Ube)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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/11/2026 has been entered.
Amendments of Claims 1, 13 and 16 to 20 are acknowledged.
Cancelation of Claims 5 to 7 is acknowledged.
New Claim 23 is acknowledged.
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 1 to 4, 8 to 12, 17 and 23 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 1 and 17:
Both claims include the limitation “generating a custom schedule to optimize process performance”. The limitation is indefinite because even though it is mentioned in the Specification with exact the same words, there is no explanation of what the optimization entices or how is it accomplished.
Regarding Claim 23:
The Claim includes the limitation “the method further comprising robotically moving the connection weld relative to the first container or the second container”. It is unclear how a connection weld can be moved once it is done.
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 19, 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Rowley (US 2011/0287534) in view of Landherr (US 2003/0141009), Shinohara (WO 2020255929) and Ahlfors (US 2020/0025782).
Regarding Claim 1:
Rowley discloses an automated 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 discloses that the process of filling is a completely automated closed process (Paragraphs 0002, 0006); Rowley discloses in paragraph 0059 that “Each syringe is then separated from the source by severing its attached tubing with a tubing sealer, and that tubing is then sterile welded to the tubing attached to a final product container”; paragraph 0058 “product bag and syringe may be provided with integrally connected pieces of tubing that can be spliced and separated via sterile tubing welding”; but does not specifically disclose providing, by a robotic arm, movements of containers and tubes, comprising robotically loading a first tube and a second tube into a welding mount robotically loading a first tube and a second tube into the welding mount.
Ahlfors teaches an automated system and method for automatic processing executable without handling by a human operator; configured to automatically process the plurality of batches without cross-contamination between batches, e.g., under GMP conditions, that involves filling containers (Paragraph 0173, media fill stations 420, 420’), and is configured for the robotic handling of various types of cell processing containers 314 including trays, flasks, bottles, tubes and vials (Paragraph 0152); while Shinohara teaches using a robotic arm, (container attachment / detachment device 14 may be carried in by an operator or may be carried out automatically. When it is performed automatically, for example, a robot arm or the like is separately arranged) the process involves the use of a welder as part of the attachment / detachment device 14 (BioWelder manufactured by Sartorius Stedim Japan) when operating on a closed chamber on a sterile state.
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 Ahlfors and Shinohara and provide a robotic arm for handling movements of containers and tubes and to separate and weld the tubings, placing the tubes on a welding mount as required for welding and separating when operating on closed sterile environment, without handling by a human operator; configured to automatically execute the plurality of operations without cross-contamination.
Note, several other references will be provided in the in the Conclusions that also teach the use of robotic arms in particular for handling tubes and loading a welding device.
Rowley discloses optimizing the components (Paragraph 0156) but not specifically automatically scheduling the movements by generating a custom schedule to optimize process performance.
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 broadly generate an schedule to optimize process performance since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art; and it would also be obvious to do it automatically 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:
Rawley discloses wherein the first container comprises a cell culture medium and the second and/or third container comprises cultured cells, and wherein the cell culture medium is transferred from the first container to the cultured cells; 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).
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.
Rowley discloses that the process of filling is a completely automated closed process (Paragraphs 0002, 0006), Rowley discloses in paragraph 0059 that “Each syringe is then separated from the source by severing its attached tubing with a tubing sealer, and that tubing is then sterile welded to the tubing attached to a final product container”; paragraph 0058 “product bag and syringe may be provided with integrally connected pieces of tubing that can be spliced and separated via sterile tubing welding”; but does not specifically disclose providing, by a robotic arm, movements of containers and tubes; robotically loading a first tube and a second tube into a welding mount robotically loading a first tube and a second tube into the welding mount.
Ahlfors teaches an automated system and method for automatic processing executable without handling by a human operator; configured to automatically process the plurality of batches without cross-contamination between batches, e.g., under GMP conditions, that involves filling containers (Paragraph 0173, media fill stations 420, 420’), and is configured for the robotic handling of various types of cell processing containers 314 including trays, flasks, bottles, tubes and vials (Paragraph 0152); while Shinohara teaches using a robotic arm, (container attachment / detachment device 14 may be carried in by an operator or may be carried out automatically. When it is performed automatically, for example, a robot arm or the like is separately arranged) the process involves the use of a welder as part of the attachment / detachment device 14 (BioWelder manufactured by Sartorius Stedim Japan) when operating on a closed chamber on a sterile state.
