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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/29/2026 has been entered.
Claim Objections
The previous claim objections are withdrawn in light of the amendments.
Claims 15 is objected to because of the following informalities:
Regarding claim 15, line 12 the term “packing element” should be “packing elements”.
Regarding claim 15, lines 17-18 are repeated on lines 6-7. Lines 17-18 should be cancelled.
Regarding claim 15, last line, the term “packing elements” should be “polyhedral packing elements”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The previous 35 U.S.C. § 112(b) rejections are withdrawn in light of the amendments.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 12 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 12, the claim is lacking written description. Although there is an example given in paragraph [0026] of the instant specification about the largest dimension of the packing elements being 2 mm and bridges with a diameter of 0.1 mm, this is not the same as claiming a ratio of any individual element to the interaction between the packing elements at a ratio of 20:1. The latter limitation is broader in scope than the example given. For example, a size of 20 cm ÷ 1 cm would satisfy the ratio of 20:1, but the written description is lacking for these sizes. Instead, claim 13 correctly claims the sizes (a largest diameter of 2 mm; a bridge with a diameter of 0.1 mm) and a wider range of ratios (the largest diameter of 2 mm). In other words the ratio can depict any units of the individual dimensions (i.e., cm or microns or inches, etc.) but the specification only has dimensions in mm, thus the claimed ratio is broader compared to what disclosed in the specification and thus is new matter.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 11 recites the limitation “the interactions” in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 12 recites the limitation “the interaction” in line 2. There is insufficient antecedent basis for this limitation in the claim.
Regarding the dependent claim 13, this claim is rejected for the same reason as the base claim upon which they depend.
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, 3, and 9-15 are rejected under 35 U.S.C. 103 as being unpatentable over Dumont (US 20240002769) (previously disclosed) in view of Ling-396 (US 20210317396) (previously disclosed).
Regarding claim 1, Dumont discloses a monolithic packed bed bioreactor (abstract) comprising:
a reactor shell (paragraph [0014]);
an inlet port leading into the reactor shell (paragraph [0072] and Fig. 17);
an outlet port leading out of the reactor shell (paragraph [0072] and Fig. 17);
a media bed (paragraph [0008] “structured fixed bed”) comprising a plurality of packing elements (paragraph [0008] “a scaffold or lattice formed of multiple interconnected units of objects”) enclosed within the reactor shell (paragraph [0014]) and between inlet port (paragraph [0072] and Fig. 17) and the outlet port (paragraph [0072] and Fig. 17), wherein said packing elements have one or more shapes (paragraph [0047]) occurring in a continuously repeating array (Fig. 2 and paragraph [0047]);
wherein the inlet port (paragraph [0072] and Fig. 17) and the outlet port (paragraph [0072] and Fig. 17), the reactor shell (paragraph [0014]), and packing elements form a single monolithic structure (paragraphs [0073]-[0074]); and
wherein the media bed is retained in the reactor shell solely by being connected thereto (paragraph [0073] “unitary structure during a single additive manufacturing (e.g., 3D printing) process).
PNG
media_image1.png
567
475
media_image1.png
Greyscale
Dumont, Fig. 2
Dumont does not disclose:
and wherein the one or more shapes of the packing elements in the continuously repeating array that are in contact with an inner wall of the reactor shell are truncated wherein only a portion of the one or more shapes exists and merges into the inner wall;
a dispersion plate embedded into the reactor shell, positioned between the inlet port and the media bed and configured to distribute fluid flowing from the inlet port across the media bed;
wherein the inlet port and the outlet port, the reactor shell, the dispersion plate, and the packing elements form a single monolithic structure.
Ling-396 discloses wherein the one or more shapes of the packing elements in the continuously repeating array (paragraph [0057]; Figs. 1c-1d and 7a) that are in contact with an inner wall of the reactor shell are truncated wherein only a portion of the one or more shapes exists and merges into the inner wall (paragraph [0093]; and Figs. 7b, 7e-7f, 11a).
