DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/28/2024 and 07/22/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 13, and 16 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 2 recites the limitation "the at least one permeability zone" in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 2 depends, recites a plurality of permeability zones rather than at least one permeability zone.
Claim 16 recites the limitation " the at least one permeability zone" in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 41, from which claim 16 depends, recites a plurality of permeability zones rather than at least one permeability zone.
Dependent claims are rejected for the same reason as the base claim(s) upon which they depend.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ferrie et al. (US Patent Application Publication 2020/0248124) in view of Simón Soria (US Patent Application Publication 2022/0056391).
Regarding claim 1, Ferrie et al. discloses a fixed-bed bioreactor system for culturing cells (Abstract, para. 13), the system comprising:
a cell culture vessel comprising an inlet (408), an outlet (410), and at least one interior reservoir fluidly connected to and disposed in a fluid pathway between the inlet and the outlet (para. 108-109) (Fig. 10A, sheet 12 of 34); and
a cell culture matrix disposed in the reservoir (para. 108) in a wound configuration around a winding axis extending in a direction from the inlet to the outlet (para. 107-108) (Fig. 8, sheet 10 of 34), the cell culture matrix comprising a structurally defined substrate comprising a substrate material (para. 83, 99-100) defining a plurality of pores (para. 85), the substrate material being configured for adhering cells thereto (para. 83), the pores having an opening size on the order of microns (para. 91), the substrate configured to allow fluid to flow throughout the substrate in the wound condition (para. 107);
wherein the substrate comprises a length extending in a direction tangential to the winding axis (para. 99, 107) (Fig. 8, sheet 10 of 34).
Ferrie et al. is silent as to a plurality of permeability zones in the cell culture matrix, each of the plurality of permeability zones comprising an opening in the substrate, the opening being larger than a diameter of any of the plurality of pores, wherein the plurality of permeability zones comprises a variable periodicity along a length of the substrate in the wound configuration.
Simón Soria discloses a fixed-bed bioreactor system for culturing cells (Abstract, para. 61), the system comprising a cell culture substrate in a wound configuration around a winding axis (Abstract, para. 16, 61, 93), the cell culture substrate configured for adhering cells thereto (para. 61, 77), the cell culture substrate comprising a length extending in a direction tangential to the winding axis (Figs. 1-4, sheets 1-2 of 7). Simón Soria discloses it was known in the art that spiral-wound cell culture substrates suffer from issues of decreased fluid flow especially at the inner spiral space (para. 4-9). To overcome these issues, Simón Soria discloses providing the cell culture substrate with a plurality of openings therein (para. 54) (Figs. 3A-3D, sheet 2 of 7), the openings having a size on the order of millimeters (para. 98), wherein providing the openings desirably improves fluid flow throughout the cell culture substrate (para. 66-67, 96) (thus, the openings form a plurality of permeability zones in the substrate, each of the plurality of zones comprising an opening in the substrate). Simón Soria further discloses wherein the frequency of the openings may vary along the length of the substrate to provide different effects in different regions (para. 83), in other words, the plurality of permeability zones comprises a variable periodicity along a length of the substrate in the wound configuration.
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the cell culture matrix disclosed by Ferrie et al. to comprise a plurality of permeability zones in the cell culture matrix, each of the plurality of permeability zones comprising an opening in the substrate, the opening being larger than a diameter of any of the plurality of pores, wherein the plurality of permeability zones comprises a variable periodicity along a length of the substrate in the wound configuration, e.g., by providing a plurality of millimeter-scale openings such that frequency (periodicity) varies along a length of the substrate as disclosed by Simón Soria, as Simón Soria discloses that it was known in the art to provide such a configuration to improve fluid flow in the context of a wound cell culture substrate thereby improving culture conditions and additionally to allow an operator to investigate different flow conditions at different regions.
Regarding claim 2, Ferrie et al. in view of Simón Soria teaches the plurality of permeability zones, as set forth above, and Simón Soria discloses wherein each of the plurality of permeability zones comprises higher permeability than a standard permeability of the cell culture matrix outside of the at least one permeability zone (i.e., sections comprising the openings have higher permeability than sections without openings) (para. 54, 66-67); therefore, the prior art combination arrives at the claimed subject matter.
