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
Claim 8 is objected to because of the following informalities: in line 1, the term “wherein multilayer substrate” should be written as “wherein the multilayer substrate”. Appropriate correction is required.
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.
Claims 9-14 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 9 recites the limitation "the multilayer substrate" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. It is believed that claim 9 should be dependent on claim 2. Claims 10-14 are rejected as being dependent on claim 9.
Claim 14 recites the limitation "the bioreactor vessel" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim. It is believed that the claim should instead recite “the cell culture vessel”.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ferrie (US 20200248121)1
With respect to claims 1, 4 and 15, Ferrie discloses a packed-bed bioreactor system for culturing cells. The system includes a cell culture vessel (Figure 6:300) comprising at least one interior reservoir, an inlet (Figure 6:310) fluidly connected to the reservoir, and an outlet (Figure 6:312) fluidly connected to the reservoir. A cell culture matrix (Figure 6:306) is disposed in the reservoir and arranged as a fixed bed comprising a substrate configured for adhering cells thereto. This is described in paragraphs [0097] and [0098]. Ferrie expressly states in paragraphs [0075]-[0078] that the cell culture matrix is configured to maintain a uniform laminar flow within the reservoir throughout the cell culture matrix (“Embodiments include a porous cell-culture matrix made from an ordered and regular array of porous substrate material that enables uniform cell seeding and media/nutrient perfusion”). In the alternative, it is noted that recitations relating to how the system is used (here, “maintain a uniform flow rate”) are afforded reduced patentable weight in the context of a device claim. Apparatus claims cover what a device is, not what a device does. A claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim. See MPEP 2114.
With respect to claims 2 and 3, Ferrie discloses the system as described above. Ferrie further shows that the cell culture matrix is a multilayer substrate, and that each substrate layer (Figure 6:308) is characterized by a regular and uniform physical structure and porosity.
With respect to claims 5-8, Ferrie discloses the system as described above. Ferrie further teaches that the substrate layers (Figure 6:308) extend across a width of the reservoir and are configured as stacked disks. Each of the stacked disks are porous and characterized by a regular and uniform pattern of openings (i.e., pores). See paragraphs [0081]-[0085].
With respect to claims 9-13, Ferrie discloses the system as described above. Ferrie additionally teaches that the stacked substrate layers (Figure 6:308) are woven substrates formed by a plurality of interwoven fibers (Figure 1A:102). See paragraphs [0081]-[0085]. Fig. 6 shows that the stacked substrate layers are in physical contact with each other and are not separated by a spacer material or barrier.
With respect to claim 14, Ferrie discloses the system as described above. Ferrie shows in Fig. 6 that the cell culture matrix 306 is disposed in the bioreactor vessel such that a bulk flow direction (see arrows) of media through the bioreactor vessel is perpendicular to first and second side surfaces of each disk.
With respect to claim 16, Ferrie discloses the system as described above. Ferrie teaches in paragraph [0090] that media may be perfused through the cell culture matrix as a plug flow. In the alternative, it is noted that recitations relating to how the system is used (here, “plug flow”) are afforded reduced patentable weight in the context of a device claim. Apparatus claims cover what a device is, not what a device does. A claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim. See MPEP 2114.
With respect to claim 17, Ferrie discloses the system as described above. Ferrie shows in Fig. 24 that the cell culture matrix may exhibit a permeability of greater than 3.4 x 10-10m2.
With respect to claim 18, Ferrie discloses the system as described above. Ferrie states in paragraph [0085] that the packing thickness of each layer is from about 50 microns to 1,000 microns.
With respect to claim 19, Ferrie discloses the system as described above. Ferrie teaches in paragraph [0131] that the porosity of the fixed bed is between about 40% to 65%.
With respect to claim 20, Ferrie discloses the system as described above. Ferrie teaches in paragraphs [0085], [0092]-[0093] and [0131] that the fixed bed may be characterized by either a tight packing density or a loose packing density.
Claims 1-5, 15 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Feder (US 4201845).
