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 statement(s) (IDS) were submitted on:
02/25/2026
Accordingly, the information disclosure statement(s) are being considered by the examiner.
Claim Objections
The previous claim objections over claims 12 and 14 are withdrawn in light of the amendments.
Claim Rejections - 35 USC § 112
The previous claim rejection over claim 22 is withdrawn in light of the amendments.
Claim Rejections - 35 USC § 102 | 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 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.
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.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited); or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited).
Regarding claim 1, Housler discloses a cell culture bioreactor (abstract) comprising a plurality of zones (Fig. 1, there are at least two zones: one for liquids, another for gases) wherein each of the zones has membranes (Fig. 1B, “capillaries” and pg. 134 under Materials and Methods) and wherein a flow of a fluid to each of the zones is separately controllable (Fig. 3 and associated caption for perfusion pump and gas monitor), wherein the bioreactor comprises one or more elements (Fig. 1B, a layer of the capillary network), each element comprising a zone of perfusion membranes (Fig. 1 caption, red and blue perfusion capillaries) that intersects with a zone of gas transfer membranes (Fig. 1 caption, yellow gas capillaries), wherein each element has the membranes of the element potted in a potting material (Fig. 1, beige material between the capillaries) in a plurality of potting cavities (Fig. 1, internal space of Fig. 2, outside surface of the bioreactor) of a mold (Fig. 2, outside surface of the bioreactor), wherein each potting cavity is partially formed by a first part of the mold (Fig. 2, outside surface of the bioreactor, one part of it) and partially formed by a second part of the mold (Fig. 2, outside surface of the bioreactor, second part of it), wherein the first part of the mold (Fig. 2, outside surface of the bioreactor, one part of it) and the second part of the mold (Fig. 2, outside surface of the bioreactor, second part of it) are assembled together (Fig. 2, two parts of an outside surface of the bioreactor are together) and adhered to the potting material by the potting material (Fig. 1, beige material between the capillaries takes up the interior of the bioreactor with the capillaries).
Regarding the phrases “potted”, “formed”, “assembled together”, and “adhered to”, the limitations are a product-by-process limitation. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
Regarding the words “potted”, “formed”, and “adhered to” if it is deemed that these words are patentably distinct, Gerlach discloses these limitations:
Gerlach discloses embedding capillaries using potting techniques (pg. 985, first col., last three paragraphs see especially “The housing encloses the capillaries and flow heads (Fig. 1), which distribute the media to and collect media from the capillaries. Additional openings in the housing enable introduction of cells and temperature and pressure control. The capillaries are embedded in polyurethane (Akzo) using capillary dialyzer potting techniques.”).
In the analogous art of hollow fiber membrane bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of Housler with the embedding membrane capillary array using potting techniques of Gerlach in order to decentralize metabolite and gas exchange with low gradients (Gerlach, pg. 985, first col., penultimate paragraph).
Alternatively, the phrases “assembled together” and “adhered to” are a method of integration of parts. Integration of parts would have been obvious to one of ordinary skill in the art as a matter of obvious engineering choice. MPEP § 2144.04(V)(B). It would have been obvious to one skilled in the art before the effective filing date to modify the two molds’ parts to be put together in order to have a functioning bioreactor with a cell chamber that is not exposed to the environment.
Regarding the limitation “each element has the membranes of the element potted in a potting material in a plurality of potting cavities of a mold”, if it is deemed that modified Housler does not disclose this product-by-process limitation, Feder discloses this limitation – Feder discloses potting fibers using a potting means such as epoxy (and the like settable organic cement materials) to the sidewalls or the endwalls of the reactor (as well as, alternatively, a removable header) to seal the fiber layers with fluid-tight junctions (Feder, col. 5, lines 47-68). This disclosure also reads on adherence of the mold of the reactor and the perfusion membranes to the potting material by the potting material, as claimed in claim 1 above (see same citation, Feder, col. 5, lines 47-68).
In the analogous art of potting hollow fiber membranes in a mammalian cell culture apparatus, it would have been obvious to one skilled in the art before the effective filing date to modify the potting of modified Housler to take place within the reactor as in Feder in order to create fluid-tight connections so that the perfusion membranes do not leak and the perfusion membranes are able to connect in a fluid-tight manner to media inlet ports or feed ports and a spent media outlet port (Feder, col. 5, lines 40-68).
If it is deemed that Housler does not describe “wherein the first part of the mold and the second part of the mold are assembled together”, the assembly of two parts of a mold is a product-by-process limitation. Additionally, integration and separability of parts are both obvious features, according to MPEP §§ 2144.04(V)(B) and 2144.04(V)(C). If the two parts are not deemed to be disclosed by modified Housler, it would have been obvious to one skilled in the art before the effective filing date to modify the two molds’ parts to be put together in order to have a functioning bioreactor with a cell chamber that is not exposed to the environment.
Claim 2 is rejected under 35 U.S.C. 102(a)(1) as anticipated by Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1; or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) applied to claim 1, in view of Zhang (US 20060199260) (previously cited) as; or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited) as applied to claim 1, further in view of Zhang (US 20060199260) (previously cited).
Regarding claim 2, Housler discloses comprising a plurality of sensors (Fig. 2 and its caption, pg. 135-136 under “Measurement of metabolic parameters in bioreactors”) comprising a dissolved oxygen concentration sensor (pg. 135 “partial pressures of O2 … in the recirculation medium were regularly measured using a blood gas analyzer”).
Regarding the limitation “and/or a dissolved oxygen concentration sensor inside of an extra-capillary space of the plurality of zones”, the limitation is phrased in the alternative. Because at least one of the limitations is rejected above, no further rejections are required at this time.
If Housler is deemed not to include a plurality of sensors comprising a dissolved oxygen concentration sensor and/or a dissolved oxygen concentration sensor inside of an extra-capillary space of the plurality of zones, Zhang discloses a plurality of sensors comprising a dissolved oxygen concentration sensor (paragraphs [0313] “two sensor foils” and [0317] “dissolved oxygen”); the dissolved oxygen sensor is inside (paragraphs [0300] and [0313]) a zone of a bioreactor (Fig. 42a and 42b, or paragraph [0313]).
In the analogous art of microbioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of modified Housler with the location of sensor foils inside of a transparent bioreactor in order to obtain information on dissolved oxygen levels and pH (Zhang, paragraph [0313]).
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.
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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1, in view of Datta (US 20100105116) (newly disclosed); or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited) as applied to claim 1, further in view of Datta (US 20100105116) (newly disclosed).
