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 .
Remarks
This office action fully acknowledges Applicant’s remarks and amendments filed on 25 August 2025 June 2025.
Claims 1-2, 4-6, and 8-12 are pending.
Claim 1 is amended.
Claims 3, 7, and 13-14 are cancelled.
No claims are withdrawn.
No claims are newly added.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 4-6, 8, and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Nozaki et al. (US 2017/0145365 A1), hereinafter “Nozaki”, in view of Clark (US PAT 5,141,718 A), hereinafter “Clark”.
Regarding Claim 1, Nozaki teaches a system for defined adjustment of the level of a flowable medium in a hollow body, the system comprising:
a tank 201 (Fig. 2A and [0028]: The cells and the culture mediums are maintained on the inside of the culture vessels 201 and 202, and it is possible to culture the cells.”) containing at least a predefined minimum volume of a flowable medium ([0032]: “the culture medium in the culture vessels 201 and 202”);
a hollow body 202/205 disposed within the tank (Fig. 2A and [0030]: “Further, the culture vessel 202 is an insertion-type culture vessel, so that the regenerative tissues are present on the inside thereof…The bottom surface of the cell culture insertion container 202 is of a porous membrane 213, and has a plurality of holes with a diameter of, for example, about 0.4 μm.” – The insert container has one or more openings through its bottom surface via the porous membrane 213. – Additionally, the lid 205 provides the upper wall of the hollow body, forming the “hollow” space within.);
and one or more channels 215, each including a channel inlet and a channel outlet (Fig. 2A and [0030]: “In the connector part 214, the first port 215 is placed so that in the culture vessel 202, the opening ends thereof comes slightly below the upper end of the culture vessel 202.”),
wherein the hollow body is configured as a sample holder ([0030]: “Further, the culture vessel 202 is an insertion-type culture vessel, so that the regenerative tissues [the sample] are present on the inside thereof.”),
wherein each channel inlet is positioned in a region of the hollow body configured to contain a volume of gas enclosed between a wall of the hollow body facing the flowable medium and the flowable medium (Fig. 2A shows pockets of imprisoned gas between the insert container 202 and the flowable medium – see also para. [0056]. Further note that those walls of the culture vessel 202 forming the gas pocket are positioned as facing the flowable medium, particularly given that they are submerged in the flowable medium below the gas pocket.),
wherein each channel outlet is located outside the hollow body and outside a volume of the flowable medium in the tank (Fig. 2A shows the lower inlet of flow channel 215 the upper outlet of the flow channel 215 is arranged outside the insert container 202 and outside the culture medium.),
and wherein the one or more channels are each configured to allow the gas enclosed between the wall of the hollow body and the flowable medium to be discharged from the hollow body through the respective channel inlets to the channel outlets ([0052]: “the other stream is connected to a first exhaust gas opening/closing valve 303” – Fig. 3 shows the channel 215 as connected to the gas exhaust valve 303, thereby allowing gas enclosed between the wall of the hollow body 202 and the flowable medium to be discharged from the hollow body 202 through the channel 215. Examiner further notes that while Nozaki teaches the channel 215 as a feed supply channel, the apparatus is appropriately structured such that that the channel 215 is fully capable of removing gas from the system. And wherein it is further noted that the channel 217 as seen through Fig. 3 is also configured with an exhaust valve for removing gas from the system. – See also paras. [0052-0056 and 0060-0062].);
as in Claim 1.
Further regarding Claim 1, Nozaki does not specifically teach the device discussed above wherein the sample holder comprises: a plurality of wells formed on an upper side of the hollow body and configured to receive a sample fluid, and one or more openings formed on a lower side of the hollow body; wherein the one or more openings are located entirely below a surface of the flowable medium, wherein the wells, in operation of the system, are fluidically separated from the flowable medium, as in Claim 1.
