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 with traverse of Group I, claims 1 and 3-19, in the reply filed on 8/17/2026 is acknowledged. The traversal is on the ground(s) that a search for art drawn to a co-culture bioreactor is likely to reveal art drawn to the co-culture system and thus, there should be no undue search burden for examining Groups I and II together. This is not found persuasive because the restriction was evaluated under Unity of Invention, and the lack of Unity of Invention was determined because the technical features of at least two chambers, a selectively permeable membrane associated with each chamber, and a pump associated with each chamber is known in the art and the co-culture bioreactor of the instant application, which includes these technical features, does not make a contribution over the prior art. In addition, the special technical feature, as amended, is disclosed by Hickey et al. (US 2011/0256597 A1) – see rejection below. The requirement is still deemed proper and is therefore made FINAL
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/23/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities:
It is recommended that "each of the selectively permeable membranes being in fluid communication with the outlet of one chamber and the inlet of . Appropriate correction is required.
I. Appropriate correction is required.
Claim 4 is objected to because of the following informalities:
It is recommended that ". Appropriate correction is required.
Claim 7 is objected to because of the following informalities:
It is recommended that ". Appropriate correction is required.
It is recommended that ". Appropriate correction is required.
It is recommended that ". Appropriate correction is required.
Claim 8 is objected to because of the following informalities:
It is recommended that ". Appropriate correction is required.
It is recommended that ". Appropriate correction is required.
It is recommended that ". Appropriate correction is required.
Claim 9 is objected to because of the following informalities:
It is recommended that ". Appropriate correction is required.
It is recommended that ". Appropriate correction is required.
Claim 10 is objected to because of the following informalities:
It is recommended that ". Appropriate correction is required.
Claim 11 is objected to because of the following informalities:
It is recommended that ". Appropriate correction is required.
It is recommended that ". Appropriate correction is required.
Claim 15 is objected to because of the following informalities:
It is recommended that ". Appropriate correction is required.
Claim 17 is objected to because of the following informalities:
It is recommended that ". Appropriate correction is required.
Claim 18 is objected to because of the following informalities:
It is recommended that ". 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.
Claims 6-11 and 14 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 6 recites the limitation "the " in line . There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the cylindrical housing" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the " in line. There is insufficient antecedent basis for this limitation in the claim.
Claim 14 recites the limitation "the" in line. It is unclear whether this limitation refers to the first selectively permeable membrane, the second selectively permeable membrane, or both.
Dependent claims are rejected for the same reason as the base claim(s) upon which they depend.
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, 3, 5, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hickey et al. (US 2011/0256597 A1).
Regarding claim 1, Hickey et al. discloses a co-culture bioreactor (para. 0030, claim 11 “co-culture”) comprising
at least a first chamber and a second chamber (Fig. 5 bioreactors 27, 29, 31), each chamber configured to house a distinct microorganism cell type in a shared culture medium (para. 0030, claim 11 “co-culture”) and each chamber having an inlet and an outlet for the shared culture medium (Fig. 5 lines 38, 40, 42);
a first selectively permeable membrane associated with the first chamber and a second selectively permeable membrane associated with the second chamber (para. 0032 “membranes”; Fig. 5), each of the selectively permeable membranes being in fluid communication with the outlet of one chamber and the inlet of one or more other chambers (para. 0032; Fig. 5), each of the selectively permeable membranes being individually configured to prevent permeation of microorganism cells from the one chamber it is associated with through the membrane and into the one or more other chambers whilst allowing culture medium and selected biomolecules to permeate therethrough (para. 0032 “the membranes concurrently serve as the support upon which the fermenting cells grow as a biofilm and are thus retained in a concentrated layer”); and
a first pump in fluid communication with the outlet of the first chamber and the inlet of the second chamber and configured to pump culture medium in the first chamber across the first selectively permeable membrane such that a first permeate stream from the first selectively permeable membrane is formed and directed to the inlet of the second chamber and a second pump in fluid communication with an outlet of the second chamber and an inlet of the first chamber and configured to pump culture medium in the second chamber across the second selectively-permeable membrane such that a second permeate stream from the second selectively-permeable membrane is formed and directed to the inlet of the first chamber in use (para. 0032 “liquid is passed in the liquid side of the membranes via pumping”; Fig. 5).
