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 .
Claim Objections
The previous claim objections are withdrawn in light of the amendments.
Claim 12 is objected to because of the following informalities:
Regarding claim 12, in line 2, the phrase “any individual element” should be “any individual packing element”. This wording conforms better with the wording in parent claim 11 as well as independent claim 1.
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The previous 35 U.S.C. § 112(b) rejections are withdrawn in light of the amendments.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 originally filed application does not have support for the broad limitation given in the claim. 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, and the word “ratio” is not in the specification. To clarify this limitation, please use the dimensions 2 mm and 0.1 mm, respectively.
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 and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Dumont (US 20240002769) (previously disclosed) in view of Seeto (US 20240002768) (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]) 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 (paragraphs [0012] “fused together”, [0024], and [0056]; the bioreactor and matrix are of unitary construction); and
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).
Dumont does not disclose:
a dispersion plate 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.
Seeto discloses:
a dispersion plate (paragraph [0016]) between the inlet port (paragraph [0016]) and the media bed (paragraph [0016] “cell culture substrate”) and configured to distribute fluid flowing from the inlet port across the media bed (paragraph [0030]).
In the analogous art of fixed bed bioreactor systems, 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 Seeto in order to evenly distribute fluid across the substrate for the improved diffusion of nutrients (Seeto, paragraph [0032]).
Regarding the phrase “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). Additionally, 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 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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Dumont (US 20240002769) (previously disclosed) in view of Seeto (US 20240002768) (previously disclosed) as applied to claim 1, further in view of Ling (US 20210317396) (previously disclosed).
Regarding claim 3, 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 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, paragraph [0106]) by having a large surface to volume ratio in comparison to a conventional roller bottle (Ling, paragraph [0080]).
Regarding the limitation about specific surface area disclosed by Ling, the following calculation was used based on information about vessel volume and matrix surface area from Ling, 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 inherently discloses a specific surface area of at least 650 m2 / m3.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Dumont (US 20240002769) (previously disclosed) in view of Seeto (US 20240002768) (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.
Burns (US 20200291340) (previously disclosed) – This invention is a lattice for cell culture that has been 3D printed.
Response to Arguments
Applicant’s arguments filed 11/05/2025 have been fully considered but they are not persuasive.
Regarding Applicant remarks, pgs. 5-6 of 11, the remarks about the claim objections and claim rejections under 35 U.S.C. § 112(b) are acknowledged.
Regarding Applicant remarks, pgs. 6-7 of 11, Applicant has alleged reasons for why the invention is considered helpful, but does not provide clear evidence that the invention is neither anticipated nor obvious over the prior art.
Regarding Applicant remarks, pg. 8 of 11, first paragraph, Applicant has alleged that Dumont does not disclose truncated objects. Contrarily, Dumont discloses that “[t]he objects may be bound, printed or fused together to form the fixed bed structure or matrix” and such methods to manufacture this formation can include “[t]he methods of bonding or fusing can include local welding, SLS or other 3D printing methodologies, but are not limited to such techniques” (Dumont, paragraph [0012]). Furthermore, Dumont describes “the structure comprises one or more monolithic structures integrated in a cell culture vessel or bioreactor. In some embodiments, the matrix and the bioreactor are both manufactured using the same process (e.g., SLS), such that the vessel and the fixed bed are co concurrently formed” (Dumont, paragraph [0014]). These paragraphs show that the fixed bed and the bioreactor meet the claim limitations above regarding truncated packing elements in contact with the inner wall of the reactor shell. Further remarks directed to the method of manufacture of Dumont can be directed to the evidence provided above (i.e., Dumont, paragraph [0014] as well as other paragraphs provided in Dumont, such as paragraphs [0020] and [0025]).
Regarding Applicant remarks, pg. 8 of 11, final paragraph, Applicant describes that Seeto’s design is for mammalian cells rather than microbial cells and that the design is overly cumbersome. Although mammalian cells are mentioned in the background section of Seeto’s publication (Seeto, paragraph [0009] and the manufacturing of viral vectors on commercial scale in paragraph [0013]), the only portion of Seeto’s invention that is cited is the dispersion plate which has a similar function in the instant invention: to distribute fluid flowing from the inlet port across the media bed. A motivation statement is given for the combination of Dumont in view of Seeto: to modify Dumont’s bioreactor with the dispersion plate of Seeto in order to evenly distribute fluid across the substrate for the improved diffusion of nutrients (Seeto, paragraph [0032]). Similarly, in the instant invention, “[t]he dispersion plate 5 operates to help ensure even distribution of fluid flow into and across the media bed 4” (instant specification, paragraph [0018]). Additionally, regarding the use of microbes versus mammalian cells with the invention, the material or article worked upon by the apparatus does not limit the apparatus claims. MPEP § 2115. Also, 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).
Regarding Applicant remarks, pg. 9 of 11, first paragraph, Ling discloses a void fraction of above 75% (Ling, paragraph [0106]). Regardless of the shape of Ling’s internal structure (the shapes of the packing elements are not claimed until claims 9 and 10 of the instant claim set), the void fraction is present, as is the surface area in Ling’s invention, as described through inherency via the calculation provided in the previous Office action. Ling’s invention satisfies the limitations of claim 3. Allegations that Ling’s invention could not tolerate a shear force are not relevant as a fluid velocity and shear force are an intended use or manner of operating the instant invention.
Regarding Applicant remarks, pg. 9 of 11, final paragraph, Meyer-Blumenroth discloses “at least one of … polyamides” as a base material for its monolithic structure (Meyer-Blumenroth, paragraph [0094]). Allegations that the polyamide of Meyer-Blumenroth does not support the growth of cells are unsupported.
Regarding Applicant remarks, pg. 10 of 11, middle paragraph, about mammalian cell lines, see arguments above regarding Applicant remarks, pg. 8 of 11, final paragraph.
Additionally, in response to Applicant’s arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
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
THIS ACTION IS MADE FINAL. 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.
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/N.G.E./Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799