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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on 03/17/2026 has been entered.
Modification to the Application Data Sheet (ADS) Requested
The Application Data Sheet (ADS) was found to contain different spellings of a town with the same address among different inventors:
Marlboro
Marlborough, MA, USA
Please modify the ADS appropriately.
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.
Claims 1-4, 8, and 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Liderfelt (US 10,760,041) (previously cited) in view of Singh (US 20030036192) (previously cited), Bleile (US 20140166653) (newly cited), and evidentiary reference Merriam-Webster.com Dictionary (“Strip”) (newly cited).
Regarding claim 1, Liderfelt discloses a bioreactor (abstract) comprising:
a flexible bioreactor wall (abstract) defining a bioreactor chamber (abstract), said flexible bioreactor wall further defining a bioreactor port therethrough (abstract; Fig. 5a, elements 35 or 36 port; col. 6, lines 35-41);
a filter (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50) disposed within the bioreactor chamber (abstract), said filter comprising:
first and second overlying planar porous membranes perimetrically bound to each other so as to define a filter cavity therebetween (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50),
wherein one of said first and second porous membranes (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50) defines an open aperture therethrough (Fig. 5a (side view) and 5b (top view), elements 35 and 36; col. 6, lines 35-45 “fluidically connected to a first… and a second … port in the bag), and
an elongate hollow conduit (Fig. 5a, elements 35 and 36 have conduits to the outside of the bioreactor bag) having a first portion affixed to said open aperture (Fig. 5a (side view) and 5b (top view), elements 35 and 36; col. 6, lines 35-45 “fluidically connected to a first… and a second … port in the bag) of said filter (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50) and a second portion affixed to said bioreactor port (Fig. 5a, elements 35 and 36 have conduits to the outside of the bioreactor bag) such that said filter cavity is in fluid communication (col. 6, lines 35-45 “fluidically connected to a first… and a second … port in the bag) with said bioreactor port (abstract; Fig. 5a, elements 35 or 36 port; col. 6, lines 35-41);
wherein said filter (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50) is constrained to movement (Fig. 6a, element of tubing descending from elements 45 and 46 would allow for movement within the bag) within a predetermined constrained volume (col. 5, line 60 to col. 6, line 5 “supports to prevent bulging”) within the bioreactor chamber (abstract) via one or more tethers (Fig. 5a, element 39; col. 5, line 60 to col. 6, line 5).
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If it is deemed that the embodiments of Liderfelt’s Figs. 5 and 6 need be combined to reject the claim, the following motivation statement is also disclosed:
It would have been obvious to one skilled in the art before the effective filing date to modify the embodiments of Liderfelt to be combinable in order to freely move the pouch within the bag, but also keep the pouch from getting stuck in a single area of the bag, ensuring a constrained degree of freedom of the pouch.
Liderfelt does not disclose:
an open bioreactor port fitment secured to said flexible bioreactor wall at said bioreactor port;
a substantially planar open mesh disposed in said filter cavity;
an open outlet port fitment secured to said filter at said open aperture; and,
wherein the one or more tethers are flexible strips.
Singh discloses:
Regarding features 1 and 3, Singh discloses an open port fitment (paragraph [0022]; Fig. 2A, element 27 “hose barb port”).
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify Liderfelt with two of the open port fitments of Singh in order to obtain an assembly that can connect tubing to an external pump to harvest fluid from the bioreactor. In addition, regarding features 1 and 3, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B).
Regarding feature 2, Singh discloses a substantially planar open mesh (paragraph [0022]; Fig. 2A “polyethylene mesh”) disposed in a filter cavity (Figs. 2A and 2B).
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt with the substantially planar open mesh of Singh in order to prevent the bottom filtration membrane from being sucked flat against the upper layer of the filter, which would choke off flow (Singh, paragraph [0022]).
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Regarding feature 4, Liderfelt already discloses one or more tethers (Fig. 5a, element 39; col. 5, line 60 to col. 6, line 5).
