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
Claims 27, 32, 33, 36, 40, 43, 44, and 49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/20/2025.
Applicant’s election of Group I in the reply filed on 08/20/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
It is noted that Claims 27, 32, 33, 36, 40, 43, 44, and 49 have further been cancelled by Applicants.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
Claim 47 states a microplate is within the chambers. Applicant’s specification does not have the support for this limitation.
Claim Objections
Claims 1 and 14 are objected to because of the following informalities:
Claim 1 uses periods throughout the claim. Claims should not contain periods except at the end and in abbreviations. See MPEP 608.01(m).
Claim 14 states “the first chamber has an aerobic environment the second chamber has”. Examiner believes this is a typographical error and should read “the first chamber has an aerobic environment and the second chamber has”
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 19, 20, 30 and 47 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 19 recites the limitation "the bacterial environment" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. For examination purposes, it is interpreted as the anaerobic environment.
Claim 20 states “ the chamber” in line 1. It is unclear whether this is referring to the first chamber or second chamber. For examination purposes, it is interpreted as being the first chamber.
Claim 30 states “sample volumes.. enable various analytical techniques”. It is unclear how a sample volume can enable an analytical technique. The sample volume can be analyzed by different analytical techniques, but it is unclear how the techniques are enabled by the volume. Further clarification is requested.
Claim 30 states “multiple chambers in parallel”. It is unclear if these are the same as the first chamber and the second chamber or different chambers. For examination purposes, it is interpreted as the first and second chambers.
Claim 47 states “on a microplate within the first chamber… on the microplate within the second chamber” in lines 2-3. It is unclear how a microplate can be both within the first chamber and within the second chamber. Further clarification is requested.
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, 3, 8, 10, 15, 30, and 31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Andrews (US5346826A).
Regarding Claim 1, Andrews teaches the following:
A bioreactor, a metabolite holding tank, a solution holding tank, a dilute solution holding tank, and a cell collection tank (col 10, lines 5-10)(a perfusion bioreactor system)
A bioreactor 12 (first chamber) comprising an inner tubular dialysis membrane 22 (an inner membrane) and an outer cylindrical vessel 24 (an outer wall) and the arrangement of the membrane 22 and the vessel 24 provides an inner reaction zone 26 within the membrane (an inner volume) and an outer reaction zone 28 in the space between the wall of the vessel and the wall of the membrane (an outer volume surrounding the inner membrane)(col 10, lines 8-20)
A primary solution holding tank 16 (a second chamber with an outer wall defining an outer volume comprising all the contents in the chamber)(col 10, line 39)
Primary nutrient solution is fed from the holding tank 16 (second chamber) through line 42 (hollow conduit) and through the valves 44, 46, and 48 into the inside of the tubular membrane 22 (part of the first chamber)(orifice in each of the chambers which allows fluid communication between the first and second chambers)(col 10, lines 39-53)
Primary nutrient solution is fed from the holding tank 16 and pumped by pump 42a (first pump) through line 42 (hollow conduit) and into the inside of tubular membrane 22 (first chamber)(a first pump in fluid communication with the hollow conduit, the first pump to move fluid between the first chamber and the second chamber)(para 32)
Cells grow within the inner reaction zone 26 (the inner membrane houses cells in the inner volume)(col 10, line 54)
The primary nutrient solution is suitable medium for culturing cells and as stated above, is pumped from the second chamber to the first meaning both chambers contain the medium.
Note: the second chamber does not contain the optional inner membrane and therefore any limitations relating to the inner membrane of the second chamber have not been addressed.
Regarding Claim 3, Andrews teaches all of the limitations of Claim 1 (see above). Andrews further teaches the following:
The cell product stream from the inner reaction zone 26 (inner volume of the first chamber) flows out through line 76 (a sampling orifice in fluid communication with the inner volume that allows removal of fluid from the inner volume)(col 11, lines 10-15)
The dilute nutrient solution is pumped by pump 52 in line 54, moving it through the outer reaction zone 28 (outer volume of the first chamber)(a sampling orifice in fluid communication with the outer volume that allows removal of fluid from the outer volume)(col 10, lines 58-65)
The primary solution holding tank 16 (second chamber) has valved line 31 (sampling orifice) which is in fluid communication with the outer volume that allows removal of fluid from the outer volume (col 10, lines 50-55)
Regarding Claim 8, Andrews teaches all of the limitations of Claim 1 (see above). Andrews further teaches primary nutrient solution is fed from the holding tank 16 (second chamber) through line 42 and into the inside of the tubular membrane 22 (part of the first chamber)(fluid removed from the outer volume of the second chamber is mixed in the first chamber via an orifice)(col 10 lines 39-50).
