DETAILED ACTION
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 188, 190, 192, 193, 195-197, 200 and 202 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Maoz (US 20230272321).
With respect to claims 188 and 202, Maoz discloses a cell culture device suitable for preparing a compartmentalized in vitro model using neuronal cells. The device includes an insert (Figure 1A:1) that is insertable into a reservoir (Figure 1C:21) of a culture plate (Figure 3B:74) configured to receive a culture medium fluid therein. The insert includes a bottom wall (Figure 1A:9) having a top surface for receiving a microfluidic layer, a side wall extending upwardly from the bottom wall to define a cell culture medium chamber, and an insert opening formed through the bottom wall to enable fluid communication between the reservoir and the cell culture medium chamber. The microfluidic layer is defined by a membrane (Figure 1A:2) that extends over the insert opening and a plurality of channels (Figure 1B:14 and Figure 1B:16) capable of being used to orient axonal growth. For example, the microfluidic layer may include a ”reducer” insert (Figure 7A:150) that comprises a microfluidic layer defining at least one microchannel (see Figs. 7A-7E). The reducer is placed on top of the membrane to complete the microfluidic layer structure. Maoz further states that an upwardly extending feed well comprising a seeding chamber (Figure 1C:26A) is configured to receive neuronal cells and additional culture medium and is in communication with the channels of the microfluidic layer to enable at least a portion of the additional culture medium fluid to flow therein. This is taught in paragraphs [0042], [0075], [0088]-[0091] and [0095]-[0097].
With respect to claims 190 and 192, Maoz discloses the apparatus as described above. The channels of the microfluidic layer are shown in Figs. 1B, 2B and 7C-7E to extend to a peripheral edge of the microfluidic layer and across an entire thickness of the microfluidic layer.
With respect to claim 193, Maoz discloses the apparatus as described above. As previously discussed, Maoz states that a membrane (Figure 1A:2) is provided as a bottom surface of the microfluidic layer to help define culture medium flow through the channels.
With respect to claim 195, Maoz discloses the apparatus as described above. Maoz further teaches that a biological model including cells (Figure 1C:25) is received on an upper surface of the microfluidic layer.
With respect to claim 196, Maoz discloses the apparatus as described above. Maoz states that the bottom wall 9 extends inwardly from the side wall to stabilize the biological model in cooperation with a support element (Figure 1A:4) at a given position.
With respect to claim 197, Maoz discloses the apparatus as described above. Maoz indicates that the side wall includes engaging elements (Figure 1C:28A and Figure 1C:28B) that stabilize the insert in the reservoir of the cell culture plate.
With respect to claim 200, Maoz discloses the apparatus as described above. Maoz teaches that a feed well feeding system (Figure 1C:29A) is in fluid communication with the feed well to supply additional culture medium to the feed well.
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.
Claim 189 is rejected under 35 U.S.C. 103 as being unpatentable over Maoz (US 20230272321) as applied to claim 188, and further in view of Paves (US 20240182831).
Maoz discloses the apparatus as described above, however does not appear to teach that the channels of the microfluidic layer extend radially from a central region of the microfluidic layer.
Paves discloses a cell culture device for preparing a compartmentalized in vitro model comprising an insert that is inserted into a reservoir of a cell culture plate. The insert includes an upwardly extending feed well (Figure 2H:270) and bottom and side walls that define a cell culture chamber therein. An insert opening (Figure 2F:245) is provided within the bottom wall and communicates with a microfluidic layer comprising a plurality of channels (Figure 2E:266) that extend radially from a central region of the microfluidic layer. This is described in at least paragraphs [0033]-[0040].
Before the effective filing date of the claimed invention, it would have been obvious to provide the Maoz insert with a central feed well and a plurality of channels that extend radially from the central feed well. Paves shows that this is an alternative way to deliver cells and media to a cell culture insert (“Chemical gradients of diffusible factors such as cytokines, growth factors, hormones, and antibodies are also supported” and “The pressure gradient can be controlled across the hydrogel region 250 by controlling the amount of liquid volume added in the reservoirs 238 and/or the central chamber 270. Chemical gradients and fluid flow can then be generated in accordance with the present embodiments from left to right, right to left or from top to side”). A mere rearrangement of parts (here, modifying the configuration of the Maoz channels) that produces a predictable and/or minimal change in operation is considered to be prima facie obvious. See MPEP 2144.04.
Claims 191, 194, 196, 198 and 199 are rejected under 35 U.S.C. 103 as being unpatentable over Maoz (US 20230272321) as applied to claims 188, 195 and 197, and further in view of Eddington (US 20100112690) and Angeloni (WO 2016180836).
With respect to claims 191 and 194, Maoz discloses the apparatus as described above, however does not state clearly indicate if the channels are open-top channels that may be closed by a cover.
Eddington discloses a cell culture insert that includes a bottom wall, a side wall and a cell culture medium chamber. The chamber is in communication with a microfluidic layer (Figure 6:30) having a plurality of channels formed between a plurality of protrusions (Figure 6:64). The channels extend between a feed well (Figure 4:35) and an exhaust port (Figure 4:39). The channels are configured as open-top channels that are sealed by a cover (Figure 4:48) configured to provide a fluid tight closure.