Regarding claim 3, Ferrie et al. discloses the wound configuration, as set forth above, wherein the length has a first end at the interior of the wound configuration of the cell culture matrix (Fig. 8, sheet 10 of 34). Ferrie et al. in view of Simón Soria teaches wherein the periodicity varies along the length to provide different effects at different regions, as set forth above.
The prior art combination does not expressly teach wherein the periodicity decreases along the length from the first end of the substrate material.
Nonetheless, it has been held that a person of ordinary skill has good reason to pursue the known options within his or her technical grasp (MPEP 2143.1.E). In this case, the issue of reduced fluid flow within a wound substrate was a known problem, and Simón Soria discloses providing openings along the length of the substrate to overcome the problem, wherein periodicity can vary along the length, as discussed above. Furthermore, the skilled artisan would recognize that there are a finite number of ways to arrange openings to achieve variable periodicity along the length, including arranging the openings such that periodicity decreases from a first end within the interior of the wound configuration, and the skilled artisan could have pursued the different arrangement techniques with a reasonable expectation of success. Therefore, it would have been obvious to try an arrangement such that periodicity decreases along the length from the first end of the substrate material.
Regarding claim 4, Ferrie et al. discloses the wound configuration, as set forth above, wherein the length has a first end at the interior of the wound configuration of the cell culture matrix (Fig. 8, sheet 10 of 34). Ferrie et al. in view of Simón Soria teaches wherein the periodicity varies along the length to provide different effects at different regions, as set forth above.
The prior art combination does not expressly teach wherein the periodicity increases along the length from the first end of the substrate material.
Nonetheless, it has been held that a person of ordinary skill has good reason to pursue the known options within his or her technical grasp (MPEP 2143.1.E). In this case, the issue of reduced fluid flow within a wound substrate was a known problem, and Simón Soria discloses providing openings along the length of the substrate to overcome the problem, wherein periodicity can vary along the length, as discussed above. Furthermore, the skilled artisan would recognize that there are a finite number of ways to arrange openings to achieve variable periodicity along the length, including arranging the openings such that periodicity increases from a first end within the interior of the wound configuration, and the skilled artisan could have pursued the different arrangement techniques with a reasonable expectation of success. Therefore, it would have been obvious to try an arrangement such that periodicity increases along the length from the first end of the substrate material.
Regarding claim 5, Ferrie et al. discloses wherein the cell culture matrix comprises a plurality of layers of the substrate material that are wound together in the wound configuration (winding the substrate yields a plurality of adjacent layers, see para. 91 and Fig. 8; alternatively, the substrate itself may comprise a multilayer configuration prior to winding, see para. 101), or alternatively Simón Soria discloses wherein the portion of the substrate comprising the openings discussed in claim 1, above, is provided as an additional layer upon a base layer that does not comprise the openings forming the permeability zones (para. 58, 85) (Figs. 1-4) and thus the prior art combination meets the claimed subject matter.
Regarding claim 6, Ferrie et al. discloses that each of the plurality of layers of the substrate material comprises one or more permeability zones comprising an opening (e.g., each of layers 202 and 204 is a mesh comprising an opening, see para. 101 and Fig. 3A; it is noted that claim 6 does not require that “one or more permeability zones comprising an opening” are the same as “a plurality of permeability zones in the cell culture matrix, each of the plurality of permeability zones comprising an opening” from claim 1).
Regarding claim 7, Ferrie et al. in view of Simón Soria teaches wherein at last one of the plurality of layers of the substrate material does not comprise a permeability zone, as set forth in the rejection of claim 5, above.
Regarding claim 8, Ferrie et al. in view of Simón Soria teaches the openings of the permeability zones, as set forth above, and Simón Soria further discloses wherein the openings have a length and a width (para. 54) (Fig. 3A-3D, sheet 2 of 7).
The prior art combination does not expressly teach wherein the length is longer than the width. Nonetheless, it has been held recitations of relative dimensions do not introduce a patentable distinction over the prior art (MPEP 2144.04). Therefore, the recitation of the length being longer than the width does not introduce a patentable distinction.
Regarding claim 9, Ferrie et al. in view of Simón Soria teaches wherein each opening has a length, as set forth above. Ferrie et al. discloses wherein the winding axis extends in a direction from the inlet to the outlet, as set forth above, and Simón Soria discloses wherein a length of each opening extends about 90⁰ relative to a direction of the winding axis (Figs. 1-2, sheets 1-2 of 7). Therefore, the prior art combination arrives at the claimed subject matter.
