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 .
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 1-7 and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Wagner (US 20240253032) in view of Fuhr (US 5925511) and Wu (US 20100273262).
With respect to claims 1, 2 and 14, Wagner discloses a cell culture system and method for growing cells on a culture substrate. In some embodiments, the culture substrate may be used to support an extracellular matrix (Figure 131:13122) and adherent cells (Figure 131:13124). Paragraphs [0021], [0193] and [0774] indicate that the substrate may be configured as a microwell plate comprising a plurality of wells (i.e., depressions). Many strategies are implemented for detaching the extracellular matrix and adherent cells from the substrate. For example, a scraper (Figure 47A:4614) is configured to slide across the culture substrate to selectively remove portions of the extracellular matrix and adherent cells. Paragraphs [0376] and [0528]-[0529] further indicate that a cell removal mechanism and an extracellular removal mechanism configured as a collection reservoir, for example, are used to collect and remove cells and ECM detached by the scraper. Wagner, however, does not expressly indicate that the scraper is configured to detach cells and ECM adhering to a region of the substrate other than the plurality of depressions.
Fuhr disclose a cell culture system comprising a substrate (Figure 5:53) comprising a plurality of micro depressions (Figure 6:61) for holding cells (Figure 5:52) and an extracellular matrix. Fuhr teaches in column 9, line 43 to column 10, line 5 that a scraper is configured to detach cells and ECM adhering to regions of the substrate other than those regions defined by the plurality of micro depressions. See, for example, Fig. 13A.
Wu discloses a cell culture system comprising a substrate (Figure 2a:1 and Figure 2a:2) that is characterized by a plurality of depressions (Figure 3b:120). The depressions and top surfaces of the substrate 2 are covered by a gel (Figure 3a:5) that supports cells and, potentially, an extracellular matrix. A scraper (Figure 3a:6) is used to detach the gel from regions other than those regions defined by the plurality of depressions 120. This is described in paragraph [0031].
Before the effective filing date of the claimed invention, it would have been obvious to ensure that the Wagner scraper is configured to detach cells and ECM at top substrate surfaces but not at surfaces defined by the plurality of depressions. Fuhr and Wu show how this may be done to prepare a substrate for a culture operation by removing cells and ECM from locations other than the intended culture locations (e.g., the culture wells). Fuhr and Wu indicate that the scraper may simply be translated across a flat, flush surface defined by the tops of each depression to remove unwanted materials.
With respect to claims 3 and 4, Wagner, Fuhr and Wu disclose the combination as described above. Wagner further describes in paragraphs that an image pickup apparatus allows one to observe a state of cells during a culture process. Wagner teaches in paragraphs [0007], [0008], [0027], [0202] and [0212]-[0294] that an information processing unit uses a cell determination function to then determine which cells should then be subsequently detached. This involves a depression selection function to select the depression within which the identified cells reside.
With respect to claims 5 and 6, Wagner, Fuhr and Wu disclose the combination as described above. Wagner further describes in at least paragraph [0376] that the scraper is repeatedly moved across a detachment location in order to fully remove any remaining cellular residue. Wagner indicates that the presence of such residue may be observed using an image pickup apparatus.
With respect to claim 7, Wagner, Fuhr and Wu disclose the combination as described above. Fuhr and Wu each show scrapers that have a width larger than the width of each of the plurality of depressions. This is most evident from Fig. 3 of Wu.
With respect to claim 11, Wagner, Fuhr and Wu disclose the combination as described above. Wagner discloses a plurality of different cell detachment mechanisms configured to detach cells for selected areas of the substrate, including those areas defined by a plurality of depressions. See, for example, Figs. 44-56. As previously discussed, Wagner discloses the at least one cell collection mechanism (see Figs. 42A-42C) is provided for collecting and removing detached cells. The cell collection mechanism may also include a plurality of pumps, conduits and collection reservoirs. See, for example, paragraph [0528].
With respect to claim 12, Wagner, Fuhr and Wu disclose the combination as described above. Wagner is fundamentally drawn to maintaining and culturing cells, and therefore includes temperature, nutrient, gas, etc. control means that function as cell culture mechanisms.
With respect to claim 13, Wagner, Fuhr and Wu disclose the combination as described above. Wagner shows in the Figures that the cells are adherent cells.
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Wagner (US 20240253032) in view of Fuhr (US 5925511) and Wu (US 20100273262) as applied to claim 1, and further in view of Khine (US 20120129208).
Wagner, Fuhr and Wu disclose the combination as described above, however do not specifically describe the shape of the depressions.
Khine discloses a microwell plate comprising a plurality of depressions (Figure 1:2) for cell culture. Khine teaches in paragraphs [0078] and [0096]-[0100] that the depressions may be characterized by different shapes, including those having an inclined surface and a recessed curved surface. Khine further shows that top surfaces of the substrate between adjacent depressions have a protruding curved surface. See Fig. 2.
Before the effective filing date of the claimed invention, it would have been obvious to ensure that the depressions of Wagner include inclined and/or curved surfaces and that the regions surrounding the depressions have protruding curved surfaces. Khine teaches that it is well known in the cell culture art to produce an array of depressions having a variety of shapes and sizes, and that it is within the ability of one of ordinary skill to choose a specific configuration. Khine directly teaches that rounded and curved surfaces are particularly useful for cell culture.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Wagner (US 20240253032) in view of Fuhr (US 5925511), Wu (US 20100273262) and Wang (US 20210403942).
Wagner, Fuhr and Wu disclose the combination as described above, however do not expressly teach a method comprising a step in which an ECM is detached by the scraper and a subsequent step where cells are seeded at locations across the substrate.
Wang discloses a method for culturing cells on a substrate. Wang shows in Figs. 27A-33C a variety of different cell patterning steps in which predetermined portions of an ECM are detached from the substrate. Wang teaches that cells may be seeded on the substrate following patterning of the ECM. This is described in paragraphs [0288]-[0310] and [0325]-[0327].
Before the effective filing date of the claimed invention, it would have been obvious to use the modified Wagner method to remove portions of the ECM from the substrate prior to seeding cells of a particular cell type onto the substrate. Wang shows how at least first and second cell types may be seeded onto a substrate at different times to produce a desired pattern. Wang further shows how the areas of the substrate may be treated for the removal of ECM prior to seeding cells of a particular cell type. Wang indicates that this offers greater control over culture conditions, cell behavior and cellular development.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The Otto-Nagels (US 5900374) and Fuhr (US 20090148880) references teach the state of the art regarding cell scraping and collection.
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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