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 statement (IDS) submitted on 10/16/23 is being considered by the examiner. Claim Status Claim s 1-6, 7-16, 30, 31, and 33-34 are pending and are examined. Claim s 17-29, and 32 are cancelled. 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 1-16, 30, 31, 33, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Saxena (US Patent 4,833,083), in view of Castillo (WO 2019/122239). Regarding Claim 1, Saxena teaches a fixed-bed bioreactor system (packed bed bioreactor. Col. 1, line 6 ) for culturing cells, the system comprising: a plurality of cell culture subunits ( Fig. 1. vessel or bioreactor , bed package or matrix 22 ) , each cell culture subunit comprising: a distribution plate comprising a major surface configured to support a cell culture substrate ( Fig. 1, plate 18 , Col. 10, line 37 ) , an inlet ( Fig. 1, an inlet cap with opening 42, Col. 10, lines 37-38) , and a cell culture substrate disposed on the major surface of the distribution plate ( Fig. 1, chamber between tubular members 13 and 16 , Col. 12, lines 55-56 ) ; and a plurality of input lines configured for supplying at least one of cells, cell culture media, nutrients, and reagents to the plurality of cell culture subunits, each input line of the plurality of input lines being fluidly connected to the inlet, wherein the plurality of outlets is configured to distribute at least one of cells, cell culture media, nutrients, and reagents from the plurality of input lines substantially uniformly across the cell culture substrate (input line 51 is connected by a line 53 to a pump 54 . Col. 14, lines 39-40 ) . Saxena teaches an outlet ( opening 35 in end cap 19 constitute an outlet collection means . Col. 11, lines 44-45 . In a different embodiment illustrated in FIGS. 7 and 8 is for large capacity applications and in circumstances where larger particle size of the matrix material is desired (such as, for example, glass, ceramic or polymer beads of the size in excess of a few tenths of a millimeter or larger. It is generally similar in operation to the FIG. 1 embodiment except that it is provided with a plurality of optional, spaced inner porous tubular members and cooperating core members so as to provide a plurality of outlet flow rather than a single central outlet flow as in the embodiment of FIG. 1. Col. 16, lines 10-20 ) . Saxena is silent to plurality of outlets disposed on the major surface and in fluid communication with the inlet. However, Castillo teaches in the related art of cell culturing and bioreactor (para [0002] ) . Fig. 11A shows bioreactor 300 includes a plurality of openings 318b serving as inlets and outlets for admitting and releasing fluid . ( See para [0013] , “ a central inlet and a plurality of radially oriented outlets ”) . Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added a plurality of openings in the device of Saxena , as taught by Castillo, to separate and redirect fluid sample components (Castillo, para [ 0095] ) . Regarding Claim 2, modified Saxena teaches t he fixed-bed bioreactor system of claim 1, further comprising a vessel comprising an interior cavity configured to house the plurality of cell culture subunits ( housing or vessel 10 ) . Regarding Claim 3, modified Saxena teaches t he fixed-bed bioreactor system of claim 2, wherein the plurality cell culture subunits are modular and individually addable and/or removable from the vessel ( Fig. 1, a bed, package or matrix 22 , two are shown in Fig. 1 ) . Regarding Claim 4, modified Saxena teaches t he fixed-bed bioreactor system of claim 2 , wherein the vessel is configured to house a variable number of cell culture subunits (the vessel is capable of housing a variable number of cell culture subunits) . Regarding Claim 5, modified Saxena teaches t he fixed-bed bioreactor system of claim 1, wherein the cell culture substrate comprises a polymer ( FIGS. 1-3, by way of example, the porous tubular members 13 and 16 may be constructed of porous polymers such as polyethylene, teflon, polypropylene and the like . Col. 12, lines 55-58 ) . Regarding Claim 6, modified Saxena teaches t he fixed-bed bioreactor system of claim 1 , wherein the cell culture substrate comprises a height h that is less than or equal to a predetermined height ( Since the direction of medium flow is across a transverse or horizontal section of the culture chamber and not through its entire length, the effective bed height of the packed column of cells or microcarriers is the relatively small distance between the outer and inner porous tubes. By restricting the bed height , the length of the flow path of the culture or reaction medium will be kept to a minimum compared to the lengthwise flow of the vertical flow type culture chambers. Col. 9, lines 13-22 ) . Regarding Claim 7, modified Saxena teaches t he fixed-bed bioreactor system of claim 6, wherein the predetermined height is about 100 mm, 50 mm, 40 mm, 30 mm, 20 mm, or 10 mm ( The annular channels 14 and 17 may have a radius of 0.01 mm to over 20 feet, depending on the size and dimensions of the bioreactor. Col. 13, lines 4-6 ) . Regarding Claim 8, modified Saxena teaches t he fixed-bed bioreactor system of claim 1 , wherein the plurality of outlets is arrayed across a