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 .
Election/Restrictions
Claims 15-21,30-37 and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II (claims 30-39), drawn to a method of integrating at least one perfusion device with a stainless steel large scale bioreactor; Species 2 (Figure 8); and Species 3 (, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 22 July 2026.
Applicant’s election without traverse of Species 1 (Figure 6) made up of claims 1-7,9-13,22-26 and 28 in the reply filed on 22 July 2026 is acknowledged.
Claim Interpretation
Claims 1, 6-7, 9, 22, and 26 recite “large scale bioreactor” (claim 1 line 1 and line 2; claim 6 line 4; claim 7 line 4; claim 9 line 1 and line 2; claim 22 line 1 and line 2; claim 26 line 6). “Large” is not an arbitrary indicator and thus must be defined within the specification or the claims. Within the specification “large scale bioreactors” are defined to be “bioreactors with a capacity greater than 2,000 L” (Immediate application specification Para. [0049]).
Additionally, Claim 28 provides bounds to the size of the reactor thus defining the descriptor “large” within the claim set. The examiner will interpret “large scale bioreactor” using the bounds given in claim 28 and in the specification of the immediate application in paragraph [0049], throughout the entirety of the immediate application.
Summarizing the above “large scale bioreactors” are defined in the specification to be “bioreactors with a capacity greater than 2,000 L” (Immediate application specification Para. [0049]). Therefore, “large scale bioreactor” is herein interpreted as bioreactors with a capacity greater than 2,000 L.
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.
Claim 4 is 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.
Claim 4 recites the limitation "reusable ATF assembly" in line 5. In claim 2 of which claim 4 is dependent the perfusion device is stated to be a “single use perfusion device”, however claim 4 offers the alternative of the “single use perfusion device or the reusable ATF assembly”. Due to claim 4’s dependence on claim 2 it is unclear to the examiner whether claim 2 was simply meant to further define and specify the “single use perfusion device” or if it was intended to create a dependency branch which only includes the “single use perfusion device”.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 5, 7, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Bransby (US20200208092A1, Published Jul. 2, 2020) in view of Levinson (US20190136173A1, Published May 9, 2019) and further in view of Donahue (US20120216878A1, Published Aug. 30, 2012).
Regarding claim 1,
Primary reference Bransby discloses a bioreactor system (Bransby; Abstract, Paras. [0012, 0036]) comprising: a bioreactor (Bransby; Abstract, Paras. [0012, 0036, 0045], Figs. 1A & 1B, process vessel (bioreactor, 110)) having at least one valve assembly (Bransby; Paras. [0045, 0047-0048], Figs. 1A & 1B, valves (155, 192, 291, 292, 293)); an aseptic connector assembly (Bransby; Para. [0048], Fig. 1B, outflow channel (230), retentate channel (235); Para. [0039], aseptic connections; In paragraph [0039] it is disclosed that the system contains elements that may be sterilized and the systems contain aseptic connections, therefore the outflow channel and retentate are implied to be aseptic) coupled to the least one valve assembly of the bioreactor (Bransby; Paras. [0045, 0047-0048], Fig. 1B, valves (291, 292, 293)); and a perfusion device (Bransby; Paras. [0038, 0045, 0048], Figs. 1A & 1B, filtration unit (120, 220)) or reusable Alternating Tangential Filtration (ATF) assembly (Bransby; Para. [0045], Fig. 1A, filtration unit (120)) with an autoclaved valve assembly (Bransby; Paras. [0038-0039, 0047-0048], Figs. 1A and 1B, valves (192, 291)) coupled to the aseptic connector assembly (Bransby; Para. [0039, 0045-0048], aseptic connections; Figs. 1A and 1B, permeate channel (140, 240); In paragraph [0039] it is disclosed that the system contains elements that may be sterilized and the systems contain aseptic connections, therefore the permeate channel is implied to be aseptic).
However, Bransby does not disclose wherein the bioreactor is stainless steel; wherein the bioreactor is large scale (the definition of “large scale” defined in the specification of the immediate application in Para. [0049]); an aseptic connector assembly including a triclamp aseptic connector or a hose assembly.
Secondary reference Levinson discloses a perfusion apparatus for use in bioreactor systems which is used for withdrawing fluid cellular medium from a bioreactor at a relatively high flow rate (Levinson; Abstract). The bioreactor disclosed in Levinson is made of stainless steel (Levinson; Para. [0077], reactor formed of suitable material like stainless steel) and can have a volume larger than 2,000 L (the definition of “large scale” defined in the specification of the immediate application in Para. [0049]) (Levinson; Para. [0077], reactor volumes from 100 milliliters to 50,000 liters). Levinson further discloses that the benefit of a bioreactor made of metal is that metal allows bioreactors to be reusable rather than disposable (Levinson; Para. [0036]).
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to substitute the material of the bioreactor of Bransby with stainless steel used to form a bioreactor as taught by Levinson. Bransby and Levinson are directed to bioreactor systems. Levinson discloses that bioreactors made of metal (i.e. stainless steel) are designed to be reused. This involves applying a known technique (stainless steel as a material for a bioreactor) to a similar device to yield predictable results (a reusable stainless steel bioreactor).