Liderfelt does not disclose at least one flexible tether, however it does disclose that the tether could be a “coarse net or ribs” (col. 5, lines 65-67). It would have been obvious to one skilled in the art before the effective filing date to modify the coarse net or ribs of Liderfelt to be flexible in order to more easily collapse, package, and ship a sterile bioreactor bag during manufacture.
Additionally, Singh discloses a flexible tether (paragraph [0021]; Fig. 1, element 22 “flexible filtrate tube”), which also functions as a conduit, but could be used to flexibly tether the filter to the bioreactor chamber.
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt with the flexible tether of Singh in order to prevent the filter from clogging through use of tangential movement of the filter within the space of the bioreactor (Singh, paragraph [0021]).
Regarding the phrase “wherein the one or more tethers are flexible strips”, the Merriam-Webster.com Dictionary defines a strip as: “a long narrow piece of a material”. Under this definition (see support for using this specific definition in Applicant arguments, pg. 8 of 10, second paragraph), the ribs of modified Liderfelt function as a flexible strip, or the tubing of Singh functions as a flexible strip, as either is a long and narrow piece of material. The motivation to combine these flexible strips are given above.
Nevertheless, Bleile discloses one or more tethers are flexible strips (paragraphs [0030]-[0036]; Figs. 3A, 3B, and 4, element 50; Fig. 5, element 90; paragraph [0030], “The restraining tether 50 can be a chain, cable, rope or other tensile connecting means”).
In the analogous art of tethering components together (securing covers within tanks), it would have been obvious to one skilled in the art before the effective filing date to modify the shape of modified Liderfelt’s flexible tether to be a flexible strip of Bleile in order to use a long and narrow piece of material to tether the compartment to the bioreactor with less material waste and expense than a wider material; also, the tether is used for holding an element submerged in place (Bleile, paragraph [0036], “Being aware of a length of the restraining tether 50 … the cover 20 can be positioned to be partially submerged under the liquid surface”).
Regarding claim 2, Liderfelt discloses wherein said first porous membrane (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50; specifically, the top sheet of the two sheets) defines said open aperture (Fig. 5a (side view) and 5b (top view), elements 35 and 36; col. 6, lines 35-45 “fluidically connected to a first… and a second … port in the bag).
Regarding claim 3, Liderfelt discloses the first membrane (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50; specifically, the top sheet of the two sheets) and the bioreactor port (abstract; Fig. 5a, elements 35 or 36 port; col. 6, lines 35-41).
Liderfelt does not disclose wherein said bioreactor port fitment is secured to said first membrane so as to extend through said bioreactor port.
Singh discloses a port fitment (paragraph [0022]; Fig. 2A, element 27 “hose barb port”).
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt with an open port fitment of Singh in order to obtain an assembly that can connect tubing to an external pump to harvest fluid from the bioreactor.
Regarding the limitation “wherein said bioreactor port fitment is secured to said first membrane so as to extend through said bioreactor port”, it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt to have a port fitment of Singh secured to the first membrane and extended through the bioreactor port in order to connect tubing to an external pump to harvest fluid from the bioreactor.
Regarding claim 4, Liderfelt discloses wherein said conduit (Fig. 5a, elements 35 and 36 have conduits to the outside of the bioreactor bag) sealingly extends (Fig. 5a (side view) and 5b (top view), elements 35 and 36; col. 6, lines 35-45 “fluidically connected to a first… and a second … port in the bag) through said bioreactor port (abstract; Fig. 5a, elements 35 or 36 port; col. 6, lines 35-41) on said flexible bioreactor wall (abstract).
Liderfelt does not disclose a port fitment.
Singh discloses a port fitment (paragraph [0022]; Fig. 2A, element 27 “hose barb port”).
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt with an open port fitment of Singh in order to obtain an assembly that can connect tubing to an external pump to harvest fluid from the bioreactor.
