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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/24/202533 has been entered.
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 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Davidzon et al. (US 2018/0142201) and further in view of Sato (US 2022/0306980).
Regarding claim 1 Davidzon et al. discloses a high-density microcarrier retention device for perfusion culture, the device comprising: (See Davidzon Abstract and Fig. 1 and 3 wherein a microcarrier retention device for perfusion culture is provided.) It is also noted that limitations in the preamble do not structurally limit the claimed invention and differentiate from the cited prior art. See MPEP 2114.
a sedimentation chamber; (See Davidzon Abstract and Fig. 1 and 3 wherein a sedimentation chamber 100 is provided.
a first pipeline connected to a bioreactor and the sedimentation chamber; (See Davidzon Fig. 3 wherien a first pipeline 304 is connected to a bioreactor 302 and sedimentation chamber 100.)
a microcarrier retention filter membrane located within the sedimentation chamber; (See Davidzon Fig.1B and 3 wherein a microcarrier retention filter membrane 126/130 is provided in the sedimentation chamber.)
a second pipeline connected to a receiver and the sedimentation chamber; (See Davidzon Fig. 3 second pipeline 348 are connected to a receiver 350 and the sedimentation chamber.)
and a liquid backflushing device and an air backflushing device, each connected to the sedimentation chamber. (See Davidzon Fig. 3 wherein a buffer tank 310, pump, and vlaves, i.e. liquid backflushing device, and air tank 318 and valves, i.e. air backflushing device are each connected to the sedimentation chamber.)
It is noted that Davidzon discloses that the conduit 304, i.e. first pipeline, is disposed between the bioreactor 302 and port 116 of the chamber. (See Davidzon [0060]) Since the pipeline is between the bioreactor and not within the bioreactor and sedimentation chamber it is thus externally connected and thus must be externally connectable thereto.
Additionally assuming arguendo with respect to the tubing and/or pipe forming the conduit 302 being externally connectable to the bioreactor rather than integrally formed it is noted that such a modification would have required a mere making items seperable which would have been obvious to one of ordinary skill in the art at the time of invention because doing so allows removal and sterilization of materials as would be desirable in the device of Davidzon and because it has been held that making items seperable is obvious if it were considered desirable for any reason. In re Dulberg, 289 F.2d 522, 523, 129 USPQ 348, 349 (CCPA 1961)
Furthermore Davidzon recognizes the desirability of using ports onto which conduits are externally connected thereto (See Davidson [044] where a conduit is externally connected to a port and not integral to the device.) One of ordinary skill in the art at the time of filing would have recognized the desirability to using externally connected tubing rather than integral tubing as it represents a known and specific solution to connecting tubing to a device. Additionally, there are only two ways in which tubing may be connectable to a bioreactor device, integrally and/or externally, and the selection of one known design, i.e. externally connectable, over the other would have been obvious to one of ordinary skill in the art at the time of filing because a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Davidzon also discloses various pumps used to move fluids thoughout the device but does not specifically disclose a pump positioned along the second pipeline between the receiver and the sedimentation chamber.
Sato et al. discloses a device for growing cells comprises a bioreactor connected via a first conduit to a container in which particles are separated comprising a filter and a receiver to receive filtered fluids. The receiver and filter device are connected by a second fluid conduit comprising a pump therein to speed up filtration and movement of materials. (See Sato Abstract, Fig. 1 and [0027]-[0029] wherein a bioreactor 12 sends particles to a filtration devices 11 which is connected to a receiving container 13 via a second conduit 31 having a pump 41 therein.)
It would have been obvious to one of ordinary skill in the art at the time of filing to provide a pump in a conduit between a filtration device and a receiving container as described by Sato in the system of Davidzon because such a pump allows increased speed of fluid transfer and filtration as would be desirable in the device of Davidzon.
Regarding claim 2 Davidzon et al. discloses all the claim limitations as set forth above as well as the device wherein the high-density microcarrier retention device for perfusion culture is a high-density microcarrier retention device for adherent cell perfusion culture. (See Davidzon [0002]-[0003] wherein the device is for adherent cell culture)
Furthermore such limitations are directed to intended uses and materials worked on by the device which do not define structural elements which differentiate the claimed invention from the cited prior art. See MPEP 2114 and 2115.
Regarding claim 3 Davidzon et al. discloses all the claim limitations as set forth above as well as the device wherein the sedimentation chamber is connected to the bioreactor through one or more inclined or vertical pipelines, and the angle a between the pipelines and the horizontal plane is between 60-90 degrees. (See Davidson Fig. 3 and 1B wherein sedimentation chamber is connected to bioreactor through vertical pipeline 116 which is at an angle of 90 degrees relative to a horizontal plane, i.e. it is vertical.)
Furthermore it is noted that assuming arguendo with respect to such a configuration as such modification would involve a mere change in configuration to obtain an efficient arrangement and it has been held that a change in configuration of shape of a device is obvious, absent persuasive evidence that a particular configuration is significant. In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966).
Regarding claim 4 Davidzon et al. discloses all the claim limitations as set forth above as well as the device wherein the microcarrier retention filter membrane has a three-dimensional structure with one or more continuous or discontinuous vertical, inclined or curved retention walls. (See Davidzon Fig. 1B and [0046] wherein filter membrane has a three-dimensional structure with vertical and inclined conical retention walls.)
Regarding claim 5 Davidzon et al. discloses all the claim limitations as set forth above as well as the device wherein the three-dimensional structure has an upper cross section and a lower cross section with the same or different shapes. (See Davidzon Fig. 1B and [0046] wherein the filter has a upper cross section 126 and a different lower cross section 130)
Regarding claim 6 Davidzon et al. discloses all the claim limitations as set forth above as well as the device wherein an area of the upper cross section is greater than or equal to that of the lower cross section. (See Davidzon Fig. 1B and [0046] wherein the conical base shape provides a larger upper cross section and smaller lower cross section.)