Regarding claim 3, Housler discloses a first element (Fig. 1B, a layer of the capillary network) and a second element (Fig. 1B, another layer of the capillary network) and one or more fluid control modules in communication with the plurality of zones (Figs. 2-3 and their captions),
Housler does not disclose wherein the fluid control module is adapted to alter the flow of a fluid to the first element relative to the second element.
Datta discloses wherein the fluid control module is adapted to alter the flow of a fluid to the first element relative to the second element (Figs. 6-7, see multiple valves; paragraphs [0080]-[0082]).
In the analogous art of bioconversion processes, it would have been obvious to one skilled in the art before the effective filing date to modify the fluidic manifolds of Housler with the module control valves of Datta in order to have each valve or set of valves regulate a plurality of modules for operational functions, such as altering feed gas delivery to the modules (Datta, paragraphs [0081]-[0082]).
Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1, in view of Klimant (US 6,602,716) (previously cited), Zhang (US 20060199260) (previously cited), and Langenfeld (US 2018/0127705) (previously cited); or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited) as applied to claim 1, further in view of Klimant (US 6,602,716) (previously cited), Zhang (US 20060199260) (previously cited), and Langenfeld (US 2018/0127705) (previously cited).
Regarding claim 4, Housler does not disclose a plurality of light activated sensor foils placed inside the bioreactor on transparent windows.
Klimant discloses a plurality of light activated sensor foils (Fig. 6 and col. 7, line 48 to col. 8, line 10).
In the analogous art of optical sensor foils, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of Housler with the sensor foils of Klimant in order to take readings on different conditions in the bioreactor, including pH, CO2, NH3, and Potassium (Klimant, col. 7, line 48 to col. 8, line 10).
Zhang discloses sensor foils (paragraph [0313]) placed inside (paragraphs [0300] and [0313]) a transparent bioreactor (paragraph [0165]).
In the analogous art of microbioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of modified Housler with the location of sensor foils inside of a transparent bioreactor in order to obtain information on dissolved oxygen levels and pH (Zhang, paragraph [0313]).
Langenfeld discloses a transparent window of a bioreactor (paragraphs [0015]-[0016]).
In the analogous art of bioreactors with a sensor, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of modified Housler with the optical sensor and transparent window of Langenfeld in order to characterize and monitor the tissue and/or cells in the bioreactor (Langenfeld, paragraph [0178]-[0179]).
Regarding the phrases: “sensor foils” and “transparent windows”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify the sensor foils to be duplicated in order to obtain data from different types of sensor foils (e.g. oxygen, carbon dioxide, pH) in the bioreactor.
Regarding claim 5, Housler does not disclose a moving data collector, the moving data collector having a detector unit adapted to traverse between the plurality of sensor foils and excite the sensor foils with light and record an image of the excited sensor foils.
Modified Housler teaches the sensor foils (see rejection to parent claim 4, modified Housler in view of Zhang).
Langenfeld discloses a moving data collector (paragraph [0178] and Fig. 11C), the moving data collector having a detector unit (paragraph [0178] and Fig. 11C) adapted to … [emit] light and record an image (paragraph [0178] and Fig. 11C, “Sensor/source head 4021 can be used as a source and sensor for multi-photon microscopy and for Raman spectroscopy.”).
In the analogous art of bioreactors with a sensor, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of modified Housler with the optical sensor and transparent window of Langenfeld in order to characterize and monitor the tissue and/or cells in the bioreactor (Langenfeld, paragraph [0178]-[0179]).
Regarding the phrases “adapted to traverse between the plurality of sensor foils and excite the sensor foils with light and record an image of the excited sensor foils”, it would be considered an intended use of the moving data collector of modified Housler to image the excited sensor foils. The manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Housler would be fully capable of operating in this manner given the sensor foils of moving data collector of modified Housler.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1, in view of Baumfalk (US 2012/0132813) (previously cited); or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited) as applied to claim 1, further in view of Baumfalk (US 2012/0132813) (previously cited).
Regarding claim 6, Housler does not disclose having an aperture to hold an optical sensor body in a hole through a wall of the bioreactor.
Baumfalk discloses having an aperture to hold an optical sensor body in a hole through a wall of a bioreactor (Figs. 1-2 and paragraph [0038]).
In the analogous art of mounted optical sensors in bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of Housler with the aperture holding an optical sensor body in order to mount an optical sensor in the bioreactor to take readings of various parameters such as dissolved oxygen or pH (Baumfalk, paragraph [0009]).
Claims 7-8 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1; or, alternatively, under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1, in view of Gerlach-530 (US 20050003530) (previously cited) and Edwards (US 20110124078) (previously cited); or, alternatively, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited) as applied to claim 1, further in view of Gerlach-530 (US 20050003530) (previously cited) and Edwards (US 20110124078) (previously cited).
Regarding claim 7, Housler discloses a plurality of elements (Fig. 1B a layer of the capillary network) in a stack (Fig. 1B a layer of the capillary network, inset has multiple layers in a stack), each of the plurality of elements having associated membranes (Fig. 1B a layer of the capillary network).
Regarding the phrase “an associated mold”, Housler discloses a mold for the entire bioreactor rather than for each of the plurality of elements.
Housler does not teach the limitation “an associated mold”.
However, having a mold for each of the plurality of elements would be equivalent to having multiples of Housler’s bioreactors, each with their own mold. Therefore, this limitation is rejected under modified Housler, under duplication of parts. Mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify one mold associated with each of the one or more elements of Housler and another duplicate mold associated with each of the one or more elements in order to manufacture the entire housing of a larger and more productive bioreactor.
Furthermore, Gerlach-530 discloses multiple elements in a stack, each of the plurality of elements having an associated mold and associated membranes (Figs. 4 and 6-7; paragraphs [0045] and [0050]-[0053]).
In the analogous art of hollow fiber membrane bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of Housler with the joining of elements from different molds as in Gerlach-530 in order to artificially produce signal transmission similar to signal transmission present in the human body among different organs.
Additionally, Edwards discloses a plurality of elements in a stack, each of the plurality of elements having an associated mold and associated membranes (paragraphs [0053] and [0064]; Annotated Fig. 2, see below).
In the analogous art of scalable cell culture bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify modified Housler with the stackable modular bioreactor of Edwards in order to effectively increasing the membrane surface area and reactor volume linearly (Edwards, paragraph [0064]).