Regarding claim 8, Liderfelt discloses the conduit (Fig. 5a, elements 35 and 36 have conduits to the outside of the bioreactor bag), the filter (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50), and the bioreactor chamber (abstract).
Liderfelt does not specifically disclose: wherein said conduit assists in restricting movement of said filter to the predetermined constrained volume of said bioreactor chamber.
However, given the structures above, this manner of operation or intended use would be easily achieved, especially in light of the restraining elements (Fig. 5, element 39) of Liderfelt. Regarding the limitation, 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 Liderfelt would be fully capable of operating in this manner given the conduit, filter, bioreactor chamber, and optionally, restraining elements.
Regarding claim 11, Liderfelt discloses at least one tether (Fig. 5a, element 39 “supports 39 or restrainer elements”) having opposed ends affixed to said filter (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50) and said flexible bioreactor wall (abstract) below said filter (Fig. 5a) thereby tethering the filter to the bioreactor chamber so as to allow the filter to move within the predefined constrained volume of the bioreactor chamber (Fig. 5a).
Liderfelt does not disclose at least one flexible tether, however it does disclose that the tether could be a “coarse net or ribs” (col. 5, bottom paragraph). It would have been obvious to one skilled in the art before the effective filing date to modify the coarse net or ribs of Liderfelt to be flexible in order to more easily collapse, package, and ship a sterile bioreactor bag during manufacture.
Nevertheless, Singh discloses a flexible tether (paragraph [0021]; Fig. 1, element 22 “flexible filtrate tube”), which also functions as a conduit, but could be used to flexibly tether the filter to the bioreactor chamber.
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt with the flexible tether of Singh in order to prevent the filter from clogging through use of tangential movement of the filter within the space of the bioreactor (Singh, paragraph [0021]).
Alternatively, Bleile discloses a flexible tether (paragraphs [0030]-[0036]; Figs. 3A, 3B, and 4, element 50; Fig. 5, element 90; paragraph [0030], “The restraining tether 50 can be a chain, cable, rope or other tensile connecting means”).
In the analogous art of tethering components together (securing covers within tanks), it would have been obvious to one skilled in the art before the effective filing date to modify the shape of modified Liderfelt’s flexible tether to be a flexible tether of Bleile in order to use a long and narrow piece of material to flexibly tether the compartment to the bioreactor with less material waste and expense than a wider material; also, the tether is used for holding an element submerged in place (Bleile, paragraph [0036], “Being aware of a length of the restraining tether 50 … the cover 20 can be positioned to be partially submerged under the liquid surface”).
Regarding claim 12, Liderfelt discloses further comprising at least one tether (Fig. 5, element 39) having a first end affixed to said flexible bioreactor wall (abstract) and a conduit (Fig. 5a, elements 35 and 36 have conduits to the outside of the bioreactor bag).
Liderfelt does not disclose: at least one elongate flexible tether having a first end affixed to said bioreactor wall and an opposed second end affixed to a body of the at least one elongate flexible tether extending between said opposed ends, whereby said at least one elongate flexible tether defines an open passageway through which said conduit passes.
However, the formation of a loop to tether the bioreactor filter to the bioreactor wall is considered an obvious change in the shape of parts of a tether, which is already in Liderfelt. The claim limitation is obvious, as 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). It would have been obvious to one skilled in the art before the effective filing date to modify the tether to form a loop to hold an elongated material such as a conduit tube within the looped tether in order to allow the conduit to have some flexibility during the operation of the bioreactor, but also to have some flexibility to collapse, package, and ship a sterile bioreactor bag containing this apparatus during initial manufacture.
Alternatively, Bleile discloses a connecting loop or ring (paragraphs [0030]-[0031]).
In the analogous art of connecting tethers, it would have been obvious to one skilled in the art before the effective filing date to modify the tether of modified Liderfelt with the connecting loop or ring of Bleile in order to secure the tether to the desired element (Bleile, paragraphs [0030]-[0031]).