PNG
media_image2.png
423
493
media_image2.png
Greyscale
PNG
media_image3.png
324
505
media_image3.png
Greyscale
Ling-396, Figs. 1c and 1d
PNG
media_image4.png
401
426
media_image4.png
Greyscale
PNG
media_image5.png
399
434
media_image5.png
Greyscale
Ling-396, Figs. 7a and 7b
In the analogous art of three-dimensional fixed-bed bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify Dumont with the truncated shapes of Ling-396 in order to seal the gaps between the fixed-bed and the chamber wall, which will force the perfusion cell culture medium to pass through the interconnected pores instead of through those gaps (Ling-396, paragraph [0093]).
Ling-396 also discloses:
a dispersion plate embedded into the reactor shell, positioned between the inlet port and the media bed, and configured to distribute fluid flowing from the inlet port across the media bed (Ling-396, Figs. 8-9, element 22 “fluid distributor”, paragraphs [0065], [0079], and [0094]-[0095]).
PNG
media_image6.png
252
443
media_image6.png
Greyscale
PNG
media_image7.png
319
404
media_image7.png
Greyscale
Ling-396, Figs. 8-9
In the analogous art of three-dimensional fixed-bed bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify Dumont’s bioreactor with the dispersion plate of Ling-396 in order to provide smaller differences of shear stress to cells residing at different locations in the bioreactor (Ling-396, paragraph [0032]).
Ling-396 also discloses:
wherein the inlet port and the outlet port, the reactor shell, the dispersion plate, and the packing elements form a single monolithic structure (Ling-396, Figs. 8-9, paragraphs [0065], [0079], and [0093]-[0095]).
In the analogous art of three-dimensional fixed-bed bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the distribution plate of modified Dumont with the 3d-printed structure of Ling-396 in order to provide smaller differences of shear stress to cells residing at different locations in the bioreactor (Ling-396, paragraph [0065]).
Additionally, regarding the phrases “a dispersion plate embedded into the reactor shell, positioned between the inlet port and the media bed” as well as “wherein the inlet port and the outlet port, the reactor shell, the dispersion plate, and the packing elements form a single monolithic structure”, 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 integration of these parts to be a monolithic structure in order to be able to 3D print the entire structure at once without further assembly or labor.
Regarding claims 3 and 14, Dumont discloses wherein the media bed possesses a void fraction (paragraph [0013]; Fig. 2, space between objects for fluid flow) and a surface area (paragraph [0012]).
Dumont does not disclose wherein the media bed possesses a void fraction of at least 75% and a specific surface area of at least 650 m2 / m3.
Ling-396 discloses wherein the media bed possesses a void fraction of at least 75% (paragraph [0106]) and a specific surface area of at least 650 m2 / m3 (paragraph [0080], see inherency argument below).
In the analogous art of three-dimensional bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify modified Dumont with a media bed with a void fraction of at least 75% and specific surface area of at least 650 m2 / m3 in order to increase the cell expansion capacity (Ling-396, paragraph [0106]) by having a large surface to volume ratio in comparison to a conventional roller bottle (Ling-396, paragraph [0080]).
Regarding the limitation about specific surface area disclosed by Ling-396, the following calculation was used based on information about vessel volume and matrix surface area from Ling-396, paragraph [0080]:
Cylinder of 5 cm diameter and 15 cm height in a conventional roller bottle
5,648 cm2 surface area matrix
A
V
=
A
π
r
2
h
, wherein A is the surface area of the matrix, V is the volume of a cylinder, where r is the diameter of the cylinder, and h is the height of the cylinder, and the expression results in the ratio of surface area of the matrix divided by the volume of the cylinder.
5648
c
m
2
π
2.5
c
m
2
(
15
c
m
)
Wherein the unit conversion from the ratio of
c
m
2
c
m
3
to the ratio of
m
2
m
3
is the following:
1
c
m
2
c
m
3
∙
m
100
c
m
2
∙
100
c
m
m
3
=
100
m
2
m
3
So, to convert the above expression into the final format:
5648
c
m
2
π
2.5
c
m
2
(
15
c
m
)
∙
m
100
c
m
2
∙
100
c
m
m
3
=
a
b
o
u
t
1,918
m
2
m
3
Therefore, Ling-396 inherently discloses a specific surface area of at least 650 m2 / m3.
Regarding claim 9, Dumont discloses wherein each of the packing elements has a polyhedral shape (paragraph [0049] “octagonal” and “decahedral” listed among others).
If it is deemed that Dumont does not disclose the limitation above, 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 shape of Dumont with a decahedral shape in order to have a polyhedral shape that has a high surface area to volume ratio, but is less difficult to fabricate than a sphere.