PNG
media_image1.png
932
1366
media_image1.png
Greyscale
Edwards, Annotated Fig. 2
Regarding claim 8, Housler discloses each of the plurality of the elements having associated ports (Figs. 2-3) wherein the ports of each element separately connect (Figs. 1 and 3, the hollow fiber membranes of Fig. 1 separately connect to the bioreactor’s input and output manifolds for the perfusion loop of Fig. 3) each of the elements to one or more gaseous and/or liquid media (Fig. 3).
Regarding claim 14, Housler discloses comprising a first element (Fig. 1B one layer of the capillary network) and a second element (Fig. 1B a second layer of the capillary network) wherein the mold (Figs. 1-3, outside surface of the bioreactor) associated with the first element (Fig. 1B one layer of the capillary network) is joined to another device (Figs. 2 and 3, joined to perfusion device, noted in dashed-line box in Fig. 3).
Housler does not disclose:
the mold associated with the first element is joined to the mold associated with the second element, a base, a top plate, a harvest layer or a mixing layer.
Arguably, the limitation “is joined to” is a product-by-process limitation (how the bioreactor is assembled or made). “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
Regarding the limitation “the mold associated with the second element”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). Additionally, regarding the limitation “the mold … is joined to the mold associated with the second element”, integration of parts would have been obvious to one of ordinary skill in the art as a matter of obvious engineering choice. MPEP § 2144.04(V)(B). It would have been obvious to one skilled in the art before the effective filing date to modify one mold associated with a first element of Housler to be joined to another duplicate mold associated with a second element of Housler in order to manufacture the entire housing of a larger and more productive bioreactor.
Regarding the limitation “the mold associated with the first element is joined to the mold associated with the second element, a base, a top plate, a harvest layer or a mixing layer”, these features are claimed in the alternative. Because a duplication of the first mold would be associated with a duplication of another element, the remaining features claimed in the alternative need not be rejected at this time.
If it is deemed that modified Housler does not disclose the mold associated with the first element is joined to the mold associated with the second element, a base, a top plate, a harvest layer or a mixing layer, Gerlach-530 discloses this limitation.
Gerlach-530 discloses wherein the mold associated with the first element (a mold of the corresponding first element is, respectively, the surfaces of the bioreactor 1b with the first element being zones of membranes of bioreactor 1b) is joined to the mold associated with the second element (a mold of the corresponding first element is, respectively, the surfaces of the bioreactor 1a with the first element being zones of membranes of bioreactor 1a).
In the analogous art of hollow fiber membrane bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify Housler with the joining of the first and second elements’ molds as in Gerlach-530 in order to artificially produce signal transmission similar to neuronal strands; to help model the mathematical signaling of neurons for models of artificial intelligence; and to replicate whole sections of the nervous system (Gerlach-530, paragraph [0045]).
Additionally, Edwards wherein the mold associated the first element is joined to the mold associated with the second element, a base, a top plate, a harvest layer, or a mixing layer (paragraphs [0053] and [0064]; Annotated Fig. 2).
In the analogous art of scalable cell culture bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify modified Housler with the stackable modular bioreactor of Edwards in order to effectively increasing the membrane surface area and reactor volume linearly (Edwards, paragraph [0064]).
Regarding the limitation “a base, a top plate, a harvest layer or a mixing layer”, these features are claimed in the alternative. Because a duplication of the first mold would be associated with a duplication of another element, the remaining features claimed in the alternative need not be rejected at this time.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1, in view of Prabhudharwadkar (US 20190345433) (previously cited) and De Bartolo (“Human hepatocyte functions in a crossed hollow fiber membrane bioreactor”) (previously cited); or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited) as applied to claim 1, further in view of Prabhudharwadkar (US 20190345433) (previously cited) and De Bartolo (“Human hepatocyte functions in a crossed hollow fiber membrane bioreactor”) (previously cited).
Regarding claim 9, Housler does not disclose having multiple mixers spaced along a height of the bioreactor.
Prabhudharwadkar discloses having multiple mixers spaced along a height of a bioreactor (Fig. 1 and abstract).
In the analogous art of impellers for bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of Housler to have a multiple-level impeller in order to better reduce the size of air bubbles (with high surface area per unit volume) used for dissolved oxygen in a bioreactor to increase oxygen transfer rate to the media (Prabhudharwadkar, paragraph [0003]). A multiple mixer impeller can also be used to stir media in the bioreactor at various heights in the bioreactor for a well-mixed bioreactor.
De Bartolo discloses further reason for this configuration of a bioreactor: the cells can be held in the extra-capillary space (abstract) and the bioreactor is to be considered at least in part well-mixed (pg. 2537, paragraph under equation 9b).
In the analogous art of growing cells in the extra-capillary space of a membrane bioreactor, it would have been obvious to one skilled in the art before the effective filing date to modify Housler to have an extra-capillary space for growing cells in order to have adhesive cells adhere to the capillaries while simultaneously promoting a high mass exchange of cell culture medium (De Bartolo, abstract).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1; or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited), as applied to claim 1, further in view of Funatsu (US 6284451) (previously cited).
Regarding claim 12, Housler discloses wherein the membranes are arranged in layers and are spaced apart (Fig. 1B).
Housler does not disclose the limitation “are spaced apart by at least 0.2 mm in the layers”.
However, the limitation is obvious as a matter of routine optimization, because the membranes being spaced apart by at least 0.2 mm in the layers is a result-effective variable. The motivation for optimizing this result-effective variable is to permit quick diffusion of gases across the gas transfer membranes into the perfusion membranes, as there is a small distance for the gas to travel in diffusion. MPEP § 2144.05(II).
Alternatively, Funatsu discloses wherein the membranes are arranged in layers (Figs. 1-3) and are spaced apart by at least 0.2 mm (col. 5, lines 24-38; alternatively, col. 6, lines 30-37) in the layers (Annotated Figs. 1-3, below).
In the analogous art of cell culture modules with hollow fibers, it would have been obvious to one skilled in the art before the effective filing date to modify the spacing of modified Housler’s perfusion membranes with the spacing of Funatsu’s hollow fibers of 1000 μm or less in order to supply oxygen and nutrients to the cells and to remove waste (Funatsu, col. 5, lines 24-38).
PNG
media_image2.png
873
1192
media_image2.png
Greyscale
Funatsu, Annotated Figs. 1-3
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1; or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited) as applied to claim 1.
