A |
5310676 | Johansson et al. | May 1994 | A |
5324428 | Flaherty | Jun 1994 | A |
5342752 | Platz et al. | Aug 1994 | A |
5422197 | Zito | Jun 1995 | A |
5436151 | McGlave et al. | Jul 1995 | A |
5437994 | Emerson et al. | Aug 1995 | A |
5439757 | Zito | Aug 1995 | A |
5459069 | Palsson et al. | Oct 1995 | A |
5460964 | McGlave et al. | Oct 1995 | A |
H1509 | Eran et al. | Dec 1995 | H |
5478739 | Slivka et al. | Dec 1995 | A |
5486359 | Caplan et al. | Jan 1996 | A |
5496659 | Zito | Mar 1996 | A |
5507949 | Ho | Apr 1996 | A |
5512180 | Ho | Apr 1996 | A |
5527467 | Ofsthun et al. | Jun 1996 | A |
5543316 | Zawadzka et al. | Aug 1996 | A |
5545492 | Zito | Aug 1996 | A |
5549674 | Humes et al. | Aug 1996 | A |
5571720 | Grandics et al. | Nov 1996 | A |
5591625 | Gerson et al. | Jan 1997 | A |
5593580 | Kopf | Jan 1997 | A |
5595909 | Hu et al. | Jan 1997 | A |
5599703 | Davis et al. | Feb 1997 | A |
5605822 | Emerson et al. | Feb 1997 | A |
5605829 | McGlave et al. | Feb 1997 | A |
5605835 | Hu et al. | Feb 1997 | A |
5622857 | Goffe | Apr 1997 | A |
5626731 | Cooley et al. | May 1997 | A |
5627070 | Gruenberg | May 1997 | A |
5635386 | Palsson et al. | Jun 1997 | A |
5635387 | Fei et al. | Jun 1997 | A |
5643736 | Bruder et al. | Jul 1997 | A |
5646043 | Emerson et al. | Jul 1997 | A |
5654186 | Cerami et al. | Aug 1997 | A |
5656421 | Gebhard et al. | Aug 1997 | A |
5658995 | Kohn et al. | Aug 1997 | A |
5667985 | O'Leary et al. | Sep 1997 | A |
5670147 | Emerson et al. | Sep 1997 | A |
5674750 | Kraus et al. | Oct 1997 | A |
5684712 | Goffe et al. | Nov 1997 | A |
5686289 | Humes et al. | Nov 1997 | A |
5695989 | Kalamasz | Dec 1997 | A |
5700289 | Breitbart et al. | Dec 1997 | A |
5705534 | D'Agostino et al. | Jan 1998 | A |
5707859 | Miller et al. | Jan 1998 | A |
5712163 | Parenteau et al. | Jan 1998 | A |
5728581 | Schwartz et al. | Mar 1998 | A |
5733541 | Taichman et al. | Mar 1998 | A |
5733542 | Haynesworth et al. | Mar 1998 | A |
5736396 | Bruder et al. | Apr 1998 | A |
5744347 | Wagner et al. | Apr 1998 | A |
5750651 | Oppermann et al. | May 1998 | A |
5753506 | Johe | May 1998 | A |
5763197 | Tsukamoto et al. | Jun 1998 | A |
5763266 | Palsson et al. | Jun 1998 | A |
5766944 | Ruiz | Jun 1998 | A |
5772994 | Idstad et al. | Jun 1998 | A |
5783075 | Eddleman et al. | Jul 1998 | A |
5783216 | Faustman | Jul 1998 | A |
5785912 | Cooley et al. | Jul 1998 | A |
5804446 | Cerami et al. | Sep 1998 | A |
5806529 | Reisner et al. | Sep 1998 | A |
5807686 | Wagner et al. | Sep 1998 | A |
5811094 | Caplan et al. | Sep 1998 | A |
5811397 | Francavilla et al. | Sep 1998 | A |
5817773 | Wilson et al. | Oct 1998 | A |
5821218 | Toback et al. | Oct 1998 | A |
5827735 | Young et al. | Oct 1998 | A |
5827740 | Pittenger | Oct 1998 | A |
5830921 | Cooley et al. | Nov 1998 | A |
5833979 | Schinstine et al. | Nov 1998 | A |
5837258 | Grotendorst | Nov 1998 | A |
5837539 | Caplan et al. | Nov 1998 | A |
5840502 | Van Vlasselaer | Nov 1998 | A |
5840576 | Schinstine et al. | Nov 1998 | A |
5840580 | Terstappen et al. | Nov 1998 | A |
5842477 | Naughton et al. | Dec 1998 | A |
5843633 | Yin et al. | Dec 1998 | A |
5846796 | Cerami et al. | Dec 1998 | A |
5853247 | Shroyer | Dec 1998 | A |
5853717 | Schinstine et al. | Dec 1998 | A |
5855608 | Brekke et al. | Jan 1999 | A |
5855613 | Antanavich et al. | Jan 1999 | A |
5855619 | Caplan et al. | Jan 1999 | A |
5858747 | Schinstine et al. | Jan 1999 | A |
5858782 | Long et al. | Jan 1999 | A |
5861315 | Nakahata | Jan 1999 | A |
5866115 | Kanz et al. | Feb 1999 | A |
5866420 | Talbot et al. | Feb 1999 | A |
5868930 | Kopf | Feb 1999 | A |
5882295 | Kope | Mar 1999 | A |
5882918 | Goffe | Mar 1999 | A |
5882929 | Fofonoff et al. | Mar 1999 | A |
5888807 | Palsson et al. | Mar 1999 | A |
5902741 | Purchio et al. | May 1999 | A |
5906827 | Khouri et al. | May 1999 | A |
5906934 | Grande et al. | May 1999 | A |
5908782 | Marshak et al. | Jun 1999 | A |
5908784 | Johnstone et al. | Jun 1999 | A |
5912177 | Turner et al. | Jun 1999 | A |
5914108 | Tsukamoto et al. | Jun 1999 | A |
5922597 | Verfaillie et al. | Jul 1999 | A |
5922847 | Broudy et al. | Jul 1999 | A |
5925567 | Kraus et al. | Jul 1999 | A |
5928945 | Seliktar et al. | Jul 1999 | A |
5935849 | Schinstine et al. | Aug 1999 | A |
5938929 | Shimagaki et al. | Aug 1999 | A |
5939323 | Valentini et al. | Aug 1999 | A |
5942225 | Bruder et al. | Aug 1999 | A |
5955353 | Amiot | Sep 1999 | A |
5958763 | Goffe | Sep 1999 | A |
5965436 | Thiede et al. | Oct 1999 | A |
5972703 | Long et al. | Oct 1999 | A |
5980795 | Klotzer et al. | Nov 1999 | A |
5981211 | Hu et al. | Nov 1999 | A |
5981708 | Lawman et al. | Nov 1999 | A |
5998184 | Shi | Dec 1999 | A |
6001585 | Gramer | Dec 1999 | A |
6001643 | Spaulding | Dec 1999 | A |
6001647 | Peck et al. | Dec 1999 | A |
6004743 | Kenyon et al. | Dec 1999 | A |
6010696 | Caplan et al. | Jan 2000 | A |
6015554 | Galy | Jan 2000 | A |
6022540 | Bruder et al. | Feb 2000 | A |
6022742 | Kopf | Feb 2000 | A |
6022743 | Naughton et al. | Feb 2000 | A |
6027743 | Khouri et al. | Feb 2000 | A |
6030836 | Thiede et al. | Feb 2000 | A |
6040180 | Johe | Mar 2000 | A |
6045818 | Cima et al. | Apr 2000 | A |
6048721 | Armstrong et al. | Apr 2000 | A |
6048727 | Kopf | Apr 2000 | A |
6049026 | Muschler | Apr 2000 | A |
6054121 | Cerami et al. | Apr 2000 | A |
6060270 | Humes | May 2000 | A |
6066317 | Yang et al. | May 2000 | A |
6071691 | Hoekstra et al. | Jun 2000 | A |
6074366 | Rogers et al. | Jun 2000 | A |
6082364 | Balian et al. | Jul 2000 | A |
6083747 | Wong et al. | Jul 2000 | A |
6086643 | Clark et al. | Jul 2000 | A |
6087113 | Caplan et al. | Jul 2000 | A |
6096537 | Chappel | Aug 2000 | A |
6103117 | Shimagaki et al. | Aug 2000 | A |
6103522 | Torok-Storb et al. | Aug 2000 | A |
6110176 | Shapira | Aug 2000 | A |
6110482 | Khouri et al. | Aug 2000 | A |
6114307 | Jaspers et al. | Sep 2000 | A |
6117985 | Thomas et al. | Sep 2000 | A |
6120491 | Kohn et al. | Sep 2000 | A |
6127141 | Kopf | Oct 2000 | A |
6129911 | Faris | Oct 2000 | A |
6143293 | Weiss et al. | Nov 2000 | A |
6146360 | Rogers et al. | Nov 2000 | A |
6146888 | Smith et al. | Nov 2000 | A |
6149902 | Artavanis-Tsakonas et al. | Nov 2000 | A |
6149906 | Mosca | Nov 2000 | A |
6150164 | Humes | Nov 2000 | A |
6152964 | Van Blitterswijk et al. | Nov 2000 | A |
6162643 | Wille, Jr. | Dec 2000 | A |
6165225 | Antanavich et al. | Dec 2000 | A |
6165785 | Ogle et al. | Dec 2000 | A |
6174333 | Kadiyala et al. | Jan 2001 | B1 |
6174526 | Cerami et al. | Jan 2001 | B1 |
6174666 | Pavlakis et al. | Jan 2001 | B1 |
6179871 | Halpern | Jan 2001 | B1 |
6197325 | MacPhee et al. | Mar 2001 | B1 |
6197575 | Griffith et al. | Mar 2001 | B1 |
6200606 | Peterson et al. | Mar 2001 | B1 |
6214369 | Grande et al. | Apr 2001 | B1 |
6214574 | Kopf | Apr 2001 | B1 |
6224860 | Brown | May 2001 | B1 |
6225119 | Qasba et al. | May 2001 | B1 |
6225368 | D'Agostino et al. | May 2001 | B1 |
6228117 | De Bruijn et al. | May 2001 | B1 |
6228607 | Kersten et al. | May 2001 | B1 |
6238908 | Armstrong et al. | May 2001 | B1 |
6239157 | Mbalaviele | May 2001 | B1 |
6242252 | Reid et al. | Jun 2001 | B1 |
6248319 | Zsebo et al. | Jun 2001 | B1 |
6248587 | Rodgers et al. | Jun 2001 | B1 |
6255112 | Thiede et al. | Jul 2001 | B1 |
6258597 | Bachovchin et al. | Jul 2001 | B1 |
6258778 | Rodgers et al. | Jul 2001 | B1 |
6261549 | Fernandez et al. | Jul 2001 | B1 |
6280718 | Kaufman et al. | Aug 2001 | B1 |
6280724 | Moore | Aug 2001 | B1 |
6281012 | McIntosh et al. | Aug 2001 | B1 |
6281195 | Rueger et al. | Aug 2001 | B1 |
6287864 | Bagnis et al. | Sep 2001 | B1 |
6291249 | Mahant et al. | Sep 2001 | B1 |
6297213 | Oppermann et al. | Oct 2001 | B1 |
6299650 | Van Blitterswijk et al. | Oct 2001 | B1 |
6306424 | Vyakarnam et al. | Oct 2001 | B1 |
6306575 | Thomas et al. | Oct 2001 | B1 |
6322784 | Pittenger et al. | Nov 2001 | B1 |
6322786 | Anderson | Nov 2001 | B1 |
6326198 | Emerson et al. | Dec 2001 | B1 |
6326201 | Fung et al. | Dec 2001 | B1 |
6328765 | Hardwick et al. | Dec 2001 | B1 |
6328960 | McIntosh et al. | Dec 2001 | B1 |
6333029 | Vyakamam et al. | Dec 2001 | B1 |
6335195 | Rodgers et al. | Jan 2002 | B1 |
6338942 | Kraus et al. | Jan 2002 | B2 |
6340592 | Stringer | Jan 2002 | B1 |
6342370 | Connolly et al. | Jan 2002 | B1 |
6355239 | Bruder et al. | Mar 2002 | B1 |
6358252 | Shapira | Mar 2002 | B1 |
6361997 | Huss | Mar 2002 | B1 |
6365149 | Vyakarnam et al. | Apr 2002 | B2 |
6368636 | McIntosh et al. | Apr 2002 | B1 |
6372210 | Brown | Apr 2002 | B2 |
6372244 | Antanavich et al. | Apr 2002 | B1 |
6372494 | Naughton et al. | Apr 2002 | B1 |
6372892 | Ballinger et al. | Apr 2002 | B1 |
6376742 | Zdrahala et al. | Apr 2002 | B1 |
6379953 | Bruder et al. | Apr 2002 | B1 |
6387367 | Davis-Sproul et al. | May 2002 | B1 |
6387369 | Pittenger et al. | May 2002 | B1 |
6387693 | Rieser et al. | May 2002 | B2 |
6387964 | D'Agostino et al. | May 2002 | B1 |
6392118 | Hammang et al. | May 2002 | B1 |
6394812 | Sullivan et al. | May 2002 | B1 |
6399580 | Elias et al. | Jun 2002 | B1 |
6410320 | Humes | Jun 2002 | B1 |
6414219 | Denhardt et al. | Jul 2002 | B1 |
6416496 | Rogers et al. | Jul 2002 | B1 |
6417205 | Cooke et al. | Jul 2002 | B1 |
6419829 | Ho et al. | Jul 2002 | B2 |
6420138 | Gentz et al. | Jul 2002 | B1 |
6423681 | Barasch et al. | Jul 2002 | B1 |
6426332 | Rueger et al. | Jul 2002 | B1 |
6428802 | Atala | Aug 2002 | B1 |
6429012 | Kraus et al. | Aug 2002 | B1 |
6429013 | Halvorsen et al. | Aug 2002 | B1 |
6432653 | Okarma | Aug 2002 | B1 |
6432711 | Dinsmore et al. | Aug 2002 | B1 |
6440407 | Bauer et al. | Aug 2002 | B1 |
6440734 | Pykett et al. | Aug 2002 | B1 |
6451562 | Ruben et al. | Sep 2002 | B1 |
6454811 | Sherwood et al. | Sep 2002 | B1 |
6455678 | Yin et al. | Sep 2002 | B1 |
6458585 | Vachula et al. | Oct 2002 | B1 |
6458589 | Rambhatla et al. | Oct 2002 | B1 |
6461495 | Morrissey et al. | Oct 2002 | B1 |
6461853 | Zhu | Oct 2002 | B1 |
6464983 | Grotendorst | Oct 2002 | B1 |
6465205 | Hicks, Jr. | Oct 2002 | B2 |
6465247 | Weissman et al. | Oct 2002 | B1 |
6465249 | Reya et al. | Oct 2002 | B2 |
6468794 | Uchida et al. | Oct 2002 | B1 |
6472200 | Mitrani | Oct 2002 | B1 |
6475481 | Talmadge | Nov 2002 | B2 |
6479064 | Atala | Nov 2002 | B1 |
6482231 | Abatangelo et al. | Nov 2002 | B1 |
6482411 | Ahuja et al. | Nov 2002 | B1 |
6482645 | Atala | Nov 2002 | B2 |
6482926 | Thomas et al. | Nov 2002 | B1 |
6488925 | Ruben et al. | Dec 2002 | B2 |
6491918 | Thomas et al. | Dec 2002 | B1 |
6495129 | Li et al. | Dec 2002 | B1 |
6495364 | Hammang et al. | Dec 2002 | B2 |
6497875 | Sorrell et al. | Dec 2002 | B1 |
6498034 | Strobl | Dec 2002 | B1 |
6506574 | Rambhatla et al. | Jan 2003 | B1 |
6511510 | de Bruijn et al. | Jan 2003 | B1 |
6511767 | Calver et al. | Jan 2003 | B1 |
6511958 | Atkinson et al. | Jan 2003 | B1 |
6514514 | Atkinson et al. | Feb 2003 | B1 |
6524452 | Clark et al. | Feb 2003 | B1 |
6528052 | Smith et al. | Mar 2003 | B1 |
6528245 | Sanchez-Ramos et al. | Mar 2003 | B2 |
6531445 | Cohen et al. | Mar 2003 | B1 |
6534084 | Vyakarnam et al. | Mar 2003 | B1 |
6537807 | Smith et al. | Mar 2003 | B1 |
6541024 | Kadiyala et al. | Apr 2003 | B1 |
6541249 | Wager et al. | Apr 2003 | B2 |
6544506 | Reisner | Apr 2003 | B2 |
6548734 | Glimcher et al. | Apr 2003 | B1 |
6554589 | Grapes | Apr 2003 | B2 |
6555324 | Olweus et al. | Apr 2003 | B1 |
6555374 | Gimble et al. | Apr 2003 | B1 |
6559119 | Burgess et al. | May 2003 | B1 |
6562616 | Toner et al. | May 2003 | B1 |
6565843 | Cohen et al. | May 2003 | B1 |
6569421 | Hodges | May 2003 | B2 |
6569427 | Boyse et al. | May 2003 | B1 |
6569428 | Isner et al. | May 2003 | B1 |
6569654 | Shastri et al. | May 2003 | B2 |
6576188 | Rose et al. | Jun 2003 | B1 |
6576428 | Assenmacher et al. | Jun 2003 | B1 |
6576464 | Gold et al. | Jun 2003 | B2 |
6576465 | Long | Jun 2003 | B1 |
6582471 | Bittmann et al. | Jun 2003 | B1 |
6582955 | Martinez et al. | Jun 2003 | B2 |
6586192 | Peschle et al. | Jul 2003 | B1 |
6589728 | Csete et al. | Jul 2003 | B2 |
6589786 | Mangano et al. | Jul 2003 | B1 |
6596274 | Abatangelo et al. | Jul 2003 | B1 |
6599300 | Vibe-Hansen et al. | Jul 2003 | B2 |
6599520 | Scarborough et al. | Jul 2003 | B2 |
6610535 | Lu et al. | Aug 2003 | B1 |