Regarding claim 3, Hickey et al. discloses a co-culture bioreactor including more than two chambers (Fig. 5 bioreactors 27, 29, 31), each chamber having at least one selectively permeable membrane (para. 0032 “membranes”; Fig. 5) and at least one pump associated with it, and wherein each pump is configured to pump culture medium from the chamber the pump is associated with across the selectively permeable membrane associated with the chamber to cause a culture medium permeate stream substantially devoid of microorganism cells to be formed and directed into the one or more other chambers in use (para. 0032 “liquid is passed in the liquid side of the membranes via pumping”; para. 0032 “the membranes concurrently serve as the support upon which the fermenting cells grow as a biofilm and are thus retained in a concentrated layer”).
Regarding claim 5, Hickey et al. discloses a co-culture bioreactor wherein each of the selectively permeable membranes is configured for crossflow filtration (para. 0032 “the membranes concurrently serve as the support upon which the fermenting cells grow as a biofilm and are thus retained in a concentrated layer”) and provides a pressurized interface (para. 0036) of a selected size for culture medium and selected biomolecule exchange between chambers in use.
Regarding claim 12, Hickey et al. discloses a co-culture bioreactor wherein each selectively permeable membrane has an individually selected pore size ranging between about 0.05 µm and 0.2 µm (para. 0035).
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.
Claims 14 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Hickey et al. (US 2011/0256597 A1).
Regarding claim 14, Hickey et al. discloses that a bioreactor comprising a ceramic membrane is known in the art (para. 0033). Though Hickey et al. does not explicitly teach a ceramic membrane, it would have been obvious to a person of ordinary skill in the art to use a ceramic membrane because the substitution of one known element for another would have predictably resulted in a membrane that has a fine porous structure (para. 0033), with reasonable expectation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute a ceramic membrane to obtain the invention as specified in claim 14.
Regarding claim 18, Hickey et al. discloses a co-culture bioreactor wherein each chamber has an individually controllable temperature controller (para. 0053 “the tank provides the means of temperature and pH controls”). Hickey et al. does not disclose this feature in the embodiment shown in Fig. 5, but does disclose this feature in the embodiment shown in Fig. 4. However, it would have been obvious to one of ordinary skill in the art to substitute the tank in Fig. 5 for the tank in Fig. 4 because Hickey et al. teaches that this configuration of temperature controls sustains the activity of microbial cells in the tank (para. 0053). The substitution of one known element for another would have predictably yielded an apparatus that sustains the activity of microbial cells in the tank with reasonable expectation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the bioreactors of Fig. 5 with the tank with temperature controls of Fig. 4 to obtain the invention as specified in claim 18.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Hickey et al. (US 2011/0256597 A1) in view of Chisholm et al. (US 2013/0324406 A1).
Regarding claim 4, Hickey et al. discloses a co-culture bioreactor wherein each pump is configured to pump culture medium from the chamber the pump is associated with across the selectively permeable membrane associated with the chamber (para. 0032 “liquid is passed in the liquid side of the membranes via pumping”), but does not explicitly disclose wherein each pump is individually controllable. However, Chisholm et al. teaches a process controller which controls pumps to monitor parameters and adjust the system controls with feedback (para. 0187). It would have been obvious to a person of ordinary skill in the art to use the Chisholm et al. configuration of a controller which controls pumps in Hickey et al.’s device with a reasonable expectation that it would monitor parameters and adjust the system controls with feedback. This method for improving Hickey et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Chisholm 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 Hickey et al. and Chisholm et al. to obtain the invention as specified in claim 4.
Claims 6-11 are rejected under 35 U.S.C. 103 as being unpatentable over Hickey et al. (US 2011/0256597 A1) in view of Weissenbach et al. (US 2023/0303956 A1).
Regarding claim 6, Hickey et al. discloses a co-culture bioreactor wherein each of the selectively permeable membranes is housed in a membrane enclosure (Fig. 5 bioreactors 27, 29, 31) with an inlet for culture medium that is in fluid communication with its associated chamber (Fig. 5 lines 38, 40, 42); and a permeate outlet on the permeate side of the membrane for the permeate stream to be directed to one or more other chambers not associated with the membrane in use (Fig. 5 lines 38, 40, 42). Hickey et al. does not disclose an outlet for a cell-containing culture medium stream on a feed side of the membrane that is in fluid communication with the associated chamber for returning a cell-containing culture medium stream to the associated chamber in use. However, Weissenbach et al. teaches an outlet for cells and culture medium which allows the circulation of cells and medium in both forward flow and reverse flow (para. 0042). It would have been obvious to a person of ordinary skill in the art to use the Weissenbach et al. configuration of an outlet for cells and culture medium in Hickey et al.’s device with a reasonable expectation that it would allow the circulation of cells and medium in both forward flow and reverse flow. This method for improving Hickey et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Weissenbach 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 Hickey et al. and Weissenbach et al. to obtain the invention as specified in claim 6.