Regarding claim 13, Housler discloses wherein the one or more elements (Fig. 1B, a layer of the capillary network), the first part of the mold (Fig. 2, outside surface of the bioreactor, one part of it), a lower surface of the element (inherent to the element’s shape and dimensions, see Figure below), sides of the potting cavities of the element (inherent to the element’s shape and dimensions, see Figure below), the second part of the mold (Fig. 2, outside surface of the bioreactor, second part of it), and an upper surface of the element (inherent to the element’s shape and dimensions, see Figure below).
PNG
media_image3.png
572
998
media_image3.png
Greyscale
Housler, Fig. 1
Housler does not disclose wherein for each of the one or more elements the first part of the mold defines a lower surface of the element and sides of the potting cavities of the element and the second part of the mold defines an upper surface of the element.
Regarding this limitation, rearrangement of parts would have been obvious to one of ordinary skill in the art as an obvious matter of design choice and would not have modified the operation of the device. MPEP § 2144.04(VI)(C). Additionally, regarding the limitation “for each of the one or more elements the first part of the mold defines a lower surface of the element and sides of the potting cavities of the element and the second part of the mold defines an upper surface of the element”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify the first part of the mold and the second part of the mold of modified Housler to be rearranged or duplicated in accordance with one “or more” elements in order to hold the elements in place in the mold’s interior potting cavities.
Claims 15 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1, in view of Toner (US 6562616) (previously cited); or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited) as applied to claim 1, further in view of Toner (US 6562616) (previously cited).
Regarding claim 15, Housler discloses wherein the mold has ribs (Fig. 2, spider-web-like ribs on the bioreactors); and a membrane assembly (Fig. 1B “capillaries” and pg. 134 under Materials and Methods) inside the potting cavities (Fig. 1, internal space of Fig. 2, outside surface of the bioreactor) of the mold (Figs. 1-3, outside surface of the bioreactor).
Housler does not disclose wherein the mold has ribs adapted to locate a membrane assembly inside the potting cavities of the mold.
Toner discloses wherein the mold has ribs (col. 8, lines 53-65; Fig. 8A) adapted to locate plates (col. 8, lines 53-65) inside the mold (col. 8, lines 53-65).
In the analogous art of ribs in cell culture systems, it would have been obvious to one skilled in the art before the effective filing date to modify the mold of Housler with the mold and ribs of Toner in order to maintain a minimal dead volume within the mold of the bioreactor while allowing a cell growth spaces to be placed in the bioreactor while having manufactured the bioreactor with injection/molding techniques (Toner, col. 8, lines 53-65).
Additionally, the limitation “adapted to locate a membrane assembly inside the potting cavities of the mold” is a product-by-process limitation. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
Regarding claim 22, Housler discloses wherein the membranes are arranged in layers with spacers between adjacent layers (Fig. 1 has beige spacers between membranes that are arranged in vertical layers) in the potting cavities (Fig. 1, internal space of Fig. 2, outside surface of the bioreactor).
Housler does not disclose arrangement in layers with plates between adjacent layers.
Toner disclose arrangement in layers with plates between adjacent layers (col. 7, lines 33-46; or col. 8, lines 2-12).
In the analogous art of cell culture devices, it would have been obvious to one skilled in the art before the effective filing date to modify the apparatus of Housler to comprise layers with plates between adjacent layers as in Toner in order to culture cells in the extracellular space on the plates (Toner, col. 7, lines 33-46).
Claims 17 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1, in view of Wilkerson (US 2012/0149091) (previously cited); or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited) as applied to claim 1, further in view of Wilkerson (US 2012/0149091) (previously cited).
Regarding claim 17, Housler discloses the mold (Fig. 2, outside surface of the bioreactor).
Housler does not disclose comprising panels separating the potting cavities of the mold and a sensor attached to at least one of the panels.
Wilkerson discloses comprising panels separating cavities (paragraphs [0122] and [0139] “stackable algae panels” and Fig. 7) and a sensor attached to at least one of the panels (paragraph [0104]).
In the analogous art of photobioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of Housler with the interior stackable panels of Wilkerson in order to individually and separately control each potting cavity’s environmental conditions.
Regarding the word “potting”, the limitation is a product-by-process limitation. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
Regarding claim 24, Housler discloses the potting cavities and the mold (see rejection to claim 1, above); and some of the potting material (Fig. 1, inset, beige material between the different types of membranes) extends between the potting cavities (Fig. 1, large picture is zoomed in with the inset, but the zoomed-in portion is between at least two opposing cylindrical ends of the bioreactor and thus between at least two potting cavities).
Housler does not disclose the potting cavities are separated by panels of the mold and some of the potting material extends between the potting cavities across the panels.
Wilkerson discloses panels separating cavities (paragraphs [0122] and [0139] “stackable algae panels” and Fig. 7).
In the analogous art of photobioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of Housler with the interior stackable panels of Wilkerson in order to individually and separately control each potting cavity’s environmental conditions.
Modified Housler does not disclose some of the potting material extends between the potting cavities across the panels. However, this is a design choice and would not have modified the function of the device. Regarding this limitation, rearrangement of parts would have been obvious to one of ordinary skill in the art as an obvious matter of design choice and would not have modified the operation of the device. MPEP § 2144.04(VI)(C). It would have been obvious to one skilled in the art before the effective filing date to modify the potting material to extend across the panels in order to hold the panels in place within the potting cavities.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) as applied to claim 1, in view of Feder (US 4087327) (previously cited); or, in the alternative, under 35 U.S.C. 103 as obvious over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited) and Feder (US 4087327) (previously cited) as applied to claim 1.
Regarding claim 25, Housler discloses the first part of the mold and the second part of the mold are together (see rejection to claim 1).
Housler does not disclose “are assembled together by an adhesive”.
This limitation is a product-by-process limitation (assembled together). “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
However, the adhesive used in the product-by-process limitation lends structure to the invention. To this end, Feder discloses an adhesive that bonds to molded plastic and/or metal parts in a reactor housing (col. 2, lines 63-68 and col. 6, lines 7-19).
In the analogous art of mammalian cell culture processes, it would have been obvious to one skilled in the art before the effective filing date to modify the mold of Housler to be assembled together with an adhesive as in Feder in order to make a fluid-tight reactor that uses potting means such as epoxy (Feder, col. 5, lines 54-68).