Regarding claim 10, arguably, Dumont discloses wherein each of the packing elements has an octahedral shape (paragraph [0049] “cubic hexagonal”, depending on how the terms “cubic hexagonal” and the instant claim’s “octahedral shape” are defined).
If it is deemed that Dumont does not disclose the limitation above, 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 shape of Dumont with an octahedral shape in order to have a polyhedral shape that has a high surface area to volume ratio in comparison to a cube.
Regarding claim 11, Dumont discloses interactions between the packing elements (paragraph [0050]); and individual packing elements (paragraph [0049]).
Regarding the limitation “wherein the interactions between the packing elements are substantially smaller than a largest dimension of any individual packing element”, the claim limitation is obvious under MPEP § 2144.04(IV)(A), which states that “where the only difference between the prior art and the claims was a recitation of relative dimensions … [and the claimed device] would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device”. It would have been obvious to one skilled in the art before the effective filing date to modify the dimensions of Dumont’s packing elements to be larger than the space between them in order to provide a fixed bed that is monolithic and/or integrated and has a high surface area in the bioreactor.
Regarding claim 12, Dumont discloses individual elements (paragraph [0049]) and the interaction between the packing elements (paragraph [0050]).
Dumont does not disclose wherein a ratio between the largest dimension of any individual element and the interaction between the packing elements is about 20:1.
Regarding the limitation “wherein a ratio between the largest dimension of any individual element and the interaction between the packing elements is about 20:1”, the claim limitation is obvious under MPEP § 2144.04(IV)(A), which states that “where the only difference between the prior art and the claims was a recitation of relative dimensions … [and the claimed device] would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device”. It would have been obvious to one skilled in the art before the effective filing date to modify the dimensions of Dumont’s packing elements to be larger than the space between them by about 20:1 in order to provide a fixed bed that is monolithic and/or integrated and has a high surface area in the bioreactor.
Regarding claim 13, Dumont discloses wherein an individual packing element (paragraph [0008] “a scaffold or lattice formed of multiple interconnected units of objects”) has a largest dimension of 1 mm to 4 mm (paragraph [0054] “distance between pathways”) and is interconnected to another packing element by a bridge (Figs. 2, 2A, 2B, and 9) with a diameter of 1 to 2 mm (paragraph [0054] “diameter of the pathway(s)”).
Dumont does not disclose wherein an individual packing element has a largest dimension of 2 mm and is interconnected to another packing element by a bridge with a diameter of 0.1 mm.
However, these limitations are obvious under routine optimization. The limitation is obvious as a matter of routine optimization because the element diameter and the bridge between the elements are result-effective variables. The motivation for optimizing this result-effective variable is to provide variable properties in terms of fluid flow or cell adhesion, depending on the needs of a particular cell culturing operation (Dumont, paragraph [0053]). MPEP § 2144.05(II).
In addition, the claim limitation is obvious under MPEP § 2144.04(IV)(A), which states that “where the only difference between the prior art and the claims was a recitation of relative dimensions … [and the claimed device] would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device”. It would have been obvious to one skilled in the art before the effective filing date to modify modified Dumont’s elements to be those claimed in order to provide variable properties in terms of fluid flow or cell adhesion, depending on the needs of a particular cell culturing operation (Dumont, paragraph [0053]). MPEP § 2144.05(II).
Regarding claim 15, Dumont discloses a monolithic packed bed bioreactor (abstract) comprising:
a reactor shell (paragraph [0014]);
an inlet port leading into the reactor shell (paragraph [0072] and Fig. 17);
an outlet port leading out of the reactor shell (paragraph [0072] and Fig. 17);
a media bed (paragraph [0008] “structured fixed bed”) comprising a plurality of packing elements (paragraph [0008] “a scaffold or lattice formed of multiple interconnected units of objects”) which are enclosed within the reactor shell (paragraph [0014]) and between the inlet port (paragraph [0072] and Fig. 17) and the outlet port (paragraph [0072] and Fig. 17), wherein the media bed possesses a void fraction (paragraph [0013]; Fig. 2, space between objects for fluid flow) and a surface area (paragraph [0012]), wherein said packing elements have a polyhedral shape (paragraph [0049] “octagonal” and “decahedral” listed among others) with a largest dimension of 1 mm to 4 mm (paragraph [0054] “distance between pathways”) and interconnected to another packing element by a bridge (Figs. 2, 2A, 2B, and 9) with a diameter of 1 to 2 mm (paragraph [0054] “diameter of the pathway(s)”), occurring in a continuously repeating array (Fig. 2 and paragraph [0047]).