Regarding Claim 10, Andrews teaches all of the limitations of Claim 1 (see above). Andrews further teaches an aerobic environment within the inner reaction zone 26 (first chamber)(col 11, lines 20-25).
Regarding Claim 15, Andrews teaches all of the limitations of Claim 10 (see above). Andrews further teaches the cellular material to be yeast, mold, bacteria (microbial cells) and plant cells (col 1, lines 40-45).
Regarding Claim 30, Andrews teaches all of the limitations of Claim 3 (see above). The sample volumes being used for various analytical techniques and results is an intended use of the invention. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim (see MPEP 2114). Since Andrews teaches the sampling orifices, a sampling volume could be collected and analytical techniques could be performed.
Regarding Claim 31, Andrews teaches all of the limitations of Claim 3 (see above). Andrews further teaches a typical condition with the bioreactor using a dialysis tube 36 inches long and .5 inches in diameter (col 11, lines 30-35). This volume is about 115 mL and therefore a sample of 100mL could be taken throughout the process.
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 1 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Maekawa et al. (JPH06197772A) in view of Andrews (US5346826A).
Regarding Claim 1, Maekawa teaches the following:
A first chamber with an outer wall defining an outer volume (Fig. 1 below)
A second chamber comprising an outer wall defining an outer volume comprising all the contents of the chamber (Fig. 1, below)
A hollow conduit (4) connecting the first and second chambers via an orifice in each chamber (Fig. 1, below) which allows fluid communication between the chambers
A first pump (8) in fluid communication with the conduit which moves fluid between the first chamber and the second chamber (para 10 and Fig. 1, below)
A conduit for circulating the culture solution from the first reactor to the second reactor (each chamber comprises a suitable medium for culturing the cells)(para 7)
Maekawa further teaches ultrafiltration membrane modules 7 and the first and second reactors contain bacteria cells (para 10).
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Maekawa does not teach the first chamber to have an inner membrane defining an inner volume, the outer wall surrounding the inner membrane.
Andrews teaches a bioreactor 12 (first chamber) comprising an inner tubular dialysis membrane 22 (an inner membrane) and an outer cylindrical vessel 24 (an outer wall) and the arrangement of the membrane 22 and the vessel 24 provides an inner reaction zone 26 within the membrane (an inner volume) and an outer reaction zone 28 in the space between the wall of the vessel and the wall of the membrane (an outer volume surrounding the inner membrane)(col 10, lines 5-20). Note: the cells would then be provided within the inner membrane.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the bioreactor system of Maekawa with an inner dialysis membrane as taught by Andrews. One would have been motivated to make this modification as it would allow the cells to remain in the reactor to continue growth and allow the byproducts to pass through into the solution (Andrews, col 2, lines 25-30).
Regarding Claim 14, Maekawa in view of Andrews teach all the limitations of Claim 1 (see above). Maekawa further teaches culturing aerobic and anaerobic bacteria in separate reactors under their respective optimal conditions (the first chamber has an aerobic environment and the second chamber has an anaerobic environment)(para 1).
Claims 7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Andrews (US5346826A) in view of Vetillard et al. (CN1460122A).
Regarding Claim 7, Andrews teaches all of the limitations of Claim 1 (see above). Andrews does not teach the fluid removed from the first chamber to be mixed in the second chamber via an orifice.
Vetillard teaches a cell culture chamber and a bioreactor for the culture of animal cells (para 2). Vetillard further teaches the liquid medium in F1 chamber are connected by pipes to the container R1 in which the nutrient medium is circulated through pump P1 (para 115 and 116).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Andrews with the recirculating medium as taught by Vetillard. One would have been motivated to make this modification as it would provide the growth factors necessary for the development of the cells (para 115).
Regarding Claim 9, Andrews teaches all of the limitations of Claim 1 (see above). Andrews does not teach the volume of the first chamber being mixed to expose the second chamber to fluid containing secreted products from the cell cultured in the first chamber.
Vetillard further teaches the liquid medium in F1 chamber are connected by pipes to the container R1 in which the nutrient medium is circulated through pump P1 (para 115 and 116).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Andrews with the recirculating medium as taught by Vetillard. One would have been motivated to make this modification as it would provide the growth factors necessary for the development of the cells (para 115).