With respect to claims 1, 4 and 15, Feder discloses a packed-bed bioreactor system for culturing cells. The system includes a cell culture vessel (Figure 1:10) comprising at least one interior reservoir, an inlet (Figure 1:26,27) fluidly connected to the reservoir, and an outlet (Figure 1:28) fluidly connected to the reservoir. A cell culture matrix (Figure 2:34) is disposed in the reservoir and arranged as a fixed bed comprising a substrate configured for adhering cells thereto. This is described in column 2, line 67 to column 4, line 24. Feder expressly states that the cell culture matrix is configured to maintain a uniform laminar flow within the reservoir throughout the cell culture matrix (“the fiber bed preferably has a generally square horizontal cross section to facilitate uniform distribution of culture media in all directions”). In the alternative, it is noted that recitations relating to how the system is used (here, “maintain a uniform flow rate”) are afforded reduced patentable weight in the context of a device claim. Apparatus claims cover what a device is, not what a device does. A claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim. See MPEP 2114.
With respect to claim 2, Feder discloses the apparatus as described above. Feder states that multiple substrate layers having a regular and uniform porosity may be stacked to create the matrix 34 (“The fiber bed also can comprise several thicknesses of individual fibers superimposed one upon the other, and generally use of from about one to about 50 such thicknesses of fibers is suitable. Separate layers of fibers can be interspersed with support plates or spacers, if desired. These support plates or spacers can be similar to distributor plate 35 or can be screens and the like means which allow passage of the culture media”).
With respect to claim 3, Feder discloses the apparatus as described above. Feder further teaches that the cell culture matrix is configured as an ordered mesh structure, and therefore describes a matrix having a substantially uniform porosity (“The hollow fibers can be…arranged, for example, in an ordered…mesh form”).
With respect to claims 5 and 16, Feder discloses the apparatus as described above. Feder further shows in Fig. 2 that the reservoir has a length defined by a vertical axis, and that the cell culture matrix extends across a width of the reservoir. Fluid flows vertically across the length of the reactor and may be perfused through the cell culture matrix as a plug flow. It is noted that recitations relating to how the system is used (here, “plug flow”) are afforded reduced patentable weight in the context of a device claim. Apparatus claims cover what a device is, not what a device does. A claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim. See MPEP 2114.
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.
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.
Claims 6-14 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Feder (US 4201845) as applied to claims 1 and 2, and further in view of Sussman (US 5266476) and Castillo (US 20180282678)
With respect to claims 6-14, Feder discloses the bioreactor system as described above. As previously noted, Feder teaches that the matrix 34 may be created using multiple substrate layers (“The fiber bed also can comprise several thicknesses of individual fibers superimposed one upon the other, and generally use of from about one to about 50 such thicknesses of fibers is suitable. Separate layers of fibers can be interspersed with support plates or spacers, if desired. These support plates or spacers can be similar to distributor plate 35 or can be screens and the like means which allow passage of the culture media”). It is unclear, however, if this multilayer structure comprises stacked disks and/or woven substrates.
Sussman discloses a packed-bed bioreactor system comprising a culture vessel and a cell culture matrix. The cell culture matrix includes a vertical stack of a plurality of woven substrate disks (Figure 4A:2) separated by nonwoven fibrous disks (Figure 4A:1). See also Fig. 5, which shows the vertical matrix stack disposed in a cell culture vessel (Figure 5:62) having a bottom inlet and a top outlet.
Castillo discloses a packed-bed bioreactor system comprising a cell culture matrix comprising a plurality of stacked substrate disks (Figure 2B:10). The embodiments shown in Figs. 1A-2D show that at least two substate disks 10 physically contact each other and are not separated by an intervening spacer 11. Castillo states in paragraph [0049] that the cell culture matrix is for the immobilization of cells and is fabricated using interwoven fibers.
Before the effective filing date of the claimed invention, it would have been obvious to construct the Feder multilayer substrate using a plurality of substrate disks made from interwoven fibers. Sussman and Castillo each teach that this configuration is well known in the art and especially suitable for immobilizing and culturing cells. It is prima facie obvious to apply a known technique (here, multilayer woven substrate disks) to a known device ready for improvement to yield predictable results. See MPEP 2143. Castillo states that this configuration allows for high density cell growth and for a more homogenous distribution of cells inside the bioreactor matrix. Sussman teaches that the stacked woven disks provide a surface most suitable for anchorage dependent tissue cells.