6613798 | Porter et al. | Sep 2003 | B1 |
6616912 | Eddleman et al. | Sep 2003 | B2 |
6617070 | Morrissey et al. | Sep 2003 | B1 |
6617152 | Bryhan et al. | Sep 2003 | B2 |
6617159 | Cancedda et al. | Sep 2003 | B1 |
6623749 | Williams et al. | Sep 2003 | B2 |
6623942 | Ruben et al. | Sep 2003 | B2 |
6624108 | Clark et al. | Sep 2003 | B1 |
6626950 | Brown et al. | Sep 2003 | B2 |
6627191 | Bartelmez et al. | Sep 2003 | B1 |
6632425 | Li et al. | Oct 2003 | B1 |
6632620 | Makarovskiy | Oct 2003 | B1 |
6632934 | Moreadith et al. | Oct 2003 | B1 |
6638765 | Rosenberg | Oct 2003 | B1 |
6642048 | Xu et al. | Nov 2003 | B2 |
6642049 | Chute et al. | Nov 2003 | B1 |
6642201 | Khavinson et al. | Nov 2003 | B1 |
6645489 | Pykett et al. | Nov 2003 | B2 |
6645727 | Thomas et al. | Nov 2003 | B2 |
6645763 | Kobayashi et al. | Nov 2003 | B2 |
6649189 | Talmadge et al. | Nov 2003 | B2 |
6649595 | Clackson et al. | Nov 2003 | B2 |
6649631 | Orme et al. | Nov 2003 | B1 |
6653105 | Triglia et al. | Nov 2003 | B2 |
6653134 | Prockop et al. | Nov 2003 | B2 |
6660523 | Blom et al. | Dec 2003 | B2 |
6662805 | Frondoza et al. | Dec 2003 | B2 |
6667034 | Palsson et al. | Dec 2003 | B2 |
6667176 | Funk et al. | Dec 2003 | B1 |
6670169 | Schob et al. | Dec 2003 | B1 |
6670175 | Wang et al. | Dec 2003 | B2 |
6673603 | Baetge et al. | Jan 2004 | B2 |
6673606 | Tennekoon et al. | Jan 2004 | B1 |
6677306 | Veis et al. | Jan 2004 | B1 |
6683192 | Baxter et al. | Jan 2004 | B2 |
6685936 | McIntosh et al. | Feb 2004 | B2 |
6685971 | Xu | Feb 2004 | B2 |
6686198 | Melton et al. | Feb 2004 | B1 |
6696575 | Schmidt et al. | Feb 2004 | B2 |
6699716 | Sullivan et al. | Mar 2004 | B2 |
6703017 | Peck et al. | Mar 2004 | B1 |
6703209 | Baetscher et al. | Mar 2004 | B1 |
6706293 | Quintanilla Almagro et al. | Mar 2004 | B1 |
6709864 | Pittenger et al. | Mar 2004 | B1 |
6712850 | Vyakamam et al. | Mar 2004 | B2 |
6719969 | Hogaboam et al. | Apr 2004 | B1 |
6719970 | Costantino et al. | Apr 2004 | B1 |
6720340 | Cooke et al. | Apr 2004 | B1 |
6730314 | Jeschke et al. | May 2004 | B2 |
6730315 | Usala et al. | May 2004 | B2 |
6730510 | Roos et al. | May 2004 | B2 |
6733746 | Daley et al. | May 2004 | B2 |
6734000 | Chin et al. | May 2004 | B2 |
6740493 | Long et al. | May 2004 | B1 |
6759039 | Tsang et al. | Jul 2004 | B2 |
6759245 | Toner et al. | Jul 2004 | B1 |
6761883 | Weissman et al. | Jul 2004 | B2 |
6761887 | Kavalkovich et al. | Jul 2004 | B1 |
6767699 | Polo et al. | Jul 2004 | B2 |
6767737 | Wilson et al. | Jul 2004 | B1 |
6767738 | Gage et al. | Jul 2004 | B1 |
6767740 | Sramek et al. | Jul 2004 | B2 |
6770478 | Crowe et al. | Aug 2004 | B2 |
6777227 | Ricci et al. | Aug 2004 | B2 |
6777231 | Katz et al. | Aug 2004 | B1 |
6780612 | Ford et al. | Aug 2004 | B1 |
6787355 | Miller et al. | Sep 2004 | B1 |
6790455 | Chu et al. | Sep 2004 | B2 |
6793939 | Badylak | Sep 2004 | B2 |
6797269 | Mosca et al. | Sep 2004 | B2 |
6797514 | Berenson et al. | Sep 2004 | B2 |
6800480 | Bodnar et al. | Oct 2004 | B1 |
6802971 | Gorsuch et al. | Oct 2004 | B2 |
6805860 | Alt | Oct 2004 | B1 |
6809117 | Enikolopov et al. | Oct 2004 | B2 |
6811773 | Gentz et al. | Nov 2004 | B1 |
6811776 | Kale et al. | Nov 2004 | B2 |
6814961 | Jensen et al. | Nov 2004 | B1 |
6821513 | Fleming | Nov 2004 | B1 |
6821790 | Mahant et al. | Nov 2004 | B2 |
6828145 | Avital et al. | Dec 2004 | B2 |
6833269 | Carpenter | Dec 2004 | B2 |
6835377 | Goldberg et al. | Dec 2004 | B2 |
6835566 | Smith et al. | Dec 2004 | B2 |
6838284 | de Bruijn et al. | Jan 2005 | B2 |
6841150 | Halvorsen et al. | Jan 2005 | B2 |
6841151 | Stringer | Jan 2005 | B2 |
6841294 | Morrissey et al. | Jan 2005 | B1 |
6841355 | Livant | Jan 2005 | B2 |
6841386 | Kraus et al. | Jan 2005 | B2 |
6841542 | Bartelmez et al. | Jan 2005 | B2 |
6844011 | Faustman | Jan 2005 | B1 |
6849051 | Sramek et al. | Feb 2005 | B2 |
6849255 | Gazit et al. | Feb 2005 | B2 |
6849454 | Kelly et al. | Feb 2005 | B2 |
6849662 | Enikolopov et al. | Feb 2005 | B2 |
6852308 | Kohn et al. | Feb 2005 | B2 |
6852321 | Colucci et al. | Feb 2005 | B2 |
6852533 | Rafii et al. | Feb 2005 | B1 |
6855242 | Comninellis et al. | Feb 2005 | B1 |
6855542 | DiMilla et al. | Feb 2005 | B2 |
6863900 | Kadiyala et al. | Mar 2005 | B2 |
6866843 | Habener et al. | Mar 2005 | B2 |
6872389 | Faris | Mar 2005 | B1 |
6875430 | McIntosh et al. | Apr 2005 | B2 |
6887600 | Morrissey et al. | May 2005 | B2 |
6887704 | Peled et al. | May 2005 | B2 |
6908763 | Akashi et al. | Jun 2005 | B1 |
6911201 | Merchav et al. | Jun 2005 | B1 |
6914279 | Lu et al. | Jul 2005 | B2 |
6939955 | Rameshwar | Sep 2005 | B2 |
6965018 | Mikesell et al. | Nov 2005 | B2 |
6979321 | Geis et al. | Dec 2005 | B2 |
6988004 | Kanno et al. | Jan 2006 | B2 |
7008394 | Geise et al. | Mar 2006 | B2 |
7015037 | Furcht et al. | Mar 2006 | B1 |
7029666 | Bruder et al. | Apr 2006 | B2 |
7033339 | Lynn | Apr 2006 | B1 |
7045098 | Stephens | May 2006 | B2 |
7052517 | Murphy et al. | May 2006 | B2 |
7056493 | Kohn et al. | Jun 2006 | B2 |
7118672 | Husain et al. | Oct 2006 | B2 |
7122178 | Simmons et al. | Oct 2006 | B1 |
7160719 | Nyberg | Jan 2007 | B2 |
7169295 | Husain et al. | Jan 2007 | B2 |
7172696 | Martinez et al. | Feb 2007 | B1 |
7175763 | Husain et al. | Feb 2007 | B2 |
7192776 | Stephens | Mar 2007 | B2 |
7195711 | Gorsuch et al. | Mar 2007 | B2 |
7250154 | Kohn et al. | Jul 2007 | B2 |
7271234 | Kohn et al. | Sep 2007 | B2 |
7294259 | Cote et al. | Nov 2007 | B2 |
7300571 | Cote et al. | Nov 2007 | B2 |
7303676 | Husain et al. | Dec 2007 | B2 |
7303677 | Cote et al. | Dec 2007 | B2 |
7341062 | Chachques et al. | Mar 2008 | B2 |
7358001 | Morrissey et al. | Apr 2008 | B2 |
7361493 | Hammond et al. | Apr 2008 | B1 |
7368169 | Kohn et al. | May 2008 | B2 |
7378271 | Bader | May 2008 | B2 |
7399872 | Webster et al. | Jul 2008 | B2 |
7416884 | Gemmiti et al. | Aug 2008 | B2 |
7425440 | Malinge et al. | Sep 2008 | B2 |
7435586 | Bartlett et al. | Oct 2008 | B2 |
7438902 | Habener et al. | Oct 2008 | B2 |
7439057 | Frangos et al. | Oct 2008 | B2 |
7452529 | Brown, Jr. et al. | Nov 2008 | B2 |
7491388 | McIntosh et al. | Feb 2009 | B1 |
7494811 | Wolfinbarger, Jr. et al. | Feb 2009 | B2 |
7514074 | Pittenger et al. | Apr 2009 | B2 |
7514075 | Hedrick et al. | Apr 2009 | B2 |
7524676 | Reiter et al. | Apr 2009 | B2 |
7534609 | Merchav et al. | May 2009 | B2 |
7572374 | Gorsuch et al. | Aug 2009 | B2 |
7579179 | Bryhan et al. | Aug 2009 | B2 |
7585412 | Gorsuch et al. | Sep 2009 | B2 |
7588938 | Ma | Sep 2009 | B2 |
7598075 | Smith et al. | Oct 2009 | B2 |
7608447 | Cohen et al. | Oct 2009 | B2 |
7659118 | Furcht et al. | Feb 2010 | B2 |
7678573 | Merchav et al. | Mar 2010 | B2 |
7682823 | Runyon | Mar 2010 | B1 |
7722896 | Kohn et al. | May 2010 | B2 |
D620732 | Andrews | Aug 2010 | S |
7838122 | Kohn et al. | Nov 2010 | B2 |
7838289 | Furcht et al. | Nov 2010 | B2 |
7892829 | Pittenger et al. | Feb 2011 | B2 |
7919307 | Klaus et al. | Apr 2011 | B2 |
7927587 | Blazer et al. | Apr 2011 | B2 |
7989851 | Lu et al. | Aug 2011 | B2 |
8008528 | Kohn et al. | Aug 2011 | B2 |
8034365 | Baluca | Oct 2011 | B2 |
8075881 | Verfaillie et al. | Dec 2011 | B2 |
8147824 | Maziarz et al. | Apr 2012 | B2 |
8147863 | Kohn et al. | Apr 2012 | B2 |
8158120 | Pittenger et al. | Apr 2012 | B2 |
8158121 | Pittenger et al. | Apr 2012 | B2 |
8235067 | Gagne | Aug 2012 | B2 |
8252280 | Verfaillie et al. | Aug 2012 | B1 |
8252887 | Bolikal et al. | Aug 2012 | B2 |
8288159 | Warren et al. | Oct 2012 | B2 |
8288590 | Kohn et al. | Oct 2012 | B2 |
8298823 | Warren et al. | Oct 2012 | B2 |
8361453 | Uhrich et al. | Jan 2013 | B2 |
8377683 | Lu et al. | Feb 2013 | B2 |
8383397 | Wojciechowski et al. | Feb 2013 | B2 |
8383806 | Rameshwar | Feb 2013 | B2 |
8399245 | Leuthaeuser et al. | Mar 2013 | B2 |
8415449 | Kohn et al. | Apr 2013 | B2 |
8435781 | Kodama | May 2013 | B2 |
8461289 | Kohn et al. | Jun 2013 | B2 |
8476399 | Bolikal et al. | Jul 2013 | B2 |
8486621 | Luo et al. | Jul 2013 | B2 |
8486695 | Danilkovitch et al. | Jul 2013 | B2 |
8492140 | Smith et al. | Jul 2013 | B2 |
8492150 | Parker et al. | Jul 2013 | B2 |
8524496 | Meiron et al. | Sep 2013 | B2 |
8529888 | Meiron et al. | Sep 2013 | B2 |
8540499 | Page et al. | Sep 2013 | B2 |
8551511 | Brandom et al. | Oct 2013 | B2 |
8580249 | Blazar et al. | Nov 2013 | B2 |
8678638 | Wong | Mar 2014 | B2 |
8852570 | Pittenger et al. | Oct 2014 | B2 |
8852571 | Pittenger et al. | Oct 2014 | B2 |
8852572 | Pittenger et al. | Oct 2014 | B2 |
8852573 | Pittenger et al. | Oct 2014 | B2 |
8852574 | Pittenger et al. | Oct 2014 | B2 |
8852575 | Pittenger et al. | Oct 2014 | B2 |
9109193 | Galliher et al. | Aug 2015 | B2 |
9220810 | Ma et al. | Dec 2015 | B2 |
9441195 | Wojciechowski et al. | Sep 2016 | B2 |
9534198 | Page et al. | Jan 2017 | B2 |
9732313 | Hirschel et al. | Aug 2017 | B2 |
9777847 | Tuccelli | Oct 2017 | B2 |
10024457 | Saito | Jul 2018 | B2 |
10093956 | Hirschel et al. | Oct 2018 | B2 |
10143795 | Chen | Dec 2018 | B2 |
10351282 | Tarumoto | Jul 2019 | B2 |
10494421 | Castillo | Dec 2019 | B2 |
20010017188 | Cooley et al. | Aug 2001 | A1 |
20010019705 | Ruediger et al. | Sep 2001 | A1 |
20010020086 | Hubbell et al. | Sep 2001 | A1 |
20010021516 | Wei et al. | Sep 2001 | A1 |
20010029046 | Beaulieu | Oct 2001 | A1 |
20010033834 | Wilkison et al. | Oct 2001 | A1 |
20010036663 | Kraus et al. | Nov 2001 | A1 |
20010041687 | Mruk | Nov 2001 | A1 |
20010044413 | Pierce et al. | Nov 2001 | A1 |
20010049139 | Lagasse et al. | Dec 2001 | A1 |
20020015724 | Yang et al. | Feb 2002 | A1 |
20020018804 | Austin et al. | Feb 2002 | A1 |
20020028510 | Sanberg et al. | Mar 2002 | A1 |
20020031757 | Ohgushi et al. | Mar 2002 | A1 |
20020037278 | Ueno et al. | Mar 2002 | A1 |
20020045260 | Hung et al. | Apr 2002 | A1 |
20020064869 | Ebner et al. | May 2002 | A1 |
20020076400 | Katz et al. | Jun 2002 | A1 |
20020077687 | Ahn | Jun 2002 | A1 |
20020082698 | Parenteau et al. | Jun 2002 | A1 |
20020116054 | Lundell et al. | Aug 2002 | A1 |
20020128581 | Vishnoi et al. | Sep 2002 | A1 |
20020128582 | Farrell et al. | Sep 2002 | A1 |
20020128583 | Min et al. | Sep 2002 | A1 |
20020128584 | Brown et al. | Sep 2002 | A1 |
20020130100 | Smith | Sep 2002 | A1 |
20020132343 | Lum | Sep 2002 | A1 |
20020139743 | Critz et al. | Oct 2002 | A1 |
20020142457 | Umezawa et al. | Oct 2002 | A1 |
20020146678 | Benvenisty | Oct 2002 | A1 |
20020146817 | Cannon et al. | Oct 2002 | A1 |
20020150989 | Greene et al. | Oct 2002 | A1 |
20020151056 | Sasai et al. | Oct 2002 | A1 |
20020159981 | Peled et al. | Oct 2002 | A1 |
20020160032 | Long et al. | Oct 2002 | A1 |
20020160510 | Hariri | Oct 2002 | A1 |
20020168765 | Prockop et al. | Nov 2002 | A1 |
20020169408 | Beretta et al. | Nov 2002 | A1 |
20020182241 | Borenstein et al. | Dec 2002 | A1 |
20020182664 | Dolecek et al. | Dec 2002 | A1 |
20020188962 | Denhardt et al. | Dec 2002 | A1 |
20020197240 | Chiu | Dec 2002 | A1 |
20030021850 | Xu | Jan 2003 | A1 |
20030022390 | Stephens | Jan 2003 | A1 |
20030027330 | Lanza et al. | Feb 2003 | A1 |
20030027331 | Yan et al. | Feb 2003 | A1 |
20030032143 | Neff et al. | Feb 2003 | A1 |
20030036168 | Ni et al. | Feb 2003 | A1 |
20030040113 | Mizuno et al. | Feb 2003 | A1 |
20030049236 | Kassem et al. | Mar 2003 | A1 |
20030054331 | Fraser et al. | Mar 2003 | A1 |
20030059851 | Smith | Mar 2003 | A1 |
20030059939 | Page et al. | Mar 2003 | A1 |
20030078345 | Morrisey | Apr 2003 | A1 |
20030082795 | Shuler et al. | May 2003 | A1 |
20030086915 | Rader et al. | May 2003 | A1 |
20030089471 | Gehr et al. | May 2003 | A1 |
20030092101 | Ni et al. | May 2003 | A1 |
20030101465 | Lawman et al. | May 2003 | A1 |
20030103957 | McKerracher | Jun 2003 | A1 |
20030104568 | Lee | Jun 2003 | A1 |
20030113813 | Heidaran et al. | Jun 2003 | A1 |
20030113910 | Levanduski | Jun 2003 | A1 |
20030124091 | Tuse et al. | Jul 2003 | A1 |
20030124721 | Cheatham et al. | Jul 2003 | A1 |
20030130593 | Gonzalez | Jul 2003 | A1 |
20030133918 | Sherley | Jul 2003 | A1 |
20030138950 | McAllister et al. | Jul 2003 | A1 |
20030143727 | Chang | Jul 2003 | A1 |
20030148152 | Morrisey | Aug 2003 | A1 |
20030149011 | Ackerman et al. | Aug 2003 | A1 |
20030152558 | Luft et al. | Aug 2003 | A1 |
20030157078 | Hall et al. | Aug 2003 | A1 |