If it is deemed that Dumont does not disclose the “polyhedral shape” limitation above, 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 shape of Dumont with a decahedral shape in order to have a polyhedral shape that has a high surface area to volume ratio, but is less difficult to fabricate than a sphere.
Dumont does not disclose:
wherein the media bed possesses a void fraction of at least 75% and a specific surface area of at least 650 m2 / m3
with a largest dimension of 2 mm and interconnected to another packing element by a bridge with a diameter of 0.1 mm
and wherein the polyhedral packing elements in the continuously repeating array that are in contact with an inner wall of the reactor shell are truncated wherein only a portion of the polyhedral packing element exists and merges into the inner wall; and
a dispersion plate embedded into the reactor shell, positioned between the inlet port and the media bed, and configured to distribute fluid flowing from the inlet port across the media bed;
wherein the inlet port and the outlet port, the reactor shell, the dispersion plate, and the packing elements form a single monolithic structure.
Regarding feature 1, Ling-396 discloses wherein the media bed possesses a void fraction of at least 75% (paragraph [0106]) and a specific surface area of at least 650 m2 / m3 (paragraph [0080], see inherency argument below).
In the analogous art of three-dimensional bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify modified Dumont with a media bed with a void fraction of at least 75% and specific surface area of at least 650 m2 / m3 in order to increase the cell expansion capacity (Ling-396, paragraph [0106]) by having a large surface to volume ratio in comparison to a conventional roller bottle (Ling-396, paragraph [0080]).
Regarding the limitation about specific surface area disclosed by Ling-396, the following calculation was used based on information about vessel volume and matrix surface area from Ling-396, paragraph [0080]:
Cylinder of 5 cm diameter and 15 cm height in a conventional roller bottle
5,648 cm2 surface area matrix
A
V
=
A
π
r
2
h
, wherein A is the surface area of the matrix, V is the volume of a cylinder, where r is the diameter of the cylinder, and h is the height of the cylinder, and the expression results in the ratio of surface area of the matrix divided by the volume of the cylinder.
5648
c
m
2
π
2.5
c
m
2
(
15
c
m
)
Wherein the unit conversion from the ratio of
c
m
2
c
m
3
to the ratio of
m
2
m
3
is the following:
1
c
m
2
c
m
3
∙
m
100
c
m
2
∙
100
c
m
m
3
=
100
m
2
m
3
So, to convert the above expression into the final format:
5648
c
m
2
π
2.5
c
m
2
(
15
c
m
)
∙
m
100
c
m
2
∙
100
c
m
m
3
=
a
b
o
u
t
1,918
m
2
m
3
Therefore, Ling-396 inherently discloses a specific surface area of at least 650 m2 / m3.
Regarding feature 2, these limitations are obvious under routine optimization. The limitation is obvious as a matter of routine optimization because the element diameter and the bridge between the elements are result-effective variables. The motivation for optimizing this result-effective variable is to provide variable properties in terms of fluid flow or cell adhesion, depending on the needs of a particular cell culturing operation (Dumont, paragraph [0053]). MPEP § 2144.05(II).
In addition, the claim limitation is obvious under MPEP § 2144.04(IV)(A), which states that “where the only difference between the prior art and the claims was a recitation of relative dimensions … [and the claimed device] would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device”. It would have been obvious to one skilled in the art before the effective filing date to modify modified Dumont’s elements to be those claimed in order to provide variable properties in terms of fluid flow or cell adhesion, depending on the needs of a particular cell culturing operation (Dumont, paragraph [0053]). MPEP § 2144.05(II).
Regarding feature 3, Ling-396 discloses wherein the packing elements in the continuously repeating array (paragraph [0057]; Figs. 1c-1d and 7a) that are in contact with an inner wall of the reactor shell are truncated wherein only a portion of the polyhedral packing element exists and merges into the inner wall (paragraph [0093]; and Figs. 7b, 7e-7f, 11a).