Modified Bransby (Bransby in view of Levinson) fails to disclose wherein the bioreactor is large scale (the definition of “large scale” defined in the specification of the immediate application in Para. [0049]); an aseptic connector assembly including a triclamp aseptic connector or a hose assembly.
Levinson discloses a motivation and proof of concept of the scale up to a “large scale” bioreactor (Levinson; Para. [0077], reactor volumes from 100 milliliters to 50,000 liters).
Additionally, it has been held that mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled. MPEP §2144(IV)(A).
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the scale of the bioreactor of modified Bransby to incorporate Levinson’s teachings and motivation of large scale bioreactors to provide: wherein the bioreactor is large scale. Doing so would have a reasonable expectation of allowing for higher throughput and thus more product per collection/sampling within the system.
Modified Bransby (Bransby in view of Levinson) fails to disclose an aseptic connector assembly including a triclamp aseptic connector or a hose assembly.
Primary reference Bransby further discloses the use of steam cleaning (Bransby; Paras. [0038-0039]) as an option for the sterilization of the process system disclosed (cited above).
Secondary reference Donahue discloses a valve system for the control of fluid flows (including steam) within a bioreactor or bioactive environment (Donahue; Abstract, Para. [0002]) for the use of steam-in-place sterilization of a process system and its conduits and valves (Donahue; Abstract, Paras. [0003]).
Donahue further discloses a triclamp aseptic connector (Donahue; Paras. [0080, 0100-0102], Figs. 15-16, tri-clamp fittings (372, 374, 400), tri-clamp (376)) and a hose assembly (Donahue; Para. [0100], Fig. 15, flexible tubing (360)) as aseptic connectors for use in the steam-in-place sterilization process present in the bioreactor system (Donahue; Abstract, Para. [0002-0006]).
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the aseptic connections of Bransby by using triclamp or hose connectors as taught by Donahue. Both Bransby and Donahue are directed to bioreactor systems transporting liquid components and steam. Donahue discloses that aseptic connections using a triclamp or hose allows for steam-in-place sterilization of the process system (Donahue; Para. [0002-0006]). This involves applying a known technique (triclamp and hose aseptic connections used for transport in a bioreactor system) to a similar device (aseptic connections in a bioreactor system) to yield predictable results (a bioreactor system that has triclamp and hose aseptic connections for liquid and steam transport allowing for steam-in-place sterilization of the process system).
Regarding claim 2, Modified Bransby (Bransby in view of Levinson and Donahue) discloses all of the elements of the current invention as stated with respect to claim 1.
Primary reference Bransby further discloses a single use perfusion device (Bransby; Para. [0009, 0038]), the single use perfusion device further comprising at least one pressure sensor (Bransby; Paras. [0046-0048], Figs. 1A & 1B, sensors (181, 182, 183)), and the bioreactor system further comprises a control system coupled to the single use perfusion device (Bransby; Paras. [0046-0048], Figs. 1A & 1B, controller (180)) for monitoring pressure of the single use perfusion device via the at least one pressure sensor (Bransby; Para. [0046], controller (180), sensors (184, 185)).
Regarding claim 3, Modified Bransby (Bransby in view of Levinson and Donahue) discloses all of the elements of the current invention as stated with respect to claim 1.
Primary reference Bransby further discloses a single use perfusion device (Bransby; Para. [0009, 0038]) or reusable ATF assembly (Bransby; Para. [0045], Fig. 1A, filtration unit (120)) further comprising at least one pressure sensor (Bransby; Paras. [0046-0048], Figs. 1A & 1B, sensors (181, 182, 183)), and the bioreactor system further comprises a control system (Bransby; Paras. [0046-0048], Figs. 1A & 1B, controller (180)) coupled to the single use perfusion device or the reusable ATF assembly (Bransby; Paras. [0046-0048], Figs. 1A & 1B, controller (180)) for monitoring pressure of the single use perfusion device or the reusable ATF assembly via the at least one pressure sensor (Bransby; Para. [0046], controller (180), sensors (184, 185)).
Regarding claim 5, Modified Bransby (Bransby in view of Donahue and Levinson) discloses all of the elements of the current invention as stated with respect to claim 1.
Primary reference Bransby further discloses wherein the bioreactor has a body with a side having a top end (Bioreactors are structurally known to have a body, side, and top end by the nature of their being a bioreactor. See annotated figure 1B of Bransby below dotted lines and arrows surrounding the process vessel (110).)
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Modified Bransby does not disclose wherein one or more of the at least one valve assembly of the bioreactor and the autoclaved valve assembly is coupled to the side of the bioreactor near the top portion of the bioreactor.
However, it has been held that a mere rearrangement of elements without modification of the operation of the device involves only routine skill in the art. MPEP §2144.04 (VI)(C). The rearrangement in this case does not modify the operation of the device because one of the at least one autoclaved valve assemblies being coupled to the side of the bioreactor near the top does not affect whether or not the bioreactor system is able to successfully function as intended because an autoclaved valve assembly not connected to anything other than the reactor would not affect the bioreactors’ intended function. The benefits of this modification include being able to take a manual sample of the upper portion of the reaction volume for testing.
