DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to applicant amendment received on 11/13/2025:
Amendments of Claims 1, 2, 4 to 13, and 16 to 19 are acknowledged.
Replacement sheet for Figure 12 is acknowledged.
Amendments to the Specification to correct minor informalities on paragraphs 0057 and 0058 are acknowledged.
Drawings
The drawings were received on 13 November 2025. These drawings are acceptable.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5-7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding Claims 5 and 7:
Claim 5 reads “wherein a combined length of the first tube and the second tube is unchanged by the welding” and
Claim 7 reads “wherein a combined length of the first tube, the second tube, and the third tube is unchanged by the welding”.
Each claim is confusing since on every step of welding the length of the tubes should be reduced, in particular Figure 5 shows how the fraction of tube is used on each weld so it is unclear how the combined length stays unchanged, the Examiner was unable to find support for these limitations in the specification and wonders if the claim is incomplete for omitting essential steps, such omission amounting to a gap between the steps; but at the same time the Examiner was unable to identify the missing steps if that were the case.
Regarding Claim 6:
The Claim was amended to read: “wherein welding the first tube and the second tube, comprises forming two separate sterile connections in the first tube and the second tube with a spool piece, and the method comprises preventing, by the spool piece backflow contamination between the first container and the second container”. The claim is confusing since simply connecting a spool piece between a first and a second tool would not prevent backflow. The Examiner considers that the claim is describing the subject matter of Figures 3A to 3D, same as considered on the first action, and that on amendment the step of forming the connection simultaneously with a welder single blade was eliminated by mistake, resulting on an omission of an essential step. For prosecution it will be considered that the step was not omitted.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1 to 4, 8, 9, 12, 13, 15 to 20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Rowley (US 2011/0287534) in view of Landherr (US 2003/0141009), Immerzeel (US 2016/0346777) and Procyshyn (2009/0223592).
Regarding Claim 1:
Rowley discloses a method for sterile automated liquid transfer, comprising:
Providing a first container and a second container and a first sterile fluidical connection between the first container and the second container made by welding the first tube and the second tube (Figure 2, Source bag will be considered the first container, any one of PD1 to PD5 will be considered the second container; paragraph 30, Bag sets of the invention also may be assembled by connecting any other flexible bags with main and branch lines comprising suitable lengths of appropriate flexible tubing sterilely welded into the desired manifold arrangement),
transferring a liquid between the first container and the second container via the first sterile fluidical connection (Paragraph 0033; After preventing flow in all branch lines except that of the one bag to be filled according to the invention method, a desired volume cell suspension liquid is dispensed into the open end of the main line),
sealing and cutting the first fluidical connection between the first container and the second container to disconnect the first sterile fluidical connection (Paragraph 0025, sterilely sealing and disconnecting the branch line of a bag that has been filled, for instance, by heat welding of the tubing); wherein the steps are operated automatically by a controller (Paragraph 0033, The pump motor or mainline valve may be stopped, for instance, by a remote controller that detects the weight of liquid dispensed into the bag set or remaining in the cell source container, Paragraph 0046, The entire apparatus and method of the invention allow filling of sterile bags in a completely closed sterile system, and are also readily adapted to partial or total automation using remote control of pumps, valves and sterile tubing welding).
Rowley discloses that first sterile fluidical connection between the first container and the second container is made by welding but does not provide details on how the welding is done or how the sealing and cutting is made.
Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination (Paragraph 0104), the method comprising placing a first tube and a second tube, into a welding mount, wherein the first tube is connected to a first container and the second tube is connected to a second container (Paragraph 0007, the cavity in the patient can broadly be considered a first container and the fluid bags or discharge bags being used the second container), and welding the first tube and the second tube to form a first sterile fluidical connection between the first tube and the second tube (Figure 1 shows device 10 will be considered a welding mount that can join or separate tube 50, Figures 2B to 2D show the process of separating and sealing, while Figures 4A to 4H show the process of placing the two ends of tube 50 on the welding mount and weld them together).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to Rowley the teachings of Landherr and use the device of Landherr to form a first sterile fluidical connection between the first container and the second container and for sealing and cutting the first fluidical connection between the first container and the second container to disconnect the first sterile fluidical connection.
The modified invention of Rowley does not specifically disclose robotically loading a first tube and a second tube into the welding mount, the tubes are actually placed manually by the operator.
The use of robotic arms to automatically perform functions on sterile environments that in other environments are performed manually by a user is a common practice in the art, it is made in general to avoid contamination and can also increase production speed. Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to use a robot for loading a first tube and a second tube into the welding mount since it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art.