In the analogous art of three-dimensional fixed-bed bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify Dumont with the truncated shapes of Ling-396 in order to seal the gaps between the fixed-bed and the chamber wall, which will force the perfusion cell culture medium to pass through the interconnected pores instead of through those gaps (Ling-396, paragraph [0093]).
Additionally, regarding feature 3, the term “polyhedral” has already been disclosed above by primary reference Dumont.
Regarding feature 3, Ling-396 also discloses:
a dispersion plate embedded into the reactor shell, positioned between the inlet port and the media bed and configured to distribute fluid flowing from the inlet port across the media bed (Ling-396, Figs. 8-9, element 22 “fluid distributor”, paragraphs [0065], [0079], and [0094]-[0095]).
In the analogous art of three-dimensional fixed-bed bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify Dumont’s bioreactor with the dispersion plate of Ling-396 in order to provide smaller differences of shear stress to cells residing at different locations in the bioreactor (Ling-396, paragraph [0032]).
Regarding feature 3, Ling-396 also discloses:
wherein the inlet port and the outlet port, the reactor shell, the dispersion plate, and the packing elements form a single monolithic structure (Ling-396, Figs. 8-9, paragraphs [0065], [0079], and [0093]-[0095]).
In the analogous art of three-dimensional fixed-bed bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the distribution plate of modified Dumont with the 3d-printed structure of Ling-396 in order to provide smaller differences of shear stress to cells residing at different locations in the bioreactor (Ling-396, paragraph [0065]).
Additionally, regarding feature 3, regarding the phrases “a dispersion plate embedded into the reactor shell, positioned between the inlet port and the media bed” as well as “wherein the inlet port and the outlet port, the reactor shell, the dispersion plate, and the packing elements form a single monolithic structure”, 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 integration of these parts to be a monolithic structure in order to be able to 3D print the entire structure at once without further assembly or labor.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Dumont (US 20240002769) (previously disclosed) in view of Ling-396 (US 20210317396) (previously disclosed) as applied to claim 1, further in view of Meyer-Blumenroth (US 20230321607) (previously disclosed).
Regarding claim 4, modified Dumont teaches said single (paragraph [0066]) monolithic structure (see rejection to claim 1).
Dumont does not disclose wherein said single monolithic structure comprises polyamide.
Meyer-Blumenroth discloses a single (paragraph [0034]) monolithic structure comprising polyamide (paragraphs [0094] and [0184]; and Fig. 15).
In the analogous art of monolithic membrane filters, it would have been obvious to one skilled in the art before the effective filing date to modify the single monolithic bioreactor of modified Dumont with the polyamide of Meyer-Blumenroth in order to be manufactured by a polymer capable of being monolithically 3D printed (Meyer-Blumenroth, paragraph [0025]).
Additional Prior Art References
The prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure.
Seeto (US 20240002768) (previously cited) – This invention has a monolithic construction of a bioreactor and a fluid distribution plate.
Ling-178 (US 20170321178) (newly cited) – This invention is similar to Ling-396, cited above.
Chang (US 20220154124) (newly cited) – This invention is a bioreactor with a volume-adjustable packing layer.
Sun (US 20240344008) (newly cited) – This invention describes a uniform cell culture substrate for a fixed bed bioreactor.
Ferrie (US 20210130761) (newly cited) – This invention, by the same Applicant as Sun, above, is for a fixed bed bioreactor.
Rocco (WO 2022031709) (newly cited) – This invention describes a composite scaffold.
Berry (US 20130034898) (newly cited) – This invention contains a scaffold formed by a matrix.
Response to Arguments
Applicant’s arguments filed 06/29/2026 have been fully considered but they are not persuasive.
Regarding Applicant remarks, pgs. 6-7 of 11, the remarks about the claim objections and claim rejections under 35 U.S.C. § 112(a) are acknowledged, but not agreed upon by the examiner. The ratio limitation is not limiting in the sense that the size limitations are, because sizes in a ratio are relative to each other rather than a conventional dimension with a length, width, height, etc. For instance, a 20:1 ratio can be accomplished just as easily with a 20 cm : 1 cm set of measurements as a 20 mm : 1 mm set of measurements. Therefore, claiming the ratio instead of the specific measurements involved would be too broad a scope for the written description of the invention. In other words a ratio can depict any units of the individual dimensions but the specification only has dimensions in mm, thus the claimed ratio is broader compared to what disclosed in the specification and thus is new matter.