However, Clark teaches a sample holder 42 comprising: a plurality of wells 44 formed on an upper side of the sample holder 42 and configured to receive a sample fluid, openings covered by membrane 55 formed on a lower side of the sample holder 42; wherein the one or more openings are located entirely below a surface of the flowable medium (“In use, the closed end 60 is immersed into an aqueous growth medium in well 12 and then viable cells are introduced onto membrane 55.”), wherein the wells, in operation of the system, are fluidically separated from the flowable medium (As provided by the membrane 55. A membrane can provide fluidic separation, meaning it acts as a barrier that separates two environments while allowing controlled movement of materials, and it does so in a way that is both selective and dynamic.). Therein, this arrangement allows for culture media to be removed and added to the wells via the adjacent triangular sections 16 (Fig. 5), thereby preventing the cells contained therein from being fully dry or being disturbed/mechanically jostled.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Nozaki wherein the sample holder comprises: a plurality of wells formed on an upper side of the hollow body and configured to receive a sample fluid, and one or more openings formed on a lower side of the hollow body; wherein the one or more openings are located entirely below a surface of the flowable medium, wherein the wells, in operation of the system, are fluidically separated from the flowable medium, such as suggested by Clark, so as to for culture media to be removed and added to the wells via the tank 201 of Nozaki, thereby preventing the cells contained therein from being fully dry or being disturbed/mechanically jostled. Further, the providing of individual wells allows for higher throughput and/or multiplexed analysis of different cell types within a single device submerged in a common culture media tank.
Regarding Claim 2, the prior art meets the limitations of Claim 1 as discussed above. Further, Nozaki does not specifically teach the system discussed above wherein at least one channel of the one or more channels has an at least partially V-shaped configuration or an at least partially U-shaped configuration, as in Claim 2.
However, mere change in shape absent evidence to criticality, non-obviousness, or unexpected results associated with the claimed shape is an obvious matter of design choice – see MPEP 2144.04(IV)(B). Herein, Nozaki discloses commensurate linear channels which similarly serve the purpose of adjusting the level of a flowable medium in a hollow body and cycling cell growth media as the claimed V-shaped channels.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to provide the channels of Nozaki as having an at least partially V-shaped configuration as this configuration is merely an alternative configuration to the linear configuration taught by Nozaki, wherein both configurations serve the same or a similar purpose; and would have a reasonable expectation of success therein.
Regarding Claim 4, the prior art meets the limitations of Claim 1 as discussed above. Further, Nozaki teaches the system discussed above wherein, when the system includes a plurality of channels, all of the channel inlets of the one or more channels are disposed on one plane that is orientated orthogonally to the direction of gravitational force (Fig. 2A shows the channel inlet (the end immersed in the culture solution) as disposed on one plane that is orientated orthogonally to the direction of gravitational force, as in wherein the inlet opening is coplanar with the bottom floor of the tank 201. – Examiner further notes that Applicant has amended the claim to be recited by way of a conditional that is not positively not necessitated by the claim and is thereby not required in the prior art.), as in Claim 4.
Regarding Claim 5, the prior art meets the limitations of Claim 1 as discussed above. Further, Nozaki teaches the system discussed above wherein the tank is configured such that the tank permits an input of mechanical oscillations or resonant mechanical oscillations into a flowable medium disposed within the tank ([0042]: “By having a semi-open cavity 221, cushioning is possible when impacts and oscillations are applied to the closed-system culture vessel 101 from the side surface direction.”) and the tank is at least partially produced from metal or plastic ([0030]: “The materials are plastics having plasticity and rigidity, such as PC, PS, and polyethylene terephthalate.”), as in Claim 5.
Regarding Claim 6, the prior art meets the limitations of Claim 1 as discussed above. Further, Nozaki teaches the system discussed above wherein the tank has a plurality of connections 217/218 which are respectively suitable for feeding the flowable medium into the tank 201 and/or for discharging the flowable medium from the tank 201 ([0036]: “…a third port 217 for supplying the culture medium and the like to the culture vessel 201, and a fourth port 218 for discharging the culture medium and the like from the culture vessel 201.”), as in Claim 6.
