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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/2/26 has been entered.
Claims 1, 4-15, 20-24 remain pending, of which claim 1 has been amended.
The previous objection to the drawings, 35 USC 112a and 35 USC 112b rejections have been withdrawn due to the amendments.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
12. Claims 1, 4-9, 20-24 are rejected under 35 U.S.C. 103 as being unpatentable over ANTWILER (US 2008/0227190) in view of KNEBEL (US 2011/0111504).
Regarding claim 1, 20-21, ANTWILER discloses a plate bioreactor (cell culture system) comprising a plate 102 (standalone subunit) comprising an interior central field 108 (cavity) configured to house a membrane 112 (substrate),
a media inlet port 26 (fluid inlet) configured to supply fluid to the interior,
a media outlet port 34 (fluid outlet) configured to removed fluid from the interior, the interior central field being configured to flow fluid from the inlet 26 to the outlet 34 (Fig 2-3, 6a,b, 0021-24);
at least one tab 152 that fits into holes 154 for aligning (alignment feature), the tabs and holes are disposed on at least one of the top or bottom of the plate 102, wherein the tabs of one plate (alignment features) are configured to fit into holes 154 of another plate (alignment feature is attachment feature that connects adjacent subunits) when the plates are stacked (subunit is stackable) as in Fig 2 (0022, 0025, Fig. 3);
the substrate comprises a stack of a plurality of substrates disposed between the inlet 26 and outlet 34 (Fig 2, 6a);
wherein the central field 108, fluid inlet 26 and fluid outlet 34 are arranged to create a fluid flow path from the inlet to the outlet in which the fluid flows in a direction that is perpendicular to the plurality of substrates through vertical pipes 148a, b (0024, Fig 2, 3) and also flows through the membranes (perpendicularly) (0026);
ANTWILER discloses the flow is distributed via column 144a between the fluid inlet 26 and the interior 108 (0023-24), but does not explicitly disclose the distribution is via a first flow distribution plate configured to distribute media from the fluid inlet from a central portion of the plate comprising the fluid inlet.
However, KNEBEL discloses a bioreactor (cell culture system) comprising a tissue lumen 15 (interior cavity configured to house a cell culture substrate), in which there is a distributor plate 12 (first flow distribution plate) between a channel 27 (central fluid inlet) and the tissue lumen 15, that directs an inflowing medium to achieve an even distribution across the lumen (Fig 4a, 2, 1, 0071, 0056).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the bioreactor of ANTWILER to include the distributor plate disposed between a central portion with a fluid inlet and the tissue lumen (culture space) as taught by KNEBEL because it allows for even distribution of medium over the cells or tissue which provides an optimal supply of nutrients to the cells including by diffusion (0013, 0020).
Regarding claims 4-6, ANTWILER discloses the flow is collected through a plurality of paths 150b, 148b to an outlet column (outlet distribution) 144b between the interior 108 and the outlet 34 (0023-24, Fig 3) but does not explicitly disclose it is a second flow distribution plate.
However, KNEBEL discloses the tissue lumen (interior cavity) can have a lower distributor plate 12 or can be arranged between an upper (first flow pate) and lower distributor plate (second flow plate), the lower distributor plate arranged between the tissue lumen and the outlet such that circulation of the culture medium can be ensured (0019, 0056, Fig 2).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the bioreactor of ANTWILER to include the lower distributor plate or tissue lumen between an upper and lower distributor plate as taught by KNEBEL because it allows for even distribution of medium over the cells or tissue which provides an optimal supply of nutrients to the cells including by diffusion (0013, 0020).
Regarding claims 7-8, ANTWILER discloses the plates have membranes 112 that can be treated to allow for enhanced cell adherence and growth (cell culture substrate disposed within culture space) (0020) and are semi-permeable (porous) (0026).
Regarding claim 9, ANTWILER discloses the membrane can be made of polyvinylpyrrolidone (0020).
Regarding claim 22, ANTWILER discloses the alignment tabs and holes allow stacking of separate units (0025) and tabs fit into holes are known to be releasable.
Regarding claim 23, ANTWILER discloses the attachment features that are tabs that fit into holes (interlocking profile) (0025) but does not explicitly disclose they provide a snap fit closure or threaded connection. However, it would have been obvious to one of ordinary skill in the art to modify the attachment features of ANTWILER to include a snap fit closure or threaded connection as it would require simple substitution of a known element for connecting two objects and providing a snap fit or threaded connection would provide a tactile feedback to the user that the attachment was successful and secure.
Regarding claim 24, KNEBEL further discloses a spacer 18 and an abutment 10 (retaining features) disposed on an inside wall of the bioreactor, the spacer and abutment configured to hold the lower distributor plate 12 (second flow distribution plate) in place against the tissue lumen 15 (cell culture substrate) (Fig 2a, 3, 0053-57).
Claims 10-15 are rejected under 35 U.S.C. 103 as being unpatentable over ANTWILER (US 2008/0227190) in view of KNEBEL (US 2011/0111504) as applied above, and further in view of STOBBE (US 2014/0227769).
Regarding claims 10-13, ANTWILER does not explicitly disclose the substrate is a molded polymer lattice, 3D printed polymer lattice or woven mesh sheet with the additional features of the woven mesh as claimed.
However, STOBBE discloses the matrix core of the subunits (substrate) can be a porous matrix of woven fiber based sheets (woven mesh sheet, woven mesh sheet comprising one or more fibers) (0320) in which the fiber is less than 10mm in diameter (0342) or is a small diameter ranging 5-100 um (0125) or 0.1-1000 um (0158) and the diameter of the openings of the permeable layer are smaller than the diameter of the cells being cultivated (0034) such as an average diameter from 1-500 um (0161).
It would have been obvious to one of ordinary skill in the art to modify the membrane substrates of ANTWILER woven mesh sheet substrate as taught by STOBBE because it would have required only simple substitution of one known element for another with expected results. Furthermore, it would be obvious to one of ordinary skill in the art to select the preferred substrate with the ideal properties of fiber diameter and opening diameters for culturing the desired cell type based on design choice. Additionally, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art and is prima facie obvious. MPEP 2144.05.
Regarding claims 14-15, ANTWILER does not explicitly disclose the substrate is a dissolvable foam scaffold as claimed. However, STOBBE discloses foam blocks (0115) and that porous foam scaffolding can be used, in which the foam can be made of a variety of materials (0190-194, 0234). It would have been obvious to one of ordinary skill in the art to modify the membrane substrates of ANTWILER to be the foam substrate as taught by STOBBE because it would have required only simple substitution of one known element for another with expected results. Additionally, it would have been obvious to one having ordinary skill in the art at the time the invention to choose a foam scaffold made of a material that is dissolvable, such as the claimed pectic acid, since it has been held to be within the general skill of a worker in the art to select a known material on the basis of its suitability for the intended use as a matter of obvious design choice. MPEP 2144.07.
Response to Arguments
Applicant’s arguments with respect to claims 1, 4-15, 20-24 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Specifically applicant argues the prior art did not teach nor render obvious the amended limitations regarding a first flow distribution plate configured to distribute media from the fluid inlet from a central portion of the first flow distribution plate. However these limitations were addressed by the newly cited reference KNEBEL, see above rejections.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The reference cited on the attached PTO 892 of US Pat #420845 is related to the instant invention as it also discloses a cell culture reactor with an upper and lower flow distribution plate.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIELLE B HENKEL whose telephone number is (571)270-5505. The examiner can normally be reached M-Th 11-7 EST, Alt. Fridays.
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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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/DANIELLE B HENKEL/Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799
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