Regarding claim 13, Liderfelt discloses at least one tether (Fig. 5, element 39) having a first end affixed to said flexible bioreactor wall (abstract) and a conduit (Fig. 5a, elements 35 and 36 have conduits to the outside of the bioreactor bag).
Liderfelt does not disclose further comprising at least one elongate flexible tether having opposed a first and second ends affixed to said flexible bioreactor wall, whereby said at least one elongate flexible tether and flexible bioreactor wall define an open passageway through which said conduit passes.
However, the formation of a loop to tether the bioreactor filter to the bioreactor wall is considered an obvious change in the shape of parts of a tether, which is already in Liderfelt. The claim limitation is obvious, as 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). It would have been obvious to one skilled in the art before the effective filing date to modify the tether to form a loop to hold an elongated material such as a conduit tube within the looped tether in order to allow the conduit to have some flexibility during the operation of the bioreactor, but also to have some flexibility to collapse, package, and ship a sterile bioreactor bag containing this apparatus during initial manufacture.
Regarding claim 14, Liderfelt discloses wherein said constrained volume is spaced from (Fig. 5a) an inner surface of the bioreactor chamber (abstract) such that the filter (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50) does not touch the inner surface of the bioreactor chamber (abstract; Fig. 5a) during operation of the bioreactor (abstract; col. 5, lines 49-59 “neutral buoyancy”).
Regarding the limitation, 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 Liderfelt would be fully capable of operating in this manner given the structures of the bioreactor chamber and the filter.
Regarding claim 15, Liderfelt discloses each porous membrane (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50) and the conduit (Fig. 5a, elements 35 and 36 have conduits to the outside of the bioreactor bag) for conducting fluid (col. 3 to 4, spanning paragraph) from the filter cavity (col. 3 to 4, spanning paragraph).
Liderfelt does not disclose wherein said mesh provides a plurality of flow paths between each porous membrane and said conduit for conducting waste from said filter cavity.
Singh discloses wherein said mesh (claim 6, paragraph [0022]) provides a plurality of flow paths (paragraph [0022] and Figs. 2A to 2B) between each membrane (Fig. 2A to 2B) and said conduit (Fig. 1, element 22 “harvest tube”; paragraph [0023]) for conducting fluid (paragraph [0023]) from said filter cavity (paragraph [0023]).
In the analogous art of bioreactor bags, it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt with the many paths in the mesh of Singh in order to promote higher mass transfer rates through the mesh, and thus transport more waste out more quickly if needed.
Regarding the limitation “for conducting waste” 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 Liderfelt would be fully capable of operating in this manner given the structures of each porous membrane, the conduit, and the filter cavity.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Liderfelt (US 10,760,041) (previously cited) in view of Singh (US 20030036192) (previously cited), Bleile (US 20140166653) (newly cited), and evidentiary reference Merriam-Webster.com Dictionary (“Strip”) (newly cited) as applied to claim 1, further in view of Niazi (US 20120231504) (previously cited).
Regarding claim 5, Liderfelt discloses the bioreactor port (abstract; Fig. 5a, elements 35 or 36 port; col. 6, lines 35-41) and the bioreactor (abstract).
Liderfelt does not disclose wherein said bioreactor port is located on an underside of said bioreactor.
Niazi discloses wherein a bioreactor port is located on an underside of a bioreactor (paragraph [0022]; Fig. 1, element 10 “a valve 10 that controls removal of the nutrient medium and biological culture”).
In the analogous art of bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt with the underside bioreactor port of Niazi in order to remove nutrient medium and biological culture via gravity-assisted fluid flow.
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Liderfelt (US 10,760,041) (previously cited) in view of Singh (US 20030036192) (previously cited), Bleile (US 20140166653) (newly cited), evidentiary reference Merriam-Webster.com Dictionary (“Strip”) (newly cited), and Niazi (US 20120231504) (previously cited) as applied to claim 5, further in view of Beauchesne (US 20190211292) (previously cited).