Alternatively, regarding the limitation, integration of parts would have been obvious to one of ordinary skill in the art as a matter of obvious engineering choice. MPEP § 2144.04(V)(B). It would have been obvious to one skilled in the art before the effective filing date to modify the mold of Housler with an adhesive in order to combine the parts together in a fluid-tight manner (Feder, col. 5, lines 54-68).
Claims 16 and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Housler (“Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells”) (previously cited) in view of Gerlach (“Bioreactor for a Larger Scale Hepatocyte in vitro Perfusion”) (previously cited), Feder (US 4087327) (previously cited), Gerlach-530 (US 20050003530) (previously cited), and Edwards (US 20110124078) (previously cited).
Regarding claim 16, Housler discloses a cell culture bioreactor (abstract) comprising
a plurality of zones (Fig. 1, there are at least two zones: one for liquids, another for gases), the plurality of zones including a zone of perfusion membranes (Fig. 1 caption, red and blue perfusion capillaries) and a zone of gas transfer membranes (Fig. 1 caption, yellow gas capillaries), wherein a flow of a fluid to each of the zones is separately controllable (Fig. 3 and associated caption for perfusion pump and gas monitor), and
wherein the perfusion membranes (Fig. 1 caption, red and blue perfusion capillaries) and the gas transfer membranes (Fig. 1 caption, yellow gas capillaries) are potted in a potting material in a plurality of potting cavities of the mold (Fig. 1, beige material between the capillaries), the mold having a surface of the mold comprising an aperture (Figs. 2-3 ports on the sides of the bioreactor); whereby [there is] an extra-capillary space (ECS) within the mold (pg. 134, second col., under “Size-scaling of the bioreactor technology”, specifically “transport of culture medium in a decentralized pattern in the cell compartment”).
If it is deemed Housler does not disclose an extra-capillary space within the mold, Gerlach discloses an extra-capillary space within the mold (pg. 985, first col., under “Materials and Methods”, see especially: “The hepatocytes are seeded on the outer surface of, and between, the capillaries”; “decentralized perfusion of the cells between these capillaries”; and “The housing encloses the capillaries and flow heads (Fig. 1), which distribute the media to and collect media from the capillaries. Additional openings in the housing enable introduction of cells and temperature and pressure control. The capillaries are embedded in polyurethane (Akzo), using capillary dialyzer potting techniques.”).
In the analogous art of hollow fiber membrane bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of Housler with the embedding membrane capillary array using potting techniques of Gerlach in order to decentralize metabolite and gas exchange with low gradients (Gerlach, pg. 985, first col., penultimate paragraph).
Additionally, regarding the limitation “wherein the perfusion membranes and the gas transfer membranes are potted in a potting material in a plurality of potting cavities of the molds”, if it is deemed that modified Housler does not disclose this product-by-process limitation, Feder discloses this limitation – Feder discloses potting fibers using a potting means such as epoxy (and the like settable organic cement materials) to the sidewalls or the endwalls of the reactor (as well as, alternatively, a removable header) to seal the fiber layers with fluid-tight junctions (Feder, col. 5, lines 47-68). This disclosure also reads on adherence of the mold of the reactor and the perfusion membranes to the potting material by the potting material, as claimed in claim 1 above (see same citation, Feder, col. 5, lines 47-68).
In the analogous art of potting hollow fiber membranes in a mammalian cell culture apparatus, it would have been obvious to one skilled in the art before the effective filing date to modify the potting of modified Housler to take place within the reactor as in Feder in order to create fluid-tight connections so that the perfusion membranes do not leak and the perfusion membranes are able to connect in a fluid-tight manner to media inlet ports or feed ports and a spent media outlet port (Feder, col. 5, lines 40-68).
Housler does not disclose:
a plurality of molds stacked together;
wherein a first surface comprising a first aperture of a first one of the molds is inserted into and connected to a second surface of a second aperture of the second one of the molds;
whereby an extra-capillary space (ECS) within the first one of the molds is fluidly connected to an ECS within the second one of the molds.
Regarding feature 1, a plurality of molds would be obvious under duplication of parts. Mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to duplicate the molds for higher production of cellular product.
Additionally, Edwards discloses a plurality of molds stacked together (paragraphs [0053] and [0064]; Annotated Fig. 2).
In the analogous art of scalable cell culture bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify modified Housler with the stackable modular bioreactor of Edwards in order to effectively increasing the membrane surface area and reactor volume linearly (Edwards, paragraph [0064]).
Regarding features 1 and 2, Gerlach-530 also has a plurality of connected elements (Fig. 4) that, in other embodiments are encased in housings with apertures (Figs. 6-7). It would have been obvious to one skilled in the art before the effective filing date to modify modified Housler’s duplicated molds with the plurality of connected elements and apertures of Gerlach-530 in order to artificially produce signal transmission similar to signal transmission present in the human body among different organs. Alternatively, regarding the limitation “a plurality of molds stacked together”, rearrangement of parts would have been obvious to one of ordinary skill in the art as an obvious matter of design choice and would not have modified the operation of the device. MPEP § 2144.04(VI)(C). The physical stacking of the already connected molds of modified Housler would have been an obvious design choice and would not have modified the operation of the device, given that the duplicated molds with the elements inside are already connected.
Regarding feature 3, Gerlach-530 discloses wherein an extra-capillary space (ECS) (paragraph [0048] the interior of the container where the cells live, outside the permeable hollow fibers) within the first one of the elements (Fig. 4) is fluidly connected to an ECS within the second one of the elements (Fig. 4).
In the analogous art of bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the first element and the bioreactor of Housler with the first and second elements having molds comprising interconnected apertures, where the connection is between the first element and the second element as in Gerlach-530 in order to artificially produce signal transmission similar to signal transmission present in the human body among different organs. Once the bioreactors of modified Housler are connected, their respective ECSs would also be fluidly connected.
Again, regarding the first and second molds, duplication of Housler’s mold would have been obvious for the reasons stated above.
Regarding claim 27, Housler discloses the mold (see rejection to claim 1).
Housler does not disclose wherein the first surface is connected to the second surface by way of an adhesive, screw threads or a press fit.
Regarding the feature of multiple molds, modified Housler teaches multiple molds: regarding the limitation “a second one of the molds”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify one mold associated with each of the one or more elements of Housler to be connected to another duplicate mold associated with each of the one or more elements in order to manufacture the entire housing of a larger and more productive bioreactor.
