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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/17/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7, 9, 16 and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 7 recites the limitation "the horizontal bioreactor chambers" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "said scaffold" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 recites the limitation "the number of horizontal flow bioreactor chambers" in line 1. There is insufficient antecedent basis for this limitation in the claim. It is recommended to change this to “a number of horizontal flow bioreactor chambers”.
Claim 19 recites the limitation "the secondary site scaffold" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Appropriate corrective action is required.
Claim Rejections - 35 USC § 102
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 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 5, 6, 8, 10-12 and 14 are rejected under 35 U.S.C. 102a1 as being anticipated by Palsson et al. (US 5,459,069 A – hereafter ‘069).
‘069 discloses a device for growing stem cells (Abstract) that includes the following limitations for claim 1:
“A horizontal flow bioreactor”: ‘069 discloses a bioreactor (col. 9 lines 4-8) that allows for laminar flow to be applied horizontally across the reactor (col. 11 lines 1-6).
“a bioreactor chamber for cell growth”: ‘069 discloses a bioreactor with a chamber that is used for cell growth (Fig. 11a; col. 22 lines 44-47).
“a peristaltic pump that can regulate flow rate for a fluid tubing for delivering the fluid between the pump, the bioreactor chamber and media reservoirs”: ‘069 discloses using a peristaltic pump (col. 23 lines 23-27) that pumps culture media from a reservoir (reservoir 900; Fig. 9) to the bioreactor (bioreactor 902; col. 23 lines 27-33; Fig. 9) via tubing.
“an in-line injection port for sample insertion and/or sample extraction.”: ‘069 discloses using injection ports (Fig. 2; col. 15 lines 60-62; col. 25 lines 5-8) that are being interpreted as in-line injection ports.
‘069 discloses a device for growing stem cells (Abstract) that includes the following limitations for claim 12:
“A horizontal flow bioreactor”: ‘069 discloses a bioreactor (col. 9 lines 4-8) that allows for laminar flow to be applied horizontally across the reactor (col. 11 lines 1-6).
“a primary site having cells, said primary site fluidly terminating at a media inlet or a surface of a transwell insert”: ‘069 discloses that the cell culture surface begins and at an inlet (inlet 610; Fig. 11a; col. 19 line 66 – col. 20 line 7) that is being interpreted as the primary site that terminates and the media inlet. As the growth surface cultures is adapted for cell growth and attachment, this is being interpreted as the portion next to the inlet has cells (col. 20 lines 35-38).
“a scaffold placed between the media inlet and a media outlet”: ‘069 discloses using an extra-cellular bone matrix or sponge (col. 13 lines 2-11) that provides a growth surface between the inlet (inlet 610) and outlet (61) for culturing cells.
“a secondary site fluidly beginning at said media outlet.”: The area next to the outlet (outlet 611) of ‘069 is being interpreted as the secondary sit (col. 20 lines 35-38).
“a horizontal flid path over and through said scaffolds for migrating said cells from the primary site to the secondary site”: ‘069 discloses a horizontal flow (Fig. 11a) that moves cells from the inlet/primary site to the outlet/secondary site (col. 22 lines 44-61).
“wherein flow mimics interstitial fluid flow conditions.”: The flow of medium through ‘069 is fully capable of mimicking interstitial flow as the fluid flow through the bioreactor is the same as the flow of the claimed invention.
For claim 5, ‘069 discloses using Leur Locks for connecting elements of the system (col. 21 lines 11-16).
For claim 6, ‘069 discloses a membrane (membrane 603; Fig. 11a) that is gas permeable and overs the top of the gasket that is placed on top of the growth surface (col. 19 lines 50-58). This is being interpreted as the cap of the instant application as this a) covers the growth area and b) allows gas to vent out of the culture chamber.
For claim 8, ‘069 discloses a growth surface (surface 625; col. 22 lines 57-60) within the bioreactor chamber. It should be noted that the scaffold being inserted into the bioreactor in order to prevent flipping is an optional limitation and the prior art only needs to disclose one of these limitations in order to meet the claim limitations.
