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 statements (IDS) submitted on 03/23/2023 and 10/16/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 7 and 9 are objected to because of the following informalities:
Claim 7, line 3 comprises a repeated phrase “multi-layered vessel” of which should be deleted.
Claim 9, line 2 states “…multi-layer cell culture modules vessels are coupled”. It appears that the phrase “vessels” should be deleted given that claim 9 is dependent on claim 8 which is drawn to a plurality of multi-layer cell culture modules.
Appropriate correction is required.
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.
Claim 34 is 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 34 recites the limitation “the gas port” in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
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, 7-10, 14-16, 18-19, 23-32, 37 and 39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ho et al. (hereinafter Ho) US 2018/0371394 cited in the IDS filed 03/23/2023.
Regarding claim 1, Ho discloses a cell culture system comprising: at least one multi-layered vessel (culture vessel 1) configured for culturing cells, the multi-layered vessel comprising a cell culture space (at least two rectangular cell culture compartments having a lid, a bottom, two sides and two ends) within the multi-layered vessel; and a cabinet (supporting vessel 7) comprising an interior cavity enclosed by one or more sidewalls, the cabinet being configured to house the multi-layered vessel within the interior cavity as shown in Figs. 3A and 3B and discussed in at least paragraphs 6-10; wherein the cabinet is configured to change an orientation of the multi-layered vessel from an upright orientation to a tilted orientation via platform 18 discussed in at least paragraphs 9, 46, 54 and 58.
Regarding claim 2, Ho discloses at least one sensor (The parameters of culture vessel, supporting vessel, reservoir assembly and culture material of the at least a cell culture vessel include all physical, chemical, biophysical, biochemical, biological properties such as temperature, pH, pressure, dissolved oxygen (DO), dissolved carbon dioxide (DCO2), glucose, lactate, glutamine, glutamate, ammonium, pH, sodium, potassium, osmolality, protein, nucleic acid, cell count, cell viability, cell morphology and the like for interest of process monitoring, development and optimization. The parameters are monitored by sensors, biosensors, on-line or off-line biochemical or biophysical analyzers, imaging devices and the like) configured to sense a property within the cell culture space discussed in at least paragraph 55.
Regarding claim 3, Ho discloses wherein the sensor comprises at least one of a confluence monitor and an analyte monitor discussed in at least paragraph 55.
Regarding claim 4, Ho discloses wherein the sensor is integrated into the multi-layered vessel discussed in at least paragraphs 55-56 and shown in Fig. 1.
Regarding claim 5, Ho discloses wherein the sensor is attached to the cabinet and arranged to sense the property within the cell culture space when the multi-layered vessel is disposed in the cabinet discussed in at least paragraphs 55-56 and shown in Fig. 1.
Regarding claim 7, Ho discloses wherein the cabinet comprises multiple support surfaces (platform 18 and linear actuators 15) each configured to support the at least one multi-layered vessel multi-layered vessel discussed in at least paragraphs 9 and shown in Fig. 3B.
Regarding claim 8, Ho discloses wherein the at least one multi-layered vessel (culture vessel 1 is a multi-tray culture vessel comprising at least two rectangular cell culture compartments having a lid, a bottom, two sides and two ends, arranged in a stacked orientation with respect to each other) comprises a plurality of multi-layer cell culture modules shown in Fig. 1 and 2; and discussed in at least paragraphs 6 and 10.
Regarding claim 9, Ho discloses wherein at least some of the plurality of multi-layer cell culture modules vessels are coupled to one another as shown in at least Figs. 1, 2; and discussed in at least paragraph 10.
Regarding claim 10, Ho discloses wherein the multi-layered vessel comprises an inlet and an outlet (at least one port for medium or gas in and out of the vessel, wherein each port is in gas/fluid communication among all compartments through a gas/fluid flow pathway which allows gas/fluid to flow through a manifold and into each culture compartment, and means enabling to open and block at least one gas/fluid communication among all compartments and the flow pathway which allows fluid to flow through a manifold and into each compartment), the inlet being configured to supply liquid media to the cell culture space and the outlet is configured for passing liquid or gas into or out of the cell culture space discussed in at least paragraph 10, 13 and 57; and shown in Figs. 3A (a1, b1 and b2).