Alternatively, regarding the limitation about the connected surfaces of the molds, rearrangement of parts would have been obvious to one of ordinary skill in the art as an obvious matter of design choice and would not have modified the operation of the device. MPEP § 2144.04(VI)(C). The physical connection between the apertures of the already connected molds of modified Housler would have been an obvious design choice and would not have modified the operation of the device, given that the duplicated molds with the elements inside are already connected.
Housler does not disclose “is connected … by way of an adhesive, screw threads or a press fit”.
Arguably, this limitation is a product-by-process limitation. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
However, the adhesive used in the arguable product-by-process limitation lends structure to the invention. To this end, Feder discloses an adhesive that bonds to molded plastic and/or metal parts in a reactor housing (col. 2, lines 63-68 and col. 6, lines 7-19).
In the analogous art of mammalian cell culture processes, it would have been obvious to one skilled in the art before the effective filing date to modify the mold of Housler to be assembled together with an adhesive as in Feder in order to make a fluid-tight reactor that uses potting means such as epoxy (Feder, col. 5, lines 54-68).
Alternatively, regarding the limitation, integration of parts would have been obvious to one of ordinary skill in the art as a matter of obvious engineering choice. MPEP § 2144.04(V)(B). It would have been obvious to one skilled in the art before the effective filing date to modify the mold of Housler with an adhesive in order to combine the parts together in a fluid-tight manner (Feder, col. 5, lines 54-68).
Regarding the terms “screw threads or a press fit”, these terms are claimed in the alternative. No further rejections are required at this time.
Regarding claim 28, modified Housler discloses wherein the first aperture and the second aperture (see rejection to claim 16).
Housler does not disclose wherein one or both of the first aperture and the second aperture is bounded by a raised ring.
However, the limitation is obvious as a design choice. The configuration of the claimed shape is a matter of choice, absent persuasive evidence that the particular configuration is significant. MPEP § 2144.04(IV)(B). Additionally, it would have been obvious to one skilled in the art before the effective filing date to modify at least one of the first and second aperture to be bounded by a raised ring in order to assemble the two surfaces containing the apertures together by fitting a raised ring on one surface to a second surface, similarly to connecting (by way of screw threads) a mason jar to a ringed lid, or alternatively, connecting (by way of a press fit) a barbed port to tubing.
Additional Prior Art References
The prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure.
Haag (US 5567025) (newly disclosed) – This invention is a cylindrical port system for sterile transfer. The ports are connected via welding, brazing, adhesives, or bolted flanges (col. 5, lines 8-10).
Sigma Aldrich “New Aldrich Glass with SafetyBarb Hose Connectors” (newly disclosed) – This non-patent literature discloses barbed hose connecting gas ports.
Response to Arguments
Applicant’s arguments filed 02/25/2026 have been fully considered but they are not persuasive.
Regarding pg. 7 of 17 of Applicant arguments, the limitations “potted”, “formed”, “assembled together”, “adhered to”, and “each element has the membranes of the element potted in a potting material in a plurality of potting cavities of a mold” are product-by-process limitations. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
The structure of Housler or modified Housler discloses the instant invention as claimed in claim 1. Patentability does not depend on the process of production. Arguments of counsel against MPEP § 2113 are unpersuasive.
If it is deemed during any hypothetical appeal that a product-by-process limitation is limited by the process, regarding the product-by-process usage of a mold to shape the potting material, Feder discloses this usage of a mold.
Regarding the limitation “each element has the membranes of the element potted in a potting material in a plurality of potting cavities of a mold”, if it is deemed that modified Housler does not disclose this product-by-process limitation, Feder discloses this limitation – Feder discloses potting fibers using a potting means such as epoxy (and the like settable organic cement materials) to the sidewalls or the endwalls of the reactor (as well as, alternatively, a removable header) to seal the fiber layers with fluid-tight junctions (Feder, col. 5, lines 47-68). This disclosure also reads on adherence of the mold of the reactor and the perfusion membranes to the potting material by the potting material, as claimed in claim 1 above (see same citation, Feder, col. 5, lines 47-68).
This Office Action
Regarding the limitation “wherein the first part of the mold and the second part of the mold are assembled together and adhered to the potting material by the potting material”, the rejection to claim 1 fulfills these limitations under 102 in view of Housler using different parts of the mold of Gerlach for “the first part of the mold and the second part of the mold”. Additionally, the limitation “are assembled together and adhered to” is integration of parts, and is therefore obvious under MPEP § 2144.04(V)(B) as described above. Lastly, the phrase “assembled together and adhered to the potting material by the potting material” is still a product-by-process limitation; for the reasons set forth above in MPEP § 2113, the limitation is rejected by the either anticipated structure of Housler or the obvious structure of modified Housler.
Also, Gerlach expressly discloses using potting techniques:
Gerlach discloses embedding capillaries using potting techniques (pg. 985, first col., last three paragraphs see especially “The housing encloses the capillaries and flow heads (Fig. 1), which distribute the media to and collect media from the capillaries. Additional openings in the housing enable introduction of cells and temperature and pressure control. The capillaries are embedded in polyurethane (Akzo) using capillary dialyzer potting techniques.”).
This Office Action
Regarding the combination of Housler in view of Gerlach, the following motivation statement is given:
In the analogous art of hollow fiber membrane bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of Housler with the embedding membrane capillary array using potting techniques of Gerlach in order to decentralize metabolite and gas exchange with low gradients (Gerlach, pg. 985, first col., penultimate paragraph).
This Office Action
A citation has been given as to where the motivation to combine can be found in Gerlach, see above.
Regarding pg. 8 of 17, Gerlach’s perfusion membranes are both potted and within a housing. Applicant arguments are directed to an alternative method of manufacture “by potting membranes in an external mold that is not the housing, removing the membranes and their potting material from that external mold, and then reattaching the membranes and potting material to a housing”. These limitations are not relevant, as there is no substantial evidence that Housler, Gerlach, or any of the other relevant references cited manufacture their inventions by completing this process; additionally, the limitation would still be a product-by-process limitation; lastly, the corresponding limitations from claim 1, “wherein each element has the membranes of the element potted in a potting material in a plurality of potting cavities of a mold, wherein each potting cavity is partially formed by a first part of the mold and partially formed by a second part of the mold, wherein the first part of the mold and the second part of the mold are assembled together and adhered to the potting material by the potting material” is also still a product-by-process limitation. Again, if it is deemed during any hypothetical appeal that a product-by-process limitation is limited by the process, regarding the product-by-process usage of a mold to shape the potting material, Feder discloses this usage of a mold, see above, and the assembly of parts is obvious, see above.