Note: the second chamber does not contain the optional inner membrane and therefore does not contain cells and the limitation of the secreted products from the cells cultures in the second chamber being mixed in the first chamber is not addressed.
Claims 11, 18 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Andrews (US5346826A).
Regarding Claim 11, Andrews teaches all of the limitations of Claim 1 (see above). Andrews further teaches if desired, the conditions in the inner reaction zone could be changed to anaerobic (col 11, lines 20-30).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to change the inner reaction zone to anaerobic as Andrews teaches it to be an effective environment for the growth of cells.
Regarding Claim 18, Andrews teaches all of the limitations of Claim 11 (see above). Andrews further teaches the cells can be bacteria (col 1, lines 40-45).
Regarding Claim 25, Andrews teaches all of the limitations of Claim 1 (see above). Andrews teaches the cells to be plant cells and a metabolite byproduct stream which is recycled to improve yields (col 1, lines 45-50). Andrews does not explicitly teach the cells to sense and respond to secreted signals.
Note: Applicant’s specification described the secreted materials to be proteins, peptides, metabolites, etc.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to choose a cell which would sense and respond to secreted signals like metabolites as the system of Andrews recycles the metabolites back to the system which would improve the yield of the cells (col 1, lines 45-50).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Andrews (US5346826A) in view of Zenhausern et al. (US20180155665A1).
Andrews teaches all of the limitations of Claim 18 (see above). Andrews does not explicitly teach the anaerobic environment to comprise a mucin-coated membrane.
Zenhausern teaches a cell culture apparatus comprising two channels separated by a permeable membrane, one channel carrying epithelial cells, the other microbiota (Abstract). Zenhausern further teaches the membrane to comprise a mucin coated nanoporous membrane (Claim 19).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the membrane of Andrews with a mucin-coated membrane as taught by Zenhausern. One would have been motivated to make this modification to assist initial microbial adhesion (para 55).
Claims 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Andrews (US5346826A) in view of Ott (WO2010141803A2).
Regarding Claim 20, Andrews teaches all of the limitations of Claim 1 (see above). Andrews does not teach the first chamber to comprise human epithelial cells within a matrix-coated scaffold.
Ott teaches an organ bioreactor apparatus (Abstract). Ott further teaches extracellular matrix scaffolds (matrix-coated membrane scaffold) mounted in a bioreactor and seeded with human epithelial cells (page 20, lines 8-16).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select human epithelial cells with the membrane scaffold as taught by Ott for use in the device as taught by Andrews. One would have been motivated to make this selection as Andrews teaches his device is usable for growing eukaryotic cells (Abstract) and it would have resulted in an effective bioreactor for the growth of cells.
Regarding Claim 21, Andrews teaches all of the limitations of Claim 1 (see above). Andrews does not teach the first chamber to comprise human epithelial cells growing on a porous membrane scaffold.
Ott teaches an organ bioreactor apparatus (Abstract). Ott further teaches extracellular matrix scaffolds (porous membrane scaffold) mounted in a bioreactor and seeded with human epithelial cells (page 20, lines 8-16).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select human epithelial cells with the membrane scaffold as taught by Ott for use in the device as taught by Andrews. One would have been motivated to make this selection as Andrews teaches his device is usable for growing eukaryotic cells (Abstract) and it would have resulted in an effective bioreactor for the growth of cells.
Regarding Claim 22, Andrews teaches all of the limitations of Claim 1 (see above). Andrews does not explicitly teach one of the chambers to comprise human epithelial cells.
Ott teaches an organ bioreactor apparatus (Abstract). Ott further teaches a bioreactor is seeded with human epithelial cells (page 20, lines 8-16).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select human epithelial cells as taught by Ott for use in the device as taught by Andrews. One would have been motivated to make this selection as Andrews teaches his device is usable for growing eukaryotic cells (Abstract) and it would have resulted in an effective bioreactor for the growth of cells.
Regarding Claim 23, Andrews in view of Ott teaches all of the limitations of Claim 22 (see above). Since the inner membrane of the second chamber is optional and there are no cells within the second chamber, no microbial cells are present within the system and therefore the limitations of Claim 23 are met.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONATHAN E LEPAGE whose telephone number is (571)270-3971. The examiner can normally be reached 8:30-5:30 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Elizabeth Robinson can be reached at 571-272-7129. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.E.L./Examiner, Art Unit 1796
/ELIZABETH A ROBINSON/Supervisory Patent Examiner, Art Unit 1796