If that rejection is argued, both Immerzeel and Procyshyn teach robotic arms on similar automated sterile fluid transfer devices, the robotic arms with capabilities to operate tubes, and in particular tubes on automated filling transfer devices (Immerzeel, Figure 1, robotic arm 415 handle tube 404; and Procyshyn, Figures 5 and 6, Robotic arms 40 and 50 handle tubes 42 and 52).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to use the tube handling capabilities of the robots of Immerzeel and Procyshyn for loading a first tube and a second tube into the welding mount since it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art.
Regarding Claim 2:
As discussed for Claim 1 above, the modified invention of Rowley discloses the invention as claimed, in particular having multiple tubes connected to multiple containers (Figure 2, PD1 to PD5 can be considered second to sixth containers), welding the first and the third tube to form a second sterile fluidical connection between the first container and a third container for transferring a liquid between the first container and the third container via the second sterile fluidical connection (Figure 2, Source bag can transfer a liquid from the Source bag to PD1 to PD5), sealing the second fluidical connection between the connected first and third containers or between the connected second and third containers to disconnect the second sterile fluidical connection (Paragraph 0025, sterilely sealing and disconnecting the branch line of a bag that has been filled, for instance, by heat welding of the tubing), wherein the steps are operated automatically by a controller (Paragraph 0033, The pump motor or mainline valve may be stopped, for instance, by a remote controller that detects the weight of liquid dispensed into the bag set or remaining in the cell source container, Paragraph 0046, The entire apparatus and method of the invention allow filling of sterile bags in a completely closed sterile system, and are also readily adapted to partial or total automation using remote control of pumps, valves and sterile tubing welding).
The modified invention of Rowley does not specifically disclose placing a third tube into the welding mount.
Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination (Paragraph 0104), discloses that the method comprises:
placing a first tube connected to a first container (Paragraph 0006 and 0007, the cavity in the patient can broadly be considered a first container having a first tube) and a third tube connected to a third container (Paragraph 0007, the fluid bags or discharge bags being used the second container, while the tubes and bags of fresh dialysate solution will be considered the third tube connected to a third container, Paragraph 0009, In this way, the tube extending from the peritoneal cavity has to connect to a tube extending from either a drain bag or a bag containing fresh dialysate) into a welding mount and welding the first tube and the third tube to form a second sterile fluidical connection between the first tube and the third tube (Figure 1 shows device 10 will be considered a welding mount that can join or separate tube 50, Figures 2B to 2D show the process of separating and sealing, while Figures 4A to 4H show the process of placing the two ends of tube 50 on the welding mount and weld them together),
(f) welding the first and the third tube to form a second sterile fluidical connection between the first container and the third container; (g) transferring a liquid between the first container and the third container or between the second container and the third container via the second sterile fluidical connection; and (h) sealing the second fluidical connection between the connected first and third containers to disconnect the second sterile fluidical connection (Figures 2B to 2D show the process of separating and sealing).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to Rowley the teachings of Landherr and use the device of Landherr to also form a second sterile fluidical connection between the first container and a third container and for sealing and cutting the second fluidical connection between the first container and the third container to disconnect the second sterile fluidical connection.
Regarding Claim 3:
Rowley discloses that welding the first tube to the second tube comprises welding a fresh portion of a tube of a pre-selected length in-between the first tube and the second tube, thereby connecting the first tube and second tube (Figure 2 shows that instead of a single bag, multiple Final Product Bags can be optionally filled so the Source bag provides product to a manifold starting on a weld seal 1 and, additionally to the second tube to the corresponding Final Product Bag, a spool is required to connect the second tube to the manifold);
Regarding Claim 4:
Rowley discloses that welding the first tube and the second tube, comprises (i) forming two separate sterile connections in the first tube and the second tube, and/or (ii) welding, on one side of an existing weld, a selected length of a tubing, and adding a new weld to the opposite side of the existing weld until the selected length of tubing is used up (Figure 2, using PD1 as example, the First tube will be considered from Source Bag to a not numbered Weld Seal by PD1; the second tube would be from PD1 to the not numbered weld seal, both seals being sterile connections; welding the first tube and the second tube comprise welding on one side of an existing weld formed in the bifurcation of the first tube towards PD1 to PD5 that could be one of the weld seals 1, a spool piece of a selected length, indicated with a numeral 6” in the figure. On each installation and removal of PD1 the added tubing will we welded and cut again reducing the length of the spool piece until eventually after several welds it could be all used up).
Rowley does not specifically disclose forming two separate sterile connections in the first tube and the second tube with a heated welder blade, a laser or a cold blade combined with a heating element, preferably a heated welder blade.
Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination, and forming the sterile connections with a laser (Abstract, paragraph 0131, Figure 4A, laser unit 200).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to Rowley the teachings of Landherr and use a laser to create the sterile connections since its use is a common practice in the art.
Regarding Claim 8:
As discussed for Claim 2 above, the modified invention of Rawley discloses the invention as claimed including that the controller comprises a processor circuit, that cause steps (a)-(d) and/or (e)- (h) to be performed automatically (Paragraph 0033, The pump motor or mainline valve may be stopped, for instance, by a remote controller that detects the weight of liquid dispensed into the bag set or remaining in the cell source container, Paragraph 0046, The entire apparatus and method of the invention allow filling of sterile bags in a completely closed sterile system, and are also readily adapted to partial or total automation using remote control of pumps, valves and sterile tubing welding; automatic controllers usually include some sort of processor circuit).
Rawley also discloses moving the first container or second container to a connection interface (Figure 2, the location where the source bag and PD1 are placed can broadly be considered a connection interface and before starting both bags need to be provided);
Short of any additional limitations, the source bag can be considered that comprises a cell culture medium and the second container comprises cultured cells (Paragraphs 008, 009, 0015, 0146).
Rowley does not specifically disclose if the controller comprises a memory circuit storing instructions.
The use of memory circuits to store information of production, instructions and modes of operation, time of operation is a very common practice in the art; therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to include in the controller a memory circuit storing instructions.
Rowley discloses that the method further comprises sterilely sealing and disconnecting the branch line of a bag that has been filled by heat welding of the tubing (Paragraph 0025), but does not provide details on how the sealing and cutting are made.
Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination (Paragraph 0104), the method comprising sealing a flow path between the first container and the second container by creating, for the first tube and the second tube two separate tubing seals, with a single sealing head (Abstract, Figure 2B shows the tube 50 before sealing and cutting, while 2D shows the process of cutting to obtain the two separate tubes of Figure 2A, each connected to a separate container and sealed at the tube end by laser 200).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to Rowley the teachings of Landherr and use the device of Landherr for sealing a flow path between the first container and the second container by separating the sterile fluidical connection and making two separate tubing seals with a single sealing head.
Regarding Claim 9:
Rowley discloses that transferring a liquid between the first container and the second container comprises slightly rotating a peristaltic pump to create a positive or a negative pressure in one of the first tube or the second tube prior to opening one or more pinch valves to cause the positive or a negative pressure to draw the liquid through the first tube or the second tube (Paragraph 0038, This apparatus may also further comprise a peristaltic pump unit configured to pump liquid from the source container through the flexible tubing into the flexible bags, and advantageously either the pump unit or one or more pinch valves, or both, are remotely operable by a controller, in general the peristaltic pumps, being positive displacement pumps, generate a vacuum in the suction line).
Regarding Claim 12:
Rowley discloses that, short of any additional limitations, the source bag can be considered that comprises a cell culture vessel and the second and third containers (Figure 2, Source bag, PD1 and PD2) are designation bags (Paragraphs 008, 009, 0015, 0146) and a liquid is being transferred from the Source bag to PD1 or PD2.
Rowley, even including the teachings of Landherr does not disclose robotically loading the first, second or third tubes within the welding mount.
As already discussed for Claim 1, the use of robotic arms to automatically perform functions on sterile environments that in other environments are performed manually by a user is a common practice in the art, it is made in general to avoid contamination and can also increase production speed. Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to use a robot for loading a first tube and a second tube into the welding mount since it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art.
Regarding Claim 13:
Rowley discloses a method for sterile automated connection and liquid transfer, comprising:
Providing a first container and a second container and a first sterile fluidical connection between the first container and the second container made by welding the first tube and the second tube (Figure 2, Source bag will be considered the first container connected to a first tube, any one of PD1 to PD5 will be considered the second container and its connected to a second tube; Paragraph 30, Bag sets of the invention also may be assembled by connecting any other flexible bags with main and branch lines comprising suitable lengths of appropriate flexible tubing sterilely welded into the desired manifold arrangement),
transferring a liquid between the first container and the second container via the first sterile fluidical connection (Paragraph 0033; After preventing flow in all branch lines except that of the one bag to be filled according to the invention method, a desired volume cell suspension liquid is dispensed into the open end of the main line, Paragraph 0067, Figure 2, Sterile weld Final Product Bag as shown in FIG. 2; (3) Close valve 1 and open valve 2 to allow evacuation of air from the final product bag and tubing for a predetermined (optimized) time; (4) Close valve 2 and open valve 1 to dispense product specific-volume),
sealing and cutting the first fluidical connection between the first container and the second container to disconnect the first sterile fluidical connection (Paragraph 0025, sterilely sealing and disconnecting the branch line of a bag that has been filled, for instance, by heat welding of the tubing, Paragraph 0067, Sterilely seal and cleave the tubing to each of filled bag which may then be packaged for cryopreservation or cold storage).