Regarding Applicant arguments about Feder, Applicant has interpreted the Feder reference to say that the “‘potting means’ in Feder are only recited in relation to a removable header and … the use of a potting means such as epoxy … is not a disclosure of potting”. Feder states that the epoxy is a potting means: “The ends of the fibers can be secured to the sidewalls or endwalls of the reactor or they can be secured in a removable header with potting means such as epoxy and the like settable organic cement materials which can act as a sealant for the fibers.” (Feder, col. 5, lines 59-64). In summary, the fibers are secured with a potting means. Arguments as to Feder not disclosing perfusion membranes in a potting material in a plurality of potting cavities of a mold are unpersuasive. Arguments discussing Feder not disclosing gas transfer membranes are unpersuasive, as these are disclosed in Housler. Again, further limitations about how the structure is assembled and adhered to the potting material are unpersuasive both in light of modified Housler in view of Gerlach and Feder as well as product-by-process limitations.
Regarding pg. 9 of 17 of Applicant arguments, these Applicant arguments are directed to two parts of a mold assembled together. Both a product-by-process rejection, as well as an obvious integration of parts, apply to the limitation: “wherein the first part of the mold and the second part of the mold are assembled together and adhered to the potting material by the potting material”. As restated from above:
If it is deemed that Housler does not describe “wherein the first part of the mold and the second part of the mold are assembled together”, the assembly of two parts of a mold is a product-by-process limitation. Additionally, integration and separability of parts are both obvious features, according to MPEP §§ 2144.04(V)(B) and 2144.04(V)(C). If the two parts are not deemed to be disclosed by modified Housler, it would have been obvious to one skilled in the art before the effective filing date to modify the two molds’ parts to be put together in order to have a functioning bioreactor with a cell chamber that is not exposed to the environment.
This Office Action
No further arguments were given on how claim 1’s product-by-process limitation does not integrate two mold parts into an integral mold. At least a prima facie case of obviousness exists, even if the structure was not already anticipated by Housler. The arguments stating the opposing viewpoint without evidence are therefore moot.
Regarding pg. 9 of 17, regarding claim 3, the amended claim is examined and rejected with modified Housler in view of Datta.
Regarding pg. 9 of 17, regarding claim 13, the amended claim is examined and rejected with modified Housler.
Regarding pg. 9 of 17, regarding claim 22, the amended claim is examined for the limitation about plates between adjacent layers in the potting cavities and rejected with modified Housler in view of Toner.
Regarding pg. 10 of 17, regarding claim 2, the amended claim is examined for the limitation about a dissolved oxygen concentration sensor and/or a dissolved oxygen concentration sensor inside of an extra-capillary space of the plurality of zones and rejected with Housler or modified Housler in view of Zhang.
Regarding pg. 11 of 17, regarding claim 4, the light activated sensor foils of modified Housler are obvious due to the reasons stated above. Teaching away from the use of light activated sensor foils in Housler is only an argument of counsel and is unsubstantiated. A prima facie case of obviousness exists.
Regarding pg. 11 of 17, regarding claim 5, the claim as amended is obvious due to the intended use of the already moving data collector cited in modified Housler in view of Langenfeld. The limitation only describes how the movement is occurring, and does not further patentably distinguish it from the prior art.
Regarding the phrase “adapted to traverse between the plurality of sensor foils and excite the sensor foils with light and record an image of the excited sensor foils”, it would be considered an intended use of the moving data collector of modified Housler to traverse between the sensor foils and image the excited sensor foils. The manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Housler would be fully capable of operating in this manner given the sensor foils of moving data collector of modified Housler.
Regarding pg. 12 of 17, regarding claim 6, the claim limitations are obvious in light of modified Housler in view of Baumfalk, for the reasons set forth in the rejection above. Baumfalk discloses an aperture to hold an optical sensor body in a hole, which is combinable with Housler to take readings of various parameters, such as dissolved oxygen.
Regarding pg. 12 of 17, regarding claim 9, the claim limitations are obvious in light of modified Housler in view of Prabhudharwadkar and De Bartolo, for the reasons set forth in the rejection above. Prabhudharwadkar discloses the limitation and motivation, while De Bartolo describes an additional motivation statement:
In the analogous art of growing cells in the extra-capillary space of a membrane bioreactor, it would have been obvious to one skilled in the art before the effective filing date to modify Housler to have an extra-capillary space for growing cells in order to have adhesive cells adhere to the capillaries while simultaneously promoting a high mass exchange of cell culture medium (De Bartolo, abstract).
This Office Action
Regarding pg. 13 of 17, regarding claim 12, Housler discloses part of the limitation and modified Housler in view of Funatsu teaches the full limitation; additionally, Housler with routine optimization under the MPEP § 2144.05(II) teaches this limitation.
Regarding pg. 13 of 17, regarding claim 7, Gerlach-530 shows multiple elements in a stack (one on the other) with signal transmission between the stacked elements (Gerlach-530, Fig. 4 and paragraph [0045]). If it is deemed that Gerlach-530 does not show stacked elements, Edwards discloses this limitation as well (Edwards, paragraphs [0053] and [0064]; annotated Fig. 2).
Regarding Edwards, the combination of modified Housler in view of either Gerlach-530 or Edwards teaches claim 7. The argument about the cassettes of Edwards is irrelevant as the cassettes are elements that are stacked. For the exact limitations of the elements in claim 7, Housler already discloses these elements, or modified Housler already teaches these elements, as set forth above.
Regarding pg. 14 of 17, regarding Toner, modified Housler in view of Toner teaches claim 15, as the mold and the potting cavities of the mold are already disclosed or taught as in the rejection to claim 1. Housler additionally discloses wherein the mold has ribs and a membrane assembly. Toner discloses ribs inside the cavity of the mold as well, and uses them to locate plates inside the mold (Toner, col 8, lines 53-65). It would have been obvious to one skilled in the art before the effective filing date to modify the mold of Housler with the mold and ribs of Toner in order to maintain a minimal dead volume within the mold of the bioreactor while allowing a cell growth spaces to be placed in the bioreactor while having manufactured the bioreactor with injection/molding techniques (Toner, col. 8, lines 53-65).