Regarding claim 10, Ferrie et al. in view of Simón Soria teaches the substrate material comprising openings of the permeability zones, as set forth above.
The prior art combination does not expressly teach wherein a thickness of the substate material bordering the openings of the permeability zones is greater than a thickness of the substrate material not bordering the openings. Nonetheless, it has been held recitations of relative dimensions do not introduce a patentable distinction over the prior art (MPEP 2144.04). Therefore, the recitation of one region having a greater thickness than another does not introduce a patentable distinction.
Regarding claim 11, Ferrie et al. discloses wherein the substrate material comprises an ordered and substantially uniform array of pores (para. 82-83, 85).
Regarding claim 12, the limitation of wherein the permeability zones are “designed” to compensate for at least one of an increased permeability between the cell culture matrix and a wall of the reservoir and an increased permeability within a core of the wound cell culture matrix is understood to be recitation of the manner of production of the cell culture matrix. It has been held that the patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113). The cell culture matrix taught by the prior art combination is the same as that claimed, as set forth above, and therefore the “designed” limitation does not introduce a patentable distinction over the prior art. Nonetheless, Simón Soria discloses wherein the permeability zones are designed to compensate for increased permeability within a core of the wound cell culture matrix, as set forth above, and therefore the prior art combination arrives at the claimed subject matter.
Regarding claim 13, Ferrie et al. in view of Simón Soria teaches wherein the standard permeability is a permeability of a section of the cell culture matrix consisting of the substrate without the opening, as set forth in claim 2, above.
Regarding claim 14, Ferrie et al. discloses a fixed-bed cell culture matrix for culturing adherent-based cells in a bioreactor (Abstract, para. 13), the cell culture matrix comprising:
a structurally defined substrate comprising a substrate material (para. 83, 99-100) defining a plurality of pores (para. 85), the substrate material being configured for adhering cells thereto (para. 83), the substrate material being arranged in a wound configuration (para. 107-108) (Fig. 8, sheet 10 of 34), the pores having an opening size on the order of microns (para. 91), the substrate configured to allow fluid to flow throughout the substrate in the wound condition (para. 107);
wherein the substrate material is wound about a winding axis (para. 107-108) (Fig. 8, sheet 10 of 34), and the substrate comprises a length extending in a direction tangential to the winding axis (para. 99, 107) (Fig. 8, sheet 10 of 34).
Ferrie et al. is silent as to a plurality of permeability zones in the cell culture matrix, each of the plurality of permeability zones comprising an opening in the substrate, the opening being larger than a diameter of any of the plurality of pores.
Simón Soria discloses a fixed-bed bioreactor system for culturing cells (Abstract, para. 61), the system comprising a cell culture substrate in a wound configuration around a winding axis (Abstract, para. 16, 61, 93), the cell culture substrate configured for adhering cells thereto (para. 61, 77), the cell culture substrate comprising a length extending in a direction tangential to the winding axis (Figs. 1-4, sheets 1-2 of 7). Simón Soria discloses it was known in the art that spiral-wound cell culture substrates suffer from issues of decreased fluid flow especially at the inner spiral space (para. 4-9). To overcome these issues, Simón Soria discloses providing the cell culture substrate with a plurality of openings therein (para. 54) (Figs. 3A-3D, sheet 2 of 7), the openings having a size on the order of millimeters (para. 98), wherein providing the openings desirably improves fluid flow throughout the cell culture substrate (para. 66-67, 96) (thus, the openings form a plurality of permeability zones in the substrate, each of the plurality of zones comprising an opening in the substrate). Simón Soria further discloses wherein the frequency of the openings may vary along the length of the substrate to provide different effects in different regions (para. 83), in other words, the plurality of permeability zones comprises a variable periodicity along a length of the substrate in the wound configuration.
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the cell culture matrix disclosed by Ferrie et al. to comprise a plurality of permeability zones in the cell culture matrix, each of the plurality of permeability zones comprising an opening in the substrate, the opening being larger than a diameter of any of the plurality of pores, wherein the plurality of permeability zones comprises a variable periodicity along a length of the substrate in the wound configuration, e.g., by providing a plurality of millimeter-scale openings such that frequency (periodicity) varies along a length of the substrate as disclosed by Simón Soria, as Simón Soria discloses that it was known in the art to provide such a configuration to improve fluid flow in the context of a wound cell culture substrate thereby improving culture conditions and additionally to allow an operator to investigate different flow conditions at different regions.