Regarding claim 7, Modified Bransby (Bransby in view of Donahue and Levinson) discloses all of the elements of the current invention as stated with respect to claim 1.
Modified Bransby does not disclose wherein the aseptic connector assembly is one of: (1) an aseptic connector valve assembly having a triclamp aseptic connector, enabling a new perfusion device or ATF assembly to be coupled to the stainless steel large scale bioreactor while the bioreactor is running a cell culture by repeating a steam-in-place of the aseptic connector assembly; or (2) a hose assembly, the hose assembly coupling the at least one valve assembly of the bioreactor to the perfusion device or ATF assembly, wherein the hose assembly comprises a hose body having a first end and a second end. the first end operatively coupled to the at least one valve assembly and the second end operatively coupled to the perfusion device or ATF assembly.
However, It would have been obvious to one of ordinary skill in the art before the effective filing date to add an additional perfusion device connected by using a triclamp aseptic connecter (The connection of the second perfusion device follows the same requirements as the connection of the initial perfusion device as previously stated with respect to claim 1 when establishing Modified Bransby of claim 1), since it has been held that mere duplication of the essential working parts of a device involves only routine skill in the art. MPEP 2144.04(VI)(B).
Regarding claim 28, Modified Bransby (Bransby in view of Donahue and Levinson) discloses all of the elements of the current invention as stated with respect to claim 1.
Modified Bransby further discloses wherein the stainless steel large scale bioreactor has one of: (1) a volume of greater than 2,000 L (Levinson; Para. [0077]); or (2) a volume in the range of greater than 2,000 L to 20,000 L (Levinson; Para. [0077]).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Modified Bransby (Bransby (US20200208092A1, Published Jul. 2, 2020) in view of Levinson (US20190136173A1 Published May 9, 2019) and Donahue (US20120216878A1, Published Aug. 30, 2012)) as applied to claim 2 above, and further in view of Maggoire (US20160298810A1, Published Oct. 13, 2016).
Regarding claim 4, Modified Bransby (Bransby in view of Levinson and Donahue) discloses all of the elements of the current invention as stated with respect to claim 2.
Modified Bransby further discloses a control system configured to automatically reduce a flow rate (Bransby; Para. [0047-0048]; It is said the internal control structure of the control system disclosed allows for the regulation of the fluid flow rates within the system) in the single use perfusion device (Bransby; Paras. [0038, 0045, 0048], Figs. 1A & 1B, filtration unit (120, 220)) or the reusable ATF assembly.
However, modified Bransby does not disclose: wherein the control system configured to automatically reduce one or more of a flow rate or a pressure in the single use perfusion device or the reusable ATF assembly in response to detection of the pressure greater than the safe pressure limit and wherein the control system further comprises an alarm, the alarm configured to be activated when the control system detects a pressure greater than a safe pressure limit.
Secondary reference Maggoire discloses a single-use reactor container containing an over pressurization relief device system (Maggoire; Abstract).
Maggoire further discloses a control system (The relief valve/over-pressurization relief device) (Maggoire; Paras. [0029-0032], the over-pressurization relief device (120) will allow air our or allow for depressurization of the enclosure (100)) is configured to automatically reduce one or more of a flow rate or a pressure Maggoire; Paras. [0029-0032], the over-pressurization relief device (120) will allow air out/allow for depressurization of the enclosure (100)) in the bioreactor enclosure in response to detection of the pressure greater than the safe pressure limit (Maggoire; Para. [0031-0035], the pressure is set to be below that of the burst pressure of the enclosure/reaction area) and, wherein the control system further comprises an alarm (Maggoire; Paras. [0042, 0056, 0065-0066], Fig. 1, over-pressurization relief device (120)), the alarm configured to be activated when the control system detects a pressure greater than a safe pressure limit (Maggoire; Paras. [0040-0041]). Additionally, Maggoire discloses that the over-pressurization relief device is implemented in order to avoid the burst pressure of the bioreactor vessel and components within the system (Maggoire; Abstract, Paras. [0031-0035])
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the control system of modified Bransby to incorporate Maggoire’s over-pressurization relief system which involves setting a safe pressure limit based on the burst pressure of the apparatus of interest and an alarm activated when the pressure limit is exceeded in order to provide: wherein the control system configured to automatically reduce one or more of a flow rate or a pressure in the single use perfusion device or the reusable ATF assembly in response to detection of the pressure greater than the safe pressure limit and wherein the control system further comprises an alarm, the alarm configured to be activated when the control system detects a pressure greater than a safe pressure limit. Doing so would have a reasonable expectation of providing security in the continual use of the process vessels or perfusion devices of importance to the system. Both Bransby and Maggoire are directed to pressurized bioreactor systems. Maggoire discloses that the pressure limit alarm and control system allows for the avoidance of structural failure of the bioreactor components due to over-pressurization. This involves applying a known technique (burst pressure alarms for a bioreactor system) to a similar device (pressure control system of a bioreactor) to yield predictable results (the avoidance of structural failure of the bioreactor system due to the pressure exceeding burst pressure of the components).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Modified Bransby (Bransby (US20200208092A1, Published Jul. 2, 2020) in view of Levinson (US20190136173A1 Published May 9, 2019) and Donahue (US20120216878A1, Published Aug. 30, 2012)) as applied to claim 1 above, and further in view of Kleppen (US20170101612A1, Published Apr. 13, 2017).