20030157709 | DiMilla et al. | Aug 2003 | A1 |
20030161817 | Young et al. | Aug 2003 | A1 |
20030166272 | Abuljadayel | Sep 2003 | A1 |
20030170214 | Bader | Sep 2003 | A1 |
20030180296 | Salcedo et al. | Sep 2003 | A1 |
20030185817 | Thomas et al. | Oct 2003 | A1 |
20030202938 | Rameshwar | Oct 2003 | A1 |
20030203483 | Seshi | Oct 2003 | A1 |
20030204323 | Morrisey | Oct 2003 | A1 |
20030211602 | Atala | Nov 2003 | A1 |
20030211603 | Earp et al. | Nov 2003 | A1 |
20030216718 | Hamblin et al. | Nov 2003 | A1 |
20030219898 | Sugaya et al. | Nov 2003 | A1 |
20030223968 | Yang | Dec 2003 | A1 |
20030224420 | Hellerstein et al. | Dec 2003 | A1 |
20030224510 | Yamaguchi et al. | Dec 2003 | A1 |
20030225010 | Rameshwar | Dec 2003 | A1 |
20030232432 | Bhat | Dec 2003 | A1 |
20030232752 | Freeman et al. | Dec 2003 | A1 |
20030235909 | Hariri et al. | Dec 2003 | A1 |
20040009158 | Sands et al. | Jan 2004 | A1 |
20040009589 | Levenberg et al. | Jan 2004 | A1 |
20040010231 | Leonhardt et al. | Jan 2004 | A1 |
20040014209 | Lassar et al. | Jan 2004 | A1 |
20040018174 | Palasis | Jan 2004 | A1 |
20040018617 | Hwang | Jan 2004 | A1 |
20040023324 | Sakano et al. | Feb 2004 | A1 |
20040023370 | Yu et al. | Feb 2004 | A1 |
20040033214 | Young et al. | Feb 2004 | A1 |
20040033599 | Rosenberg | Feb 2004 | A1 |
20040037811 | Penn et al. | Feb 2004 | A1 |
20040037815 | Clarke et al. | Feb 2004 | A1 |
20040038316 | Kaiser et al. | Feb 2004 | A1 |
20040053869 | Andrews et al. | Mar 2004 | A1 |
20040062753 | Rezania et al. | Apr 2004 | A1 |
20040063205 | Xu | Apr 2004 | A1 |
20040067585 | Wang et al. | Apr 2004 | A1 |
20040071668 | Bays et al. | Apr 2004 | A1 |
20040072259 | Scadden et al. | Apr 2004 | A1 |
20040077079 | Storgaard et al. | Apr 2004 | A1 |
20040079248 | Mayer et al. | Apr 2004 | A1 |
20040087016 | Keating et al. | May 2004 | A1 |
20040091936 | West | May 2004 | A1 |
20040096476 | Uhrich et al. | May 2004 | A1 |
20040097408 | Leder et al. | May 2004 | A1 |
20040101959 | Marko et al. | May 2004 | A1 |
20040107453 | Furcht et al. | Jun 2004 | A1 |
20040110286 | Bhatia | Jun 2004 | A1 |
20040115804 | Fu et al. | Jun 2004 | A1 |
20040115806 | Fu | Jun 2004 | A1 |
20040120932 | Zahner | Jun 2004 | A1 |
20040121461 | Honmou et al. | Jun 2004 | A1 |
20040121464 | Rathjen et al. | Jun 2004 | A1 |
20040126405 | Sahatjian et al. | Jul 2004 | A1 |
20040128077 | Koebler et al. | Jul 2004 | A1 |
20040131601 | Epstein et al. | Jul 2004 | A1 |
20040132184 | Dennis et al. | Jul 2004 | A1 |
20040136967 | Weiss et al. | Jul 2004 | A1 |
20040137612 | Baksh | Jul 2004 | A1 |
20040137613 | Vacanti et al. | Jul 2004 | A1 |
20040143174 | Brubaker | Jul 2004 | A1 |
20040143863 | Li et al. | Jul 2004 | A1 |
20040151700 | Harlan et al. | Aug 2004 | A1 |
20040151701 | Kim et al. | Aug 2004 | A1 |
20040151706 | Shakhov et al. | Aug 2004 | A1 |
20040151729 | Michalopoulos et al. | Aug 2004 | A1 |
20040152190 | Sumita | Aug 2004 | A1 |
20040161419 | Strom et al. | Aug 2004 | A1 |
20040171533 | Zehentner et al. | Sep 2004 | A1 |
20040180347 | Stanton et al. | Sep 2004 | A1 |
20040191902 | Hambor et al. | Sep 2004 | A1 |
20040197310 | Sanberg et al. | Oct 2004 | A1 |
20040197375 | Rezania et al. | Oct 2004 | A1 |
20040208786 | Kevy et al. | Oct 2004 | A1 |
20040214275 | Soejima et al. | Oct 2004 | A1 |
20040219134 | Naughton et al. | Nov 2004 | A1 |
20040219136 | Hariri | Nov 2004 | A1 |
20040219563 | West et al. | Nov 2004 | A1 |
20040224403 | Bhatia | Nov 2004 | A1 |
20040229351 | Rodriguez et al. | Nov 2004 | A1 |
20040234972 | Owens et al. | Nov 2004 | A1 |
20040235158 | Bartlett et al. | Nov 2004 | A1 |
20040235160 | Nishikawa et al. | Nov 2004 | A1 |
20040235166 | Prockop et al. | Nov 2004 | A1 |
20040242469 | Lee et al. | Dec 2004 | A1 |
20040258669 | Dzau et al. | Dec 2004 | A1 |
20040259242 | Malinge et al. | Dec 2004 | A1 |
20040259254 | Honmou et al. | Dec 2004 | A1 |
20040260058 | Scheek et al. | Dec 2004 | A1 |
20040260318 | Hunter et al. | Dec 2004 | A1 |
20040265996 | Schwarz et al. | Dec 2004 | A1 |
20050002914 | Rosen et al. | Jan 2005 | A1 |
20050003460 | Nilsson et al. | Jan 2005 | A1 |
20050003527 | Lang et al. | Jan 2005 | A1 |
20050003534 | Huberman et al. | Jan 2005 | A1 |
20050008624 | Peled et al. | Jan 2005 | A1 |
20050008626 | Fraser et al. | Jan 2005 | A1 |
20050009178 | Yost et al. | Jan 2005 | A1 |
20050009179 | Gemmiti et al. | Jan 2005 | A1 |
20050009181 | Black et al. | Jan 2005 | A1 |
20050013804 | Kato et al. | Jan 2005 | A1 |
20050014252 | Chu et al. | Jan 2005 | A1 |
20050014253 | Ehmann et al. | Jan 2005 | A1 |
20050014254 | Kruse | Jan 2005 | A1 |
20050014255 | Tang et al. | Jan 2005 | A1 |
20050019801 | Rubin et al. | Jan 2005 | A1 |
20050019908 | Hariri | Jan 2005 | A1 |
20050019910 | Takagi et al. | Jan 2005 | A1 |
20050019911 | Gronthos et al. | Jan 2005 | A1 |
20050026836 | Dack et al. | Feb 2005 | A1 |
20050031587 | Tsutsui et al. | Feb 2005 | A1 |
20050031595 | Peled et al. | Feb 2005 | A1 |
20050031598 | Levenberg et al. | Feb 2005 | A1 |
20050032122 | Wang et al. | Feb 2005 | A1 |
20050032207 | Wobus et al. | Feb 2005 | A1 |
20050032209 | Messina et al. | Feb 2005 | A1 |
20050032218 | Gerlach | Feb 2005 | A1 |
20050036980 | Chaney et al. | Feb 2005 | A1 |
20050037488 | Mitalipova et al. | Feb 2005 | A1 |
20050037490 | Rosenberg et al. | Feb 2005 | A1 |
20050037492 | Xu et al. | Feb 2005 | A1 |
20050037493 | Mandalam et al. | Feb 2005 | A1 |
20050037949 | O'Brien et al. | Feb 2005 | A1 |
20050106119 | Brandom et al. | May 2005 | A1 |
20050106127 | Kraus et al. | May 2005 | A1 |
20050112447 | Fletcher et al. | May 2005 | A1 |
20050112762 | Hart et al. | May 2005 | A1 |
20050118712 | Tsai et al. | Jun 2005 | A1 |
20050130297 | Sarem et al. | Jun 2005 | A1 |
20050136093 | Denk | Jun 2005 | A1 |
20050137517 | Blickhan et al. | Jun 2005 | A1 |
20050142162 | Hunter et al. | Jun 2005 | A1 |
20050149157 | Hunter et al. | Jul 2005 | A1 |
20050152946 | Hunter et al. | Jul 2005 | A1 |
20050158289 | Simmons et al. | Jul 2005 | A1 |
20050172340 | Logvinov et al. | Aug 2005 | A1 |
20050175665 | Hunter et al. | Aug 2005 | A1 |
20050175703 | Hunter et al. | Aug 2005 | A1 |
20050178395 | Hunter et al. | Aug 2005 | A1 |
20050178396 | Hunter et al. | Aug 2005 | A1 |
20050180957 | Scharp et al. | Aug 2005 | A1 |
20050181502 | Furcht et al. | Aug 2005 | A1 |
20050182463 | Hunter et al. | Aug 2005 | A1 |
20050183731 | Hunter et al. | Aug 2005 | A1 |
20050186244 | Hunter et al. | Aug 2005 | A1 |
20050186671 | Cannon et al. | Aug 2005 | A1 |
20050187140 | Hunter et al. | Aug 2005 | A1 |
20050196421 | Hunter et al. | Sep 2005 | A1 |
20050208095 | Hunter et al. | Sep 2005 | A1 |
20050244963 | Teplyashin | Nov 2005 | A1 |
20050249731 | Aslan et al. | Nov 2005 | A1 |
20050255118 | Wehner | Nov 2005 | A1 |
20050261674 | Nobis et al. | Nov 2005 | A1 |
20050277577 | Hunter et al. | Dec 2005 | A1 |
20050281790 | Simmons et al. | Dec 2005 | A1 |
20050282733 | Prins et al. | Dec 2005 | A1 |
20050283844 | Furcht et al. | Dec 2005 | A1 |
20060002900 | Binder et al. | Jan 2006 | A1 |
20060008452 | Simmons et al. | Jan 2006 | A1 |
20060019389 | Yayon et al. | Jan 2006 | A1 |
20060054941 | Lu et al. | Mar 2006 | A1 |
20060083720 | Fraser et al. | Apr 2006 | A1 |
20060099198 | Thomson et al. | May 2006 | A1 |
20060166364 | Senesac | Jul 2006 | A1 |
20060172008 | Yayon et al. | Aug 2006 | A1 |
20060193840 | Gronthos et al. | Aug 2006 | A1 |
20060228798 | Verfaillie et al. | Oct 2006 | A1 |
20060239909 | Anderson et al. | Oct 2006 | A1 |
20060258586 | Sheppard et al. | Nov 2006 | A1 |
20060258933 | Ellis et al. | Nov 2006 | A1 |
20060259998 | Brumbley et al. | Nov 2006 | A1 |
20060280748 | Buckheit | Dec 2006 | A1 |
20060286077 | Gronthos et al. | Dec 2006 | A1 |
20070005148 | Barofsky et al. | Jan 2007 | A1 |
20070011752 | Paleyanda | Jan 2007 | A1 |
20070042462 | Hildinger | Feb 2007 | A1 |
20070065938 | Gronthos et al. | Mar 2007 | A1 |
20070105222 | Wolfinbarger et al. | May 2007 | A1 |
20070116612 | Williamson | May 2007 | A1 |
20070117180 | Morikawa et al. | May 2007 | A1 |
20070123996 | Sugaya et al. | May 2007 | A1 |
20070166834 | Williamson et al. | Jul 2007 | A1 |
20070178071 | Westenfelder | Aug 2007 | A1 |
20070196421 | Hunter et al. | Aug 2007 | A1 |
20070197957 | Hunter et al. | Aug 2007 | A1 |
20070198063 | Hunter et al. | Aug 2007 | A1 |
20070202485 | Nees et al. | Aug 2007 | A1 |
20070203330 | Kretschmar et al. | Aug 2007 | A1 |
20070208134 | Hunter et al. | Sep 2007 | A1 |
20070258943 | Penn et al. | Nov 2007 | A1 |
20070274970 | Gordon et al. | Nov 2007 | A1 |
20070275457 | Granchelli et al. | Nov 2007 | A1 |
20070295651 | Martinez et al. | Dec 2007 | A1 |
20070298015 | Beer et al. | Dec 2007 | A1 |
20080003663 | Bryhan et al. | Jan 2008 | A1 |
20080009458 | Dornan et al. | Jan 2008 | A1 |
20080032398 | Cannon et al. | Feb 2008 | A1 |
20080050770 | Zhang et al. | Feb 2008 | A1 |
20080063600 | Aguzzi et al. | Mar 2008 | A1 |
20080064649 | Rameshwar | Mar 2008 | A1 |
20080069807 | Jy et al. | Mar 2008 | A1 |
20080095676 | Andretta | Apr 2008 | A1 |
20080095690 | Liu | Apr 2008 | A1 |
20080103412 | Chin | May 2008 | A1 |
20080110827 | Cote et al. | May 2008 | A1 |
20080113426 | Smith et al. | May 2008 | A1 |
20080113440 | Gurney et al. | May 2008 | A1 |
20080153077 | Henry | Jun 2008 | A1 |
20080160597 | van der Heiden et al. | Jul 2008 | A1 |
20080166808 | Nyberg | Jul 2008 | A1 |
20080181879 | Catelas et al. | Jul 2008 | A1 |
20080190857 | Beretta et al. | Aug 2008 | A1 |
20080194017 | Esser et al. | Aug 2008 | A1 |
20080206831 | Coffey et al. | Aug 2008 | A1 |
20080220524 | Noll et al. | Sep 2008 | A1 |
20080220526 | Ellison et al. | Sep 2008 | A1 |
20080221443 | Ritchie et al. | Sep 2008 | A1 |
20080227189 | Bader | Sep 2008 | A1 |
20080268165 | Fekety et al. | Oct 2008 | A1 |
20080306095 | Crawford | Dec 2008 | A1 |
20090004738 | Merchav et al. | Jan 2009 | A1 |
20090011399 | Fischer | Jan 2009 | A1 |
20090047289 | Denhardt et al. | Feb 2009 | A1 |
20090074728 | Gronthos et al. | Mar 2009 | A1 |
20090075881 | Catelas et al. | Mar 2009 | A1 |
20090076481 | Stegmann et al. | Mar 2009 | A1 |
20090081770 | Srienc et al. | Mar 2009 | A1 |
20090081797 | Fadeev et al. | Mar 2009 | A1 |
20090092608 | Ni et al. | Apr 2009 | A1 |
20090098103 | Madison et al. | Apr 2009 | A1 |
20090098645 | Fang et al. | Apr 2009 | A1 |
20090100944 | Newby | Apr 2009 | A1 |
20090104163 | Deans et al. | Apr 2009 | A1 |
20090104692 | Bartfeld et al. | Apr 2009 | A1 |
20090104699 | Newby et al. | Apr 2009 | A1 |
20090118161 | Cruz | May 2009 | A1 |
20090181087 | Kraus et al. | Jul 2009 | A1 |
20090183581 | Wilkinson et al. | Jul 2009 | A1 |
20090191627 | Fadeev et al. | Jul 2009 | A1 |
20090191632 | Fadeev et al. | Jul 2009 | A1 |
20090191634 | Martin et al. | Jul 2009 | A1 |
20090203065 | Gehman et al. | Aug 2009 | A1 |
20090203129 | Furcht et al. | Aug 2009 | A1 |
20090203130 | Furcht et al. | Aug 2009 | A1 |
20090214382 | Burgess et al. | Aug 2009 | A1 |
20090214481 | Muhs et al. | Aug 2009 | A1 |
20090214652 | Hunter et al. | Aug 2009 | A1 |
20090215022 | Page et al. | Aug 2009 | A1 |
20090227024 | Baker et al. | Sep 2009 | A1 |
20090227027 | Baker et al. | Sep 2009 | A1 |
20090233334 | Hildinger et al. | Sep 2009 | A1 |
20090233353 | Furcht et al. | Sep 2009 | A1 |
20090233354 | Furcht et al. | Sep 2009 | A1 |
20090258379 | Klein et al. | Oct 2009 | A1 |
20090269841 | Wojciechowski et al. | Oct 2009 | A1 |
20090270725 | Leimbach et al. | Oct 2009 | A1 |
20090280153 | Hunter et al. | Nov 2009 | A1 |
20090280565 | Jolicoeur et al. | Nov 2009 | A1 |
20090291890 | Madison et al. | Nov 2009 | A1 |
20100009409 | Hubbell et al. | Jan 2010 | A1 |
20100021954 | Deshayes et al. | Jan 2010 | A1 |
20100021990 | Edwards et al. | Jan 2010 | A1 |
20100028311 | Motlagh et al. | Feb 2010 | A1 |
20100075410 | Desai et al. | Mar 2010 | A1 |
20100086481 | Baird et al. | Apr 2010 | A1 |
20100092536 | Hunter et al. | Apr 2010 | A1 |
20100093607 | Dickneite | Apr 2010 | A1 |
20100111910 | Rakoczy | May 2010 | A1 |
20100129376 | Denhardt et al. | May 2010 | A1 |
20100129912 | Su et al. | May 2010 | A1 |
20100136091 | Moghe et al. | Jun 2010 | A1 |
20100144634 | Zheng et al. | Jun 2010 | A1 |
20100183561 | Sakthivel et al. | Jul 2010 | A1 |