Regarding claim 7 Davidzon et al. discloses all the claim limitations as set forth above as well as the device wherein the lower cross section converges to a point. (See Davidzon Fig. 1B and [0046] wherein the lower cross section has a conical base which converges to a point)
Regarding claim 8 Davidzon et al. discloses all the claim limitations as set forth above as well as the device wherein a horizontal wall of the three-dimensional structure is configured to have a retention effect. (See Davidzon Fig. 1B and [0046] wherein the a horizontal wall, i.e. top 114, retains the filter, i.e. has a retention effect.)
Regarding claims 9-10 Davidzon et al. discloses all the claim limitations as set forth above as well as the device wherein the device is partially or wholly configured as a disposable device wherein the device is a reusable device. (See Davidzon Abstract and Figs. Wherein one may either dispose of the device or reuse it as they wish.)
Such limitations are directed to intended uses of the claimed device which do not define structural elements which differentiate from the claimed prior art. See MPEP 2114
Regarding claim 11 Davidzon et al. discloses all the claim limitations as set forth above as well as the device wherein the microcarrier retention filter membrane is replaceable. (See Davidzon Abstract and Figs. And [0046] Wherein one may replace/remove a filter as they wish.)
Such limitations are directed to intended uses of the claimed device which do not define structural elements which differentiate from the claimed prior art. See MPEP 2114
Claim(s) 12-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Davidzon et al. (US 2018/0142201) in view of Sato (US 2022/0306980) as applied to claims above, and further in view of Wales et al. (US 2019/0241856).
Regarding claim 12 modified Davidzon discloses all the claim limitations as set forth above as well as a method for retaining high-density microcarriers by using the high-density microcarrier retention device for perfusion culture according to claim 1, (See Rejections above) comprising the following steps:i) pumping out culture medium and microcarriers from the bioreactor through the first pipeline connected to the bioreactor to the retention device; (See Davidzon Abstract Fig. 3 and [0060] wherein culture medium with microcarriers is pumped from bioreactor 302 through first pipeline 304 into retention device 100.)
ii) harvesting the culture medium into the receiver through the second pipeline connected to the receiver above the retention device and settling the microcarriers by gravity in the retention device; iii) retaining a small amount of microcarriers still kept in the culture medium by the microcarrier retention filter member; (See Davidzon Fig. 3, 4B, and [0060] wherein culture medium is sent to receiver and microcarriers settle by gravity in the retention device and are retained by the filter.)
iv) backflushing the microcarrier retention filter membrane through the liquid backflushing device; and v) pushing remaining culture medium and microcarriers and backflushing by means of air through the air backflushing device. (See Davidzon Fig. 5A-5H wherein the filter is backwashed with liquids and air from respecting backwashing devices.)
Davidzon does not specifically disclose sending the microcarriers and fluid to the bioreactor by air backflushing.
Wales et al. discloses a device wherein a bioreactor comprises a filter and materials retained by the filter are returned to the bioreactor by performing backwashing.(See Wales abstract [0005] ,[0010], and [0054] wherien a filter is backwashed to clean the filter and return retentate materials to the bioreactor.)
It would have been obvious to one of ordinary skill in the art at the time of filing to return materials to a bioreactor by performing backwashing as described by Wales in the method of Davidzon because doing so allows the effective cleaning of a filter and prolonging filter life and allows recycling of materials reducing costs as would be desirable in the method of Davidzon.
Regarding claim 13 modified Davidzon discloses all the claim limitations as set forth above and but does not specifically disclose the method is performed by an automated control program.
It is noted that such a modification would have merely required making the device automated and would have been obvious to one of ordinary skill in the art in order to reduce operator intervention and since it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art. In re Venner, 120 USPQ 192 (CCPA 1958); In re Rundell, 9 USPQ 220 (CCPA 1931).
Regarding claim 14 modified Davidzon discloses all the claim limitations as set forth above and assuming arguendo with respect to steps i) - v) being repeated one or more times.
It is noted that such a modification would have required a mere duplication of process steps to perform multiple cell cultures and because mere duplication of parts or process steps has no patentable significance, unless a new and unexpected result is produced, since it involves only routine skill in the art.
Regarding claim 15 modified Davidzon discloses all the claim limitations as set forth above but does not specifically disclose wherein a linear fluid rate of the culture medium in the sedimentation chamber of the retention device is less than the sedimentation rate of the microcarriers.
It is noted that such a modification would have required changing a culture medium flow rate. The reference does not explicitly disclose the flow rate of culture medium being less than sedimentation rate. As the speed of pumping, shear stress on cells, and filtration times are variables that can be modified, among others, by adjusting said flow rate of culture medium, with said speed of pumping, shear stress on cells, increasing and filtration time decreasing as the flow rate is increased, the precise culture medium flow rate would have been considered a result effective variable by one having ordinary skill in the art at the time the invention was made. As such, without showing unexpected results, the claimed culture medium flow rate cannot be considered critical. Accordingly, one of ordinary skill in the art at the time the invention was made would have optimized, by routine experimentation, the culture medium flow rate in the method of Davidzon to obtain the desired balance between the pumping speed, shear stress and filtration time (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223).
Response to Arguments
Applicant’s arguments with respect to the claims have been considered but are moot because the new ground of rejection does not rely on any combination of references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. It is noted that in response to applicant’s claim amendments additional art and rational have been utilized to make up for any argued deficiencies and as such applicant’s arguments are moot.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONATHAN M HURST whose telephone number is (571)270-7065. The examiner can normally be reached on M-F 7AM-4PM.
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/JONATHAN M HURST/ Primary Examiner, Art Unit 1799