Regarding Claim 8, the prior art meets the limitations of Claim 1 as discussed above. Further, Nozaki teaches the system discussed above wherein, for each channel of the one or more channels, the channel inlet situated in the hollow body 202/205 has an opening which is configured such that surface tension of the flowable medium prevents penetration of the flowable medium into each channel (As in Fig. 2A, when any of the channels of the connector part 214 (when attached to a feed/waste tube sealed at the other end) are submerged in the culture medium, the surface tension at the inlet/outlet and air contained within the channel prevent the culture medium from entering the channel. – Examiner further notes the recitation “when the tank is filled with the flowable medium and a minimum fill volume of flowable medium is disposed within the tank” is drawn to a conditional that is not necessitated by the claim. Further, the recitation “penetration of the flowable medium into each channel” is drawn to a process limitation. As the claims are drawn to a device, such process recitation is not afforded patentable weight. – Further, the channels of Nozaki are fully capable of use with a flowable medium having a surface tension that prevents intrusion of the flowable medium into the one or more channels.), as in Claim 8.
Regarding Claim 10, the prior art meets the limitations of Claim 1 as discussed above. Further, Nozaki does not specifically teach the system discussed above wherein at least some of the channels function as spacers between a lower edge of the hollow body and a bottom of the tank and are configured for spacing the hollow body at a predefined distance from the tank bottom when the hollow body has been placed in the tank, as in Claim 10.
However, mere change in orientation or position of elements absent any criticality or unexpected result is an obvious matter of design choice – see MPEP 2144.04(VI)(C). Herein, one of ordinary skill in the art would find it obvious that the device having the claimed relative arrangement of at least some of the channels arranged between a lower edge of the hollow body and a bottom of the tank to act as spacers between the floor of the insert container and the floor of the tank would not perform differently than the prior art device, absent evidence of criticality, non-obviousness, or unexpected results associated with the position of the at least some of the channels.
It is further noted that Nozaki is similarly interested in spacing the bottom of the insert container 202 at a defined distance from the bottom of the tank 201, wherein Fig. 2A shows that the inner container 202 is restricted to a predefined position by the pressing part 204, specifically the joint portion 208 which forms an inverse truncated conical through-hole 209 that receives the culture vessel 202 – see para. [0033].
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to provide the channels of the system of Nozaki as arranged between a lower edge of the hollow body and a bottom of the tank to act as spacers between the floor of the insert container and the floor of the tank as this arrangement represents a mere alternative to the spacers/joint portions 208 of Nozaki which achieve the same purpose of the claimed channel spacers; and would have a reasonable expectation of success therein.
Examiner further notes the recitation “when the hollow body has been placed in the tank” is drawn to a conditional that is not necessitated by the claim.
Regarding Claim 11, the prior art meets the limitations of Claim 1 as discussed above. Further, Nozaki teaches the system discussed above wherein the one or more channels are attachable to the hollow body (Fig. 2A shows the channel 215 as attached to the hollow body 202 via the lid 205.), as in Claim 11.
Regarding Claim 12, the prior art meets the limitations of Claim 1 as discussed above. Further, Nozaki teaches the system discussed above wherein a volume of the flowable medium in the tank 201 corresponds to at least the minimum fill volume or is larger than the minimum fill volume (While Nozaki does not specifically discuss a minimum or maximum fill volume of the tank 201, a minimum and maximum fill volume inherently and necessarily exist within the system given that the fill volume must be at least enough to contact the lower membrane of the inner container 202 to provide basal nutrient feed, and that the fill volume must not exceed the upper opening of the tank 201 as this would cause spillage. As such, the volume of the flowable medium must be greater than the minimum fill volume and less than the maximum fill volume so as to ensure the functionality of the culture device and to prevent hazardous contamination to a user from spillage.), as in Claim 12.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Nozaki in view of Clark, as applied to Claims 1-2, 4-6, 8, and 10-12 above, and in further view of Tay et al. (US 2019/0376013 A1), referred to hereinafter as “Tay”.
Regarding Claim 9, the prior art meets the limitations of Claim 1 as discussed above. Further, Nozaki does not specifically teach the system discussed above wherein the hollow body has a plurality of internal segments which, when placing the hollow body in the tank or when filling the tank, allow a plurality of mutually separated imprisoned volumes of gas to be formed in the hollow body and each of the internal segments is associated with at least one channel inlet when the hollow body is placed in the tank, as in Claim 9.
