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, 8, 9, 12-14, 22, 23, 25-27, 30 and 33-35 are rejected under 35 U.S.C. 103 as being unpatentable over Nishio (US 20090017540) in view of Khine (US 20120129208) and Bennett (US 9790465).
With respect to claims 1 and 30, Nishio discloses a cell culture device comprising a plurality of microwells (Figure 2:3) formed using an upper portion and a lower portion. The lower portion is a substrate for cell adhesion, and the upper portion includes a plurality of corrugated sidewalls (Figure 2:1) that extend above the lower portion to create rows. Nishio further shows that the corrugated sidewalls are aligned such that a continuous gap (Figure 2:2) exists along each row between the sidewalls, such that the gap widens and narrows with each corrugation. Adjacent microwells are in fluid communication via the continuous gap. This is taught in paragraphs [0070]-[0072] and shown in Fig. 2.
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Nishio, however, shows that the bottom portion has a flat surface and therefore does not form rounded well-bottoms.
Khine discloses a cell culture substrate comprising an array of microwells (Figure 1:2) arranged in rows, wherein each microwell includes an opening defined by a top well edge (Figure 2:9), corrugated (“honeycomb”) sidewalls and a rounded bottom. This is shown in at least Fig. 1 and disclosed in paragraph [0068] (see also the annotated Figures presented in previous office actions). The corrugated sidewalls are aligned to produce microwells in the gaps between the corrugated sidewalls. The rounded bottom is expressly disclosed in paragraphs [0078], [0096], [0122]-[0125] and [0142] and shown in Fig. 2.
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Bennett discloses an array of microwells for cell culture, wherein each microwell includes an upper portion (Figure 1:110) defined by sidewalls and a lower portion (Figure 1:120) defined by a rounded bottom. The well array structure is formed when the upper portion is joined to the bottom portion. This is taught in at least column 6, lines 36-46 and column 11, lines 17-40.
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Before the effective filing date of the claimed invention, it would have been obvious to ensure that the microwells formed between Nishio’s corrugated sidewalls are characterized by a rounded bottom. Khine and Bennett each show that this may be accomplished by modifying the shape of the upper surface of Nishio’s lower portion substrate. Khine and Bennett both indicate that microwells having rounded bottom surfaces are especially suitable for the culture and creation of spheroids and embryoid bodies. See, for example, column 12, line 60 to column 13, line 23 in Bennett (“The combination of, for example, a low-attachment substrate, the well curvature in the body and the base portions, and gravity, can induce cells to self-assemble into spheroids, which cell clusters are known to maintain differentiated cell function indicative of a more in-vivo like response”) and paragraph [0122] of Khine (“Applicants achieved rounded bottom polydimethylsiloxane (PDMS) wells…critical to achieve spherical EBs”). Khine goes on to say that the rounded bottom microwells are “easily adaptable and scalable to most standard well plates and easily integrated into commercial liquid handling systems to provide an inexpensive and easy high throughput compound screening platform”.
With respect to claim 8, Nishio, Khine and Bennett disclose the combination as described above. Khine states in at least paragraph [0121] that the rounded well-bottoms comprise a non-adherent surface to prevent long-term cell adhesion.
With respect to claims 9 and 35, Nishio, Khine and Bennett disclose the combination as described above. Bennett further teaches in column 1, lines 21-43 that the rounded well bottoms are gas permeable in order to facilitate the transfer of critical gases (e.g., oxygen, carbon dioxide) to and from the adherent cells (“the spheroids can receive superior oxygenation with well-bottoms made from a polymer having gas permeable properties at a given wall thickness. Increased oxygen availability to the cells in the spheroid culture is particularly helpful for cells with high oxygen requirements such as hepatocytes”).
With respect to claims 12 and 13, Nishio, Khine and Bennett disclose the combination as described above. Each of the cited references, and especially Nishio and Khine, teach that the cell culture substrate is configured as a multi-well plate.
With respect to claim 14, Nishio, Khine and Bennett disclose the combination as described above. Khine teaches in paragraph [0008] that at least one microwell is connected to a liquid reservoir using an input channel.
With respect to claim 22, Nishio, Khine and Bennett disclose the combination as described above. Khine further states in at least paragraphs [0003] and [0006] that the device is used to culture spheroid forming cells.
With respect to claims 23 and 33, Nishio, Khine and Bennett disclose the combination as described above. Nishio shows in at least Fig. 2 that the sidewall of each microwell is continuous from top to bottom. Accordingly, the sidewalls are corrugated from an opening of each microwell to a bottom of each microwell.
With respect to claims 25-27, Nishio, Khine and Bennett disclose the combination as described above. Nishio shows in at least Fig. 2 that the sidewalls are corrugated so that the sidewalls are far apart and then come closer together without contact. Wells are formed in the gaps between corrugated sidewalls.
With respect to claim 34, Nishio, Khine and Bennett disclose the combination as described above. The Nishio substrate and Khine substrate are configured as well plates that include a peripheral edge that functions as a frame.
Response to Arguments
In response to Applicant’s amendment filed 02 January 2026, a new ground of rejection is made in view of the combination of Nishio with Khine and Bennett.
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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/NATHAN A BOWERS/Primary Examiner, Art Unit 1799