Regarding claim 7, Hickey et al. discloses a co-culture bioreactor wherein the membrane enclosure is a generally cylindrical housing and the selectively permeable membrane is generally cylindrical (para. 0058) and extends at least partially between the ends of the cylindrical housing with the inlet for the culture medium and outlet for the cell-containing culture medium stream located at opposite ends of the cylindrical membrane (Fig. 5 bioreactors 27, 29, 31).
Regarding claim 8, Hickey et al. discloses a co-culture bioreactor wherein the permeate outlet is provided in a side wall of the cylindrical housing for extracting permeate located on the permeate side of the membrane between the membrane and the side wall of the housing in use (Fig. 5 outlet in bioreactor 31 connected to line 40, outlet in bioreactor 29 connected to line 42).
Regarding claim 9, Hickey et al. discloses a co-culture bioreactor wherein the permeate outlet is near the end of the cylindrical housing which has the outlet for the cell-containing culture medium stream (Fig. 5 outlet in bioreactor 31 connected to line 40, outlet in bioreactor 29 connected to line 42).
Regarding claim 10, Hickey et al. discloses a co-culture bioreactor wherein the inlet for the culture medium is connected through the pump to the associated chamber to permit culture medium to be pumped from the chamber, across the selectively permeable membrane to create the cell-containing culture medium stream which is directed back into the associated chamber and the permeate stream which is directed to one or more other chambers, and wherein the pump is configured to continually pump culture medium across the selectively permeable membrane and thus to continually transfer permeate between the two or more different chambers and return cell-containing culture medium into the associated chamber (para. 0032; Fig. 5 bioreactors 27, 29, 31; lines 38, 40, 42). Hickey et al. does not disclose an outlet for a cell-containing culture medium. However, Weissenbach et al. teaches an outlet for cells and culture medium which allows the circulation of cells and medium in both forward flow and reverse flow (para. 0042). It would have been obvious to a person of ordinary skill in the art to use the Weissenbach et al. configuration of an outlet for cells and culture medium in Hickey et al.’s device with a reasonable expectation that it would allow the circulation of cells and medium in both forward flow and reverse flow. This method for improving Hickey et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Weissenbach 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 Hickey et al. and Weissenbach et al. to obtain the invention as specified in claim 10.
Regarding claim 11, Hickey et al. discloses a co-culture bioreactor which includes a valve between the outlet for the cell-containing culture medium stream of the membrane enclosure and the associated chamber, the valve being configured to increase the fluid flow pressure at the selectively permeable membrane to a level at which culture medium and selected biomolecules permeate therethrough (para. 0063 “The flow rate of this recirculating medium is 180 ml/min, and the pressure at the outlet of the membrane module is maintained at 5 psig by adjusting a back-pressure valve”).
Claims 13 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Hickey et al. (US 2011/0256597 A1) in view of Nagy et al. (US 2022/0325231 A1).
Regarding claim 13, Hickey et al. discloses a co-culture bioreactor wherein each selectively permeable membrane has an individually selected pore size of 0.05 µm, but does not disclose a pore size ranging between about 0.08 µm and 0.1 µm. However, Nagy et al. discloses membranes having a pore diameter of 20 to 100 nanometers (para. 0079), which can be read as 0.02 µm to 0.1 µm. Nagy et al. teaches that a pore size of 20 to 100 nanometers retain viruses on the membrane surface while permitting passage of the target substance through the membrane (para. 0079). It would have been obvious to a person of ordinary skill in the art to use the Nagy et al. configuration of pore sizes of 20 to 100 nanometers in Hickey et al.’s device with a reasonable expectation that it would retain viruses on the membrane surface while permitting passage of the target substance through the membrane. This method for improving Hickey et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Nagy 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 Hickey et al. and Nagy et al. to obtain the invention as specified in claim 13.