Regarding claim 14, Ho discloses wherein the outlet comprises a vent port configured to permit gas to escape from or enter into the cell culture space (the culture vessel 1 comprises at least one port configured to allow the active gas and culture fluid to enter and exit the culture vessel 1) discussed in at least paragraphs 15 and 57.
Regarding claim 15, Ho discloses wherein the outlet comprises a filter [21] discussed in at least paragraph 57.
Regarding claim 16, Ho discloses wherein the multi-layered vessel comprises a cell culture surface area of at least 18,000 cm2 as discussed in paragraphs 3 and 74.
Regarding claim 18, Ho discloses in paragraph 54 that The driving/rotating assembly also comprises a driving/rotating mechanism to drive the seesaw platform where the culture vessel is placed on, wherein the driving/rotating mechanism is a linear actuator which is configured to tilt the platform to right and left about the axis perpendicular to longitudinal and along the plane perpendicular to the ground by any angle of less than 180 degrees, preferably less than 15 degrees. Since the device disclosed by Ho is structurally the same as the instantly claimed. Thus, in the absence of further positively recited structure the device of Ho is capable of providing the operating conditions wherein, in the tilted orientation, a bottom of the multi-layered vessel is at about a 50 angle relative to horizontal in view of paragraphs 9, 54 and 58.
Regarding claim 19, Ho discloses in paragraph 54 that The driving/rotating assembly also comprises a driving/rotating mechanism to drive the seesaw platform where the culture vessel is placed on, wherein the driving/rotating mechanism is a linear actuator which is configured to tilt the platform to right and left about the axis perpendicular to longitudinal and along the plane perpendicular to the ground by any angle of less than 180 degrees, preferably less than 15 degrees. Since the device disclosed by Ho is structurally the same as the instantly claimed. Thus, in the absence of further positively recited structure the device of Ho is capable of providing the operating conditions wherein the tilted orientation comprises a rotation of about 50 relative to the upright orientation in view of paragraphs 9, 54 and 58.
Regarding claim 23, Ho discloses wherein the cabinet comprises a main inlet fluidly connected (via the reservoir assembly Fig. 1:33) to the cell culture space of the at least one multi-layered vessel and configured to supply liquid media to the cell culture space. See paragraphs 57, 62 and 72.
Regarding claim 24, Ho discloses wherein the main inlet is fluidly connected to multiple multi-layered vessels. See paragraphs 60 and 62.
Regarding claim 25, Ho discloses wherein the cabinet comprises a gas port configured to supply gas (gassing/bleeding assembly 32) to the interior cavity discussed in paragraphs 7, 62, 72 and 79.
Regarding claim 26, Ho discloses further comprising a gas supply fluidly connected to the gas port (As disclosed herein the bioreactor system wherein the gassing assembly is configured to supply actively the gas into the culture vessel and alter the gas composition by adjusting the flow rate of each supplied gas using a mass flow controller controlled by the control apparatus or manually regulated by a rotameter.) discussed in paragraphs 44 and 46.
Regarding claim 27, Ho discloses further comprises a temperature control system configured to control a temperature of the interior cavity (A heater fan 16 is mounted on the top of the supporting vessel 7 to control the temperature of inside of the supporting vessel 7 by a controller of the control apparatus.) discussed in paragraph 72.
Regarding claim 28, Ho discloses wherein the temperature control system comprises at least one of a heat source discussed in paragraph 72.
Regarding claim 29, Ho discloses wherein the cabinet is configured to change the orientation of the multi-layered vessel by changing an orientation of the cabinet discussed in paragraph 58.
Regarding claim 30, Ho discloses wherein the orientation of the multi-layered vessel is fixed with respect to the cabinet discussed in paragraph 58.
Regarding claim 31, the supporting vessel of Ho can be used as an incubator for the at least one closed culture vessel 1 inside of the vessel and therefore, implicitly discloses wherein the one or more sidewalls comprise an opening to the interior cavity, the opening sized to allow insertion or removal of the multi-layered vessel. See paragraphs 8 and 43.