Regarding claim 6, Liderfelt discloses the bioreactor port (abstract; Fig. 5a, elements 35 or 36 port; col. 6, lines 35-41) and the bioreactor chamber (abstract).
Liderfelt does not disclose wherein said bioreactor port is located about a transverse centerline of said bioreactor chamber.
Beauchesne discloses wherein said bioreactor port (paragraph [0026]; Fig. 1, element 104 “perfusion port”) is located about a transverse centerline (Fig. 1) of said bioreactor chamber (Fig. 1, element 100 “bioreactor”; paragraph [0023]).
In the analogous art of bioreactor bags, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor bag of modified Liderfelt with the bioreactor port located on a transverse centerline as in Beauchesne in order to locate the bioreactor port to be more accessible to a preferred side of the bioreactor for ease of handling from the perspective of the laboratory technician.
Regarding claim 7, Liderfelt discloses wherein said bioreactor port is located below a seam formed by said flexible bioreactor wall (paragraph [0021] “the ports may be mounted in one or more seams between two walls”).
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Liderfelt (US 10,760,041) (previously cited) in view of Singh (US 20030036192) (previously cited), Bleile (US 20140166653) (newly cited), and evidentiary reference Merriam-Webster.com Dictionary (“Strip”) (newly cited) as applied to claim 1, further in view of Kaisermayer (US 20140287512) (previously cited).
Regarding claim 9, Liderfelt discloses the bioreactor port (abstract; Fig. 5a, elements 35 or 36 port; col. 6, lines 35-41), the filter (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50), the conduit (Fig. 5a, elements 35 and 36 have conduits to the outside of the bioreactor bag), and that the bioreactor chamber (abstract) further includes a given amount of fluid (paragraph [0035] “cell culture medium”).
Liderfelt does not disclose wherein said bioreactor port is positioned below said filter, such that the length of said conduit will hold said filter submerged while said bioreactor chamber further includes a given amount of fluid.
Kaisermayer discloses wherein said bioreactor port (paragraph [0028]; Fig. 6a, element 24 “port”) is positioned below (Fig. 6a) said filter (paragraph [0028]; Fig. 6a, element 22 “filter material”), such that the length of said conduit will hold said filter submerged (paragraph [0055]) while said bioreactor chamber (paragraph [0034]; Fig. 6a, volume enclosed by element 27 “wall”) further includes a given amount of fluid (paragraph [0034] “liquid and smaller particles such as free cells and cell debris”).
In the analogous art of bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt with the underside bioreactor port of Kaisermayer in order to have a filter location close to the bottom wall so it is submerged in suspension, but separated from the bottom wall so that flow is improved (Kaisermayer, paragraph [0055]).
Regarding the phrase “submerged” 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 Liderfelt would be fully capable of operating in this manner given the conduit, filter, bioreactor, and cell culture medium of modified Liderfelt.
Regarding claim 10, Liderfelt discloses the conduit (Fig. 5a, elements 35 and 36 have conduits to the outside of the bioreactor bag), the flexible bioreactor wall (abstract), the filter (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50), and a tether (Fig. 5a, element 39 “supports 39 or restrainer elements”) for said filter to hold said filter while said bioreactor chamber (abstract) further includes a given amount of fluid (paragraph [0035] “cell culture medium”).
Liderfelt does not disclose wherein a portion of said conduit is affixed to a portion of said flexible bioreactor wall below said filter whereby a free portion of the conduit extending from said flexible bioreactor wall to said filter further operates as a tether for said filter to hold said filter submerged while said bioreactor chamber further includes a given amount of fluid.