Regarding claim 15, Hickey et al. discloses a co-culture bioreactor comprising selectively permeable membranes (see claim 1 above), but does not disclose wherein an additional selectively permeable membrane is provided downstream of one of the first and second selectively permeable membranes, optionally having a smaller pore size than the first or second selectively permeable membrane. However, Nagy et al. teaches an additional filter positioned downstream an outlet of the apparatus which performs purification steps external to the apparatus (para. 0083). It would have been obvious to a person of ordinary skill in the art to use the Nagy et al. configuration of an additional filter in Hickey et al.’s device with a reasonable expectation that it would perform additional purification external to the bioreactors. This method for improving Hickey et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Nagy 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 Hickey et al. and Nagy et al. to obtain the invention as specified in claim 15.
Regarding the limitation “optionally having a smaller pore size than the first or second selectively permeable membrane”, Nagy et al. discloses membranes having a pore diameter of 20 to 100 nanometers (para. 0079), which is a smaller size than the pore size disclosed by Hickey et al. (para. 0035 “0.05 µm”). Nagy et al. teaches that a pore size of 20 to 100 nanometers retain viruses on the membrane surface while permitting passage of the target substance through the membrane (para. 0079). It would have been obvious to a person of ordinary skill in the art to use the Nagy et al. configuration of pore sizes of 20 to 100 nanometers in Hickey et al.’s device with a reasonable expectation that it would retain viruses on the membrane surface while permitting passage of the target substance through the membrane. This method for improving Hickey et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Nagy 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 Hickey et al. and Nagy et al. to obtain the invention as specified in claim 15.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Hickey et al. (US 2011/0256597 A1) in view of Doherty et al. (US 11,859,214).
Regarding claim 16, Hickey et al. discloses a co-culture bioreactor comprising multiple chambers, but does not disclose wherein each chamber has a volume of about 300 ml or more. However, Doherty et al. teaches a modular system comprising vessels having a volume ranging from about 200 mL to about 600 mL (Col. 18, line 66). It has been held that in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists (MPEP § 2144.05). The claimed range is obvious in view of Doherty et al. because Doherty et al. discloses a range of about 200 mL to about 600 mL, which overlaps the claimed range of about 300 mL or more. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the claimed range from the broader prior art range because the prior art teaches the same utility of growing microorganisms (Col. 18, line 66) over the entire range.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Hickey et al. (US 2011/0256597 A1) in view of Spahr et al. (US 2019/0382700 A1).
Regarding claim 17, Hickey et al. discloses a co-culture bioreactor wherein the medium is stirred in the tank (para. 0053), but does not explicitly disclose wherein each chamber has an individually controllable stirrer. However, Spahr et al. teaches a modular bioreactor system comprising a stirring device in each reactor (Fig. 1a 7,8) which intermixes the substrate in the reactors (para. 0037). It would have been obvious to a person of ordinary skill in the art to use the Spahr et al. configuration of a stirring device in Hickey et al.’s device with a reasonable expectation that it would intermix the contents in each chamber. This method for improving Hickey et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Spahr 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 Hickey et al. and Spahr et al. to obtain the invention as specified in claim 17.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Hickey et al. (US 2011/0256597 A1) in view of Belicka et al. (US 2016/0024458 A1).
Regarding claim 19, Hickey et al. discloses a co-culture bioreactor comprising multiple chambers, but does not disclose wherein each chamber includes a sampling port for sampling culture medium or harvesting cells therefrom. However, Belicka et al. teaches a modular bioreactor system comprising a sample port which allows a user to remove a sample to determine the optical density of the inoculum culture (para. 0196). It would have been obvious to a person of ordinary skill in the art to use the Belicka et al. configuration of a sample port in modified Hickey et al.’s device with a reasonable expectation that it would allow a user to remove a sample to determine a characteristic of the culture. This method for improving modified Hickey et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Belicka 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 Hickey et al. and Belicka et al. to obtain the invention as specified in claim 19.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: Haley, III (US 2010/0279395 A1) discloses a system for cultivating microorganisms including connected chambers recirculation lines.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY LOPEZLIRA whose telephone number is (703)756-5517. The examiner can normally be reached Mon - Fri: 8:30-5:00.
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/ASHLEY LOPEZLIRA/Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799
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