With respect to claims 17-20, Feder, Castillo and Sussman disclose the combination as described above. These references teach the claimed permeability, packing thickness, porosity and packing density values set forth in the claims. Furthermore, it is well within the ability of one of ordinary skill to determine an optimum permeability, packing thickness, porosity and packing density through routine experimentation. Castillo, for example, teaches in paragraphs [0035]-[0048] that these parameters are result effective variables that may adjusted as needed based on the requirements of a particular cell culture application.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 7-11, 14, 15 and 19-29 of copending Application No. 18/714,867 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of copending Application No. 18/714,867 include limitations drawn to
A packed-bed bioreactor system for culturing cells, the system comprising:
a cell culture vessel comprising at least one interior reservoir, an inlet fluidly connected to the reservoir, and an outlet fluidly connected to the reservoir; and
a cell culture matrix disposed in the reservoir and arranged as a fixed bed, the cell culture matrix comprising a substrate configured for adhering cells thereto,
wherein the cell culture matrix is configured to maintain a uniform flow within the reservoir throughout the cell culture matrix.
Provisional claim 10, in particular, describes uniform fluid flow through the cell culture matrix.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-11, 13-31, 34, 52 and 53 of copending Application No. 18/293,676 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of copending Application No. 18/293,676 include limitations drawn to
A packed-bed bioreactor system for culturing cells, the system comprising:
a cell culture vessel comprising at least one interior reservoir, an inlet fluidly connected to the reservoir, and an outlet fluidly connected to the reservoir; and
a cell culture matrix disposed in the reservoir and arranged as a fixed bed, the cell culture matrix comprising a substrate configured for adhering cells thereto,
wherein the cell culture matrix is configured to maintain a uniform flow within the reservoir throughout the cell culture matrix.
Provisional claim 1, in particular, describes uniform fluid flow through the cell culture matrix.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Pat. No. 11,434,4602.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of U.S. Pat. No. 11,434,460 include limitations drawn to
A packed-bed bioreactor system for culturing cells, the system comprising:
a cell culture vessel comprising at least one interior reservoir, an inlet fluidly connected to the reservoir, and an outlet fluidly connected to the reservoir; and
a cell culture matrix disposed in the reservoir and arranged as a fixed bed, the cell culture matrix comprising a substrate configured for adhering cells thereto,
wherein the cell culture matrix is configured to maintain a uniform flow within the reservoir throughout the cell culture matrix.
Claim 25, in particular, describes uniform fluid flow through the cell culture matrix.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Pat. No. 11,661,5763.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of U.S. Pat. No. 11,661,567 include limitations drawn to
A packed-bed bioreactor system for culturing cells, the system comprising:
a cell culture vessel comprising at least one interior reservoir, an inlet fluidly connected to the reservoir, and an outlet fluidly connected to the reservoir; and
a cell culture matrix disposed in the reservoir and arranged as a fixed bed, the cell culture matrix comprising a substrate configured for adhering cells thereto,
wherein the cell culture matrix is configured to maintain a uniform flow within the reservoir throughout the cell culture matrix.
Claim 2, in particular, describes uniform fluid flow through the cell culture matrix.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Pat. No. 11,920,117.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of U.S. Pat. No. 11,920,117 include limitations drawn to
A packed-bed bioreactor system for culturing cells, the system comprising:
a cell culture vessel comprising at least one interior reservoir, an inlet fluidly connected to the reservoir, and an outlet fluidly connected to the reservoir; and
a cell culture matrix disposed in the reservoir and arranged as a fixed bed, the cell culture matrix comprising a substrate configured for adhering cells thereto,
wherein the cell culture matrix is configured to maintain a uniform flow within the reservoir throughout the cell culture matrix.
Claim 13, in particular, describes uniform fluid flow through the cell culture matrix.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The Gabelle (US 20240060095) and Stobbe (US 9228579) references teach the state of the art regarding packed-bed bioreactors.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
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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.
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/NATHAN A BOWERS/Primary Examiner, Art Unit 1799
1 It is noted that the Ferrie publications 20210024868, 20200248121, 20200248120, 20200248122 and 20200248124 are all essentially identical and each represent a potential ground of rejection under 35 U.S.C. 102
2 This double patenting rejection is presented in the alternative to a 35 U.S.C. 102 rejection involving patent publication US 2020/0248120 (which would be identical to the current rejection involving US 2020/0248121). In the event that an exception is applied under 35 U.S.C. 102(b) to disqualify such an art rejection, this double patenting rejection will apply
3 This double patenting rejection is presented in the alternative to the 35 U.S.C. 102 rejection involving patent publication US 2020/0248121. In the event that an exception is applied under 35 U.S.C. 102(b) to disqualify the art rejection, this double patenting rejection will apply
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