DETAILED ACTION
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.
Claims 1 and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Hsieh (US 20200131466) in view of Kamm (US 20140057311) and Murthy (US 20210115402).
With respect to claim 1, Hsieh discloses a microenvironment-simulated cell culture system comprising a cell culture chip having a mainbody (Figure 1:120) and a cell culture chamber (Figure 1:140). The cell culture chamber includes a first side portion and a second side portion that are disposed on two ends of the cell culture chamber along a long axis of the mainbody.
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Two fluid delivery ports (Figure 4A:127) are separately disposed on the mainbody and are respectively connected to the cell culture chamber. A fluid storage device (Figure 1:110) is pipe-connected to the cell culture chip via tubes (Figure 1:128) that interface with one of the fluid delivery ports 127. A fluid driving member (Figure 1:160) is pipe-connected to the fluid storage device via tubes 128 and is pipe-connected to the cell chip by the other one of the fluid delivery ports 127. This is described in paragraphs [0026]-[0034]. Hsieh further shows in Fig. 5B that the cell culture chamber is substantially a long-stripped slot comprising two long sides parallel to the long axis of the mainbody, and wherein a length ratio of a short side of the cell culture chamber to one of the long sides is between 1:1 and 1:4. See Fig. 5B.
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Hsieh further appears to show that two delivery ports are disposed along a direction parallel to the short side of the cell culture chamber.
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Hsieh teaches in paragraphs [0043] and [0052] that cells are seeded (“loaded”) into the cell culture chamber. Hsieh, however, does not expressly state that this is accomplished using a sample loading well connected to the second side portion, or that the two fluid delivery ports are connected to the first side portion.
Kamm discloses a microenvironment-simulated cell culture system comprising a cell culture chip having a mainbody and a cell culture chamber having first and second side portions. Two delivery ports are connected to a first side portion of the cell culture chamber, such that they are disposed along a direction parallel to the first and second (short) side portions. Kamm further shows that at least one sample loading well is connected to the second side portion of the cell culture chamber. This is described in paragraphs [0109]-[0111] and [0131]-[0143].
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Murthy discloses a microenvironment-simulated cell culture system comprising a cell culture chamber (Figure 2:124) in communication with two fluid delivery ports (Figure 2:136, 138). A fluid storage device (Figure 2:132) and a fluid driving member (Figure 2:140) are both pipe-connected to the cell culture chamber. Murthy additionally teaches in paragraphs [0054], [0074] and [0094] that a sample loading well (Figure 2:126) is connected to the cell culture chamber for cell seeding.
Before the effective filing date of the claimed invention, it would have been obvious to provide the Hsieh system with a sample loading well disposed on the mainbody. Kamm and Murthy show that an independent cell loading/seeding well is useful because it allows one to deliver cells to the culture chamber independently from a fluid medium perfusion stream. Murthy further teaches that a sample loading well may take many known forms and would operate according to known principles (“Reservoirs and wells used for loading one or more samples onto the fluidic device of the present invention includes but are not limited to, syringe, cartridges, vials, Eppendorf tubes and cell culture materials (e.g., 96 well plates”). Kamm further demonstrates how it is known to provide a plurality of fluid delivery ports so that they communicate directly with the cell culture chamber through a first side. Those of ordinary skill would have understood that the specific location of the two fluid delivery ports in Hsieh represents a prima facie obvious design choice, given that it would not substantially affect device operation. See MPEP 2144.04 “Rearrangement of Parts”.
With respect to claim 8, Hsieh, Kamm and Murthy disclose the combination as described above. Hsieh further teaches that the fluid storage device is for storing a cell culture medium, and that the fluid driving member is for continuously driving the cell culture medium from an inlet to an outlet. Murthy teaches a similar operation. Alternatively, it is noted that 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.
With respect to claim 9, Hsieh, Kamm and Murthy disclose the combination as described above. Hsieh further teaches in paragraph [0036] that the fluid driving member is a peristaltic pump.
With respect to claim 10, Hsieh, Kamm and Murthy disclose the combination as described above. Those of ordinary skill would have found it obvious to optimize the length ratio of the Hsieh short side to long side through routine experimentation. See MPEP 2144.05. Hsieh already shows in Fig. 5B that the ratio is approximately 1:2, and so little to no additional modification would be necessary to meet the claimed limitation.
Claims 2-6 are rejected under 35 U.S.C. 103 as being unpatentable over Hsieh (US 20200131466) in view of Kamm (US 20140057311) and Murthy (US 20210115402) as applied to claim 1, and further in view of Burdon (US 6572830).
With respect to claims 2 and 3, Hsieh, Kamm and Murthy disclose the combination as described above. Hsieh further teaches that the cell culture chip is a multi-layer structure comprising first, second, third, fourth and fifth base plates (see mainbody in Fig. 4B and cell culture chamber in Fig. 5B). The base plates are characterized by fluid delivery ports that are stacked in sequence to form at least one loading channel. At least one base plate functions as a covering unit that covers a channel or culture chamber. Hsieh, however, does not expressly teach up to seven base plates.
Burdon discloses a microfluidic chip formed by stacking essentially any number of base plates, such as up to seven base plates. Plates are stacked in sequence to form fluid channels, delivery ports and loading channels (Figure 1:30, 32, 36). See Fig. 1. This is taught throughout the reference, including column 2, line 8 to column 3, line 9.
Before the effective filing date of the claimed invention, it would have been obvious to fabricate the Hsieh microfluidic chip using essentially any number of stacked base plates arranged in different orders to create different channel and chamber configurations. Burdon shows that it is within the ability of one of ordinary skill to experiment with different layering strategies to create different reactor designs. A mere duplication of parts – here, the provision of at least seven base plates – to produce a known and predictable effect is considered to be prima facie obvious, especially when the duplication is identified by the prior art as being useful and advantageous for a specific purpose. See MPEP 2144.04 “Duplication of Parts”.
With respect to claims 4-6, Hsieh, Kamm, Murthy and Burdon disclose the combination as described above. Murthy and Burdon (“Microfluidic devices are most commonly made from silicon, glass, or plastic substrates”) further teach the use of impermeable materials, such as polystyrene, and transparent materials, such as glass.
Response to Arguments
In response to Applicant’s amendment filed 11 December 2025, the previous rejections have been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the combination of Hsieh with Kamm and Murthy.
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.
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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