wherein the step of welding the first tube and the second tube to form a first sterile fluidical connection between the first container and the second container and the step of sealing the first fluidical connection between the first container and the second container to disconnect the first sterile fluidical connection comprise welding, on one side of an existing weld, a selected length of a tubing, and adding new welds to the added tubing until the selected length of tubing is used up (Figure 2, using PD1 as example, the First tube will be considered from Source Bag to a not numbered Weld Seal by PD1; the second tube would be from PD1 to the not numbered weld seal; welding the first tube and the second tube comprise welding on one side of an existing weld formed in the bifurcation of the first tube towards PD1 to PD5 that could be one of the weld seals 1, a spool piece of a selected length, indicated with a numeral 6” in the figure. On each installation and removal of PD1 the added tubing will we welded and cut again shortening the length of the spool piece until eventually after several welds it could be all used up).
Rowley discloses that first sterile fluidical connection between the first container and the second container is made by welding but does not provide details on how the welding is done or how the sealing and cutting is made.
Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination (Paragraph 0104), the method comprising placing a first tube and a second tube, into a welding mount, wherein the first tube is connected to a first container and the second tube is connected to a second container (Paragraph 0007, the cavity in the patient can broadly be considered a first container and the fluid bags or discharge bags being used the second container), and welding the first tube and the second tube to form a first sterile fluidical connection between the first tube and the second tube (Figure 1 shows device 10 will be considered a welding mount that can join or separate tube 50, Figures 2B to 2D show the process of separating and sealing, while Figures 4A to 4H show the process of placing the two ends of tube 50 on the welding mount and weld them together).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to Rowley the teachings of Landherr and use the device of Landherr to form a first sterile fluidical connection between the first container and the second container and for sealing and cutting the first fluidical connection between the first container and the second container to disconnect the first sterile fluidical connection.
As discussed above, the modified invention of Rowley discloses the invention as claimed, in particular having multiple tubes connected to multiple containers (Figure 2, PD1 to PD5 can be considered second to sixth containers), welding the first and the third tube to form a second sterile fluidical connection between the first container and a third container for transferring a liquid between the first container and the third container via the second sterile fluidical connection (Figure 2, Source bag can transfer a liquid from the Source bag to PD1 to PD5), sealing the second fluidical connection between the connected first and third containers or between the connected second and third containers to disconnect the second sterile fluidical connection (Paragraph 0025, sterilely sealing and disconnecting the branch line of a bag that has been filled, for instance, by heat welding of the tubing), wherein the steps are operated automatically by a controller (Paragraph 0033, The pump motor or mainline valve may be stopped, for instance, by a remote controller that detects the weight of liquid dispensed into the bag set or remaining in the cell source container, Paragraph 0046, The entire apparatus and method of the invention allow filling of sterile bags in a completely closed sterile system, and are also readily adapted to partial or total automation using remote control of pumps, valves and sterile tubing welding).
The modified invention of Rowley does not specifically disclose placing a third tube into the welding mount.
Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination (Paragraph 0104), discloses that the method comprises:
placing a first tube connected to a first container (Paragraph 0006 and 0007, the cavity in the patient can broadly be considered a first container having a first tube) and a third tube connected to a third container (Paragraph 0007, the fluid bags or discharge bags being used the second container, while the tubes and bags of fresh dialysate solution will be considered the third tube connected to a third container, Paragraph 0009, In this way, the tube extending from the peritoneal cavity has to connect to a tube extending from either a drain bag or a bag containing fresh dialysate) into a welding mount and welding the first tube and the third tube to form a second sterile fluidical connection between the first tube and the third tube (Figure 1 shows device 10 will be considered a welding mount that can join or separate tube 50, Figures 2B to 2D show the process of separating and sealing, while Figures 4A to 4H show the process of placing the two ends of tube 50 on the welding mount and weld them together),
(f) welding the first and the third tube to form a second sterile fluidical connection between the first container and the third container; (g) transferring a liquid between the first container and the third container or between the second container and the third container via the second sterile fluidical connection; and (h) sealing the second fluidical connection between the connected first and third containers to disconnect the second sterile fluidical connection (Figures 2B to 2D show the process of separating and sealing).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to Rowley the teachings of Landherr and use the device of Landherr to also form a second sterile fluidical connection between the first container and a third container and for sealing and cutting the second fluidical connection between the first container and the third container to disconnect the second sterile fluidical connection.