However, Tay teaches a respective device for cell culture wherein the body on which cells grow has a plurality of internal segments/rows of wells 58 (Fig. 1A) and each of the internal segments is associated with at least one channel inlet so as to direct fluids to and/or away from each segment ([0010]: “The present devices can include of an array of wells and channels passing over respective subsets of the wells such that each channel can direct fluids to and/or away from a corresponding subset of the wells. Each well can serve as a culture chamber for growing cells.”). Wherein this arrangement thereby allows for more fine-tuned control over the culture of cells, wherein the conditions of certain segments can be adjusted depending on parameters relating to the cells contained therein.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the system of Nozaki such that the hollow body has a plurality of internal segments and each of the internal segments is associated with at least one channel inlet when the hollow body is placed in the tank, such as suggested by Tay, so as to provide an arrangement that allows for more fine-tuned control over the culture of cells, wherein the conditions of certain segments can be adjusted depending on parameters relating to the cells contained therein; and would have a reasonable expectation of success therein.
Examiner further notes the recitation “when placing the hollow body in the tank or when filling the tank” is drawn to a conditional that is not necessitated by the claim. Further, the recitations “placing the hollow body in the tank” and “filling the tank” are drawn to process limitations. As the claims are drawn to a device, such process recitations are not afforded patentable weight.
Further regarding Claim 9, while Nozaki/Tay does not specifically discuss a plurality of mutually separated imprisoned volumes of gas being formed in the hollow body when placing the hollow body in the tank or when filling the tank, the commensurately structured hollow body of Nozaki/Tay would similarly trap separately imprisoned volumes of gas when the internal segments of the modified insert container 202 of Nozaki are sealed with the lid 205 of Nozaki.
Response to Arguments
35 USC 102 and 103
Applicant argues that Nozaki does not teach the discrete wells of the amended Claim 1 requiring the hollow body be configured such as a microwell plate.
Applicant’s arguments are not persuasive because Applicant’s amendments necessitated the addition of the newly cited prior art of Clark herein teaching a hollow body of discrete wells having openings at the bottoms of each of the wells so as to allow for culture media to be drained and introduced to the wells without disturbing the cells contained therewithin, as discussed above in the body of the action.
Thus, examiner sets forth the rejection of Claims 1-2, 4-6, 8, and 10-12 as unpatentable under 35 USC 103 over Nozaki in view of Clark.
Applicant further argues that the membrane of Nozaki provides fluid communication between the interior of the hollow body and the flowable medium, thus failing to meet the amended Claim 1 requirement requiring fluid separation between the wells and the flowable medium.
Applicant’s arguments are not persuasive because a membrane provides fluidic separation between compartments separated thereby. A membrane provides fluidic separation between chambers in a fluidic device by acting as a physical, semi-permeable barrier. It allows for the controlled exchange of molecules, gases, or pressure without mixing the bulk fluids. Applicant may wish to recite the well as being “fluidically isolated” from the flowable medium, or specify the wells as being fully enclosed. Further, Examiner suggests Applicant further specify the structure of the openings on the bottom of the hollow body, such as having first and second openings at a peripheral edge of the hollow body as seen through Fig. 1, utilizing language provided by the specification.
Applicant further argues that Nozaki fails to teach the amended Claim 1 recitation where the walls creqating the enclosure of trapped gas are facing the flowable medium, and alleges that the channel inlets are not positioned in the gas pocket.
Applicant’s arguments are not persuasive because the inlet of channel 215 (bottom side opening) is shown in Fig. 2A as being positioned within the volume of enclosed gas of the hollow body 202 (above/adjacent to the flowable medium). Further, the wall of the hollow body forming said gas pocket is facing the flowable medium, given that it is partially submerged within the flowable medium. See the annotated Fig. 2A below.
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In view of the discussion above, Examiner maintains that Claim 1 and dependents thereof remain unpatentable in view of Nozaki; and further in view of Clark with respect to the added multiwell aspects.
Applicant further argues that Tay fails to cure the alleged deficiencies of Nozaki discussed above. However, Tay is not relied on for curing any deficiency of Nozaki in Claim 1, wherein Applicant’s additional details of the hollow body are provided for by Clark, as newly cited herein as necessitated by Applicant’s amendments.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/B.J.K./Examiner, Art Unit 1798
/NEIL N TURK/Primary Examiner, Art Unit 1798
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