20100183585 | Van Zant et al. | Jul 2010 | A1 |
20100203020 | Ghosh | Aug 2010 | A1 |
20100230203 | Karayianni | Sep 2010 | A1 |
20100248366 | Fadeev et al. | Sep 2010 | A1 |
20100278933 | Sayeski et al. | Nov 2010 | A1 |
20100285453 | Goodrich | Nov 2010 | A1 |
20100285590 | Verfaillie et al. | Nov 2010 | A1 |
20100291180 | Uhrich | Nov 2010 | A1 |
20100291181 | Uhrich et al. | Nov 2010 | A1 |
20100297234 | Sugino et al. | Nov 2010 | A1 |
20100304427 | Faris et al. | Dec 2010 | A1 |
20100304482 | Deshayes et al. | Dec 2010 | A1 |
20100310524 | Bechor et al. | Dec 2010 | A1 |
20100316446 | Runyon | Dec 2010 | A1 |
20110085746 | Wong et al. | Apr 2011 | A1 |
20110111498 | Oh et al. | May 2011 | A1 |
20110129447 | Meretzki et al. | Jun 2011 | A1 |
20110129486 | Meiron | Jun 2011 | A1 |
20110143433 | Oh et al. | Jun 2011 | A1 |
20110159584 | Gibbons et al. | Jun 2011 | A1 |
20110171182 | Abelman | Jul 2011 | A1 |
20110171659 | Furcht et al. | Jul 2011 | A1 |
20110177595 | Furcht et al. | Jul 2011 | A1 |
20110212493 | Hirschel et al. | Sep 2011 | A1 |
20110256108 | Meiron et al. | Oct 2011 | A1 |
20110256160 | Meiron et al. | Oct 2011 | A1 |
20110293583 | Aberman | Dec 2011 | A1 |
20120028352 | Oh et al. | Feb 2012 | A1 |
20120051976 | Lu et al. | Mar 2012 | A1 |
20120058554 | Deshayes et al. | Mar 2012 | A1 |
20120064047 | Verfaillie et al. | Mar 2012 | A1 |
20120064583 | Edwards et al. | Mar 2012 | A1 |
20120118919 | Cianciolo | May 2012 | A1 |
20120122220 | Merchav et al. | May 2012 | A1 |
20120135043 | Maziarz et al. | May 2012 | A1 |
20120145580 | Paruit et al. | Jun 2012 | A1 |
20120156779 | Anneren et al. | Jun 2012 | A1 |
20120178885 | Kohn et al. | Jul 2012 | A1 |
20120189713 | Kohn et al. | Jul 2012 | A1 |
20120208039 | Barbaroux et al. | Aug 2012 | A1 |
20120219531 | Oh et al. | Aug 2012 | A1 |
20120219737 | Sugino et al. | Aug 2012 | A1 |
20120226013 | Kohn et al. | Sep 2012 | A1 |
20120231519 | Bushman et al. | Sep 2012 | A1 |
20120237557 | Lewitus et al. | Sep 2012 | A1 |
20120295352 | Antwiler | Nov 2012 | A1 |
20120308531 | Pinxteren et al. | Dec 2012 | A1 |
20120315696 | Luitjens et al. | Dec 2012 | A1 |
20130004465 | Aberman | Jan 2013 | A1 |
20130039892 | Aberman | Feb 2013 | A1 |
20130058907 | Wojciechowski et al. | Mar 2013 | A1 |
20130059383 | Dijkhuizen Borgart et al. | Mar 2013 | A1 |
20130101561 | Sabaawy | Apr 2013 | A1 |
20130143313 | Niazi | Jun 2013 | A1 |
20130157353 | Dijkhuizen Borgart et al. | Jun 2013 | A1 |
20130259843 | Duda et al. | Oct 2013 | A1 |
20130319575 | Mendyk | Dec 2013 | A1 |
20130323213 | Meiron et al. | Dec 2013 | A1 |
20130337558 | Meiron et al. | Dec 2013 | A1 |
20140004553 | Parker et al. | Jan 2014 | A1 |
20140017209 | Aberman et al. | Jan 2014 | A1 |
20140030805 | Kasuto et al. | Jan 2014 | A1 |
20140051162 | Nankervis | Feb 2014 | A1 |
20140051167 | Nankervis et al. | Feb 2014 | A1 |
20140112893 | Tom et al. | Apr 2014 | A1 |
20140186937 | Smith et al. | Jul 2014 | A1 |
20140193895 | Smith et al. | Jul 2014 | A1 |
20140193911 | Newby et al. | Jul 2014 | A1 |
20140242039 | Meiron et al. | Aug 2014 | A1 |
20140248244 | Danilkovitch et al. | Sep 2014 | A1 |
20140315300 | Oh et al. | Oct 2014 | A1 |
20140342448 | Nagels | Nov 2014 | A1 |
20150004693 | Danilkovitch et al. | Jan 2015 | A1 |
20150104431 | Pittenger et al. | Apr 2015 | A1 |
20150111252 | Hirschel et al. | Apr 2015 | A1 |
20150125138 | Kamieli et al. | May 2015 | A1 |
20150175950 | Hirschel et al. | Jun 2015 | A1 |
20150225685 | Hirschel et al. | Aug 2015 | A1 |
20150247122 | Tom et al. | Sep 2015 | A1 |
20150259749 | Santos et al. | Sep 2015 | A1 |
20160362650 | Wojciechowski et al. | Dec 2016 | A1 |
20160362652 | Page et al. | Dec 2016 | A1 |
20180010082 | Jaques et al. | Jan 2018 | A1 |
20180030398 | Castillo | Feb 2018 | A1 |
20180155668 | Hirschel et al. | Jun 2018 | A1 |
20190194628 | Rao et al. | Jun 2019 | A1 |
20190344269 | Johnson et al. | Nov 2019 | A1 |
20230366483 | Tanabe | Nov 2023 | A1 |
Number | Date | Country |
---|---|---|
1016332 | Aug 1977 | CA |
4007703 | Sep 1991 | DE |
10244859 | Apr 2004 | DE |
10327988 | Jul 2004 | DE |
102012200939 | Jul 2013 | DE |
102014116592 | May 2016 | DE |
750938 | Jan 1997 | EP |
906415 | Apr 1999 | EP |
959980 | Dec 1999 | EP |
1007631 | Jun 2000 | EP |
1028737 | Aug 2000 | EP |
1028991 | Aug 2000 | EP |
1066052 | Jan 2001 | EP |
1066060 | Jan 2001 | EP |
1084230 | Mar 2001 | EP |
1147176 | Oct 2001 | EP |
1220611 | Jul 2002 | EP |
1223956 | Jul 2002 | EP |
1325953 | Jul 2003 | EP |
1437404 | Jul 2004 | EP |
1437406 | Jul 2004 | EP |
1447443 | Aug 2004 | EP |
1452594 | Sep 2004 | EP |
1062321 | Dec 2004 | EP |
1484080 | Dec 2004 | EP |
1498478 | Jan 2005 | EP |
1036057 | Oct 2005 | EP |
1605044 | Dec 2005 | EP |
1756262 | Feb 2007 | EP |
1771737 | Apr 2007 | EP |
1882030 | Jan 2008 | EP |
1908490 | Apr 2008 | EP |
1971679 | Sep 2008 | EP |
1991668 | Nov 2008 | EP |
2027247 | Feb 2009 | EP |
2200622 | Jun 2010 | EP |
2208782 | Jul 2010 | EP |
2264145 | Dec 2010 | EP |
2303293 | Apr 2011 | EP |
2311938 | Apr 2011 | EP |
2331957 | Jun 2011 | EP |
2334310 | Jun 2011 | EP |
2334783 | Jun 2011 | EP |
2361968 | Aug 2011 | EP |
2366775 | Sep 2011 | EP |
2465922 | Jun 2012 | EP |
2548951 | Jan 2013 | EP |
2561066 | Feb 2013 | EP |
2575831 | Apr 2013 | EP |
2591789 | May 2013 | EP |
2624845 | Aug 2013 | EP |
2626417 | Aug 2013 | EP |
2641606 | Sep 2013 | EP |
2689008 | Jan 2014 | EP |
2694639 | Feb 2014 | EP |
2697362 | Feb 2014 | EP |
2739720 | Jun 2014 | EP |
2807246 | Dec 2014 | EP |
1414671 | Nov 1975 | GB |
2297980 | Aug 1996 | GB |
2360789 | Oct 2001 | GB |
3285 | May 2007 | HU |
2003052360 | Feb 2003 | JP |
5548207 | Jul 2014 | JP |
115206 | Apr 2003 | MY |
9013306 | Nov 1990 | WO |
9105238 | Apr 1991 | WO |
9106641 | May 1991 | WO |
9109194 | Jun 1991 | WO |
9425571 | Nov 1994 | WO |
9629395 | Sep 1996 | WO |
9639035 | Dec 1996 | WO |
9705826 | Feb 1997 | WO |
9729792 | Aug 1997 | WO |
9739104 | Oct 1997 | WO |
1997-040137 | Oct 1997 | WO |
9831403 | Jul 1998 | WO |
9851317 | Nov 1998 | WO |
9851785 | Nov 1998 | WO |
9905180 | Feb 1999 | WO |
9924391 | May 1999 | WO |
9924490 | May 1999 | WO |
9927167 | Jun 1999 | WO |
9949015 | Sep 1999 | WO |
0006704 | Feb 2000 | WO |
0009018 | Feb 2000 | WO |
0016420 | Mar 2000 | WO |
0017326 | Mar 2000 | WO |
0029002 | May 2000 | WO |
0032225 | Jun 2000 | WO |
0044058 | Jul 2000 | WO |
0054651 | Sep 2000 | WO |
0056405 | Sep 2000 | WO |
0059933 | Oct 2000 | WO |
0069449 | Nov 2000 | WO |
0075196 | Dec 2000 | WO |
0077236 | Dec 2000 | WO |
2001000783 | Jan 2001 | WO |
2001011011 | Feb 2001 | WO |
2001018174 | Mar 2001 | WO |
2001021766 | Mar 2001 | WO |
2001025402 | Apr 2001 | WO |
2001029189 | Apr 2001 | WO |
0122810 | Apr 2001 | WO |
2001034167 | May 2001 | WO |
2001049851 | Jul 2001 | WO |
2001054706 | Aug 2001 | WO |
2001-094541 | Dec 2001 | WO |
2002042422 | May 2002 | WO |
2002057430 | Jul 2002 | WO |
2002092794 | Nov 2002 | WO |
2002101385 | Dec 2002 | WO |
2003010303 | Feb 2003 | WO |
2003014313 | Feb 2003 | WO |
2003016916 | Feb 2003 | WO |
2003023018 | Mar 2003 | WO |
2003023019 | Mar 2003 | WO |
2003025167 | Mar 2003 | WO |
2003029402 | Apr 2003 | WO |
2003040336 | May 2003 | WO |
2003042405 | May 2003 | WO |
2003046161 | Jun 2003 | WO |
2003055989 | Jul 2003 | WO |
2003061685 | Jul 2003 | WO |
2003061686 | Jul 2003 | WO |
2003068961 | Aug 2003 | WO |
2003072064 | Sep 2003 | WO |
2003078609 | Sep 2003 | WO |
2003078967 | Sep 2003 | WO |
2003080816 | Oct 2003 | WO |
2003082145 | Oct 2003 | WO |
2003085099 | Oct 2003 | WO |
2003089631 | Oct 2003 | WO |
2003091398 | Nov 2003 | WO |
2003095631 | Nov 2003 | WO |
2004001697 | Dec 2003 | WO |
2004012226 | Feb 2004 | WO |
2004016779 | Feb 2004 | WO |
2004018526 | Mar 2004 | WO |
2004018655 | Mar 2004 | WO |
2004026115 | Apr 2004 | WO |
2004029231 | Apr 2004 | WO |
2004042023 | May 2004 | WO |
2004042033 | May 2004 | WO |
2004042040 | May 2004 | WO |
2004044127 | May 2004 | WO |
2004044158 | May 2004 | WO |
2004046304 | Jun 2004 | WO |
2004050826 | Jun 2004 | WO |
2004053096 | Jun 2004 | WO |
2004055155 | Jul 2004 | WO |
2004056186 | Jul 2004 | WO |
2004065616 | Aug 2004 | WO |
2004069172 | Aug 2004 | WO |
2004070013 | Aug 2004 | WO |
2004072264 | Aug 2004 | WO |
2004073633 | Sep 2004 | WO |
2004074464 | Sep 2004 | WO |
2004076642 | Sep 2004 | WO |
2004076653 | Sep 2004 | WO |
2004087870 | Oct 2004 | WO |
2004094588 | Nov 2004 | WO |
2004096975 | Nov 2004 | WO |
2004104166 | Dec 2004 | WO |
2004106499 | Dec 2004 | WO |
2004113513 | Dec 2004 | WO |
2005001033 | Jan 2005 | WO |
2005001081 | Jan 2005 | WO |
2005003320 | Jan 2005 | WO |
2005007799 | Jan 2005 | WO |
2005010172 | Feb 2005 | WO |
2005011524 | Feb 2005 | WO |
2005012480 | Feb 2005 | WO |
2005012510 | Feb 2005 | WO |
2005012512 | Feb 2005 | WO |
05014775 | Feb 2005 | WO |
2005028433 | Mar 2005 | WO |
05044972 | May 2005 | WO |
2005056747 | Jun 2005 | WO |
05051316 | Jun 2005 | WO |
2005063303 | Jul 2005 | WO |
2005075636 | Aug 2005 | WO |
2005107760 | Nov 2005 | WO |
2006009291 | Jan 2006 | WO |
2006032075 | Mar 2006 | WO |
2006032092 | Mar 2006 | WO |
2006108229 | Oct 2006 | WO |
2006113881 | Oct 2006 | WO |
2006121445 | Nov 2006 | WO |
06124021 | Nov 2006 | WO |
06129312 | Dec 2006 | WO |
2007115367 | Oct 2007 | WO |
2007115368 | Oct 2007 | WO |
2008006168 | Jan 2008 | WO |
2008011664 | Jan 2008 | WO |
2008017128 | Feb 2008 | WO |
2008028241 | Mar 2008 | WO |
08040812 | Apr 2008 | WO |
2008116261 | Oct 2008 | WO |
2008149129 | Dec 2008 | WO |
2009026635 | Mar 2009 | WO |
09058146 | May 2009 | WO |
09080054 | Jul 2009 | WO |
09081408 | Jul 2009 | WO |
2009140452 | Nov 2009 | WO |
09132457 | Nov 2009 | WO |
2009144720 | Dec 2009 | WO |
10005527 | Jan 2010 | WO |
2010019886 | Feb 2010 | WO |
10014253 | Feb 2010 | WO |
10019997 | Feb 2010 | WO |
2010026573 | Mar 2010 | WO |
2010026574 | Mar 2010 | WO |
2010026575 | Mar 2010 | WO |
2010036760 | Apr 2010 | WO |
2010059487 | May 2010 | WO |
10061377 | Jun 2010 | WO |
10068710 | Jun 2010 | WO |
10071826 | Jun 2010 | WO |
10083385 | Jul 2010 | WO |
10111255 | Sep 2010 | WO |
10119036 | Oct 2010 | WO |
10123594 | Oct 2010 | WO |
2011025445 | Mar 2011 | WO |
2011132087 | Oct 2011 | WO |
2011147967 | Dec 2011 | WO |
2012072924 | Jun 2012 | WO |
2012127320 | Sep 2012 | WO |
2012138968 | Oct 2012 | WO |
2012140519 | Oct 2012 | WO |
2012171026 | Dec 2012 | WO |
2012171030 | Dec 2012 | WO |
2013110651 | Aug 2013 | WO |
2014037862 | Mar 2014 | WO |
2014037863 | Mar 2014 | WO |
2014068508 | May 2014 | WO |
2014128306 | Aug 2014 | WO |
2014128634 | Aug 2014 | WO |
2014131846 | Sep 2014 | WO |
2014141111 | Sep 2014 | WO |
2015004609 | Jan 2015 | WO |
2015118148 | Aug 2015 | WO |
2015118149 | Aug 2015 | WO |
2015131143 | Sep 2015 | WO |
2017072201 | May 2017 | WO |
2019-155027 | Aug 2019 | WO |
Entry |
---|
U.S. Appl. No. 18/113,151, filed Feb. 23, 2023, Andrew Gloor et al. |
Nehlin JO, Just M, Rustan AC (2011) Human myotubes from myoblast cultures undergoing senescence exhibit defects in glucose and lipid metabolism. Biogerontology 12: 349-365. |
Unknown author, “New Victories for Adult Stem Cell Research,” New York, Feb. 6, 2007. |
Newton R, Priyadharshini B, Turka LA. Immunometabolism of regulatory T cells. Nat Immunol. 2016; 17(6):618-25. |
Ng TH, Britton GJ, Hill EV, Verhagen J, Burton BR, Wraith DC. Regulation of adaptive immunity; the role of interleukin-10. Front Immunol. 2013;4:129. |
Nikolaychik, V. V., M. M. Samet, and P. I. Lelkes. “A New, Cryoprecipitate Based Coating for Improved Endothelial Cell Attachment and Growth on Medical Grade Artificial Surfaces.” ASAIO Journal (American Society for Artificial Internal Organs: 1992) 40.3 (1994): M846-52. |
Nish SA, Schenten D, Wunderlich FT, Pope SD, Gao Y, Hoshi N, Yu S, Yan X, Lee HK, Pasman L, Brodsky I, Yordy B, Zhao H, Bruning J, Medzhitov R. T cell-intrinsic role of IL-6 signaling in primary and memory responses. Elife. 2014;3: e01949. |
Niwayama, Jun, et al. “Analysis of hemodynamics during blood purification therapy using a newly developed noninvasive continuous monitoring method.” Therapeutic Apheresis and Dialysis 10.4 (2006): 380-386. |
Nugent, Helen M., et al. “Adventitial endothelial implants reduce matrix metalloproteinase-2 expression and increase luminal diameter in porcine arteriovenous grafts.” Journal of vascular surgery 46.3 (2007): 548-556. |