Regarding claim 6, Modified Bransby (Bransby in view of Levinson and Donahue ) discloses all of the elements of the current invention as stated with respect to claim 1.
Primary reference Bransby discloses a bioreactor having a body and a bottom portion (Bransby; Bioreactors are structurally known to have a body, side, and top end by the nature of their being a bioreactor. See annotated figure 1B of Bransby above with respect to claim 5; see the dotted lines and arrows surrounding the process vessel (110)), wherein the bioreactor is configured to be at least partially disposed in a pit (A bioreactor has the ability to be disposed within a pit. Since the pit itself is not being claimed as a component of the bioreactor system this limitation is considered to be intended use. MPEP 2114(II)).
Modified Bransby does not disclose one or more of the at least one valve assembly of the stainless steel large scale bioreactor and the autoclaved valve assembly is coupled against a bottom weld seam of the bottom portion of the bioreactor. Specifically, modified Bransby does not disclose the presence of a bottom weld seam, nor does it disclose the autoclaved valve assembly couple against said seam.
Secondary reference Kleppen discloses a bioreactor assembled via welding (Kleppen; Para. [0031, 0157]), and that a welding assembly method makes for a more cost-effective reactor due to the speed and affordability of welding (Kleppen; Para. [0031]).
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the bioreactor assembly method of Bransby by using welding as taught by Kleppen to provide: wherein the bioreactor has a bottom weld seam. Both Bransby and Kleppen are directed to bioreactor systems. Kleppen discloses the welding is a fast and cost-effective way of manufacturing reactors. This involves applying a known technique (welding to manufacture a bioreactor) to a similar device (a bioreactor) to yield predictable results (fast and affordably manufactured bioreactor).
Newly modified Bransby (Modified Bransby in view of Kleppen) does not disclose wherein the autoclaved valve assembly is coupled against the bottom weld seam of the bioreactor.
However, it has been held that a mere rearrangement of element without modification of the operation of the device involves only routine skill in the art. MPEP §2144.04 (VI)(C). The rearrangement in this case does not modify the operation of the device because since the bioreactor device is assumed to have equal distribution of all cellular and media components the placement of an autoclaved valve assembly does not affect the operation of the device. The benefits of moving the autoclaved valve assembly against the bottom weld seam of the reactor assembly include the autoclave valve assembly of the large scale bioreactor being at a height that would require less structural or additional aids for maintenance or manual human interaction with the autoclaved valve assembly to occur.
Claims 9-11 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bransby (US20200208092A1, Published Jul. 2, 2020) in view of Levinson (US20190136173A1, Published May 9, 2019).
Regarding claim 9, Bransby discloses a large scale bioreactor system (Bransby; Abstract, Paras. [0012, 0036]) comprising: a bioreactor (Bransby; Abstract, Paras. [0012, 0036, 0045], Figs. 1A & 1B, process vessel (bioreactor, 110)) having a side (Bransby; Bioreactors are structurally known to have a body, side, and top end by the nature of their being a bioreactor. See annotated figure 1B of Bransby above with respect to claim 5; see the dotted lines and arrows surrounding the process vessel (110)); an autoclaved valve assembly (Bransby; Paras. [0045, 0047-0048], Figs. 1A & 1B, valves (155, 192, 291, 292, 293), filtration unit (120)) coupled to the bioreactor; at least one aseptic connector (Bransby; Para. [0039], aseptic connections; Para. [0048], Fig. 1B, outflow channel (230), retentate channel (235); In paragraph [0039] it is disclosed that the system contains elements that may be sterilized and the systems contain aseptic connections, therefore the outflow channel and retentate are implied to be aseptic.) coupled to the autoclaved valve assembly (Para. [0039], In paragraph [0039] it is disclosed that the system contains elements that may be sterilized using an autoclave or steam sterilization); and an irradiated single use perfusion device (Bransby; Paras. [0038-0039], gamma irradiation used to sterilize the perfusion device; Any component can be single use if it is used one time. Single usability is an intended use limitation. See MPEP 2114(II)) coupled to the at least one aseptic connector (Bransby; Paras. [0039, 0045], aseptic connections; Fig. 1A, filtration unit (120); “These reusable systems (perfusion systems) may further contain aseptic connection to a process vessel” (Para. [0039,] lines 2-3).
Bransby does not teach a stainless steel large scale bioreactor or an autoclaved valve assembly coupled to the side of the bioreactor.
Secondary reference Levinson discloses a perfusion apparatus for use in bioreactor systems which is used for withdrawing fluid cellular medium from a bioreactor at a relatively high flow rate (Levinson; Abstract). The bioreactor disclosed in Levinson is made of stainless steel (Levinson; Para. [0077], reactor formed of suitable material like stainless steel) and can have a volume larger than 2,000 L (the definition of “large scale” defined in the specification of the immediate application in Para. [0049]) (Levinson; Para. [0077], reactor volumes from 100 milliliters to 50,000 liters). Levinson further discloses that the benefit of a bioreactor made of metal is that metal allows bioreactors to be reusable rather than disposable (Levinson; Para. [0036]).