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 Ahlfors and Shinohara and provide a robotic arm for handling movements of containers and tubes and to separate and weld the tubings, placing the tubes on a welding mount as required for welding and separating when operating on closed sterile environment, without handling by a human operator; configured to automatically execute the plurality of operations without cross-contamination.
Note, several other references will be provided in the in the Conclusions that also teach the use of robotic arms in particular for handling tubes and loading a welding device.
Rowley does not disclose if the method comprises automatically determining the selected length for the spool piece.
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 automatically determine the selected length for the spool piece, 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 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.
Rowley discloses that the process of filling is a completely automated closed process (Paragraphs 0002, 0006), Rowley discloses in paragraph 0059 that “Each syringe is then separated from the source by severing its attached tubing with a tubing sealer, and that tubing is then sterile welded to the tubing attached to a final product container”; paragraph 0058 “product bag and syringe may be provided with integrally connected pieces of tubing that can be spliced and separated via sterile tubing welding”; but does not specifically disclose the device comprising a robotic arm configured to move containers and tubes; the welding mount configured to be robotically loaded, by the robotic arm.
Ahlfors teaches an automated system and method for automatic processing executable without handling by a human operator; configured to automatically process the plurality of batches without cross-contamination between batches, e.g., under GMP conditions, that involves filling containers (Paragraph 0173, media fill stations 420, 420’), and is configured for the robotic handling of various types of cell processing containers 314 including trays, flasks, bottles, tubes and vials (Paragraph 0152); while Shinohara teaches using a robotic arm, (container attachment / detachment device 14 may be carried in by an operator or may be carried out automatically. When it is performed automatically, for example, a robot arm or the like is separately arranged) the process involves the use of a welder as part of the attachment / detachment device 14 (BioWelder manufactured by Sartorius Stedim Japan) when operating on a closed chamber on a sterile state.
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 Ahlfors and Shinohara and provide a robotic arm for handling movements of containers and tubes and to separate and weld the tubings, placing the tubes on a welding mount as required for welding and separating when operating on closed sterile environment, without handling by a human operator; configured to automatically execute the plurality of operations without cross-contamination.
Rowley does not disclose the controller to control the robotic arm to move the connection weld relative to the first container or the second container.
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 0025, sterilely sealing and disconnecting the branch line of a bag that has been filled, for instance, by heat welding of the tubing; Paragraph 0035, the invention method provides for sterilely sealing and disconnecting the branch line of a bag that has been filled, typically by sterilely welding closed and cutting the branch line tubing; 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).
Since the modified invention of Rowley requires the use of a robotic arm to affect the welding and handling of tubing and containers, and Rowley discloses that the welding is controlled by a controller, it would be 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 have the same controller operate the robotic arm and do the connection welding in positions relative to the first or the second container since the arms do the manipulation so the welding can be executed.
Regarding Claim 17:
Rowley discloses optimizing the components (Paragraph 0156) but not that the controller is programmed to automatically scheduling the movements by generating a custom schedule to optimize process performance.
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 broadly generate an schedule to optimize process performance since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art; and it would also be obvious to do it automatically 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 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 a cutting device, wherein the welding mount is moveable to move the first tube and the second tube.
As already discussed for Claim 16, Landherr teaches a device 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 cutting device, clamps and/or holders (Figure 2A, tube holders 70, 72) to hold and guide both sides of the tubing 50 to be cut and separated (Figures 2B to 2D) or to be welded together (Figures 4A to 4F), so it can be considered that the mount is movable.
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 make welding mount moveable to move the first tube and the second tube close or apart each other.
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 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).
Regarding Claim 23:
As already discussed for Claim 1, Rowley discloses welding the first tube and the second tube forms a connection weld providing the first sterile fluidical connection between the first container and the second container.