Regarding claim 32, the supporting vessel of Ho can be used as an incubator for the at least one closed culture vessel 1 inside of the vessel and therefore, implicitly discloses wherein the cabinet comprises a door covering the opening, the door being configured to seal the interior cavity when the multi-layered vessel is disposed in the interior cavity. See paragraphs 8 and 43.
Regarding claim 37, since the device disclosed by Ho is structurally the same as the instantly claimed. Thus, in the absence of further positively recited structure the device of Ho is capable of providing the operating conditions wherein, an orientation of the multi-layered vessel is variable with respect to an orientation of the cabinet in view of paragraphs 7, 46 and 54.
Additionally, it is noted that apparatus claims cover what a device is, not what a device does or how it is to be used. A claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim. See MPEP § 2114.
Regarding claim 39, Ho discloses a plurality of culture vessels for holding respective culture material including medium and cells as implied in paragraphs 40-41. The contents (e.g., at least one of a 2D adherent cell culture film and a 3D microcavity film) of the plurality of culture vessels depend on the intended use of the apparatus, which in turn does not patentably distinguish it from the prior art. See MPEP § 2114.
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.
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.
Claims 6, 11-13, 20-21, 17, 33-36 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Ho US 2018/0371394 as applied above to claims 1-5, 7-10, 14-16, 18-19, 23-32, 37 and 39.
Regarding claim 6, Ho does not explicitly disclose wherein the multi-layered vessel comprises at least one sensor window through which the sensor is configured to sense the property within the cell culture space. Ho does however, disclose the use of on-line and off-line analyzers in paragraph 55. Therefore, Ho implicitly discloses at least one sensor window through which the sensor is configured to sense the property within the cell culture space.
Regarding claim 11, Ho discloses the culture vessel 1 is connected through two ports 2 and 3 with flexible tubing or the likes to the supply of respiratory gas, culture material, fresh medium, reagents or the storage of spent fluid, medium, gas and reagents from the reservoir assembly 33 and to exit to a vessel 20 with air filter 21 in the reservoir assembly 33 discussed in at least paragraph 57.
Ho does not explicitly disclose that the inlet (port 2) is disposed in a lower portion of the multi-layered vessel.
However, absent unexpected results, it would have been prima facie obvious to one of ordinary skill in the art to arrange the inlet a lower portion of the multi-layered vessel, since it has been held that rearranging parts of an invention involves only routine skill in the art. See MPEP §2144.04 (VI-C).
Regarding claim 12, Ho discloses the culture vessel 1 is connected through two ports 2 and 3 with flexible tubing or the likes to the supply of respiratory gas, culture material, fresh medium, reagents or the storage of spent fluid, medium, gas and reagents from the reservoir assembly 33 and to exit to a vessel 20 with air filter 21 in the reservoir assembly 33 discussed in at least paragraph 57.
Ho does not explicitly disclose that the outlet (port 3) is disposed in an upper portion of the multi-layered vessel.
However, absent unexpected results, it would have been prima facie obvious to one of ordinary skill in the art to arrange the outlet an upper portion of the multi-layered vessel, since it has been held that rearranging parts of an invention involves only routine skill in the art. See MPEP §2144.04 (VI-C).
Regarding claim 13, Ho discloses a modified vessel with relocation of the gas exit port 3 to the opposite diagonal corner of inlet port 2 so that the gas flow can travel the longest distance across the compartment in each tray. shown in Fig. 4 (3); and discussed in at least paragraph 67.
Regarding claim 17, Ho does not explicitly disclose wherein the cell culture surface area is about 50,000 cm2. However, Ho does disclose that the length of vessel 1 can also be extended to increase the surface area per vessel see paragraph 72.
Therefore, since providing a cell culture surface area of about 50,000 cm2 would only require a mere change in the size (or dimension) of a component which is generally recognized as being within the level of ordinary skill in the art, a mere change in size or dimension of the device, i.e. depth, would have been prima facie obvious to one of ordinary skill in the art. Furthermore, where the only difference between the prior art and the claims is a recitation of relative dimensions of the claimed device, and the device having the claimed dimensions would not perform differently than the prior art device, the claimed device is not patentably distinct from the prior art device. See MPEP §2144.04 (IV)(A).