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to substitute the material of the bioreactor of Bransby with stainless steel used to form a bioreactor as taught by Levinson. Bransby and Levinson are directed to bioreactor systems. Levinson discloses that bioreactors made of metal (i.e. stainless steel) are designed to be reused. This involves applying a known technique (stainless steel as a material for a bioreactor) to a similar device to yield predictable results (a reusable stainless steel bioreactor).
Modified Bransby (Bransby in view of Levinson) fails to disclose wherein the bioreactor is large scale (the definition of “large scale” defined in the specification of the immediate application in Para. [0049]); an aseptic connector assembly including a triclamp aseptic connector or a hose assembly.
Levinson discloses a motivation and proof of concept of the scale up to a “large scale” bioreactor (Levinson; Para. [0077], reactor volumes from 100 milliliters to 50,000 liters).
Additionally, it has been held that mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled. MPEP §2144(IV)(A).
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the scale of the bioreactor of modified Bransby to incorporate Levinson’s teachings and motivation of large scale bioreactors to provide: wherein the bioreactor is large scale. Doing so would have a reasonable expectation of allowing for higher throughput and thus more product per collection/sampling within the system.
Modified Bransby does not teach an autoclaved valve assembly coupled to the side of the bioreactor.
However, it has been held that a mere rearrangement of elements without modification of the operation of the device involves only routine skill in the art. MPEP §2144.04 (VI)(C). The rearrangement in this case does not modify the operation of the device because where the device is coupled to the bioreactor does not change the function of the perfusion device since it can be assumed that the bioreactor has an even distribution of reaction component, thus the position in of the autoclaved valve assembly and as a result where the perfusion device is placed should not affect the overall function of the device and bioreactor system. The benefits of this modification include allowing for a straight input into the perfusion device to ensure a consistent flow into the perfusion device.
Regarding claim 10, Bransby in view of Levinson discloses all of the elements of the current invention as stated with respect to claim 9.
Primary reference Bransby further discloses an autoclaved valve assembly (Bransby; Paras. [0045, 0047-0048], Figs. 1A & 1B, valves (155, 192, 291, 292, 293), filtration unit (120)) configured to be coupled at least one aseptic connector (Bransby; Para. [0039], aseptic connections; Para. [0048], Fig. 1B, outflow channel (230), retentate channel (235); In paragraph [0039] it is disclosed that the system contains elements that may be sterilized and the systems contain aseptic connections, therefore the outflow channel and retentate are implied to be aseptic).
Bransby does not disclose a second autoclaved valve assembly configured to be coupled to the side of the bioreactor adjacent to the first valve assembly, and at least one aseptic connector configured to be coupled to the second autoclaved valve assembly.
However, Bransby discloses the claimed invention except for the second autoclaved valve assembly coupled to the side of the bioreactor and coupled to an aseptic connector. It would have been obvious to one of ordinary skill in the art before the effective filing date to include a second of the coupled autoclaved valve assembly and aseptic connector as previously mentioned with respect to claim 9, since it has been held that mere duplication of the essential working parts of a device involves only routine skill in the art. MPEP 2144.04(VI)(B).
Modified Bransby does not disclose wherein the second autoclaved valve assembly coupled to at least one aseptic connecter is configured to be coupled to the side of the bioreactor.
However, it has been held that a mere rearrangement of elements without modification of the operation of the device involves only routine skill in the art. MPEP §2144.04 (VI)(C). The rearrangement in this case does not modify the operation of the device because the positioning of an autoclaved valve assembly has no effect on the operation of the bioreactor as a whole. The benefits of this modification include having a larger surface area for the assembly to be set and at a more manageable height to be manually accessed.
Regarding claim 11, Bransby in view of Levinson discloses all of the elements of the current invention as stated with respect to claim 9.
Primary reference Bransby discloses wherein the irradiated single use perfusion device (Bransby; Paras. [0038-0039], gamma irradiation used to sterilize the perfusion device; Any component can be single use if it is used one time. Single usability is an intended use limitation. See MPEP 2114(II)) further comprises at least one pressure sensor (Bransby; Paras. [0046-0048], Figs. 1A & 1B, sensors (181, 182, 183)), and the bioreactor system further comprises a control system coupled to the irradiated single use perfusion device for monitoring pressure of the single use perfusion device via the at least one pressure sensor (Bransby; Paras. [0046-0048], Figs. 1A & 1B, controller (180)).
Regarding claim 13, modified Bransby (Bransby in view of Levinson) discloses all of the elements of the current invention as stated with respect to claim 9.
Modified Bransby discloses wherein the bioreactor has a body with a side having a top end (Bransby; Bioreactors are structurally known to have a body, side, and top end by the nature of their being a bioreactor. See annotated figure 1B of Bransby above with respect to claim 5; see the dotted lines and arrows surrounding the process vessel (110)), wherein the autoclaved valve assembly is coupled to the side of the bioreactor near the top end of the bioreactor (See claim 9; The recitation of “near” is relative without the use of a reference for distance or as to what is defined to be “near”).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Bransby (US20200208092A1, Published Jul. 2, 2020) in view of Levinson (US20190136173A1, Published May 9, 2019) as applied to claim 11 above, and further in view of Maggoire (US20160298810A1, Published Oct. 13, 2016).