diameter of the major surface ( while the outlet collection means consists of the vertical grooves 45 in core member 15', and radial passages 40, central passage 41 and threaded opening 35 as in FIG. 3. Col. 14, lines 18-20 ) . Regarding Claim 9, modified Saxena teaches t he fixed-bed bioreactor system of claim 1 , wherein the distribution plate of a first cell culture subunit of the plurality of cell culture subunits comprises a central plate bore sized to allow an input line of a second cell culture subunit of the plurality of cell culture subunits to pass through the first cell culture subunit ( an inlet end plate , cap or member generally indicated at 18, an outlet end plate cap or member generally indicated at 19, each including an inwardly protruding sections 20 and 21 . Col. 10, lines 18-21 ) . Regarding Claim 10, modified Saxena teaches t he fixed-bed bioreactor system of claim 9, wherein the cell culture substrate comprises a central substrate bore coaxially aligned with the central plate bore ( spaced passages or channels 40 and a central opening or passage 41 . Col. 11, lines 40-41 ) . Regarding Claim 11, modified Saxena teaches t he fixed-bed bioreactor system of claim 9 , wherein the inlet is disposed radially outward from the central plate bore ( an inlet end plate , cap or member generally indicated at 18, an outlet end plate cap or member generally indicated at 19, each including an inwardly protruding sections 20 and 21 . Col. 10, lines 18-21 ) . Regarding Claim 12, modified Saxena teaches t he fixed-bed bioreactor system of claim 11, wherein at least one of the plurality of input lines is curved or bent such that the input line is configured to pass through a central plate bore of a first cell culture subunit and then extend radially outward to the inlet of a second cell culture subunit ( a medium input line 51 and an output line 52 for spent cultures or reaction medium and/or cell or enzyme products. Input line 51 is connected by a line 53 to a pump 54 via a valve 55 of an on-line sampling mechanism 56, with pump 54 being connected via a line 57 to a stirred vessel 58. Col. 14, lines 37-42 ) . Regarding Claim 13, modified Saxena teaches t he fixed-bed bioreactor system of claim 1, wherein the cell culture substrate comprises at least one cored section configured to increase permeability of fluid throughout the cell culture substrate ( The porous tubular members 13 and 16 are coaxial with respect to each other and have a permeability compatible with the support or matrix material 22 for allowing a desired flow rate of reaction or culture medium to pass therethrough. Col. 10, lines 32-35 ) . Regarding Claim 14, modified Saxena teaches t he fixed-bed bioreactor system of claim 1 , further comprising a media conditioning vessel supplying the plurality of input lines ( the separation media . Col. 16, line 36 ) . Regarding Claim 15, modified Saxena teaches t he fixed-bed bioreactor system of claim 1, further comprising a plurality of media conditioning vessels supplying the plurality of input lines ( two different culture media . Col. 19, lines 21-22 ) . Regarding Claim 16, modified Saxena teaches t he fixed-bed bioreactor system of claim 1, wherein the cell culture substrate comprises a dissolvable foam scaffold ( The housing or vessel 10 and core member 15 may be constructed of poly ethylene or poly acrylic materials . Col. 12, lines 65-67. P olyethylene would be a foam material) . Regarding Claim 30, modified Saxena teaches t he fixed-bed bioreactor system of claim 1 , wherein the cell culture substrate comprises a structurally defined porous material ( The support or matrix materials of bed 22 may consist of beads, mesh or sheet s . Col. 13, lines 11-13. FIGS. 1-3, by way of example, the porous tubular members 13 and 16 may be constructed of porous polymer . Col. 12, lines 55-57 ). Regarding Claim 31, modified Saxena teaches t he fixed-bed bioreactor system of claim 30, wherein the cell culture substrate comprises a plurality of layers of the structurally defined porous material ( The support or matrix materials of bed 22 may consist of beads, mesh or sheet s . FIGS. 1-3, by way of example, the porous tubular members 13 and 16 may be constructed of porous polymer . Col. 13, lines 11-13). Regarding Claim 33, modified Saxena teaches t he fixed-bed bioreactor system of claim 30 , wherein the cell culture substrate comprises at least one of a molded polymer lattice, a 3D-printed polymer lattice sheet, and a woven mesh sheet ( The support or matrix materials of bed 22 may consist of beads, mesh or sheet s . Col. 13, lines 11-13 ) . Regarding Claim 34, modified Saxena teaches t he fixed-bed bioreactor system of claim 1 , wherein the cell culture substrate comprises a substantially uniform porosity ( FIGS. 1-3, by way of example, the porous tubular members 13 and 16 may be constructed of porous polymer . Col. 12, lines 55-57 ) . Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT JACQUELINE BRAZIN whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-1457 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8-5 . 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. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /JB/ /CHARLES CAPOZZI/ Supervisory Patent Examiner, Art Unit 1798