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 .
Election/Restrictions
Applicant’s election of Invention I, claims 1-18, in the reply filed on 05/05/2026 is acknowledged. Claims 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. This election was made without traverse in the reply filed on 05/05/2026.
Priority
Receipt is acknowledged of certified copies of papers (Taiwan Application No. 111128412 filed on July 28th, 2022) required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 09/20/2023 has been considered and made of record.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 15-17 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Merchav et al. (US 20050176143 A1) (referenced in 892).
Regarding claim 1, Merchav et al. teaches a bioreactor apparatus (para. [0002]), comprising:
a liquid storage chamber for storing a culture medium (See annotated FIG. 1 on the following page – element 1 (medium reservoir));
a pump (FIG. 1, element 9 (peristaltic pump));
a culture chamber (FIG. 1, element 5 (plug or container of plug flow bioreactor)) having an accommodating space to accommodate the culture medium and a cell to be cultured (para. [0089]);
a pipeline connected to the liquid storage chamber, the pump, and the culture chamber to form a closed loop (FIG. 1);
wherein the pump is configured to provide pressure to drive the flow of the culture medium in a closed loop (para. [0113]). Therefore, this claim is anticipated.
Regarding claim 2, Merchav et al. teaches the bioreactor apparatus of claim 1. Merchav et al. further teaches the culture chambers connected to each other in parallel (para. [0112]). Therefore, the claim is anticipated.
Regarding claim 15, Merchav et al. teaches the bioreactor apparatus of claim 1. Merchav et al. further teaches injection port (FIG. 1, element 4), which allows injection for seeding onto the scaffold of the bioreactors (culture chambers). Thus, injection port allows the adding of an additional substance (stromal cells) into the pipeline. The injection port is structurally the same as the connector of claim 15 – as it allows a substance to be added into the system. Thus, this claim limitation is anticipated.
PNG
media_image1.png
391
674
media_image1.png
Greyscale
Regarding claim 16, Merchav et al. teaches a bioreactor system (See FIG. 1 above), being a closed loop system and comprising:
the bioreactor apparatus of claim 1 (See claim 1 rejection);
a culture medium stored in the liquid storage chamber to be transported through the pipelines to the culture chambers (element 1 – medium reservoir)
a cell culture in the culture chambers (para. [0063] and [0086]). Therefore, the claim is anticipated
Regarding claim 17, Merchav et al. teaches the bioreactor system of claim 16. Furthermore, the culture chamber comprises a liquid section and a gas section, and the liquid section comprises the culture medium for culturing the cells (See FIG. 1 above).
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 3-8 are rejected under 35 U.S.C. 103 as being unpatentable over Merchav et al. (already referenced), as applied to claim 1, in view of Ballew et al. (US 10843186 B1) (referenced in 892).
Regarding claim 3, Merchav et al. teaches the apparatus of claim 1. Merchav et al. teaches that the container used for the bioreactor plug (culture chambers) are columns (this is interpreted as meeting the claim limitation of the culture chamber having an opposite top and bottom part). Merchav et al. fails to teach that the top part has an inlet. Ballew et al. teaches closed fluid receiving and sampling container (abstract, FIG. 4), where the container (FIG. 1B, element 22) is used in a recirculating bioreactor. Ballew et al. specifically teaches container (FIG. 1B, element 22) holds lid (FIG. 2A, element 68), which possess inlet connector (element 26) and outlet connector (element 28 – which connects to the bottom allows media to exit, element 62 – lower siphon end)). Ballew et al. further teaches this lid design of three connectors (element 26, 28, 30) at the top allows “only three avenues of fluid communication between the internal cavity of the receptacle 52 and the outside is through the three connectors 26, 28, 30” (Col 3, Lines 55-67).
PNG
media_image2.png
610
667
media_image2.png
Greyscale
It would have been prima facie obvious to one of ordinary skill, in the art at the time, to use Ballew et al.’s teaching a lid with inlet and outlets at the top in Merchav et al.’s bioreactor device because the lid would allow only fluid communication to be between the internal cavity of the receptacle 52 and the outside. This method of improving Merchav et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Ballew et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Merchav et al. and Ballew et al. to obtain the invention specified in claim 3.