Rowley discloses that welding the first tube and the second tube, comprises (i) forming two separate sterile connections in the first tube and the second tube, and/or (ii) welding, on one side of an existing weld, a selected length of a tubing, and adding a new weld to the opposite side of the existing weld until the selected length of tubing is used up (Figure 2, using PD1 as example, the First tube will be considered from Source Bag to a not numbered Weld Seal by PD1; the second tube would be from PD1 to the not numbered weld seal, both seals being sterile connections; welding the first tube and the second tube comprise welding on one side of an existing weld formed in the bifurcation of the first tube towards PD1 to PD5 that could be one of the weld seals 1, a spool piece of a selected length, indicated with a numeral 6” in the figure. On each installation and removal of PD1 the added tubing will we welded and cut again reducing the length of the spool piece until eventually after several welds it could be all used up).
Rowley does not specifically disclose forming two separate sterile connections in the first tube and the second tube with a heated welder blade, a laser or a cold blade combined with a heating element, preferably a heated welder blade.
Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination, and forming the sterile connections with a laser (Abstract, paragraph 0131, Figure 4A, laser unit 200).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to Rowley the teachings of Landherr and use a laser to create the sterile connections since its use is a common practice in the art.
The modified invention of Rowley does not specifically disclose robotically loading a first tube and a second tube into the welding mount, the tubes are actually placed manually by the operator.
The use of robotic arms to automatically perform functions on sterile environments that in other environments are performed manually by a user is a common practice in the art, it is made in general to avoid contamination and can also increase production speed. Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to use a robot for loading a first tube and a second tube into the welding mount since it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art.
If that rejection is argued, both Immerzeel and Procyshyn teach robotic arms on similar automated sterile fluid transfer devices, the robotic arms with capabilities to operate tubes, and in particular tubes on automated filling transfer devices (Immerzeel, Figure 1, robotic arm 415 handle tube 404; and Procyshyn, Figures 5 and 6, Robotic arms 40 and 50 handle tubes 42 and 52).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to use the tube handling capabilities of the robots of Immerzeel and Procyshyn for loading a first tube and a second tube into the welding mount since it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art.
Regarding Claim 15:
Rowley discloses that all of the steps are operated automatically by a controller (Paragraph 0033, The pump motor or mainline valve may be stopped, for instance, by a remote controller that detects the weight of liquid dispensed into the bag set or remaining in the cell source container, Paragraph 0046, The entire apparatus and method of the invention allow filling of sterile bags in a completely closed sterile system, and are also readily adapted to partial or total automation using remote control of pumps, valves and sterile tubing welding).
Regarding Claim 16:
Rowley discloses a device, comprising:
(i) a first tube fluidically coupled to a first container and a second tube fluidically coupled to a second container (Figure 1, the Source bag will be considered the first container, the Final Product bag will be considered the second container, the first tube would be from the Source Bag to the Sterile weld/Seal and the second tube from the Sterile weld/Seal to the Final Product Bag);
(ii) a welding element configured to fluidically couple the first tube with the second tube by welding (Figure 1, Paragraph 0041, typically a pre-sterilized flexible bag which can be aseptically filled by sterilely welding flexible tubing to the container; the Sterile weld/Seal was made by an unspecified welding element);
(iii) a pump configured to transfer a liquid from the first container to the second container (Figure 1, Dispensing Pump); and
(iv) a controller comprising a processor circuit configured to execute the instructions, wherein, upon executing the instructions, the controller causes the welding element to fluidically couple the first tube and the second tube (Paragraph 0046, The entire apparatus and method of the invention allow filling of sterile bags in a completely closed sterile system, and are also readily adapted to partial or total automation using remote control of pumps, valves and sterile tubing welding, according to methods well known in the art of process control and automation).
the device is further configured for use in bioprocessing of cells (Paragraph 0046, the apparatus and method of the invention are used for aseptically dispensing live mammalian cells into sterile, flexible bags, for instance, for cryopreservation in liquid nitrogen).
fluidically couple the first tube and the second tube optionally via a spool piece of a selected length; (Figure 2 shows that instead of a single bag, multiple Final Product Bags can be optionally filled so the Source bag provides product to a manifold starting on a weld seal 1, the manifold can be considered a spool and, and the second tube connects the manifold to the corresponding Final Product Bag, the spool is required to connect the first tube to second tube).