Okano et al (Tokyo Women's Medical College, Japan) demonstrated the recovery of endothelial cells and hepatocytes from plasma-treated polystyrene dishes grafted with PNIAAm (Journal of Biomedical Materials Research, 1993). |
Onishi Y, Fehervari Z, Yamaguchi T, Sakaguchi S. Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc Natl Acad Sci U S A. 2008;105(29):10113-8. |
Onyszchuk G, LeVine SM, Brooks WM, Berman NE. Post-acute pathological changes in the thalamus and internal capsule in aged mice following controlled cortical impact injury: A magnetic resonance imaging, iron histochemical, and glial immunohistochemical study. Neuroscience letters. 2009;452:204-208. |
Pacella I, Procaccini C, Focaccetti C, Miacci S, Timperi E, Faicchia D, Severa M, Rizzo F, Coccia EM, Bonacina F, Mitro N, Norata GD, Rossetti G, Ranzani V, Pagani M, Giorda E, Wei Y, Matarese G, Barnaba V, Piconese S. Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth. Proc Natl Acad Sci U S A. 2018;115(28):E6546-E6555. |
Parhi, Purnendu, Avantika Golas, and Erwin A. Vogler. “Role of Proteins and Water in the Initial Attachment of Mammalian Cells to Biomedical Surfaces: A Review.” Journal of Adhesion Science and Technology 24.5 (2010): 853-888. |
Pati S, Gerber MH, Menge TD, Wataha KA, Zhao Y, Baumgartner JA, Zhao J, Letourneau PA, Huby MP, Baer LA, Salsbury JR, Kozar RA, Wade CE, Walker PA, Dash PK, Cox CS, Jr., Doursout MF, Holcomb JB. Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock. PloS one. 2011;6:e25171. |
Pati S, Khakoo AY, Zhao J, Jimenez F, Gerber MH, Harting M, Redell JB, Grill R, Matsuo Y, Guha S, Cox CS, Reitz MS, Holcomb JB, Dash PK. Human mesenchymal stem cells inhibit vascular permeability by modulating vascular endothelial cadherin/beta-catenin signaling. Stem cells and development. 2011;20:89-101. |
Peters JH, Preijers FW, Woestenenk R, Hilbrands LB, Koenen HJ, Joosten I. Clinical grade Treg: GMP isolation, improvement of purity by CD127 Depletion, Treg expansion, and Treg cryopreservation. PLoS One. 2008;3(9):e3161. |
Peters, R.; Jones, M.; Brecheisen, M.; Startz, T.; Vang, B.; Nankervis, B.; Frank, N.; Nguyen, K. (2012) TerumoBCT. https://www.terumobct.com/location/north-america/products-and-services/Pages/Quantum-Materials.aspx. |
Porter CM, Horvath-Arcidiacono JA, Singh AK, Horvath KA, Bloom ET, Mohiuddin MM. Characterization and expansion of baboon CD4+CD25+ Treg cells for potential use in a non-human primate xenotransplantation model. Xenotransplantation. 2007; 14(4):298-308. |
Povsic TJ, O'Connor CM, Henry T, et al. (2011) A double-blind, randomized, controlled, multicenter study to assess the safety and cardiovascular effects of skeletal myoblast implantation by catheter delivery in patients with chronic heart failure after myocardial infarction. Am Heart J 162(4): 654-662. |
Prockop, Darwin J., Carl A. Gregory, and Jeffery L. Spees. “One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues.” Proceedings of the National Academy of Sciences 100.suppl_1 (2003): 11917-11923. |
Q. L. Hao, et al. A functional comparison of CD34+CD38= cells in cord blood and bone marrow. Blood 86:3745-3753, 1995. |
Rahmahwati, Nurlaela, Deana Wahyuningrum, and Anita Alni. “The Synthesis of Polyethersulfone (PES) Derivatives for the Immobilization of Lipase Enzyme.” Key Engineering Materials. vol. 811. Trans Tech Publications Ltd, 2019. |
Rey-Jurado, Emma, et al. “Assessing the importance of domestic vaccine manufacturing centers: an overview of immunization programs, vaccine manufacture, and distribution.” Frontiers in immunology 9 (2018): 26. |
Roballo KC, Dhungana S, Z. J, Oakey J, Bushman J. Localized delivery of immunosuppressive regulatory T cells to peripheral nerve allografts promotes regeneration of branched segmental defects. Biomaterials. 2019;209:1-9. |
Rodrigues, C., Fernandes, T., Diogo, M., Lobato da Silva, C., Cabral, J. Stem Cell Cultivation in Bioreactors. 2011. Biotechnology Advances v. 29, pp. 815-829. |
Ronco C1, Levin N, Brendolan A, Nalesso F, Cruz D, Ocampo C, Kuang D, Bonello M, De Cal M, Corradi V, Ricci Z. Flow distribution analysis by helical scanning in polysulfone hemodialyzers: effects of fiber structure and design on flow patterns and solute clearances. Hemodial Int. Oct. 2006; 10(4):380-8. |
Ronco, C., Brendolan, A., Crepaldi, C., Todighiero, M., Scabardi, M. Blood and Dialysate Flow Distributions in Hollow-Fiber Hemodialyzers Analyzed by Computerized Helical Scanning Technique. 2002. Journal of the American Society of Nephrology. V. 13, pp. S53-S61. |
Rosenblum MD, Way SS, Abbas AK. Regulatory T cell memory. Nat Rev Immunol. 2016;16(2):90-101. |
Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, Ye X, Treuting P, Siewe L, Roers A, Henderson WR, Jr., Muller W, Rudensky AY. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity. 2008;28(4):546-58. |
Rudensky, Alexander Y. “Regulatory T cells and Foxp3.” Immunological reviews 241.1 (2011): 260-268. |
Ryu, Min-Hyung, and Mark Gomelsky. “Near-infrared light responsive synthetic c-di-GMP module for optogenetic applications.” ACS synthetic biology 3.11 (2014): 802-810. |
S. Koestenbauer, et al. Protocols for Hematopoietic Stem Cell Expansion from Umbilical Cord Blood. Cell Transplantation 18: 1059-1068, 2009. |
S. L. Smith, et al. Expansion of neutrophil precursors and progenitors in suspension cultures of CD34+ cells enriched from human bone marrow. Experimental Hematology 21:870-877, 1993. |
Safinia N, Grageda N, Scotta C, Thirkell S, Fry LJ, Vaikunthanathan T, Lechler RI, Lombardi G. Cell Therapy in Organ Transplantation: Our Experience on the Clinical Translation of Regulatory T Cells. Front Immunol. 2018;9:354. |
Sahay A, Scobie KN, Hill AS, O'Carroll CM, Kheirbek MA, Burghardt NS, Fenton AA, Dranovsky A, Hen R. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature. 2011;472:466-470. |
Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;155(3):1151-64. |
Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T. Immunologic tolerance maintained by CD25+CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev. 2001;182:18-32. |
Schild, Howard G. “Poly (N-isopropylacrylamide): experiment, theory and application.” Progress in polymer science 17.2 (1992): 163-249. |
Schmitz R, Alessio A, Kina P. The Physics of PET/CT scanners. Imaging Research Laboratory, Department of Radiology, University of Washington http://depts.washington.edu/imreslab/education/Physics%20of%20PET.pdf, 2013, 16 pages. |
Schwartz RH. T cell anergy. Annu Rev Immunol. 2003;21:305-34. |
Shevkoplyas et al., “The Force Acting on a Superparamagnetic Bead due to an Applied Magnetic Field,” Lab on a Chip , 7, pp. 1294-1302, 2007. |
Shimazu Y, Shimazu Y, Hishizawa M, Hamaguchi M, Nagai Y, Sugino N, Fujii S, Kawahara M, Kadowaki N, Nishikawa H, Sakaguchi S, Takaori-Kondo A. Hypomethylation of the Treg-Specific Demethylated Region in FOXP3 Is a Hallmark of the Regulatory T-cell Subtype in Adult T-cell Leukemia. Cancer Immunol Res. 2016;4(2):136-45. |
Shimizu et all., “Fabrication of Pulsatile Cardiac Tissue Grafts Using a Novel 3-Dimensional Cell Sheet Manipulation Technique and Temperature-Responsive Cell Culture Surfaces,” Circulation Research, vol. 90, Feb. 22, 2022, e40-e48, pp. 1-9. |
Sigma-Aldrich Cheimcals Mitomycin C (M4287) MSDS, v4.4, Jul. 7, 2011. |
Sirsi, S. and Borden, M., “Microbubble Composition, Properties, and Biomedical Applications,” Bubble Science, Engineering & Technolology, vol. 1, No. 1-2, pp. 3-17, 2009. |
Smith C, Okern G, Rehan S, et al. Ex vivo expansion of human T cells for adoptive immunotherapy using the novel Xeno-free CTS Immune Cell Serum Replacement. Clinical & Translational Immunology 2015;4:e31. |
Somerville et al., “Clinical Scale Rapid Expansion of Lymphocytes for Adoptive Cell Transfer Therapy in the WAVE® Bioreactor,” Journal of Translational Medicine, vol. 10, No. 69, pp. 1-11, 2012. |
Somerville, R. and Dudley, M., “Bioreactors Get Personal,” Oncolmmunology, vol. 1, No. 8, pp. 1435-1437, Nov. 2012. |
Spectrum Labs KrosFlo Research IIi TFF System, 2013, Spectrum Laboratories, Inc., 4 pages. |
Stafano Tiziani, et al. Metabolomic Profiling of Drug Response in Acute Myeloid Leukaemia Cell lines. PLOSone 4(1):e4251 (Jan. 22, 2009). |
Abumiya, et al at National Cardiovascular Center Research Institute in Japan, suggest that subjecting human umbilical vein endothelial cells (HUVECs) to laminar shear stress for a period of 8 hours increased the relative expression of VEGFR-2 mRNA (Ateriosclerosis, Thrombosis, and Vascular Biology, 2002). |
Afzali B, Edozie FC, Fazekasova H, Scotta C, Mitchell PJ, Canavan JB, Kordasti SY, Chana PS, Ellis R, Lord GM, John S, Hilton R, Lechler RI, Lombardi G. Comparison of regulatory T cells in hemodialysis patients and healthy controls: implications for cell therapy in transplantation. Clin J Am Soc Nephrol. 2013;8(8):1396-405. |
Akram, Khondoker M., et al. “Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms.” Respiratory research 14.1 (2013): 1-16. |
Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Fibroblasts and Their Transformations: The Connective-Tissue Cell Family. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26889. |
Alenazi, Noof A., et al. “Modified polyether-sulfone membrane: A mini review.” Designed monomers and polymers 20.1 (2017): 532-546. |
Almeida L, Lochner M, Berod L, Sparwasser T. Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol. 2016;28(5):514-524. |
Amy Putnam, Todd M. Brusko, Michael R. Lee, Weihong Liu, Gregory L. Szot, Taumoha Ghosh, Mark A. Atkinson, and Jeffrey A. Bluestone. Expansion of human regulatory T-Cells from patients with Type 1 Diabetes. Diabetes, 58: 652-662, 2009. |
Anurathapan et al., “Engineered T cells for cancer treatment,” Cytotherapy, vol. 16, pp. 713-733, 2014. |
Aronowski J, Samways E, Strong R, Rhoades HM, Grotta JC. An alternative method for the quantitation of neuronal damage after experimental middle cerebral artery occlusion in rats: Analysis of behavioral deficit. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 1996;16:705-713. |
Arrigoni, Chiara, et al. “Rotating versus perfusion bioreactor for the culture of engineered vascular constructs based on hyaluronic acid.” Biotechnology and bioengineering 100.5 (2008): 988-997. |
Azar, Toni, Jody Sharp, and David Lawson. “Heart rates of male and female Sprague-Dawley and spontaneously hypertensive rats housed singly or in groups.” Journal of the American Association for Laboratory Animal Science 50.2 (2011): 175-184. |
Baecher-Allan, Clare, et al. “CD4+CD25high regulatory cells in human peripheral blood.” The Journal of Immunology 167.3 (2001): 1245-1253. |
Bai/Delaney (Nohla Therapeutics) showed that expanding Cord Blood-derived CD34+CD38-CD45RA—HSPCs in a biodegradable zwitterionic hydrogel with a rNotch ligand cocktail for 24 days mitigated HSPC differentiation and promoted self-renewal of lymphoid and myeloid cell phenotypes in an NSG mouse model (Nature Medicine, 2019). |
Ballas CB, Zielske SP, Gerson SL (2002) Adult bone marrow stem cells for cell and gene therapies: implications for greater use. J Cell Biochem Suppl 38: 20-28. |
Ballke C, Gran E, Baekkevold ES, Jahnsen FL. Characterization of Regulatory T-Cell Markers in CD4+ T Cells of the Upper Airway Mucosa. PLoS One. 2016;11(2):e0148826. |
Baraniak PR, McDevitt TC (2010) Stem cell paracrine actions and tissue regeneration. Regen Med 5(1): 121-143. |
Barckhausen C, Rice B, Baila S, et al. (2016) GMP-Compliant Expansion of Clinical-Grade Human Mesenchymal Stromal/Stem Cells Using a Closed Hollow Fiber Bioreactor. Methods Mol Biol 1416: 389-412. |
Barker et al. “CD34+ Cell Content of 126 341 Cord Blood Units in the US Inventory: Implications for Transplantation and Banking,” blood Advances, vol. 3, No. 8, pp. 1267-1271, Apr. 23, 2019. |
Bazarian JJ, Cernak I, Noble-Haeusslein L, Potolicchio S, Temkin N. Long-term neurologic outcomes after traumatic brain injury. The Journal of head trauma rehabilitation. 2009;24:439-451. |
Bending D, Pesenacker AM, Ursu S, Wu Q, Lom H, Thirugnanabalan B, Wedderburn LR. Hypomethylation at the regulatory T cell-specific demethylated region in CD25hi T cells is decoupled from FOXP3 expression at the inflamed site in childhood arthritis. J Immunol. 2014;193(6):2699-708. |