Angeloni discloses a cell culture insert that includes a bottom wall, a side wall and a cell culture medium chamber. The chamber is in communication with a microfluidic layer (Figure 2:1) defined by a plurality of open-top wells (see Fig. 3).
Before the effective filing date of the claimed invention, it would have been obvious to form the channel in the microfluidic layer of Maoz as open-top channels configured to be sealed by a removable cover. As evidenced by Eddington and Angeloni, inserts having microfluidic layers characterized by open-top flow structures allow cells to freely interact with the culture medium disposed in the surrounding fluid environment. Eddington further shows how the open-top structures may be sealed using a removable cover when it is necessary to protect against contamination and loss of fluid.
With respect to claims 196, 198 and 199, Maoz, Eddington and Angeloni disclose the combination as described above. Angeloni further shows how the side wall includes inwardly protruding projections (Figure 15:17) that stabilize the microfluidic layer. Angeloni shows that the insert includes an upwardly extending feed well with a downwardly converging portion (Figure 2:14). Eddington teaches in paragraph [0042] that the insert may have a non-circular, rectilinear shape characterized by vertices formed by intersecting edges. It is well established that mere changes in shape that produce a minimal or predictable change in device operation are considered to be prima facie obvious. See MPEP 2144.04.
Claims 203-207 are rejected under 35 U.S.C. 103 as being unpatentable over Maoz (US 20230272321) as applied to claim 202, and further in view of Collins (US 20210055283).
Maoz discloses the apparatus as described above, however does not state that the microfluidic-layer receiving portion includes an electrode layer comprising a plurality of electrodes.
Collins discloses a cell culture device comprising an insert having a bottom wall characterized by a microfluidic layer-receiving portion. This is taught in paragraph [00263] and shown in Figs. 7A and 7B. Paragraphs [0076], [0086]-[0092] and [0271]-[0282] indicate that an electrode layer comprising an array of electrodes is provided to stimulate neuronal cells and measure a subsequent cellular response. The electrodes may function as sensors and may be in communication with an electrical or optical transducer. Collins teaches that an electronic control and analysis means is provided to evaluate information obtained from the electrodes and provide data regarding changes in potential and impedance, as well as voltammetry and amperometry recordings.
Before the effective filing date of the claimed invention, it would have been obvious to provide the Maoz insert with an electrode layer configured to evaluate cell growth and behavior using an array of electrodes. Collins indicates in at least paragraph [0285] that cells must be electrically stimulated in order to create accurate and useful in vitro models. Collins further states that changes in impedance and electrical potential may be used to determine changes in cell activity and differentiation, and may signal when it is necessary to adjust culture and flow conditions. Collins additionally teaches that electrode arrays are useful for observing a response to an applied input, such as a drug, growth factor, toxin, or other stimuli agent.
Allowable Subject Matter
Claim 201 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The prior art does not teach a cell culture device comprising an insert having the claimed feed well feeding system. Although funnel shapes are known in the art, the prior art does not teach a funnel specifically designed to interface with the insert as claimed, such that the funnel engages a feed well and seeding chamber.
Response to Arguments
Applicant's arguments filed 04 August 2026 have been fully considered but they are not persuasive.
Applicant primarily argues that the membrane layer 22 of Maoz is not a microfluidic layer comprising channels. Although it is agreed that the membrane 22 of Maoz is not itself a microfluidic layer in isolation, it is noted that Maoz teaches a microfluidic layer that includes the membrane as a surface. The microfluidic layer is produced through a combination of structures, such as the membrane 22, the channels 14, 16 and the “reducer” insert 150. The channels of the microfluidic layer are shown in at least Figs. 1B and 7C.
Applicant argues that the conduits 14, 16 and the “insert-reducer” are used to reduce an active surface area of the membrane and control flow and shear stress, but are not configured for orienting axonal growth. The limitations “for preparing a compartmentalized in vitro module using neuronal cells” and “for orienting axonal growth” are intended-use recitations that are afforded reduced patentable weight in the context of an apparatus claim. Apparatus claims cover what a device is, not what a device does. A claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim. See MPEP 2114. Here, it is unclear why the Maoz channels could not be used to accommodate neuronal cells and orient axonal growth, and it is not believed that any specific structure is necessary to read on the broad language of “for orienting axonal growth”. The claims do not require any particular degree of efficacy, and those of ordinary skill would be capable of using the Maoz system to produce an in vitro model using neuronal cells with at least some level of success. Maoz teaches all of the physical structure set forth in independent claims 188 and 207, and therefore there is a strong presumption that the disclosed system is capable of operating according to the suggested intended-use.
Applicant lastly argues that Maoz does not teach an upwardly extending feed well. However, the inlet 6A, 12A, 13A, 26A is defined as an upwardly extending feed well that defines a seeding chamber. The inlet is in communication with the channels of the microfluidic layer to allow for the flow of culture medium.
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Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached at (571) 272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NATHAN A BOWERS/Primary Examiner, Art Unit 1799
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