Rowley does not specifically disclose if the controller comprises a memory circuit storing instructions.
The use of memory circuits to store information of production, instructions and modes of operation, time of operation is a very common practice in the art; therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to include in the controller a memory circuit storing instructions.
Rowley discloses that first sterile fluidical connection between the first container and the second container is made by welding but does not provide details on how the welding is done or how the sealing and cutting is made.
Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination (Paragraph 0104), the method comprising placing a first tube and a second tube, into a welding mount, wherein the first tube is connected to a first container and the second tube is connected to a second container (Paragraph 0007, the cavity in the patient can broadly be considered a first container and the fluid bags or discharge bags being used the second container), and welding the first tube and the second tube to form a first sterile fluidical connection between the first tube and the second tube (Figure 1 shows device 10 will be considered a welding mount that can join or separate tube 50, Figures 2B to 2D show the process of separating and sealing, while Figures 4A to 4H show the process of placing the two ends of tube 50 on the welding mount and weld them together).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to Rowley the teachings of Landherr and use the device of Landherr to form a first sterile fluidical connection between the first container and the second container and for sealing and cutting the first fluidical connection between the first container and the second container to disconnect the first sterile fluidical connection.
The modified invention of Rowley does not specifically disclose robotically loading a first tube and a second tube into the welding mount, the tubes are actually placed manually by the operator.
The use of robotic arms to automatically perform functions on sterile environments that in other environments are performed manually by a user is a common practice in the art, it is made in general to avoid contamination and can also increase production speed. Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to use a robot for loading a first tube and a second tube into the welding mount since it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art.
If that rejection is argued, both Immerzeel and Procyshyn teach robotic arms with capabilities to operate tubes, and in particular tubes on automated filling transfer devices (Immerzeel, Figure 1, robotic arm 415 handle tube 404; and Procyshyn, Figures 5 and 6, Robotic arms 40 and 50 handle tubes 42 and 52).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to use the tube handling capabilities of the robots of Immerzeel and Procyshyn for loading a first tube and a second tube into the welding mount since it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art.
Regarding Claim 17:
As discussed above, the modified invention of Rowley discloses the invention as claimed, and in particular that the controller automatically operates the welding, transfer of fluid, sealing and disconnection and that the controller is configured (i) to automatically activate the welding element over the first tube and the second tube; and/or (ii) to automatically seal a flow path between the first container and the second container (Paragraph 0033, The pump motor or mainline valve may be stopped, for instance, by a remote controller that detects the weight of liquid dispensed into the bag set or remaining in the cell source container, Paragraph 0046, The entire apparatus and method of the invention allow filling of sterile bags in a completely closed sterile system, and are also readily adapted to partial or total automation using remote control of pumps, valves and sterile tubing welding).
The modified invention of Rowley does not disclose that the controller also controls the robotic loading of the welding mount.
As already discussed for Claim 16, Immerzeel teach using a robotic arm on similar automated sterile fluid transfer devices, the robotic arms being controlled by the same controller that controls the complete automated sterile fluid transfer device (Immerzeel, Paragraph 0046, Controller 440 controls the whole process on controlled environment enclosure 420).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to the modified invention of Rowley the teachings of Immerzeel and use the same controller that automatically operates the welding, transfer of fluid, sealing and disconnection to control also the robotic loading of the welding mount so the whole operation of the sterile automated transfer system is controlled by a single controlled and avoid any chance of conflicts.
Regarding Claim 18
As discussed for Claim 16 above, the modified invention of Rowley discloses the invention as claimed.
The modified invention of Rowley does not specifically disclose if the welding element comprises clamps and/or holders and a cutting device, preferably a heated welder blade, a laser or a cold blade.
As already discussed for Claim 16, Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination comprising clamps and/or holders (Figure 2A, tube holders 70, 72) to hold and guide the tubing 50 to be cut and separated (Figures 2B to 2D) or to be welded together (Figures 4A to 4F).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to the modified invention of Rowley the teachings of Landherr and include clamps and/or holders to hold and guide the tubing to be cut and separated or to be welded together.
Regarding Claim 19
As discussed for Claim 16 above, the modified invention of Rowley discloses the invention as claimed.
The modified invention of Rowley does not disclose if the device comprises a sealing device combined with the cutting device, wherein the combined cutting and sealing device is a heated welder blade or a laser; configured to seal and cut the flow path.
Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination comprising a sealing device combined with the cutting device, wherein the combined cutting and sealing device is a heated welder blade or a laser; configured to seal and cut the flow path (Figures 2B to 2D, Paragraphs 0158 and 159 cutting and sealing device not numbered for tubing 50, Hammer 110 will be considered the cutting and sealing device, heated by a laser unit 200, cutting the tubing 50, after the hammer 110 is reversed the tubing 50 is pulled apart resulting in two sealed ends) avoiding liquid dripping from the open ends or contamination inside of the disconnected tubing ends.
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to the modified invention of Rowley the teachings of Landherr and include a combined cutting and sealing device including a heated welder blade or a laser configured to seal and cut the flow path so the tubing is cut and sealed on the same operation, avoiding liquid dripping from the open ends or contamination inside of the disconnected tubing ends.
Regarding Claim 20:
As discussed for Claim 16 above, the modified invention of Rowley discloses the invention as claimed, including the use of a spool to connect the first to the second tube (Figure 2, the manifold is required to connect the first and second tube) and that the device is automatically operated (Paragraph 0046, The entire apparatus and method of the invention allow filling of sterile bags in a completely closed sterile system, and are also readily adapted to partial or total automation using remote control of pumps, valves and sterile tubing welding, according to methods well known in the art of process control and automation).
Rowley discloses that first sterile fluidical connection between the first container and the second container is made by welding but does not provide details on how the welding is done or how the sealing and cutting is made.
Landherr teaches a device and method that can fully automate aseptically the process of making and separating sterile fluidical connections between connected or disconnected tubing to limit user touch contamination (Paragraph 0104), the method comprising placing two pieces of tube, into a welding mount, and welding together both tubes to form a first sterile fluidical connection between them (Figure 1 shows device 10 will be considered a welding mount that can join or separate tube 50, Figures 2B to 2D show the process of separating and sealing, while Figures 4A to 4H show the process of placing the two ends of tube 50 on the welding mount and weld them together).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to Rowley the teachings of Landherr and use the device of Landherr to form a sterile fluidical connection between the first tube and one end of the spool and the second tube and the other end of the spool and for sealing and cutting the fluidical connection between the first container and the second container.
Regarding Claim 22:
Rowley discloses that the controller automatically operates the loading of the welding mount, welding, transfer of fluid, sealing and disconnection and that the controller is configured (i) to automatically activate the welding element over the first tube and the second tube; and/or (ii) to automatically seal a flow path between the first container and the second container (Paragraph 0033, The pump motor or mainline valve may be stopped, for instance, by a remote controller that detects the weight of liquid dispensed into the bag set or remaining in the cell source container, Paragraph 0046, The entire apparatus and method of the invention allow filling of sterile bags in a completely closed sterile system, and are also readily adapted to partial or total automation using remote control of pumps, valves and sterile tubing welding).
Claims 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Rowley (US 2011/0287534) in view of Landherr (US 2003/0141009), Immerzeel (US 2016/0346777) and Procyshyn (2009/0223592) as applied to Claims 1 and 8 above, and further in view of Eapen (US 2017/0204361).
Regarding Claim 10:
As discussed for Claim 1 above, the modified invention of Rowley discloses the invention as claimed.
The modified invention of Rowley does not disclose a solution including a nucleic acid or a viral particle.
Eapen teaches a system and process of providing and an aseptic process of creating personalized immunotherapeutic compositions using a similar system of tubings, containers, sterile weld (Paragraph 0114) pumps and valves of Rowley (Figure 51), the method comprises transferring a liquid between a first container and a second container (Paragraphs 109 and 0120, a colony containing a Listeria construct, that comprises a nucleic acid sequence is picked from a plate to inoculate a pre-determined volume of fermentation media, that will be considered a cell culture) for transducing a plurality of cells therein.
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to the modified invention of Rowley the teachings of Eapen and use the device of the modified invention of Rowley to prepare the personalized immunotherapeutic compositions since both require at least two containers, a pump to transfer liquids, tubing and sterile welding.
Regarding Claim 11:
As discussed for Claim 8 above, the modified invention of Rowley discloses the invention as claimed.
The modified invention of Rowley does not disclose if the cell culture comprises immune cells that are T cells.
Eapen teaches a system and process of providing and an aseptic process of creating personalized immunotherapeutic compositions using a similar system of tubings, containers, sterile weld (Paragraph 0114) pumps and valves of Rowley (Figure 51), the cell culture comprises immune cells that are T cells (Paragraph 0050).
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to the modified invention of Rowley the teachings of Eapen and include T-cells in the cell culture if the device of the modified invention of Rowley is being used to manufacture personalized immunotherapeutic compositions as Eapen.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Rowley (US 2011/0287534) in view of Landherr (US 2003/0141009), Immerzeel (US 2016/0346777) and Procyshyn (2009/0223592) as applied to Claim 16 above, and further in view of Wang (CN 209144154).