Berendse M, Grounds MD, Lloyd CM (2003) Myoblast structure affects subsequent skeletal myotube morphology and sarcomere assembly. Exp Cell Res 291(2): 435-450. |
Bernard, A., Payton, Mar. 1995. “Fermentation and Growth of Escherichia coli for Optimal Protein Production”, John Wiley & Sons. Current Protocols in Protein Science (1995) 5.3.1-5.3.18. |
Berney SM, Schaan T, Wolf RE, van der Heyde H, Atkinson TP. CD2 (OKT11) augments CD3-mediated intracellular signaling events in human T lymphocytes. J Investig Med. 2000;48(2):102-9. |
Bioheart Clinical Trial Clinica 1302 Apr. 18, 2008. |
Biomolecular and Cellular Interactions with the Hollow Fiber Membrane Currently Used in the Quantum® Cell Expansion System. 12th NJ Symposium on Biomaterials Science, Oct. 6-7, 2014, New Brunswick, NJ. |
Blache C, Chauvin JM, Marie-Cardine A, Contentin N, Pommier P, Dedreux I, Francois S, Jacquot S, Bastit D, Boyer O. Reduced frequency of regulatory T cells in peripheral blood stem cell compared to bone marrow transplantations. Biol Blood Marrow Transplant. 2010; 16(3):430-4. |
Bluestone et al. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Science Translational Medicine 7(315):1-34, 2015. |
Bluestone JA, Tang Q. Treg cells-the next frontier of cell therapy. Science. 2018;362(6411):154-155. |
Blum S, Moore AN, Adams F, Dash PK. A mitogen-activated protein kinase cascade in the ca1/ca2 subfield of the dorsal hippocampus is essential for long-term spatial memory. The Journal of neuroscience : the official journal of the Society for Neuroscience. 1999;19:3535-3544. |
Boitano, Anthony E., et al. “Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells.” Science 329.5997 (2010): 1345-1348. |
Bojun Li et al. Heparin-induced conformation changes of fibronectin within the extracellular matrix promote hMSC osteogenic differentiation. Biomaterials Science 3: 73-84, 2015. |
Boquest AC, Shahdadfar A, Brinchmann JE, Collas P. Isolation of Stromal Stem Cells from Human Adipose Tissue. Methods Mol Biol. 2006;325:35-46. doi: 10.1385/1-59745-005-7:35. PMID: 16761717. |
Borden, M. and Longo, M., “Dissolution Behavior of Lipid Monolayer-Coated, Air-Filled Microbubbles: Effect of Lipid Hydrophobic Chain Length,” Langmuir, vol. 18, pp. 9225-9233, 2002. |
Bourke, Sharon L., and Joachim Kohn. “Polymers derived from the amino acid L-tyrosine: polycarbonates, polyarylates and copolymers with poly (ethylene glycol).” Advanced drug delivery reviews 55.4 (2003): 447-466. |
Brand, K. and Hermfisse, U., “Aerobic Glycolysis by Proliferating Cells: a Protective Strategy against Reactive Oxygen Species,” The FASEB Journal, vol. 11, pp. 388-395, Apr. 1997. |
Brentjens et al., “CD19-Targeted T Cells Rapidly Induce Molecular Remission in Adults with Chemotherapy-Refractory Acute Lympohblastic Leukemia,” Science Translational Medicine, vol. 5, Issue 177, pp. 1-9, Mar. 20, 2013. |
Brentjens et al., “Safety and Persistance of Adoptively Transferred Autologous CD19-Target T Cells in Patients with Relapsed or Chemotherapy Refractory B-Cell Leukemias,” Blood, vol. 118, No. 18, pp. 4817-4828, Nov. 3, 2011. |
Brunstein C, Miller J, Cao Q, Mckenna D, Hippen K, Curtsinger J, DeFor T, Levine B, June C, Rubinstein P, McGlave P, Blazar B, Wagner J. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood 2011; 117(3):1061-1070. |
C. H. Weaver, et al. An Analysis of Engraftment Kinetics as a function of the CD34 Content of the Peripheral Blood Progenitor Cell Collections in 692 Patients After the Administration of Myeloblative Chemotherapy. Blood 86(10): 3691-3969, 1995. |
Cano, Àngels, Cristina Minguillon, and Cristina Palet. “Immobilization of endo-1, 4-β-xylanase on polysulfone acrylate membranes: Synthesis and characterization.” Journal of membrane science 280.1-2 (2006): 383-388. |
Carswell, K. and Papoutsakis, E. “Culture of Human T Cells in Stirred Bioreactors for Cellular Immunotherapy Applications: Shear, Proliferation, and the IL-2 Receptor,” Biotechnology and Bioengineering, vol. 68, No. 3, pp. 329-338, May 5, 2000. |
Celeste Nelson et al., Emergent patterns of growth controlled by multicellular form and mechanics, (in Christopher Chen's Lab demonstrated, in separate experiments, that curved surfaces with a radius of curvature (200 ?m) that is greater than the cell diameter and surfaces that have undulating special patterning (depressions) increase the patterned growth of ECs [PNAS 102(33): 11594-11599, 2005]. |
Chapman NM, Chi H. mTOR signaling, Tregs and immune modulation. Immunotherapy. 2014;6(12):1295-311. |
Chaudhry A, Samstein RM, Treuting P, Liang Y, Pils MC, Heinrich JM, Jack RS, Wunderlich FT, Bruning JC, Muller W, Rudensky AY. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity. 2011;34(4):566-78. |
Chen, C. and Broden, M., “The Role of Poly(theylene glycol) Brush Architecture in Complement Activation on Targeted Microbubble Surfaces,” Biomaterials, vol. 32, No. 27, pp. 6579-6587, Jun. 17, 2011. |
Choi W, Kwon SJ, Jin HJ, et al. (2017) Optimization of culture conditions for rapid clinical-scale expansion of human umbilical cord blood-derived mesenchymal stem cells. Clin Transl Med 6(1): 38. |
Chullikana A, Majumdar AS, Gottipamula S, et al. (2015) Randomized, double-blind, phase I/II study of intravenous allogeneic mesenchymal stromal cells in acute myocardial infarction. Cytotherapy 17(3): 250-261. |
Coeshott C, Vang B, Jones M, Nankervis B. Large-scale expansion and characterization of CD3(+) T-cells in the Quantum((R)) Cell Expansion System. J Transl Med. 2019;17(1):258. |
Coombes JL, Robinson NJ, Maloy KJ, Uhlig HH, Powrie F. Regulatory T cells and intestinal homeostasis. Immunol Rev. 2005;204:184-94. |
Coquillard C. mTOR Signaling in Regulatory T cell Differentiation and Expansion. SOJ Immunology. 2015;3(1):1-10. |
Creed JA, DiLeonardi AM, Fox DP, Tessler AR, Raghupathi R. Concussive brain trauma in the mouse results in acute cognitive deficits and sustained impairment of axonal function. Journal of neurotrauma. 2011;28:547-563. |
Cuchiara, Maude L., et al. “Covalent immobilization of stem cell factor and stromal derived factor 1a for in vitro culture of hematopoietic progenitor cells.” Acta biomaterialia 9.12 (2013): 9258-9269. |
Da Silva, Ricardo MP, Joao F. Mano, and Rui L. Reis. “Smart thermoresponsive coatings and surfaces for tissue engineering: switching cell-material boundaries.” TRENDS in Biotechnology 25.12 (2007): 577-583. |
Dash PK, Hochner B, Kandel ER. Injection of the camp-responsive element into the nucleus of aplysia sensory neurons blocks long-term facilitation. Nature. 1990;345:718-721. |
Dash PK, Johnson D, Clark J, Orsi SA, Zhang M, Zhao J, Grill RJ, Moore AN, Pati S. Involvement of the glycogen synthase kinase-3 signaling pathway in tbi pathology and neurocognitive outcome. PloS one. 2011;6:e24648. |
Dash PK, Mach SA, Blum S, Moore AN. Intrahippocampal wortmannin infusion enhances long-term spatial and contextual memories. Learn Mem. 2002;9:167-177. |
Dash PK, Orsi SA, Zhang M, Grill RJ, Pati S, Zhao J, Moore AN. Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats. PloS one. 2010;5:e11383. |
Dash PK, Zhao J, Orsi SA, Zhang M, Moore AN. Sulforaphane improves cognitive function administered following traumatic brain injury. Neuroscience letters. 2009;460:103-107. |
Davila et al., “Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B cell Acute Lymphoblastic Leukemia,” Science Translational Medicine, vol. 6, No. 224, pp. 1-10, Feb. 19, 2014. |
Dejana E, Orsenigo F, Lampugnani MG. The role of adherens junctions and ve-cadherin in the control of vascular permeability. Journal of cell science. 2008; 121:2115-2122. |
Dejana E, Spagnuolo R, Bazzoni G. Interendothelial junctions and their role in the control of angiogenesis, vascular permeability and leukocyte transmigration. Thrombosis and haemostasis. 2001;86:308-315. |
Dejana E, Tournier-Lasserve E, Weinstein BM. The control of vascular integrity by endothelial cell junctions: Molecular basis and pathological implications. Developmental cell. 2009;16:209-221. |
Del Pino A, Ligero G, Lopez MB, et al. (2015) Morphology, cell viability, karyotype, expression of surface markers and plasticity of three primary cell line cultures before and after the cryostorage in LN2 and GN2. Cryobiology 70(1): 1-8. |
Delaney, Colleen, et al. “Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution.” Nature medicine 16.2 (2010): 232-236. |
Ding, Zhongli, Guohua Chen, and Allan S. Hoffman. “Synthesis and purification of thermally sensitive oligomer? enzyme conjugates of poly (N-isopropylacrylamide)? trypsin.” Bioconjugate chemistry 7.1 (1996): 121-125. |
Dixon CE, Clifton GL, Lighthall JW, Yaghmai AA, Hayes RL. A controlled cortical impact model of traumatic brain injury in the rat. Journal of neuroscience methods. 1991;39:253-262. |
Dominici M, Le Blanc K, Mueller I, et al. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4): 315-317. |
Durrani S, Konoplyannikov M, Ashraf M, Haider KH (2010) Skeletal myoblasts for cardiac repair. Regen Med 5(6): 919-932. |
Esensten JH, Muller YD, Bluestone JA, Tang Q. Regulatory T-cell therapy for autoimmune and autoinflammatory diseases: The next frontier. J Allergy Clin Immunol. 2018;142(6):1710-1718. |
Fakin R, Hamacher J, Gugger M, Gazdhar A, Moser H, Schmid RA. Prolonged amelioration of acute lung allograft rejection by sequential overexpression of human interleukin-10 and hepatocyte growth factor in rats. Exp Lung Res. 2011;37(9):555-62. |
Fedorov et al., “PD-1- and CTLA-4-Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses,” Science Translational Medicine, vol. 5, No. 215, pp. 1-12, Dec. 11, 2013. |
Ferreira LMR, Muller YD, Bluestone JA, Tang Q. Next-generation regulatory T cell therapy. Nat Rev Drug Discov. 2019;18(10):749-769. |
Fischbach, Michael A., Jeffrey A. Bluestone, and Wendell A. Lim. “Cell-based therapeutics: the next pillar of medicine.” Science translational medicine 5.179 (2013): 179ps7-179ps7. |
Fisk, Nicholas M., et al. “Can routine commercial cord blood banking be scientifically and ethically justified?.” PLoS medicine 2.2 (2005): e44. |
Forbes Jun. 23, 2014 article “Will this man cure cancer?”. |
Fowler DH. Rapamycin-resistant effector T-cell therapy. Immunol Rev. 2014;257(1):210-25. |
Fraser H, Safinia N, Grageda N, Thirkell S, Lowe K, Fry LJ, Scotta C, Hope A, Fisher C, Hilton R, Game D, Harden P, Bushell A, Wood K, Lechler RI, Lombardi G. A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials. Mol Ther Methods Clin Dev. 2018;8:198-209. |
Frauwirth KA, Riley JL, Harris MH, Parry RV, Rathmell JC, Plas DR, Elstrom RL, June CH, Thompson CB. The CD28 signaling pathway regulates glucose metabolism. Immunity. 2002;16(6):769-77. |
Fuchs A, Gliwinski M, Grageda N, Spiering R, Abbas AK, Appel S, Bacchetta R, Battaglia M, Berglund D, Blazar B, Bluestone JA, Bornhauser M, Ten Brinke A, Brusko TM, Cools N, Cuturi MC, Geissler E, Giannoukakis N, Golab K, Hafler DA, van Ham SM, Hester J et al. Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization. Front Immunol. 2017;8:1844. |
G0211: Study for Gamma Irradiation of Bioreactor Membranes, undated, available at least one year prior to Jun. 1, 2020, author unknown, 3 pages. |
Galgani M, De Rosa V, La Cava A, Matarese G. Role of Metabolism in the Immunobiology of Regulatory T Cells. J Immunol. 2016;197(7):2567-75. |
Garlie, Nina K., et al. “T cells coactivated with immobilized anti-CD3 and anti-CD28 as potential immunotherapy for cancer.” Journal of immunotherapy (Hagerstown, Md.: 1997) 22.4 (1999): 336-345. |
Gedaly R, De Stefano F, Turcios L, Hill M, Hidalgo G, Mitov MI, Alstott MC, Butterfield DA, Mitchell HC, Hart J, Al-Attar A, Jennings CD, Marti F. mTOR Inhibitor Everolimus in Regulatory T Cell Expansion for Clinical Application in Transplantation. Transplantation. 2019; 103(4):705-715. |
Gimble, Jeffrey M., Adam J. Katz, and Bruce A. Bunnell. “Adipose-derived stem cells for regenerative medicine.” Circulation research 100.9 (2007): 1249-1260. |
Gingras AC, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001;15(7):807-26. |
Godin, Michel, et al. “Measuring the mass, density, and size of particles and cells using a suspended microchannel resonator.” Applied physics letters 91.12 (2007): 123121. |