Regarding claim 15, Ferrie et al. in view of Simón Soria teaches wherein the plurality of permeability zones comprises a variable periodicity along a length of the substrate in the wound configuration, as set forth above.
Regarding claim 16, Ferrie et al. in view of Simón Soria teaches the plurality of permeability zones, as set forth above, and Simón Soria discloses wherein each of the plurality of permeability zones comprises higher permeability than a standard permeability of the cell culture matrix outside of the at least one permeability zone (i.e., sections comprising the openings have higher permeability than sections without openings) (para. 54, 66-67); therefore, the prior art combination arrives at the claimed subject matter.
Regarding claim 17, Ferrie et al. discloses the wound configuration, as set forth above, wherein the length has a first end at the interior of the wound configuration of the cell culture matrix (Fig. 8, sheet 10 of 34). Ferrie et al. in view of Simón Soria teaches wherein the periodicity varies along the length to provide different effects at different regions, as set forth above.
The prior art combination does not expressly teach wherein the periodicity decreases or increases along the length from the first end of the substrate material.
Nonetheless, it has been held that a person of ordinary skill has good reason to pursue the known options within his or her technical grasp (MPEP 2143.1.E). In this case, the issue of reduced fluid flow within a wound substrate was a known problem, and Simón Soria discloses providing openings along the length of the substrate to overcome the problem, wherein periodicity can vary along the length, as discussed above. Furthermore, the skilled artisan would recognize that there are a finite number of ways to arrange openings to achieve variable periodicity along the length, including arranging the openings such that periodicity decreases or increases from a first end within the interior of the wound configuration, and the skilled artisan could have pursued the different arrangement techniques with a reasonable expectation of success. Therefore, it would have been obvious to try an arrangement such that periodicity decreases or decreases along the length from the first end of the substrate material.
Regarding claim 18, Ferrie et al. discloses wherein the cell culture matrix comprises a plurality of layers of the substrate material that are wound together in the wound configuration (winding the substrate yields a plurality of adjacent layers, see para. 91 and Fig. 8; alternatively, the substrate itself may comprise a multilayer configuration prior to winding, see para. 101), or alternatively Simón Soria discloses wherein the portion of the substrate comprising the openings discussed in claim 1, above, is provided as an additional layer upon a base layer that does not comprise the openings forming the permeability zones (para. 58, 85) (Figs. 1-4) and thus the prior art combination meets the claimed subject matter.
Regarding claim 19, Ferrie et al. in view of Simón Soria teaches the openings of the permeability zones, as set forth above, and Simón Soria further discloses wherein the openings have a length and a width (para. 54) (Fig. 3A-3D, sheet 2 of 7), wherein a length of each opening extends about 90⁰ relative to a direction of the winding axis (Figs. 1-2, sheets 1-2 of 7). Therefore, the prior art combination arrives at the claimed subject matter of wherein the length of the opening extends in a direction between 0 and 90⁰ relative to a direction of the winding axis.
The prior art combination does not expressly teach wherein the length is longer than the width. Nonetheless, it has been held recitations of relative dimensions do not introduce a patentable distinction over the prior art (MPEP 2144.04). Therefore, the recitation of the length being longer than the width does not introduce a patentable distinction.
Regarding claim 20, Ferrie et al. in view of Simón Soria teaches the substrate material comprising openings of the permeability zones, as set forth above.
The prior art combination does not expressly teach wherein a thickness of the substate material bordering the openings of the permeability zones is greater than a thickness of the substrate material not bordering the openings. Nonetheless, it has been held recitations of relative dimensions do not introduce a patentable distinction over the prior art (MPEP 2144.04). Therefore, the recitation of one region having a greater thickness than another does not introduce a patentable distinction.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Fakhar et al. (US Patent Application Publication 2025/0034503) is directed to a cell culture substrate comprising pores and channels, the substrate in a wound configuration.
Conclusion
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/HOLLY KIPOUROS/Primary Examiner, Art Unit 1799
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