Kaisermayer discloses wherein a portion of said conduit (Fig. 6b, element 22 extends downwards on either side of the “filter material”, element 22) is affixed to a portion of said flexible bioreactor wall (Fig. 6b) below said filter (Fig. 6b, element 22 “filter material”) whereby a free portion of the conduit extending from said flexible bioreactor wall to said filter further operates as a tether (Fig. 6b, element 22 extends downwards on either side of the “filter material”, element 22) for said filter to hold said filter submerged (paragraph [0055]) while said bioreactor chamber (Fig. 6b) further includes a given amount of fluid (paragraph [0050] “cell culture medium”).
In the analogous art of bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt with the conduit and tether of Kaisermayer in order to attach the port to the filter via a tubing, while keeping the filter submerged in the suspension to avoid filter cake and have no suction of gases (Kaisermayer, paragraph [0055]).
Regarding the phrase “submerged” 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 Liderfelt would be fully capable of operating in this manner given the conduit, filter, bioreactor, and cell culture medium of modified Liderfelt.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Liderfelt (US 10,760,041) (previously cited) in view of Singh (US 20030036192) (previously cited), Bleile (US 20140166653) (newly cited), and evidentiary reference Merriam-Webster.com Dictionary (“Strip”) (newly cited) as applied to claim 1, further in view of Beauchesne (US 20190211292) (previously cited).
Regarding claim 16, Liderfelt discloses a conduit (Fig. 5a and 5b, elements 35 and 36) so as to draw fluid (col. 3 to 4, spanning paragraph) from said bioreactor chamber (abstract) through said filter cavity (col. 3 to 4, spanning paragraph) into said conduit (Fig. 5a and 5b, elements 35 and 36).
Liderfelt does not disclose further comprising a pump for selective engagement with said conduit so as to draw waste products from said bioreactor chamber through said filter cavity into said conduit.
Beauchesne discloses further comprising a pump (paragraph [0044]) for engagement (paragraph [0044]) with a port (paragraph [0044]). Beauchesne also discloses drawing waste products (paragraph [0047]) from the bioreactor chamber (paragraph [0047]) through said filter cavity (paragraph [0047]) into a conduit (paragraph [0047] “filtrate tube”).
In the analogous art of bioreactor bags, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor bag of modified Liderfelt with a pump and waste outlet as in Beauchesne in order to have a waste bag next to the bioreactor bag to help in receiving the waste from the bioreactor perfusion process to maintain the volume inside the bioreactor as it is fed with nutrients during perfusion.
Regarding the phrase “a pump for selective engagement with said conduit so as to draw waste products from said bioreactor chamber through said filter cavity into said conduit” it would have been obvious to one skilled in the art before the effective filing date to modify modified Liderfelt with a pump so that a pump, such as a peristaltic pump with external tubing from a bioreactor, would have selective engagement for the placement of tubing inside the pump if desired. This would allow the tubing to be placed inside or outside the pump if needed during different stages of setup of the bioreactor, or during operation of the bioreactor. Additionally, regarding the limitation, 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 Liderfelt would be fully capable of operating in this manner given the structures of a pump, conduit, and bioreactor chamber.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1, 11, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 11, 13-14, and 16 of copending Application No. 16625173 (Ali) (previously cited) in view of Liderfelt (US 10,760,041) (previously cited) and Singh (US 20030036192) (previously cited).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 1, Ali discloses in its claims:
a bioreactor comprising:
a flexible bioreactor wall defining a bioreactor chamber (claim 16), said flexible bioreactor wall further defining a bioreactor port therethrough (claim 1, “the filter is fluidically connected to an exterior of the bioreactor chamber through at least one fluid conduit”);
a filter disposed within the bioreactor chamber (claim 1), said filter comprising:
a first membrane (claim 4, “upper layer”) and a second overlying planar porous membrane (claim 4 “a filtration membrane”) bound to each other so as to define a filter cavity therebetween (claim 4, “a filtration membrane coupled to the upper layer”),
a mesh disposed in said filter cavity (claim 6),
an elongate hollow conduit having a first portion affixed to said outlet port fitment of said filter and a second portion affixed to said bioreactor port such that said filter cavity is in fluid communication with said bioreactor port (claim 1, “the filter is fluidically connected to an exterior of the bioreactor chamber through at least one fluid conduit”).
wherein said filter (claim 1) is constrained to movement (claim 1) within a predetermined constrained volume (claim 1) within the bioreactor chamber (claim 1) via one or more tethers (claim 1), wherein the one or more tethers are flexible strips (claim 11).