Golab K, Leveson-Gower D, Wang XJ, Grzanka J, Marek-Trzonkowska N, Krzystyniak A, Millis JM, Trzonkowski P, Witkowski P. Challenges in cryopreservation of regulatory T cells (Tregs) for clinical therapeutic applications. Int Immunopharmacol. 2013;16(3):371-5. |
Goldring CE, Duffy PA, Benvenisty N, Andrews PW, Ben-David U, Eakins R, French N, Hanley NA, Kelly L, Kitteringham NR, Kurth J, Ladenheim D, Laverty H, McBlane J, Narayanan G, Patel S, Reinhardt J, Rossi A, Sharpe M, Park BK. Assessing the safety of stem cell therapeutics. Cell stem cell. 2011;8:618-628. |
Griesche, Nadine, et al. “A simple modification of the separation method reduces heterogeneity of adipose-derived stem cells.” cells tissues organs 192.2 (2010): 106-115. |
Gutcher I, Donkor MK, Ma Q, Rudensky AY, Flavell RA, Li MO. Autocrine transforming growth factor-beta1 promotes in vivo Th17 cell differentiation. Immunity. 2011;34(3):396-408. |
Haack-Sorensen M, Follin B, Juhl M, et al. (2016) Culture expansion of adipose derived stromal cells. A closed automated Quantum Cell Expansion System compared with manual flask-based culture. J Transl Med 14(1): 319. |
Hall ED, Sullivan PG, Gibson TR, Pavel KM, Thompson BM, Scheff SW. Spatial and temporal characteristics of neurodegeneration after controlled cortical impact in mice: More than a focal brain injury. Journal of neurotrauma. 2005;22:252-265. |
Hami et al., “GMP Production and Testing of Xcellerated T Cells for the Treatment of Patients with CLL,” Cytotherapy, pp. 554-562, 2004. |
Hamm RJ, Dixon CE, Gbadebo DM, Singha AK, Jenkins LW, Lyeth BG, Hayes RL. Cognitive deficits following traumatic brain injury produced by controlled cortical impact. Journal of neurotrauma. 1992;9:11-20. |
Hanley PJ, Mei Z, Durett AG, et al. (2014) Efficient manufacturing of therapeutic mesenchymal stromal cells with the use of the Quantum Cell Expansion System. Cytotherapy 16(8): 1048-1058. |
Harimoto, Masami, et al. “Novel approach for achieving double-layered cell sheets co-culture: overlaying endothelial cell sheets onto monolayer hepatocytes utilizing temperature-responsive culture dishes.” Journal of Biomedical Materials Research: An Official Journal of the Society for Biomaterials, the Japanese Society for Biomaterials, and the Australian Society for Biomaterials and the Korean Society for Biomaterials 62.3 (2002): 464-470. |
He N, Fan W, Henriquez B, Yu RT, Atkins AR, Liddle C, Zheng Y, Downes M, Evans RM. Metabolic control of regulatory T cell (Treg) survival and function by Lkb1. Proc Natl Acad Sci U S A. 2017;114(47):12542-12547. |
He X, Landman S, Bauland SC, van den Dolder J, Koenen HJ, Joosten I. A TNFR2-Agonist Facilitates High Purity Expansion of Human Low Purity Treg Cells. PLoS One. 2016; 11(5):e0156311. |
Heskins, Michael, and James E. Guillet. “Solution properties of poly (N-isopropylacrylamide).” Journal of Macromolecular Science—Chemistry 2.8 (1968): 1441-1455. |
Hill JA, Feuerer M, Tash K, Haxhinasto S, Perez J, Melamed R, Mathis D, Benoist C. Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity. 2007;27(5):786-800. |
Högstedt, Benkt, Anita Karlsson, and Anders Holmén. “Frequency and size distribution of micronuclei in lymphocytes stimulated with phytohemagglutinin and pokeweed mitogen in workers exposed to piperazine.” Hereditas 109.(1988): 139-142. |
Hollyman et al., “Manufacturing Validation of Biologicall Functional T Cells Targeted to CD19 Antigen for Autologous Adoptive Cell Therapy,” J Immunother, vol. 32, No. 2, pp. 169-180, Feb.-Mar. 2009. |
MRI| Small Animal Imaging| University of Colorado Cancer Center, http://www.ucdenver.edu/academics/colleges/medicalschool/centers/cancercenter/Research/sharedresources/AnimalImaging/smallanimalimaging/Pages/MRI.aspx, 2019, 2 pages. |
ISCT Webinar “Volume Reduction technology for Large Scale Harvest or Post-thaw Manipulation of Cellular Therapeutics”. Feb. 8, 2012, 60 pages. |
Itkin, Tomer, and Tsvee Lapidot. “SDF-1 keeps HSC quiescent at home.” Blood, The Journal of the American Society of Hematology 117.2 (2011): 373-374. |
Iwashima, Shigejiro, et al. “Novel culture system of mesenchymal stromal cells from human subcutaneous adipose tissue.” Stem cells and development 18.4 (2009): 533-544. |
Jang, Eugene, et al. “Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle.” Proceedings of the National Academy of Sciences 109.5 (2012): 1679-1684. |
Jarocha D, Stangel-Wojcikiewicz K, Basta A, Majka M (2014) Efficient myoblast expansion for regenerative medicine use. Int J Mol Med 34(1): 83-91. |
Jo CH, Lee YG, Shin WH, et al. (2014) Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells 32(5): 1254-1266. |
Johansson, Ulrika, et al. “Pancreatic islet survival and engraftment is promoted by culture on functionalized spider silk matrices.” PloS one 10.6 (2015): e0130169. |
John Carvell, et al. Monitoring Live Biomass in Disposable Bioreactors, BioProcess International 14(3)s, Mar. 2016. |
John Nicolette, et al (Abbott Laboratories). In Vitro Micronucleus Screening of Pharmaceutical Candidates by Flow Cyto9metry in Chinese Hamster V79 Cells, Environmental and Molecular Mutagenesis 00:000-000, 2010. |
John P. Carvell and Jason E. Dowd. On-line measurements and control of viable cell density in cell culture manufacturing processes using radio frequency impedance. Cytotechnology 50: 35-48, 2006. |
Johnson, Patrick A., et al. “Interplay of anionic charge, poly (ethylene glycol), and iodinated tyrosine incorporation within tyrosine?derived polycarbonates: Effects on vascular smooth muscle cell adhesion, proliferation, and motility.” Journal of Biomedical Materials Research Part A: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials 93.2 (2010): 505-514. |
Johnston LC, Su X, Maguire-Zeiss K, Horovitz K, Ankoudinova I, Guschin D, Hadaczek P, Federoff HJ, Bankiewicz K, Forsayeth J. Human interleukin-10 gene transfer is protective in a rat model of Parkinson's disease. Mol Ther. 2008;16(8):1392-9. |
Jones M, Varella-Garcia M, Skokan M, et al. (2013) Genetic stability of bone marrow-derived human mesenchymal stromal cells in the Quantum System. Cytotherapy 15(11): 1323-1339. |
Jones2016ISCT 2016 Poster 69. |
Joy, Abraham, et al. “Control of surface chemistry, substrate stiffness, and cell function in a novel terpolymer methacrylate library.” Langmuir 27.5 (2011): 1891-1899. |
Kalamasz et al., “Optimization of Human T-Cell Expansion Ex Vivo Using Magnetic Beads Conjugated with Anti-CD3 and Anti-CD28 Antibodies,” J Immunother, vol. 27, No. 5, pp. 405-418, Sep.-Oct. 2004. |
Klapper et al., “Single-Pass, Closed-System Rapid Expansion of Lymphocyte Cultures for Adoptive Cell Therapy,” Journal of Immunological Methods, 345, pp. 90-99, Apr. 21, 2009. |
Klein, Elias, Eva Eichholz, and Don H. Yeager. “Affinity membranes prepared from hydrophilic coatings on microporous polysulfone hollow fibers.” Journal of membrane science 90.1-2 (1994): 69-80. |
Korpanty et al., “Tageting Vascular Enothelium with Avidin Microbubbles,” Ultrasound in Medicine and Biology, vol. 31, No. 9, pp. 1279-1283, May 24, 2005. |
Krauss et al., “Signaling Takes a Breath—New Quantitative Perspectives on Bioenergetics and Signal Transduction,” Immunity, vol. 15, pp. 497-502, Oct. 2001. |
Kulikov, A. V., et al. “Application of multipotent mesenchymal stromal cells from human adipose tissue for compensation of neurological deficiency induced by 3-nitropropionic acid in rats.” Bulletin of experimental biology and medicine 145.4 (2008): 514-519. |
Kumar P, Marinelarena A, Raghunathan D, Ragothaman VK, Saini S, Bhattacharya P, Fan J, Epstein AL, Maker AV, Prabhakar BS. Critical role of OX40 signaling in the TCR-independent phase of human and murine thymic Treg generation. Cell Mol Immunol. 2019; 16(2):138-153. |
Kwan, J. and Borden, M., “Lipid Monolayer Collapse and Microbubble Stability,” Advances in Colloid and Interface Science, vols. 183-184, pp. 82-99, Aug. 21, 2012. |
Lee et al., “Continued Antigen Stimulation Is Not Required During CD4+ T Cell Clonal Expansion,” The Journal of Immunology, 168, pp. 1682-1689, 2002. |
Lee, Jae W., et al. “Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung.” Proceedings of the national academy of Sciences 106.38 (2009): 16357-16362. |
Levine, B., “T Lymphocyte Engineering ex vivo for Cancer and Infectious Disease,” Expert Opinion on Biological Therapy, vol. 4, No. 4, pp. 475-489, 2008. |
Lum et al., “Ultrasound Radiation Force Enables Targeted Deposition of Model Drug Carriers Loaded on Microbubbles,” Journal of Controlled Release, 111, pp. 128-134, 2006. |
M. R. Koller, et al. Clinical-scale human umbilical cord blood cell expansion in a novel automated perfusion culture system. Bone Marrow Transplantion 21:653-663, 1998. |
Malin, Stephen F., et al. “Noninvasive prediction of glucose by near-infrared diffuse reflectance spectroscopy.” (1999): 1651-1658. |
Malone et al., “Characterization of Human Tumor-Infiltrating Lymphocytes Expanded in Hollow-Fiber Bioreactors for Immunotherapy of Cancer,” Cancer Biotherapy & Radiopharmaceuticals, vol. 16, No. 5, pp. 381-390, 2001. |
Mao AS, Mooney DJ (2015) Regenerative medicine: current therapies and future directions. Proc Natl Acad Sci USA 112(47): 14452-14459. |
Marek-Trzonkowska, Natalia, et al. “Administration of CD4+CD25highCD127- regulatory T cells preserves ß-cell function in type 1 diabetes in children.” Diabetes care 35.9 (2012): 1817-1820. |
Streltsova et al., “Recurrent Stimulation of Natural Killer Cell Clones with K562 Expressing Membrane-Bound interleukin-21 Affects Their Phenotype, Interferon-y Production, and Lifespan,” International Journal of Molecular Sciences, vol. 20, No. 443, 2019, pp. 1-18. |
Markgraf CG, Clifton GL, Aguirre M, Chaney SF, Knox-Du Bois C, Kennon K, Verma N. Injury severity and sensitivity to treatment after controlled cortical impact in rats. Journal of neurotrauma. 2001; 18:175-186. |
Mathew et al. A Phase I Clinical Trials I with Ex Vivo Expanded Recipient Regulatory T cells in Living Donor Kidney Transplants. Nature, Scientific Reports 8:7428 (1-12), 2018. |
Matthay, Michael A., et al. “Therapeutic potential of mesenchymal stem cells for severe acute lung injury.” Chest 138.4 (2010): 965-972. |
Maynard CL, Harrington LE, Janowski KM, Oliver JR, Zindl CL, Rudensky AY, Weaver CT. Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin 10. Nat Immunol. 2007;8(9):931-41. |
McKenna DH, Jr., Sumstad D, Kadidlo DM, et al. Optimization of cGMP purification and expansion of umbilical cord blood-derived T-regulatory cells in support of first-in-human clinical trials. Cytotherapy 2017;19:250-62. |
McLimans W, Kinetics of Gas Diffusion in Mammalian Cell Culture Systems. Biotechnology and Bioengineering 1968; 10:725-740. |
McMurtrey, Richard J. “Analytic models of oxygen and nutrient diffusion, metabolism dynamics, and architecture optimization in three-dimensional tissue constructs with applications and insights in cerebral organoids.” Tissue Engineering Part C: Methods 22.3 (2016): 221-249. |
Menge, Tyler, et al. “Mesenchymal stem cells regulate blood-brain barrier integrity through TIMP3 release after traumatic brain injury.” Science translational medicine 4.161 (2012): 161ra150-161ra150. |
Miska J, Lee-Chang C, Rashidi A, Muroski ME, Chang AL, Lopez-Rosas A, Zhang P, Panek WK, Cordero A, Han Y, Ahmed AU, Chandel NS, Lesniak MS. HIF-1alpha Is a Metabolic Switch between Glycolytic-Driven Migration and Oxidative Phosphorylation-Driven Immunosuppression of Tregs in Glioblastoma. Cell Rep. 2019;27(1):226-237 e4. |
Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, Parizot C, Taflin C, Heike T, Valeyre D, Mathian A, Nakahata T, Yamaguchi T, Nomura T, Ono M, Amoura Z, Gorochov G, Sakaguchi S. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity. 2009;30(6):899-911. |
Murugappan, G., et al. “Human hematopoietic progenitor cells grow faster under rotational laminar flows.” Biotechnology progress 26.5 (2010): 1465-1473. |
Nankervis B, Jones M, Vang B et al. (2018) Optimizing T Cell Expansion in a Hollow-Fiber Bioreactor. Curr Stem Cell Rep. Advanced online publication. https://doi.org/10.1007/s40778-018-0116-x. |
Nankervis, Brian, et al. “Optimizing T cell expansion in a hollow-fiber bioreactor.” Current Stem Cell Reports 4.1 (2018): 46-51. |