Regarding claim 4, modified Merchav et al. teaches the device of claim 3. The resulting combination of Merchav et al. and Ballew et al. of claim 3 would encompass a culture chamber comprising a lid and a tube, with the lid is disposed on the top part and forms the inlet and the outlet. Therefore, the claim is prima facie obvious.
Regarding claim 5, modified Merchav et al. teaches the apparatus of claim 4. Furthermore, the combination of Merchav et al. and Ballew et al. of claim 4 would encompass a structure with an outlet perpendicular to the lid. Modified Merchav et al., however, fails to teach that the inlet is disposed obliquely relative to the lid. Nevertheless, disposing the inlet obliquely relative to the lid instead of perpendicularly (as taught by Ballew et al.) would amount to rearrangement of parts (MPEP 2144.04.V), as modifying the inlet to be obliquely relative to the lid would not have modified the operation of the device (reJapikse, 181 F.2d 1019, 86 USPQ 70), and is therefore prima facie obvious.
Regarding claim 6, modified Merchav et al. teaches the apparatus of claim 5, but fails to teach that the lid and inlet form an angle of 30 degrees to 60 degrees. Ballew et al.’s lid forms an angle perpendicular (90 degrees) between the lid and inlet. Nevertheless, having the inlet at an angle of 30 degrees to 60 degrees would amount to rearrangement of parts (MPEP 2144.04.V), as modifying the inlet to be 30 degrees to 60 degrees relative to the lid would not have modified the operation of the device, and is therefore prima facie obvious.
Regarding claim 7, modified Merchav et al. teaches the apparatus of claim 3. Ballew et al. further teaches that lid (element 68) attaches to an inner pipe (element 60 - outlet tube), which has an opposite first opening and second opening (See annotated FIG. 1B above), with first opening connected to the outlet (Annotated FIG. 1B above) and second opening located at the bottom part of the culture chamber (Annotated FIG. 1B above). Thus, the combination of the references of claim 3 would encompass a structure with a lid containing an inner pipe with a first and second opening, and is therefore, prima facie obvious.
Regarding claim 8, modified Merchav et al. teaches the apparatus of claim 7. Ballew et al. further teaches “The insert subassembly 53 also includes a siphon or outlet tube 60 leading downward from the outlet connector 28 to an angled siphon end 62 in close proximity to a lower end of the receptacle 52. The lower end of the receptacle 52 may be tapered so that the siphon end 62 is capable of removing all but trace amounts of liquid within the receptacle” (Col. 3 – 7th paragraph). The combination of the references of claim 7 would encompass a structure configured for allowing culture media in the accommodating space to enter the inner pipe through the second opening (element 62 – siphon end) and leave through the first opening and outlet (element 28). Thus, the claim limitation is prima facie obvious.
Claims 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Merchav et al. (already referenced) in view of Ballew et al. (already referenced), as applied to claim 7, and in further view of De et al. (US 20190048305 A1) (referenced in 892).
Regarding claim 9, modified Merchav et al. teaches the device of claim 7, but fails to teach an outer pipe sleeved around an inner pipe. De et al. teaches an outer pipe (See annotated FIG. 5A, vessel – element 202) sleeved around an inner pipe (FIG. 5A, inner vessel – element 246) – which is configured to have spent media and cell secreted material removed in the outer compartment while performing continuous cell culturing (para. [0029]). De et al. further teaches that the vessel 202 contains caps (219a and 219b – structurally an opposite third and fourth opening), which enable fresh media to enter and spent media to exit the system (para. [0040]).
It would have been prima facie obvious to one of ordinary skill, in the art at the time, to use De et al.’s teaching of an outer pipe sleeved around an inner pipe in modified Merchav et al.’s bioreactor device because an inner pipe nested in an outer pipe (openings in the outer tube) enables cell secreted material and spent media to be removed from the culture during continuous cell culturing. This method of improving modified Merchav et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of De et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Merchav et al. and De et al. to obtain the invention specified in claim 9.
Regarding claim 10, modified Merchav et al. teaches the device of claim 9. Furthermore, De et al.’s teaching of openings located on the outer pipe of claim 9 encompasses a structure that enables culture medium to enter the outer pipe through an inlet and third opening. Thus, the claim is prima facie obvious.