In the analogous art of bioreactor bag filter apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of the embodiment from claims 1 and 16 with the bioreactor of the embodiment from claims 1, 4, 6, and 11 in order to have a bioreactor bag that contains a flexibly tethered filter, so that the filter cannot touch the inner surface of the bioreactor chamber in use but can still move while in a predefined volume spaced from the inner surface of the bioreactor chamber (Ali, claim 1).
Ali does not disclose in its claims:
an open bioreactor port fitment secured to said flexible bioreactor wall at said bioreactor port;
a first overlying planar porous membrane perimetrically bound to the second overlying planar porous membrane
a substantially planar open mesh
wherein one of said first and second porous membranes defines an open aperture therethrough, and
an open outlet port fitment secured to said filter at said open aperture
Regarding features 1 and 5, Singh discloses an open port fitment (paragraph [0022]; Fig. 2A, element 27 “hose barb port”).
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify Liderfelt with two of the open port fitments of Singh in order to obtain an assembly that can connect tubing to an external pump to harvest fluid from the bioreactor. In addition, regarding features 1 and 5, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B).
Regarding feature 2, Liderfelt discloses a first overlying planar porous membrane perimetrically bound to the second overlying planar porous membrane (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50).
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify modified Ali with two planar porous membranes bound to each other as in Liderfelt in order to obtain a filter assembly that can help perfuse a bioreactor by drawing off excess or waste media without withdrawing the cell population.
Regarding feature 3, Singh discloses a substantially planar open mesh (paragraph [0022]; Fig. 2A “polyethylene mesh”).
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify modified Ali with the substantially planar open mesh of Singh in order to prevent the bottom filtration membrane from being sucked flat against the upper layer of the filter, which would choke off flow (Singh, paragraph [0022]).
Regarding feature 4, Liderfelt discloses wherein one of said first and second porous membranes (Fig. 5a, element 34 “two sheets of membrane”; col. 5, lines 45-50) defines an open aperture therethrough (Fig. 5a (side view) and 5b (top view), elements 35 and 36; col. 6, lines 35-45 “fluidically connected to a first… and a second … port in the bag).
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify the first and second porous membranes of modified Ali with an open aperture therethrough of Liderfelt in order to obtain a filter assembly that can help perfuse a bioreactor by drawing off excess or waste media without withdrawing the cell population.
Regarding claim 11, Ali discloses in its claims:
further comprising at least one flexible tether (claim 10) having opposed ends affixed to said filter and said flexible bioreactor wall (claim 9) thereby flexibly tethering (claim 10) the filter to the bioreactor chamber so as to allow the filter to move within the predefined constrained volume of the bioreactor chamber (claim 1).
Ali does not disclose in its claims:
said flexible bioreactor wall below said filter.
Liderfelt discloses a flexible bioreactor wall (abstract) below a filter (Fig. 5a).
In the analogous art of bioreactor bag filtration apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify the location of the flexible bioreactor wall that is flexibly tethered like Ali to be below a filter as in Liderfelt, so that the filter may be submerged within the bioreactor chamber; alternatively, this positioning can be used to prevent bulging of the filter compartment within the bioreactor chamber (Liderfelt, col. 5, line 60 to col. 6, line 5); also, it would be advantageous to have a bioreactor bag have flexibility in order to more easily collapse, package, and ship the sterile bioreactor bag during manufacture.
Regarding claim 15, Ali discloses in its claims:
wherein said mesh provides a plurality of flow paths between each porous membrane and said conduit (claim 6).