Regarding claim 12, Bransby in view of Levinson discloses all of the elements of the current invention as stated with respect to claim 11.
Modified Bransby (Bransby in view of Levinson) discloses a control system configured to automatically reduce a flow rate (Bransby; Para. [0047-0048]; It is said the internal control structure of the control system disclosed allows for the regulation of the fluid flows) in the single use perfusion device (Bransby; Paras. [0038, 0045, 0048], Figs. 1A & 1B, filtration unit (120, 220)) or the reusable ATF assembly.
However, modified Bransby does not disclose wherein the control system configured to automatically reduce one or more of a flow rate or a pressure in the single use perfusion device or the reusable ATF assembly in response to detection of the pressure greater than the safe pressure limit and wherein the control system further comprises an alarm, the alarm configured to be activated when the control system detects a pressure greater than a safe pressure limit.
Secondary reference Maggoire discloses a single-use reactor container containing an over pressurization relief device system (Maggoire; Abstract).
Maggoire further discloses a control system (The relief valve/over-pressurization relief device) (Maggoire; Paras. [0029-0032], the over-pressurization relief device (120) will allow air our or allow for depressurization of the enclosure (100)) is configured to automatically reduce one or more of a flow rate or a pressure Maggoire; Paras. [0029-0032], the over-pressurization relief device (120) will allow air our or allow for depressurization of the enclosure (100)) in the bioreactor enclosure in response to detection of the pressure greater than the safe pressure limit (Maggoire; Para. [0031-0035], the pressure is set to be below that of the burst pressure of the enclosure/reaction area) and, wherein the control system further comprises an alarm (Maggoire; Paras. [0042, 0056, 0065-0066], Fig. 1, over-pressurization relief device (120)), the alarm configured to be activated when the control system detects a pressure greater than a safe pressure limit (Maggoire; Paras. [0040-0041]). Additionally, Maggoire discloses that the over-pressurization relief device is implemented in order to avoid the burst pressure of the bioreactor vessel and components within the system (Maggoire; Abstract, Paras. [0031-0035])
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the control system of modified to incorporate Maggoire’s over-pressurization relief system which involves setting a safe pressure limit based on the burst pressure of the apparatus of interest and an alarm activated when the pressure limit is exceeded in order to provide security in the continual use of the process vessels or perfusion devices of importance to the system. Both Bransby and Maggoire are directed to pressurized bioreactor systems. Maggoire discloses that the pressure limit alarm and control system allows for the avoidance of structural failure of the bioreactor components due to over-pressurization. This involves applying a known technique (burst pressure alarms for a bioreactor system) to a similar device (pressure control system of a bioreactor) to yield predictable results (the avoidance of structural failure of the bioreactor system due to the pressure exceeding burst pressure of the components).
Claims 22-23 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Bransby (US20200208092A1, Published Jul. 2, 2020) in view of Levinson (US20190136173A1, Published May 9, 2019) and Linz (US20250250526A1, Priority date of Apr. 12, 2022).
Regarding claim 22,
Primary reference Bransby discloses a bioreactor system comprising: a bioreactor (Bransby; Abstract, Paras. [0012, 0036, 0045], Figs. 1A & 1B, process vessel (bioreactor, 110)) and a feed container at a working level of the bioreactor (Bransby; ) and a feed container coupled to the bioreactor system (Bransby; Para. [0045], Figs. 1A & 1B, diafiltration fluid vessel (150); outflows of vessel pass through flow control (155) into the diafiltration fluid channel (160) and into the process vessel (110)).
Bransby does not disclose a stainless steel large scale bioreactor; at least one stainless steel transfer panel having a plurality of inputs coupled to the bioreactor; and a plurality of feed containers coupled to the at least one stainless steel transfer panel at a working level of the bioreactor.
Secondary reference Levinson discloses a stainless steel large scale bioreactor (Levinson; Para. [0077], reactor formed of suitable material like stainless steel, reactor volumes from 100 milliliters to 50,000 liters); and that metal bioreactors are typically designed to be reused (Levinson; Para. [0036]).
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to substitute the material of the bioreactor of Bransby with stainless steel used to form a bioreactor as taught by Levinson. Bransby and Levinson are directed to bioreactor systems. Levinson discloses that bioreactors made of metal (i.e. stainless steel) are designed to be reused. This involves applying a known technique (stainless steel as a material for a bioreactor) to a similar device to yield predictable results (a reusable stainless steel bioreactor).
Modified Bransby (Bransby in view of Levinson) fails to disclose wherein the bioreactor is large scale (the definition of “large scale” defined in the specification of the immediate application in Para. [0049]); at least one stainless steel transfer panel having a plurality of inputs coupled to the bioreactor.
Levinson discloses a motivation and proof of concept of the scale up to a “large scale” bioreactor (Levinson; Para. [0077], reactor volumes from 100 milliliters to 50,000 liters).