Regarding Applicant remarks, pgs. 8-9 of 11, Applicant has alleged reasons for the design of the truncated portions of the packing elements and describes the invention.
Regarding Applicant remarks, pg. 9-10 of 14, Applicant has alleged that Dumont does not disclose truncated objects. Regarding this limitation, Ling-396 discloses these truncated objects, see above.
Regarding Applicant remarks, pg. 11 of 14, secondary reference Seeto is considered. However, secondary reference Seeto has been dropped from this Office Action in view of Ling-396, which also discloses the subject matter of Seeto, see above.
Regarding Applicant remarks, pg. 11 of 14, secondary reference Ling-396 is considered. Applicant’s arguments are drawn to the different structures of interconnected voids of Ling-396 and how they are not shaped similarly to the ordered lattice of spheres of Dumont. As already described above, Dumont’s ordered lattice need not be shaped like spheres, but can be other shapes as well. If it is deemed necessary to provide motivation for a different shape, 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 shape of modified Dumont to have the claimed shape as described above, for the reasons set forth above. The void fraction, as described by Ling-396, need not be confined to a specific shape; it would have been obvious to one skilled in the art before the effective filing date to modify the shape of the voids to be the voids claimed in the claimed shapes as described above, for the reasons set forth above. Ling-396’s packing efficiency of spherical voids is described as previously set forth in the last Office Action in Ling-396, paragraph [0106]: “For the 3D bioreactor herein, packing efficiency preferably has a value of greater than 64.0%, more preferably greater than 70.0% and most preferably a value greater than 75.0%”. Remaining Applicant arguments about the packing elements and their respective voids are based on shapes that are disclosed by Dumont or otherwise obvious.
Regarding Applicant remarks, pg. 12 of 14, regarding the surface area calculation, the Ling-396 reference discloses monolayer culture (Ling-396, paragraph [0057]). However, the claim is drawn to a specific surface area that is fulfilled by Ling-396 and its inherent surface area calculation.
Additionally, the claim is not commensurate in scope with the arguments about a monolayer cell culture. The cells of the bioreactor are not claimed, whether in a stacked or monolayer formation. It is possible that if the cells were to be claimed in the present bioreactor in a stacked or monolayer formation, this may be a manner of intended use of the structure of the bioreactor. Applicant is reminded that the material or article worked upon by the apparatus does not limit the apparatus claims. MPEP § 2115. This limitation is a manner of operating or intended use of a claimed apparatus and does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Dumont would be fully capable of operating in this manner given the monolithic bioreactor. Additionally, the configuration of cells within the instant invention is not described in the specification or original claim set.
Also, Dumont is capable of adherent cell culture in a two-dimensional manner (Dumont, paragraphs [0009] and [0012]), similarly to Ling-396, so the combination of these two inventions appears to be in concordance with their intended operation.
Regarding Applicant remarks, pg. 12 of 14, regarding the disclosure of Meyer-Blumenroth in claim 4, claim 4 only recites “The bioreactor of claim 1, wherein said single monolithic structure comprises polyamide.” No further details are given on the polyamide. Meyer-Blumenroth, however, specifically states that membrane filters are for, among other applications, pharmaceutical and biotechnological usage (Meyer-Blumenroth, paragraph [0003]), and that their monolithic membrane filter can comprise polyamides (paragraph [0094]). Allegations that the polyamides of Meyer-Blumenroth would not work in a biotechnological environment are unsubstantiated.
Regarding Applicant remarks, pg. 13 of 14, regarding the alleged use of bacterial lines for the instant invention, bacterial cells and the intended uses / manners of operation of the bioreactor for these bacterial cells are not claimed. Additionally, Applicant is reminded that the material or article worked upon by the apparatus does not limit the apparatus claims. MPEP § 2115. This limitation is a manner of operating or intended use of a claimed apparatus and does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Dumont would be fully capable of operating in this manner given the monolithic bioreactor.
Regarding the remaining dependent claims, these claims are rejected as the independent claim is still rejected and no further arguments were made regarding the dependent claims.
Conclusion
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. 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