Rowley does not disclose if method further comprising robotically moving the connection weld relative to the first container or the second container.
The Claim was rejected under 112(b) as unclear, and as expressed seems like it just requires moving a connection weld optionally in one direction or the other, both of them apparently resulting in a positive result or solving no stated problem; therefore, it will be considered an obvious matter of design choice.
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), Shinohara (WO 2020255929) and Ahlfors (US 2020/0025782) 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), Shinohara (WO 2020255929) and Ahlfors (US 2020/0025782) 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
Applicant’s arguments with respect to the rejection of the Claims in combination with the references Immerzeel (US 2016/0346777) and Procyshyn (2009/0223592) have been considered but are moot because the references were replaced by Shinohara (WO 2020255929) and Ahlfors (US 20200025782), both teaching specifically the use of robotic arms for moving containers tubes and in particular the arm placing the tubes to be welded. Note that the main reference Rowley (US 2011/0287534) discloses a main controller, attaching and separating tubes by welding and that all the process is automated; the main thing missing from Rowley is the specific mention of a robotic arm, something that is very common in the art and that already Immerzeel (US 2016/0346777) and Procyshyn (2009/0223592) disclose using robotic arms for moving tubings, according to the Applicants arguments they are the “only evidence of record for what those of skill in the art would do if seeking providing an automatic means to replace manual activity from the proposed combination”. The Examiner has to disagree, noting that “broadly” replacing manual activity for automatic is obvious and the Applicant is only broadly claiming a “robotic arm” that is not even really described in the Specification where the use of the claimed robotic arm is only optional; like in Paragraph 0071 that reads:
“It should be appreciated that methods disclosed herein may be performed manually and/or by one or more robotic devices such as robots or robotic arms.”
Regarding Claim 1:
The Claim was amended to include the limitations “providing, by a robotic arm, movements of containers and tubes" as well as "automatically scheduling the movements by generating a custom schedule to optimize process performance." Arguing that no such combination of features is provided by the cited art.
The Examiner disagrees, as indicated above Shinohara (WO 2020255929) and Ahlfors (US 20200025782), both teaching specifically the use of robotic arms for moving containers tubes and in particular the arm placing the tubes to be welded.
Additionally, the limitation “automatically scheduling the movements by generating a custom schedule to optimize process performance” is considered indefinite because even though it is mentioned in the Specification with exact the same words, there is no explanation of what the optimization entices or how is it accomplished; and broadly “automatically” doing an activity that can be done manually is considered obvious.
The same arguments apply to claims 16 and 17, note that the controller of Rowley is already disclosed as controlling the whole process and it would be obvious to have it controlling the arms since already controls the welding and disconnecting.
Regarding Claim 13:
The Claim was amended to include the limitation “wherein the method comprises automatically determining the selected length for the spool piece”. Same as discussed above, 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 20:
The Claim was amended to include the limitation “to simultaneously fluidically couple the first tube with one side of the spool piece and the other side of the spool piece with the second tube by welding”. The limitation is not disclosed by any reference on the record.
Allowable Subject Matter
Claims 14 and 20 are 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 corresponding base claim and any intervening claims.
Regarding Claim 14:
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.
Regarding Claim 20:
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 a spool that is interposed between with a welder single blade.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Same as discussed for the last action, the Examiner considers that Immerzeel (US 2016/0346777) and Procyshyn (2009/0223592) teach manipulating tubing and containers with a robotic arm; Eapen (US 2017/0204361) teaches a device similar to Rowley, including also aseptic welding. could have been used in combination, Watanabe (US 5554253) and Sano (US 2006/0005371) disclose welding mounts for tubings very relevant to the claims; Spencer (US 4610670) (US 5141592) and Shaposka (US 4793880) teach making sterile connections of tubing using robotic arms; while Spencer (US 5141592) teach clamp arms configured for holding tubes.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/EDUARDO R FERRERO/Examiner, Art Unit 3731
/ROBERT F LONG/Primary Examiner, Art Unit 3731
Prosecution Insights