Regarding claim 11, modified Merchav et al. teaches the device of claim 9. Furthermore, De et al.’s teaching of a third and fourth opening on the outer pipe encompasses a structure where the diameter of the third opening is larger than a diameter of the fourth opening, and is therefore, prima facie obvious.
Claims 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Merchav et al. (already referenced) in view of Ballew et al. (already referenced), De et al. (already referenced) as applied to claim 9, and in further view of Zhang et al. (CN 107488578 B – MT attached) (referenced in 892).
Regarding claim 12, modified Merchav et al. teaches the device of claim 9. Modified Merchav et al. however fails to teach that the outer pipe has a plurality of holes positioned on a wall of the outer pipe to allow culture medium to flow out of the outer pipe through the holes. Zhang et al. teaches an inner filter cylinder (element 7) containing a plurality of holes present in reactor (FIG. 1). Zhang et al. further teaches that the inner filter cylinder separates biomass powder, cellulase from the bacterial solution, buffer solution, and medium found in the outer cylinder (element 5), and allows the cultured biomass to be stirred and further treated following fermentation (para. [0042-0043] of MT).
It would have been prima facie obvious to one of ordinary skill, in the art at the time, to use Zhang et al.’s teaching of an inner filter cylinder (element 7) in modified Merchav et al.’s bioreactor device with an outer pipe because the filter element separates cultured biomass from the exterior chamber, enabling separation and further treatment following fermentation. This method of improving modified Merchav et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Zhang et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Merchav et al. and Zhang et al. to obtain the invention specified in claim 12.
Regarding the limitation “to allow the culture medium to flow out of the outer pipe through the holes” it has been held that 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 the claimed apparatus from the prior art apparatus if the prior art teaches all the structural limitations of the claim (MPEP § 2114 II). Therefore, the apparatus disclosed by Zhang et al. would be fully capable of achieving every claimed intended use because the prior art apparatus contains a filter cylinder element used for separating cultured biomass, and would be structurally capable of allowing culture medium to flow out through the apertures present.
Regarding claim 13, modified Merchav et al. teaches the device of claim 12. Furthermore, Zhang et al. teaches of apertures arranged at intervals between 30 degrees to 180 degrees in a radial direction in inner filter cylinder (element 7). Thus, the combination of references of claim 12 would encompass a structure of holes arranged at intervals of 30 to 180 degrees in a radial direction of the outer pipe. Therefore, the claim is prima facie obvious.
Regarding claim 14, modified Merchav et al. teaches the device of claim 12. Furthermore, Zhang et al. teaches of apertures arranged asymmetrically in inner filter cylinder (element 7). Thus, the combination of references of claim 12 would encompass a structure of holes arranged asymmetrically. Therefore, the claim is prima facie obvious.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Merchav et al. (already referenced), as applied to claim 16, in view of Engler et al. (US 20190218492 A1) (referenced in 892).
Regarding claim 18, Merchav et al. teaches the bioreactor system of claim 16. Merchav et al. fails to teach that the bioreactor system further comprises a sensor for sensing an ingredient of the culture medium. Engler et al. teaches a bioreactor apparatus with a sensor within the bioreactor adapted and configured to measure the dissolved oxygen concentration in the perfusate (abstract). Furthermore, Engler et al. teaches that the sensor in the device allows for quantifying and controlling oxygen concentration within a bioreactor containing a cell-containing sample that is actively consuming oxygen (para. [0004]).
It would have been prima facie obvious to one of ordinary skill, in the art at the time, to use Engler et al.’s teaching a sensor in Merchav et al.’s bioreactor device because sensor measuring dissolved oxygen concentration allows quantifying and controlling the concentration for the cell culture. This method of improving Merchav et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Engler et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Merchav et al. and Engler et al. to obtain the invention specified in claim 18.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIUS FRANCIS YOH whose telephone number is (571)272-3489. The examiner can normally be reached Monday-Friday: 7:30-5 PM.
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, 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.F.Y./ Examiner, Art Unit 1799
/William H. Beisner/ Primary Examiner, Art Unit 1799
Prosecution Insights