For claim 10, the chamber of ‘069 is being interpreted as symmetric as shown in Figure 11a.
For claim 11, ‘069 discloses an outlet (outlet 611) that can function as a drain (Fig. 11a; col. 20 lines 35-38).
For claim 14, the tumor cells are being interpreted as material operated on by an apparatus which does not structurally define the claimed invention over the prior art. See MPEP §2115. Furthermore, it should be noted that the cells are not incorporated into the scaffold and therefore have not been incorporated structurally into the claimed bioreactor, i.e. seeding the scaffold, cells are attached to the scaffold, the cells are imbedded in the scaffold.
Therefore, ‘069 meets the limitations of claims 1, 5, 6, 10-12 and 14.
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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Palsson et al. (US 5,469,069 A – hereafter ‘069) in view of Gramer (US 6,001,585 A – hereafter ‘585).
‘069 (Palsson) discloses using silicone tubing within the system (col. 10 lines 57-59), but does not specify that the silicone tubing is peroxide cured silicone tubing.
‘585 (Gramer) discloses a hollow fiber bioreactor (Abstract) that for claim 3 includes using peroxide cured silicone tubing (col. 6 line 67 – col. 7 line 1). This provides the advantage of having a tubing that is able to be sterilized by conventional techniques such as autoclaving, ethylene oxide and irradiation (col. 65 lines 62-64).
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to include the tubing of ‘585 within ‘069 in order to provide a biocompatible tubing for use in cell growth (col. 6 lines 65-67). The suggestion for doing so at the time would be to provide a tubing that is able to be sterilized by conventional techniques such as autoclaving, ethylene oxide and irradiation (col. 65 lines 62-64).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Palsson et al. (US 5,459,069 A – hereafter ‘069) in view of Truong et al. (US 2023/0295551 A1 – hereafter ‘551; it should be noted that ‘551 has an earliest effective filing date of 08/17/2020).
‘069 (Palsson) differs from claim 4 regarding the material used for the reservoirs. It should be noted that borosilicate glass is well-known and a conventional material within the biological and chemical arts and would have been obvious to one of ordinary skill in the art to use as a reservoir barring evidence to the contrary.
‘551 (Truong) discloses a perfusion bioreactor system for microbial synthesis (Abstract) that for claim includes using borosilicate glass ([0063]) for the reservoirs. Borosilicate glass provides a container that is sturdy, leak-proof, able to withstand the autoclaving process and remain inactive at biological conditions ([0063]).
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to include the borosilicate glass reservoirs of ‘551 within ‘069 in order to provide a biological compatible reservoir. The suggestion for doing so at the time would have been in order to provide a container that is sturdy, leak-proof, able to withstand the autoclaving process and remain inactive at biological conditions ([0063]).
Claims 2, 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Palsson et al. (US 5,459,069 A – hereafter ‘069) in view of Peyser et al. (US 2023/0098953 A1 – hereafter ‘953; it should be noted that ‘953 has an earliest effective filing date of 09/30/,2021).
‘069 (Palsson) differs from claim 2 regarding the use of a multi-channel pump.
‘953 (Peyser) discloses a high-throughput screening tool that uses hollow fibers (Abstract) that for claim 2 includes using a multi-channel pump ([0041]; pump 150; Fig. 1). This allows the pump to send multiple streams to separate modules and to function as a common pump to send a fluid flow across multiple filter modules/units.
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to include a multi-channel pump as suggested by ‘953 within ‘069 in order to supply culture media to more than one bioreactor unit. The suggestion for doing so at the time would have been in order to supply different modules with a flow of culture media ([0041]).
‘069 discloses the following limitations for claim 15:
“An incubator”: ‘069 discloses that the bioreactor can be within an incubator (col. 23 lines 41-43) and that the perfusion chambers, i.e. the bioreactors, are placed in an incubator (col. 27 lines 56-65).
“a plurality of horizontal flow bioreactor chambers”: ‘069 discloses a plurality of chambers within the incubator (col. 27 lines 56-65).