Additionally, it has been held that mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled. MPEP §2144(IV)(A).
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the scale of the bioreactor of modified Bransby to incorporate Levinson’s teachings and motivation of large scale bioreactors to provide: wherein the bioreactor is large scale. Doing so would have a reasonable expectation of allowing for higher throughput and thus more product per collection/sampling within the system. Modified Bransby does not disclose at least one stainless steel transfer panel having a plurality of inputs coupled to the bioreactor.
Secondary reference Linz discloses a multiport device (Linz; Abstract, Para. [0015]) for use in a bioreactor utilizing a perfusion device (Linz; Para. [0011]) for an upstream process of cell culture (Linz; Abstract, Paras. [0001-0003])
Linz further discloses at least one stainless steel transfer panel (Linz; Para. [0044], multiport device (32, 42,)) having a plurality of inputs (Linz; Para. [0044, 0056-0057], multiport device (32, 42)) coupled to the bioreactor.
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the input system of the bioreactor of Bransby by adding the stainless steel multiport device as taught by Linz. Both Bransby and Linz are directed to bioreactor systems. Linz discloses that the benefit of the multiport device is that it allows for a large variety of inputs and outputs (Linz; Paras. [0044, 0056-0057]). This involves applying a known technique (a device to allow for multiple inputs and output into a bioreactor) to a similar device (a bioreactor with an input and output) to yield predictable results (bioreactor that can utilize a variety of inputs and outputs) (This modification would allow the diafiltration fluid vessel (150) of Bransby to be connected to the multiport device (Linz) allowing for feed into the process vessel (110) of Bransby).
Bransby in view of Levinson and Linz discloses the claimed invention except for a plurality of feed containers. It would have been obvious to one of ordinary skill in the art before the effective filing date to include a plurality of feed containers connected to a multiport device to allow for input into the bioreactor, since it has been held that mere duplication of the essential working parts of a device involves only routine skill in the art. MPEP 2144.04(VI)(B).
Regarding claim 23, Bransby in view of Levinson and Linz discloses all of the elements of the current invention as stated with respect to claim 22.
Bransby in view of Levinson and Linz does not disclose wherein the at least one stainless steel transfer panel is a first stainless steel transfer panel, and wherein the bioreactor system further comprises one or more additional stainless steel transfer panels, each of which is configured to be coupled to additional, multiple feed containers.
Bransby in view of Levinson and Linz discloses the claimed invention except for wherein the bioreactor system further comprises one or more additional stainless steel transfer panels. It would have been obvious to one of ordinary skill in the art before the effective filing date to include multiple multiport devices each with multiple feed containers as previously stated with respect to claim 22, since it has been held that mere duplication of the essential working parts of a device involves only routine skill in the art. MPEP 2144.04(VI)(B).
Regarding claim 26, Bransby in view of Levinson and Linz discloses all of the elements of the current invention as stated with respect to claim 22.
Bransby in view of Levinson and Linz discloses a bioreactor that has a body with a side having a top end (Bransby; Bioreactors are structurally known to have a body, side, and top end by the nature of their being a bioreactor. See annotated figure 1B of Bransby above with respect to claim 5; see the dotted lines and arrows surrounding the process vessel (110)).
Bransby in view of Levinson and Linz does not teach at least one valve assembly that is coupled to the side of the bioreactor near the top end of the bioreactor.
However, it has been held that a mere rearrangement of elements without modification of the operation of the device involves only routine skill in the art. MPEP §2144.04 (VI)(C). The rearrangement in this case does not modify the operation of the device because where the device is coupled to the bioreactor does not change the function of the perfusion device since it can be assumed that the bioreactor has an even distribution of reaction component, thus the position in of the autoclaved valve assembly and as a result where the perfusion device is placed should not affect the overall function of the device and bioreactor system. The benefits of this modification include allowing for a straight input into the perfusion device to ensure a consistent flow into the perfusion device.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Bransby (US20200208092A1, Published Jul. 2, 2020) in view of Levinson (US20190136173A1, Published May 9, 2019) and Linz (US20250250526A1, Priority date of Apr. 12, 2022) as applied to claim 22 above, and further in view of Gaddum (US20220250095A1, Published Aug. 11, 2022).
Regarding claim 24, Bransby in view of Levinson and Linz discloses all of the elements of the current invention as stated with respect to claim 22.
Bransby in view of Levinson and Linz discloses wherein the plurality of feed containers (See claim 22 above), and, wherein the at least one feed container is at least one single use feed container (Intended use limitation. See MPEP 2114(II). Anything can be used a single time).
Bransby in view of Levinson and Linz does not disclose wherein the plurality of feed containers further comprises at least one pressure sensor, and the bioreactor system further comprises a control system for monitoring pressure of at least one feed container of the plurality of single use feed containers via the at least one pressure sensor.