Regarding the phrase “for conducting waste from said filter cavity”, 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 Ali would be fully capable of operating in this manner given the fluid distribution mesh disposed between the upper layer and the filtration membrane of the filter.
Response to Arguments
Applicant’s arguments filed 03/17/2026 have been fully considered but they are not persuasive.
Regarding pg. 7 of 10 of Applicant arguments, last paragraph, modified Liderfelt in view of Singh and Bleile teach a filter disposed within a bioreactor as claimed in independent claim 1, wherein the filter is constrained to movement within a predefined constrained volume within the bioreactor chamber via one or more tethers, where the one or more tethers are flexible strips.
Regarding pg. 8 of 10 of Applicant arguments, first paragraph, Liderfelt discloses that the supports from Fig. 5A, element 39 may also be ribs or a coarse net. Arguably, the ribs of Liderfelt could be considered tethers that are strips. Modified Liderfelt could be argued to be a flexible rib, and therefore teach a flexible strip as a tether as an obvious modification to the rib element of Liderfelt.
Regarding pg. 8 of 10 of Applicant arguments, second paragraph, the Merriam-Webster.com Dictionary defines a “strip” to be “a long narrow piece of material”. However, this definition does not preclude a strip of tubing, which is a conduit. Both Liderfelt and Singh disclose strips of tubing that are used as conduits as well as flexible tethers, much like the instant claims 8 through 10 do. Therefore, the tubing of Liderfelt or Singh can be argued to be a tether that is a flexible strip. The Applicant’s own claims (instant claims 8 through 10, which depend from the tethers being flexible strips in independent claim 1) appear to teach against the interpretation alleged in the Applicant arguments: that a flexible strip cannot be a strip of tubing that comprises a conduit in addition to being a flexible tether. Therefore, Liderfelt and Singh apply to this claim limitation, and the Applicant arguments are not commensurate in scope with the claims.
Regarding pg. 8 of 10 of Applicant arguments, third paragraph, Applicant asserts that the Examiner is relying on an unduly broad interpretation of Applicant’s claims. However, again, Applicant arguments are not commensurate in scope with the claimed limitations. The arguments (for a sub-volume within the bioreactor chamber) do not appear in the claims. Instead, “a predetermined constrained volume within the bioreactor chamber” is the limitation that is given in independent claim 1. This volume is not limited in any fashion in the claim, other than it is to be constrained within the bioreactor chamber and that the volume is to be predetermined. The volume of the entire bioreactor chamber could be designated to be the volume and it would exactly fit the claim language; hypothetically, a range of a sub-volume from 0% to 100% of a total volume, inclusive, can still include the sub-volume at 100% of a total volume. The total volume is just the maximum endpoint of that range. Nevertheless, for a sub-volume, see newly cited Bleile, below.
Regarding pg. 8 of 10 of Applicant arguments, fourth and fifth paragraphs, see above arguments. In addition, regarding the dependent claims, these claims are rejected as the independent claim is still rejected and no further arguments were made regarding the dependent claims.
Additionally, newly cited reference Bleile has been used in the rejections above to support the previously cited prior art and arguments indicating obviousness of flexible strips acting as flexible tethers. Bleile’s citations, see the rejection to claim 1 above, also disclose these limitations. Bleile discloses a flexible strip acting as a volume-constraining tether, relevant to Applicant arguments given in pg. 8 of 10, second paragraph (about flexible strips that are tethers, see paragraphs [0030]-[0031]) and third paragraph (about a sub-volume within the bioreactor chamber, see paragraph [0036], “Being aware of a length of the restraining tether 50 … the cover 20 can be positioned to be partially submerged under the liquid surface”), as refuted above.
Lastly, regarding the non-statutory double patenting rejection, previously rejected claim 1, as well as newly rejected claims 11 and 15 have been found to be rejectable under obviousness-type double patenting.
Conclusion
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/N.G.E./Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799
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