Regarding claim 20, Ho does not explicitly disclose wherein multiple multi-layered vessels are disposed on each of the multiple support surfaces.
Absent unexpected results, it would have been prima facie obvious to one of ordinary skill in the art to utilize multiple multi-layered vessels such that wherein multiple multi-layered vessels are disposed on each of the multiple support surfaces, since it has been held that mere duplication of the essential working parts of a device involves only routine skill in the art. See MPEP §2144.04 (VI-B).
Regarding claim 21, Ho discloses that the inlets of the multi-layered vessel are disposed on one of the multiple support surfaces are manifolded together as discussed in at least paragraphs 10 and 13.
While Ho does not explicitly disclose multiple multi-layered vessels, absent unexpected results, it would have been prima facie obvious to one of ordinary skill in the art to utilize multiple multi-layered vessels s, since it has been held that mere duplication of the essential working parts of a device involves only routine skill in the art. See MPEP §2144.04 (VI-B).
Regarding claim 33, Ho does not explicitly disclose wherein the cabinet comprises a gas-impermeable enclosure within the interior cavity. Ho does disclose in paragraph 43 that supporting vessel [7] may be temperature controlled and used as an incubator for the at least a closed culture vessel [1] inside of the supporting vessel. Also see paragraph 8. Ho also discloses in paragraph 73 that In the static culture both the cells attached on the culture surface of the vessel and the medium remain static under a controlled environmental condition such as a CO2 incubator or the like for the entire culture time. In the other hand, for the dynamic culture the cells attached on the culture surface of the vessel constantly or frequently moving against the medium or vice versa under a controlled environmental condition such as a CO2 incubator or the like for the entire culture process. Lastly, Ho discloses that the supporting vessel performs all culture process automatically in a closed system as discussed in paragraph 78.
Therefore, in view of the teachings above, the supporting vessel of Ho implicitly discloses wherein the cabinet comprises a gas-impermeable enclosure within the interior cavity, the gas-impermeable enclosure being configured to enclosure the at least one multi-layered vessel.
Assuming arguendo, that one of ordinary skill in the art would not consider the supporting vessel of Ho to be a gas-impermeable enclosure. It would have been prima facie obvious to one of ordinary skill in the art to provide a gas-impermeable enclosure in order to provided and maintain the requisite environmental conditions of a CO2 incubator as discussed in paragraph 73 of Ho.
Regarding claim 34, Ho discloses wherein the gas port is coupled to an opening in the gas-impermeable enclosure as shown in Fig. 1:32 and discussed in at least paragraph 5.
Regarding claim 35, Ho discloses that the supporting vessel may be temperature controlled and used as an incubator for the at least a closed culture vessel inside of the supporting vessel discussed in at least paragraphs 8 and 43. However, Ho does not explicitly disclose a separate incubation enclosure configured to house the cabinet.
Absent unexpected results, it would have been prima facie obvious to one of ordinary skill in the art to provide incubation enclosure configured to house the cabinet, since it has been held that forming in one piece an article which has formerly been formed in two pieces and put together involves only routine skill in the art. See MPEP §2144.04 (V-B).
Regarding claim 36, Ho discloses wherein the incubation enclosure comprises one or more ports configured for at least one of supplying liquid media to the multi-layered vessel and carrying signals from sensors of the cell culture system to an exterior of the incubation enclosure as shown in Fig. 1:33 and discussed in at least paragraph 5.
Regarding claim 38, Ho discloses wherein the multi-layered vessel comprises a gas-permeable substrate (The gas from the incubator diffuses through a filtered cap and a manifold into each tray of the culture vessel and the oxygen further diffuses through the medium and is transferred to the cells which are attached on the bottom surface of tray.) separating the cell culture space from the interior cavity discussed in at least paragraph 44.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYDIA EDWARDS whose telephone number is (571)270-3242. The examiner can normally be reached on Monday-Thursday 6:30-5:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Elizabeth Robinson can be reached on 571-272-7129. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LYDIA EDWARDS/Primary Examiner, Art Unit 1796