Regarding Claim 21:
As discussed for Claim 16 above, the modified invention of Rowley discloses the invention as claimed and also an interlock valve configured to avoid back contamination between the first container and the second container; a peristaltic pump between the first tube and the second tube to prevent backflow between the first container and the second container; and/or (iii) an pinch valve between the first tube and the second tube to prevent backflow between the first container and the second container (Figure 2 shows a plurality of valves 1 to 9, Paragraph 0023 some of the valves can be “pinch valves” and the fluid is pumped by a peristaltic pump).
The modified invention of Rowley does not specifically disclose the use of interlocking valves, but note that the claimed “interlocking valves” are configured to avoid back contamination between the first container and the second container, but no structure is disclosed, but the term is used for valves that include an interlock mechanism to prevent incorrect operation so the valves can only be completely open or completely closed.
Wang teaches the use of interlocking valves on a Seed Tank Aseptic Controllable Quantity Type Inoculating Device to provide an aseptic connection between two containers (Figures 1 and 2, interlocking valve 27) to prevent contamination.
Therefore, it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to incorporate to the modified invention of Rowley the teachings of Wang and use interlocking valves to prevent incorrect operation so the valves can only be completely open or completely closed when providing an aseptic connection to avoid contamination.
Response to Arguments
Regarding the Applicants arguments about the rejections under 35 U.S.C. § 112(b) of Claims 1 to 22, the amendments make moot the rejections made in the last action, so the rejections are withdrawn. The amendment of Claim 9 allowed for a proper rejection under 35 U.S.C. 103 as had been indicated as possible in the previous action. The Examiner made new rejections under 35 U.S.C. § 112(b) of Claims 5 to 7.
Regarding the Applicants arguments regarding neither Rowley (US 2011/0287534) or Landherr (US 2003/0141009) not disclosing the "robotically loading” a first tube, a second tube or a third tube into a welding mount, the Examiner agrees that no reference on the record has been found that specifically teach such limitation, but at the same time, as indicated in the office action, the use of robotic arms to automatically perform functions on sterile environments, that in other environments are performed manually by a user, is a common practice in the art. Robotic arms are used to avoid contamination by direct handling and can also increase production speed. Therefore, the Examiner considers that it would have been obvious to a person having ordinary skill in the art to which the claimed invention pertains, before the effective filing date of the claimed invention, to use a robot for loading the tubes into the welding mount since it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art. At the same time the Examiner provides two references, Immerzeel (US 2016/0346777) and Procyshyn (2009/0223592), that teach using robotic arms to manipulate tubing is sterile chambers.
Allowable Subject Matter
Claim 14 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The Claim includes limitations such as mushrooming length, a gripper width, a gap, and a seal width, and welding the selected length of tubing comprises slicing a piece of the third tubing having the first length that are described on Figure 5 and that are taught by references such as Watanabe (US 5554253) or Sano (US 2006/0005371); but also includes limitations regarding the lengths of the tubings such as:
“the selected length of a tubing comprises a multiple of a first length, the first length including a mushrooming length, a gripper width, a gap, and a seal width”,
“determining the selected length of tubing so that a length of the second tubing is equal to a length of the third tubing after completing step (f)”, and
“the method further comprises determining the selected length of tubing in steps (b) and (f) based on a number of a latest cycle and a desired length for a tubing coupled to a container for liquid transfer in the latest cycle”
That are not taught by any reference on the record or there is any motivation to modify any reference to include such limitation.
Claim 6 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Regarding Claim 6: The Examiner interpreted the Claim as representing the device of the embodiments of Figures 3A to 3D. No reference on the record teaches welding simultaneously the first and the second tubes to the spool with a welder single blade.
No prior art rejection has been applied against claims 5 and 7 because they are so indefinite as to make evaluating the claim language and the prior art meaningless. Applicant should not consider the claims to be potentially allowable merely because no prior art rejection has been applied.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. In particular several references could be used to replace Rowley to reject at least the independent claims, such as Schick (US 6712963) or Eapen (US 2017/0204361). Also, Watanabe (US 5554253) and Sano (US 2006/0005371) disclose welding mounts for tubings very relevant to the claims.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EDUARDO R FERRERO whose telephone number is (571)272-9946. The examiner can normally be reached M-F 9:30-7:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, SHELLEY SELF can be reached at 571-272-4524. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EDUARDO R FERRERO/Examiner, Art Unit 3731
/STEPHEN F. GERRITY/Primary Examiner, Art Unit 3731 8 December 2025
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