“an epithelial to mensenchymal transition (EMT) test-bed comprising some of the horizontal flow bioreactors”: In light of the specification, this appears to be drawn to the intended use for the perfusion chambers (see MPEP §2114) and does not include any structural elements that would further define the claimed invention over the prior art. Moreover, some of the perfusion chambers of ‘069 are fully capable of being an EMT test-bed. Finally, if this is based on a scaffold providing a culture surface for anchorage-dependent cells, this structural element is not claimed within the instant claim 15.
“a multi-channel pump”: ‘069 discloses using a peristaltic pump (col. 23 lines 23-27) that pumps culture media from a reservoir (reservoir 900; Fig. 9) to the bioreactor (bioreactor 902; col. 23 lines 27-33; Fig. 9).
“a mensenchymal to epithelial transition (MET) test-bed comprising some of the horizontal flow bioreactor chambers.”: In light of the specification, this appears to be drawn to the intended use for the perfusion chambers (see MPEP §2114) and does not include any structural elements that would further define the claimed invention over the prior art. Moreover, some of the perfusion chambers of ‘069 are fully capable of being an MET test-bed. Finally, if this is based on a scaffold providing a culture surface for anchorage-dependent cells, this structural element is not claimed within the instant claim 15.
‘069 (Palsson) differs from claim 15 regarding the use of a multi-channel pump.
‘953 (Peyser) discloses a high-throughput screening tool that uses hollow fibers (Abstract) that for claim 15 includes using a multi-channel pump ([0041]; pump 150; Fig. 1). This allows the pump to send multiple streams to separate modules and to function as a common pump to send a fluid flow across multiple filter modules/units.
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to include a multi-channel pump as suggested by ‘953 within ‘069 in order to supply culture media to more than one bioreactor unit. The suggestion for doing so at the time would have been in order to supply different modules with a flow of culture media ([0041]).
For claim 16, ‘069 discloses a plurality of bioreactors within an incubator, but does not specify that the bioreactors are arranged in parallel.
‘953 (Peyser) discloses that the hollow fiber modules can be arranged in parallel with parallel flow paths ([0041]). Each of the flow paths flow through each module by using a multi-channel pump. This allows the feed stream to be divided into separate flow paths for each unit ([0044]). This allows the flow to be under substantially the same flow conditions to each unit.
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to employ the parallel flow paths as suggested by ‘953 within ‘069 in order to supply the parallel flow paths at the same rate ([0053]). The suggestion for doing so at the time would have been in order to allow the flow to be under substantially the same flow conditions to each unit ([0044]).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Palsson et al. (US 5,459,069 A – hereafter ‘069) in view of Zhang et al. (US 2006/0199260 – hereafter ‘260) and Albeladi et al. (Role of cross-linking process on the performance of PMMA. Internation Journal of Biosensors & Bioelectronics, 2017; 3(3):279-284).
‘069 (Palsson) differs from claim 7 regarding the housing being made of cross-linked PMMA.
‘260 (Zhang) discloses a microscale bioreactor (Abstract) that for claim 7 includes a housing made of PMMA ([0176]) as this provides greater mechanical stability while also providing excellent optical transparency in the visible region.
Therefore, it would have been obvious for one of ordinary skill in the art at the time of filing to use PMMA for the housing as suggested by ‘260 within ‘069 in order to provide good structural support for the bioreactor ([0177]). The suggestion for doing so at the time would have been in order to provide greater mechanical stability while also providing excellent optical transparency in the visible region ([0176]).
Modified ‘260 does not specify that the PMMA is a cross-linked PMMA.
Albeladi discusses the process of cross-linking PMMA (Abstract) and the effects on the physical properties of cross-linking that for claim 7 includes the cross-linking effects on various characteristics of the polymer including an increase in mechanical stability, surface hardness and tensile strength (Page 279, Table 1).
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to include the crosslinking of Albeladi within modified ‘069 in order to improve the physical properties of PMMA. The suggestion for doing so at the time would have been in order to improve the properties of PMMA such as mechanical behavior (page 279, Introduction).
Claims 1 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Lannutti et al. (US 2010/0273258 A1 – hereafter ‘258) in view of Palsson et al. (US 5,469,069 A – hereafter ‘069).