Additionally, the limitation “adapted to locate a membrane assembly inside the potting cavities of the mold” is a product-by-process limitation. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
Regarding pg. 14 of 17, regarding claim 17 and regarding Wilkenson and the panels separating the potting cavities of the mold and a sensor attached to at least one of the panels, Wilkenson is analogous art as there are sensors and panels in photobioreactors as well as bioreactors. Also, a motivation statement is given:
In the analogous art of photobioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of Housler with the interior stackable panels of Wilkerson in order to individually and separately control each potting cavity’s environmental conditions.
This Office Action
Furthermore, upon further search and/or consideration, Toner also has panels separating the potting cavities of the mold Toner (Fig. 3E; or, col. 13, lines 10-32). Regarding the word “potting”, the limitation is also a product-by-process limitation.
Regarding pg. 14 of 17, regarding claim 24, modified Housler does not teach some of the potting material extends between the potting cavities across the panels. However, this is a design choice and would not have modified the function of the device. Regarding this limitation, rearrangement of parts would have been obvious to one of ordinary skill in the art as an obvious matter of design choice and would not have modified the operation of the device. MPEP § 2144.04(VI)(C). It would have been obvious to one skilled in the art before the effective filing date to modify the potting material to extend across the panels in order to hold the panels in place within the potting cavities. Additionally, Applicant arguments about resulting change in the size and shape of the interior of the Housler device are unpersuasive in view of MPEP §§ 2144.04(IV)(A) and 2144.04(IV)(B), respectively, obvious “Changes in Size/Proportion” and obvious “Changes in Shape”.
Regarding pg. 15 of 17, regarding claim 25, Housler discloses the first part of the mold and the second part of the mold are together with perfusion membranes and gas transfer membranes; Feder discloses an adhesive that bonds to molded plastic and/or metal parts in a reactor housing. Additionally, the limitation is a product-by-process limitation. For the motivation given below, modified Housler in view of Feder is combinable:
In the analogous art of mammalian cell culture processes, it would have been obvious to one skilled in the art before the effective filing date to modify the mold of Housler to be assembled together with an adhesive as in Feder in order to make a fluid-tight reactor that uses potting means such as epoxy (Feder, col. 5, lines 54-68).
This Office Action
Alternatively, regarding the limitation, integration of parts would have been obvious to one of ordinary skill in the art as a matter of obvious engineering choice. MPEP § 2144.04(V)(B).
Regarding pg. 15 of 17, regarding feature 1, “a plurality of molds stacked together”, modified Housler in view of Edwards teach a plurality of molds stacked together. Additionally, duplicating the molds is duplication of parts, and is therefore obvious under MPEP § 2144.04(VI)(B).
Regarding feature 2, “wherein a first surface comprising a first aperture of a first one of the molds is inserted into and connected to a second surface of a second aperture of the second one of the molds”, Gerlach-530 also has a plurality of connected elements (Fig. 4) that, in other embodiments are encased in housings with apertures (Figs. 6-7). Connecting these elements at their apertures would have been an obvious re-arrangement of parts. Additionally, the physical stacking of already connected molds of modified Housler would have been an obvious design choice and would not have modified the operation of the device, given that the duplicated molds with the elements inside are already connected.
Regarding feature 3, “whereby an extra-capillary space (ECS) within the first one of the molds is fluidly connected to an ECS within the second one of the molds”, this feature is obvious in light of the membranes present in modified Housler, as the membranes of Gerlach-530 are porous. Gerlach-530 discloses that their hollow fibers are porous so that substances are in fluidic communication with both the lumens of the hollow fibers and the extracellular space (paragraph [0048] “permeable” and “pore size for such porosity is most advantageous at <1 micrometer so substances can enter and leave”). Additionally, Gerlach-530 also discloses that one element is fluidly connected to another element (Fig. 4). The combination of modified Housler (with obvious duplication of molds) thereby renders the molds’ extracellular spaces fluidly connected to one another. Regarding the phrase “via the first aperture and the second aperture”, these terms are already present in modified Housler, from feature 2, above.
Regarding feature 4, “wherein the perfusion membranes and the gas transfer membranes are potted in a potting material in a plurality of potting cavities of the molds”, this is a product-by-process limitation, see similar arguments to the rejection of claim 1, above. Regarding Feder, the fibers are secured with a potting means. Arguments as to Feder not disclosing perfusion membranes in a potting material in a plurality of potting cavities of a mold are unpersuasive.
Regarding pg. 16 of 17 of Applicant arguments, regarding claim 27, the arguments are not commensurate in scope with the claims. Claim 27 states: “The bioreactor of claim 16 wherein the first surface is connected to the second surface by way of an adhesive, screw threads or a press fit.” Therefore, whether the adhesive of Feder is permanent or not, an adhesive is disclosed, thereby fulfilling the claim language. Regarding the connection between the first surface and the second surface (claimed previously in independent claim 16 as “a surface of the mold comprising an aperture and wherein a first surface comprising a first aperture of a first one of the molds is inserted into and connected to a second surface of a second aperture of the second one of the molds”), the way these surfaces are connected is either a product-by-process limitation and therefore patentably indistinct from the prior art, or, alternatively, if the connection is deemed to be part of the structure of the claim, Feder discloses an epoxy potting adhesive. Additionally, the connection is an obvious integration of parts under MPEP § 2144.04(V)(B) “Making Integral”.
Regarding pg. 17 of 17 of Applicant arguments, regarding claim 28, the limitation “wherein one or both of the first aperture and the second aperture is bounded by a raised ring” is obvious as a design choice. The configuration of the claimed shape is a matter of choice, absent persuasive evidence that the particular configuration is significant. MPEP § 2144.04(IV)(B). Additionally, it would have been obvious to one skilled in the art before the effective filing date to modify at least one of the first and second aperture to be bounded by a raised ring in order to assemble the two surfaces containing the apertures together by fitting a raised ring on one surface to a second surface, similarly to connecting (by way of screw threads) a mason jar to a ringed lid, or alternatively, connecting (by way of a press fit) a barbed port to tubing. Examples of wherein one or both of the first aperture and the second aperture is bounded by a raised ring is disclosed in Haag, see additional prior art above (col. 5, lines 8-10; Figs. 3 through 6I; claim 4) or Sigma Aldrich “New Aldrich Glass with SafetyBarb Hose Connectors” (e.g., pgs. 1 through 3 of non-patent literature from WayBack Machine).
Conclusion
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN G ESPERON whose telephone number is 571-272-9807, and whose fax number is 571-273-8464. The examiner can normally be reached 9 am - 6 pm Monday through Thursday, and 9 am - 6 pm every other Friday.
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.
/N.G.E./Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799
Prosecution Insights