Secondary reference Gaddum discloses a cellular separation system (Gaddum; Abstract) for use in cell culture workflows (Gaddum; Paras. [0001-0003]) and that the pressure sensor control system allows for consistency of flowrates within the system (Gaddum; [0033-0034])
Gaddum further discloses wherein the plurality of feed containers further comprises at least one pressure sensor (Gaddum; Para. [0083]), and the bioreactor system further comprises a control system for monitoring pressure of at least one feed container (Gaddum; Paras. [0033-0035, 0041, 0105, 0107], feed vessel (150, 250, 350, 450, 550, 650, 750)) of the plurality of single use feed containers via the at least one pressure sensor.
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the feed containers and pressure sensing control system of Bransby by adding a pressure sensor to one of the feed containers to monitor the pressure within the feed container as taught by Gaddum to provide: wherein the plurality of feed containers further comprises at least one pressure sensor, and the bioreactor system further comprises a control system for monitoring pressure of at least one feed container of the plurality of single use feed containers via the at least one pressure sensor. Doing so would allow for consistent and constant flow rates into the bioreactor. Both Bransby and Gaddum are directed to pressure regulation components and controls within a bioreactor system. This involves applying a known technique (pressure regulation of the feed containers) to a similar device (a bioreactor system with feed containers and pressure regulation for the reactor volume) to yield predictable results (pressure regulation within the feed containers of the bioreactor system allowing for consistent feed flowrates to the bioreactor).
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Bransby (US20200208092A1, Published Jul. 2, 2020) in view of Levinson (US20190136173A1, Published May 9, 2019), Linz (US20250250526A1, Priority date of Apr. 12, 2022), and Gaddum (US20220250095A1, Published Aug. 11, 2022) as applied to claim 24 above, and further in view of Maggoire (US20160298810A1, Published Oct. 13, 2016).
Regarding claim 25, Bransby in view of Levinson, Linz, and Gaddum discloses all of the elements of the current invention as stated with respect to claim 25.
Bransby discloses, as previously mentioned in claims a bioreactor comprising at least one pressure sensor (Bransby; Paras. [0046-0048], Figs. 1A & 1B, sensors (181, 182, 183)), and the bioreactor system further comprises a control system (Bransby; Paras. [0046-0048], Figs. 1A & 1B, controller (180)) coupled to the single use perfusion device or the reusable ATF assembly (Bransby; Paras. [0046-0048], Figs. 1A & 1B, controller (180)) for monitoring pressure of the single use perfusion device or the reusable ATF assembly via the at least one pressure sensor (Bransby; Para. [0046], controller (180), sensors (184, 185)).
However, Bransby in view of Levinson, Linz, and Gaddum does not disclose wherein the control system further comprises an alarm, the alarm configured to be activated when the control system detects a pressure greater than a safe pressure limit, the control system configured to automatically reduce one or more of a flow rate or a pressure in the at least one single use feed container of the plurality of single use feed containers in response to detection of the pressure greater than the safe pressure limit.
Gaddum discloses a control system configured to automatically reduce one or more of a flow rate or a pressure (Gaddum; Paras. [0033-0035, 0041, 0105, 0107], feed vessel (150, 250, 350, 450, 550, 650, 750)) in the at least one single use feed container of the plurality of single use feed containers in response to detection of the pressure greater than the safe pressure limit (Intended use limitation. See MPEP 2114(II). Anything can be used a single time).
Bransby in view of Levinson, Linz, and Gaddum does not disclose wherein the control system further comprises an alarm, the alarm configured to be activated when the control system detects a pressure greater than a safe pressure limit.
Maggoire discloses wherein the control system further comprises an alarm (13. Maggoire; Paras. [0042, 0056, 0065-0066], Fig. 1, over-pressurization relief device (120)), the alarm configured to be activated when the control system detects a pressure greater than a safe pressure limit (Maggoire; Paras. [0040-0041]), the control system configured to automatically reduce one or more of a flow rate or a pressure in the at least one single use feed container (The relief valve/over-pressurization relief device) (Maggoire; Paras. [0029-0032], the over-pressurization relief device (120) will allow air our or allow for depressurization of the enclosure (100)) is configured to automatically reduce one or more of a flow rate or a pressure Maggoire; Paras. [0029-0032], the over-pressurization relief device (120) will allow air out/allow for depressurization of the enclosure (100)) of the plurality of single use feed containers in response to detection of the pressure greater than the safe pressure limit (Maggoire; Para. [0031-0035], the pressure is set to be below that of the burst pressure of the enclosure/reaction area).
Maggoire additionally discloses that the over-pressurization relief device is implemented in order to avoid the burst pressure of the bioreactor vessel and components within the system (Maggoire; Abstract).
Therefore, it would be obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the pressure control system of modified Bransby by including a pressure relief and alert system when the pressure limit is exceeded as taught by Maggoire to provide: wherein the control system further comprises an alarm, the alarm configured to be activated when the control system detects a pressure greater than a safe pressure limit. Doing so allows for the avoidance of structural failure of the bioreactor components due to over-pressurization (Maggoire; Abstract). Both Bransby and Maggoire are directed to pressurized bioreactor systems. This involves applying a known technique (burst pressure alarms emergency relief system for a bioreactor system) to a similar device (pressure control system) to yield predictable results (the avoidance of structural failure of portions the bioreactor system due to the pressure exceeding burst pressure of the components).
Conclusion
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/D.L.B./Examiner, Art Unit 1758
/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
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