Nedoszytko B, Lange M, Sokolowska-Wojdylo M, Renke J, Trzonkowski P, Sobjanek M, Szczerkowska-Dobosz A, Niedoszytko M, Gorska A, Romantowski J, Czarny J, Skokowski J, Kalinowski L, Nowicki R. The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part II: The Treg role in skin diseases pathogenesis. Postepy Dermatol Alergol. 2017;34(5):405-417. |
Unknown Author, StAR_Abstract, 2014, 1 page. |
Startz et al.May 2016 TBCT T-cell White Paper. |
Startz, T., et al. “Maturation of dendritic cells from CD14+ monocytes in an automated functionally closed hollow fiber bioreactor system.” Cytotherapy 16.4 (2014): S29. |
Steven M. Bryce, et al.(Litron Laboratories). In vitro micronucleus assay scored by flow cytometry provides a comprehensive evaluation of cytogenetic damage and cytotoxicity. Mutation Research 630(1-2): 78-91, 2007. |
Steven M. Bryce, et al.(Novartis Pharma AG, Johnson & Johnson Pharmaceutical Research, GlaxoSmithKline). Interlaboratory evaluation of a flow cytometric, high content in vitro micronucleus assay. Genetic Toxicology and Environmental Mutagenesis 650: 181-195, 2008. |
Stuart, Martien A. Cohen, et al. “Emerging applications of stimuli-responsive polymer materials.” Nature materials 9.2 (2010): 101-113. |
Su LF, Del Alcazar D, Stelekati E, Wherry EJ, Davis MM. Antigen exposure shapes the ratio between antigen-specific Tregs and conventional T cells in human peripheral blood. Proc Natl Acad Sci U S A. 2016;113(41):E6192-E6198. |
Takezawa, Toshiaki, Yuichi Mori, and Katsutoshi Yoshizato. “Cell culture on a thermo-responsive polymer surface.” Bio/technology 8.9 (1990): 854-856. |
The effect of rocking rate and angle on T cell cultures grown in Xuri™ Cell Expansion Systems, Aug. 2014, GE Healthcare UK Limited, 4 pages. |
Trzonkowski et al., “Ex Vivo Expansion of CD4+ CD25+ T Regulatory Cells for Immunosuppressive Therapy,” Cytometry Part A, 75A, pp. 175-188, 2009. |
Trzonkowski, Piotr, et al. “First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+ CD25+ CD127? T regulatory cells.” Clinical immunology 133.1 (2009): 22-26. |
Tsvetkov, Ts, et al. “Isolation and cryopreservation of human peripheral blood monocytes.” Cryobiology 23.6 (1986): 531-536. |
Underwood, P. Anne, et al. “Effects of base material, plasma proteins and FGF2 on endothelial cell adhesion and growth.” Journal of Biomaterials Science, Polymer Edition 13.8 (2002): 845-862. |
Urbich, et al from the Goethe-Universitat, demonstrated that human endothelial cells increased VEGFR-2 mRNA expression when exposed to 5-15 dynes/cm2 of constant shear force for a period of 6-24 hours (FEBS, 2002). |
Van der Net JB, Bushell A, Wood KJ, Harden PN. Regulatory T cells: first steps of clinical application in solid organ transplantation. Transpl Int. 2016;29(1):3-11. |
Van der Windt GJ, Pearce EL. Metabolic switching and fuel choice during T-cell differentiation and memory development. Immunol Rev. 2012;249(1):27-42. |
Vera et al., “Accelerated Production of Antigen-Specific T-Cells for Pre-Clinical and Clinical Applications Using Gas-Permeable Rapid Expansion Cultureware (G-Rex),” J Immunother, vol. 33, No. 3, pp. 305-315, Apr. 2010. |
Villa, Alma Y. Camacho, et al. “CD133+ CD34+ and CD133+ CD38+ blood progenitor cells as predictors of platelet engraftment in patients undergoing autologous peripheral blood stem cell transplantation.” Transfusion and Apheresis Science 46.3 (2012): 239-244. |
Visser EP1, Disselhorst JA, Brom M, Laverman P, Gotthardt M, Oyen WJ, Boerman OC. Spatial resolution and sensitivity of the Inveon small-animal PET scanner. J Nucl Med. Jan. 2009;50(1):139-47. |
Von Laer, D., et al. “Loss of CD38 antigen on CD34+ CD38+ cells during short-term culture.” Leukemia 14.5 (2000): 947-948. |
Wagner Jr, John E., et al. “Phase I/II trial of StemRegenin-1 expanded umbilical cord blood hematopoietic stem cells supports testing as a stand-alone graft.” Cell stem cell 18.1 (2016): 144-155. |
Walker, Peter A., et al. “Direct intrathecal implantation of mesenchymal stromal cells leads to enhanced neuroprotection via an NF?B-mediated increase in interleukin-6 production.” Stem cells and development 19.6 (2010): 867-876. |
Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, McCormick LL, Fitzgerald P, Chi H, Munger J, Green DR. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity. 2011;35(6):871-82. |
Wang, Jiamian, John A. Jansen, and Fang Yang. “Electrospraying: possibilities and challenges of engineering carriers for biomedical applications—a mini review.” Frontiers in Chemistry 7 (2019): 258. |
Ward H, Vigues S, Poole S, Bristow AF. The rat interleukin 10 receptor: cloning and sequencing of cDNA coding for the alpha-chain protein sequence, and demonstration by western blotting of expression in the rat brain. Cytokine. 2001;15(5):237-40. |
Wawman, Rebecca Ellen, Helen Bartlett, and Ye Htun Oo. “Regulatory T cell metabolism in the hepatic microenvironment.” Frontiers in immunology 8 (2018): 1889. |
Weber et al., “White Paper on Adoptive Cell Therapy for Cancer with Tumor-Infiltrating Lymphocytes: A Report of the CTEP Subcommittee on Adoptive Cell Therapy,” Clinical Cancer Research, vol. 17, No. 7, pp. 1664-1673, Apr. 1, 2011. |
Weiss RA, Weiss MA, Beasley KL, Munavalli G (2007) Autologous cultured fibroblast injection for facial contour deformities: a prospective, placebo-controlled, Phase III clinical trial. Dermatol Surg 33(3): 263-268. |
Widdel, F. 2010. “Theory and measurement of bacterial growth” http://www.mpi-bremen.de/Binaries/Binary13037/Wachstumsversuch.pdf. |
Yamada, Noriko, et al. “Thermo?responsive polymeric surfaces; control of attachment and detachment of cultured cells.” Die Makromolekulare Chemie, Rapid Communications 11.11 (1990): 571-576. |
Yang, Hee Seok, et al. “Suspension culture of mammalian cells using thermosensitive microcarrier that allows cell detachment without proteolytic enzyme treatment.” Cell transplantation 19.9 (2010): 1123-1132. |
Yi, Zhuan, et al. “A readily modified polyethersulfone with amino-substituted groups: its amphiphilic copolymer synthesis and membrane application.” Polymer 53.2 (2012): 350-358. |
Yoshinari, Masao, et al. “Effect of cold plasma-surface modification on surface wettability and initial cell attachment.” International Journal of Biomedical and Biological Engineering 3.10 (2009): 507-511. |
Zappasodi et al., “The Effect of Artificial Antigen-Presenting Cells with Preclustered Anit-CD28/-CD3/LFA-1 Monoclonal Antibodies on the Induction of ex vivo Expansion of Functional Human Antitumor T Cells,” Haematologica, vol. 93, No. 10, pp. 1523-1534, 2008. |
Zemmour D, Zilionis R, Kiner E, Klein AM, Mathis D, Benoist C. Publisher Correction: Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR. Nat Immunol. 2018; 19(6):645. |
Zeng B, Kwak-Kim J, Liu Y, Liao AH. Treg cells are negatively correlated with increased memory B cells in pre-eclampsia while maintaining suppressive function on autologous B-cell proliferation. Am J Reprod Immunol. 2013;70(6):454-63. |
Zheng, et al at the University of lowa have shown that the differential effects of pulsatile blood flow and cyclic stretch are an important growth stimulus (American Journal of Physiology—Heart and Circulatory Physiology, 2008). |
Anamelechi, Charles C., et al. “Streptavidin binding and endothelial cell adhesion to biotinylated fibronectin.” Langmuir 23.25 (2007): 12583-12588. |
Barker, Juliet N., et al. “CD34+ cell content of 126 341 cord blood units in the US inventory: implications for transplantation and banking.” Blood advances 3.8 (2019): 1267-1271. |
Bluestone, Jeffrey A., et al. “Type 1 diabetes immunotherapy using polyclonal regulatory T cells.” Science translational medicine 7.315 (2015): 315ra189-315ra189. |
Claudio G. Brunstein, Jeffrey S. Miller, Qing Cao, Daivd H. McKenna, Keli L. Hippen, Julie Curtsinger, Todd Defor, Bruce L. Levine, Carl H. June, Pablo Rubinstein, Philip B. McGlave, Bruce R. Blazar, and John E. Wagner. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood, 117(3): 1061-1070, 2010. |
Lang, Julie, et al. “Generation of hematopoietic humanized mice in the newborn BALB/c-Rag2nullIl2r?null mouse model: a multivariable optimization approach.” Clinical Immunology 140.1 (2011): 102-116. |
Kim, Do-Hyung, et al. “mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery.” Cell 110.2 (2002): 163-175. |
Kishore M, Cheung KCP, Fu H, Bonacina F, Wang G, Coe D, Ward EJ, Colamatteo A, Jangani M, Baragetti A, Matarese G, Smith DM, Haas R, Mauro C, Wraith DC, Okkenhaug K, Catapano AL, De Rosa V, Norata GD, Marelli-Berg FM. Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis. Immunity. 2017;47(5):875-889 e10. |
Klysz D, Tai X, Robert PA, Craveiro M, Cretenet G, Oburoglu L, Mongellaz C, Floess S, Fritz V, Matias MI, Yong C, Surh N, Marie JC, Huehn J, Zimmermann V, Kinet S, Dardalhon V, Taylor N. Glutamine-dependent alpha-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation. Sci Signal. 2015;8(396): ra97. |
Lampugnani MG, Caveda L, Breviario F, Del Maschio A, Dejana E. Endothelial cell-to-cell junctions. Structural characteristics and functional role in the regulation of vascular permeability and leukocyte extravasation. Bailliere's clinical haematology. 1993;6:539-558. |
Lataillade, Jean-Jacques, et al. “Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival.” Blood, The Journal of the American Society of Hematology 95.3 (2000): 756-768. |
Lindstein, Tullia, et al. “Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway.” Science 244.4902 (1989): 339-343. |
Liotta, Francesco, et al. “Frequency of regulatory T cells in peripheral blood and in tumour?infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma.” BJU international 107.9 (2011): 1500-1506. |
Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, Gottlieb PA, Kapranov P, Gingeras TR, Fazekas de St Groth B, Clayberger C, Soper DM, Ziegler SF, Bluestone JA. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med. 2006;203(7):1701-1711. |
Mathew, James M., et al. “A phase I clinical trial with ex vivo expanded recipient regulatory T cells in living donor kidney transplants.” Scientific reports 8.1 (2018): 1-12. |
Ueda, Ryosuke, et al. “Interaction of natural killer cells with neutrophils exerts a significant antitumor immunity in hematopoietic stem cell transplantation recipients.” Cancer medicine 5.1 (2015): 49-60. |
Jin, H., and J. Bae. “Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow.” 22nd Annual ISCT Meeting (2016): S29. |
Bai, Tao, et al. “Expansion of primitive human hematopoietic stem cells by culture in a zwitterionic hydrogel.” Nature medicine 25.10 (2019): 1566-1575. |
Horwitz, Mitchell E., et al. “Phase I/II study of stem-cell transplantation using a single cord blood unit expanded ex vivo with nicotinamide.” Journal of Clinical Oncology 37.5 (2019): 367-373. |
Lee III, Daniel W., et al. “Long-term outcomes following CD19 Car T cell therapy for B-ALL are superior in patients receiving a fludarabine/cyclophosphamide preparative regimen and post-CAR hematopoietic stem cell transplantation.” Blood 128.22 (2016): 218. |
Goh, Celeste, Sowmya Narayanan, and Young S. Hahn. “Myeloid-derived suppressor cells: the dark knight or the joker in viral infections?.” Immunological reviews 255.1 (2013): 210-221. |
Pati, Shibani, and Todd E. Rasmussen. “Cellular therapies in trauma and critical care medicine: Looking towards the future.” PLoS Medicine 14.7 (2017): e1002343. |
Pati, Shibani, et al. “Lyophilized plasma attenuates vascular permeability, inflammation and lung injury in hemorrhagic shock.” PloS one 13.2 (2018): e0192363. |
Celeste Nelson et al.in Christopher Chen's Lab demonstrated, in separate experiments, that curved surfaces with a radius of curvature (200 ?m) that is greater than the cell diameter and surfaces that have undulating special patterning (depressions) increase the patterned growth of ECs [PNAS 102(33): 11594-11599, 2005]. |
Maria Streltsova, Dean Lee (Nationwide Children's Hospital, OSU, Columbus, OH) et al (Int'l Journal of Molecular Sciences, 2019). |
International Search Report and Written Opinion issued in the corresponding International Application No. PCT/US2023/013826; mailed on Jul. 3, 2023 (total 19 pages). |
Number | Date | Country | |
---|---|---|---|
20230272862 A1 | Aug 2023 | US |
Number | Date | Country | |
---|---|---|---|
63314931 | Feb 2022 | US |