‘258 discloses a system for growing cells in vitro (Abstract) that includes the following limitations for claim 1:
“A horizontal flow bioreactor”: ‘’258 discloses a Transwell system ([0023]) that cultures cells and is being interpreted as the horizontal flow bioreactor of the instant claim. In light of the specification, one of the bioreactor systems is a Transwell system and as ‘258 teaches this same structure, this would read on the claimed horizontal flow bioreactor.
“a bioreactor chamber for cell growth”: ‘258 discloses an insert (insert 10; Fig. 1; [0023]) that is being interpreted as the bioreactor chamber of the instant application.
“a peristaltic pump that can regulate flow rate for a fluid tubing for delivering the fluid between the pump, the bioreactor chamber and media reservoirs”: ‘258 discloses using a pump to supply fluid from a reservoir to the bioreactor ([0106]).
“an in-line injection port for sample insertion and/or sample extraction.”: ‘258 discloses using injection ports that supply cells and material to the well and are being interpreted as in-line injection ports.
‘258 differs from the instant claim regarding the use of a peristaltic pump.
‘069 discloses a device for growing stem cells (Abstract) that for claim 1 includes using a peristaltic pump (col. 23 lines 23-27) that pumps culture media from a reservoir (reservoir 900; Fig. 9) to the bioreactor (bioreactor 902; col. 23 lines 27-33; Fig. 9) via tubing.
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to substitute the syringe pump of ‘258 with the peristaltic pump of ‘069 in order to supply culture media to the bioreactor. The suggestion for doing so at the time would have been in order to pump fresh media through the tubing and into the bioreactor by controlling the media exchange rate and flow rate through the bioreactor (col. 16 lines 26-31).
For claim 9, ‘258 discloses inserting a Transwell insert above the cells at the bottom of the well ([0023]). These wells are seeded on a fiber ([0122]) and then inserted into a well where this fiber is being interpreted as the scaffold of the instant application.
Allowable Subject Matter
Claim 13 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 following is a statement of reasons for the indication of allowable subject matter: For claim 13, the prior art fails to teach or fairly suggest where the primary site is an upper bioreactor chamber and the secondary site is a lower bioreactor chamber.
Claim 19 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: For claim 19, the prior art fails to teach or fairly suggest where the secondary site scaffold is a bone mimetic scaffold, a lung mimetic scaffold, a liver mimetic scaffold or a brain mimetic scaffold. It should be noted that claim 19 would also be allowable for the same reasons as claim 17 as discussed below.
Claims 17, 18 and 20 are allowed.
The following is an examiner’s statement of reasons for allowance: For claim 17, the prior art taken either singly or in combination fails to teach or reasonably suggest the following limitation when taken in context of the claim as a whole a method for modeling tumor growth that includes providing a horizontal flow bioreactor that includes a first and second bioreactor chamber and includes the steps of introducing tumor cells into the horizontal flow bioreactor and flowing a medium from the first bioreactor chamber to the second bioreactor chamber where the flow mimics interstitial fluid flow conditions around the cells.
The closest prior art is Palsson et al. (US 5,469,069 A) that discloses a horizontal bioreactor that induces a horizontal fluid flow, but Palsson does not teach or fairly suggest the steps of providing a first and second bioreactor chamber, introducing tumor cells and flowing medium that mimics interstitial fluid flow conditions around the cells.
The next closest prior art is Lannutti et al. (US 2010/0273258 A1 which discloses a Transwell insert with a pump and injection ports, but Lannutti does not teach or fairly suggest the steps of providing a first and second bioreactor chamber, introducing tumor cells and flowing medium that mimics interstitial fluid flow conditions around the cells.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Vellinger et al. (US 2002/0146816 A1) discloses a bioreactor for the automated cultivation and processing of living cells remotely both on earth and in low gravity.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL L HOBBS whose telephone number is (571)270-3724. The examiner can normally be reached Variable, but generally 8AM-5PM M-F.
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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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/MICHAEL L HOBBS/Primary Examiner, Art Unit 1799